red. Abbreviations: Bc, brachium conjunctivum; PPRF, paramedian
Reciprocal connections between these cortical areas and the parvocell
pontine reticular formation; riMLF, rostral interstitial nucleus of the medial
ular red nucleus have been documented, mainly for the motor and
longitudinal fasciculus.
premotor areas. These projections are somatotopically organized; they
occupy the lateral portion of the parvocellular red nucleus. Prefrontal
projections are located more medially. The parvocellular red nucleus
in the midbrain. The corticospinal tract provides the magnocellular red connects with the dorsal lamina of the principal olivary nucleus through
nucleus with a collateral innervation. Both tracts influence distal move the central tegmental tract. Motor input is transmitted by the dorsal
ments of the limbs. During primate evolution, the corticospinal system lamina to segments of the D2 zone located in the motor regions of the
increases in prominence at the cost of the rubrospinal system, which cerebellum; nonmotor input is transmitted to the ansiform lobule
comes to occupy a subsidiary position in the human brain. (HVII) and the tonsil (HIX).
Climbing fibres innervating the C1, C3 and Y zones and the anterior In humans, the D2 zone accounts for most of the cerebellar hemi
interposed nucleus take their origin from the rostral dorsal accessory sphere. This is exemplified by its development (see Fig. 22.13) and by
olive, which receives a somatotopically organized cutaneous input, the size of the different components of its circuitry. In Figure 22.19,
mainly through the dorsal column and trigeminal nuclei, and contains the first ever published lithograph of a section through the pontine
a refined cutaneous map of the entire contralateral body surface tegmentum (Stilling 1846), the central tegmental tract can be recog
(Gellman et al 1983). The corticospinal and rubrospinal tracts provide nized immediately as one of the largest fibre systems in the brainstem.
the dorsal column nuclei with a collateral innervation. Several explanations have been offered for the size of the dentate and


It should be emphasized that the concept of the cerebellum as a its connections. They include the complexity of the cortical motor
motor system is closely allied to the circuitry of the C1, C3 and Y zones, system, which is a major target of the dentate nucleus. (Multiple,
and to the anterior interposed nucleus and its output systems. The interconnected premotor and posterior parietal areas involved in the
double decussation of the brachium conjunctivum and the rubrospinal preparation of movement converge on the primary motor cortex; the
and corticospinal tracts is responsible for the clinical observation that precise contribution of the cerebellum to these processes is not
lesions of the cerebellum affect the ipsilateral half of the body. For most known.) Other possible explanations are the increased connectivity of
of the other modules with predominantly cerebral cortical connections, the dentate with the prefrontal cortex subserving its nonmotor func
the functional relations are much less clear. tions (Stoodley and Schmahmann 2009), and an increase in the
The connections of the posterior interposed (globose) and dentate dentateparietal projection, given that nonmotor functions also
nuclei are arranged according to the same plan. They ascend and decus involve the parietal cortex.
sate in the brachium conjunctivum, and terminate in a group of nuclei During evolution, the shapes of the dentate and the principal olivary
at the mesodiencephalic junction that includes the parvocellular red nucleus change from compact nuclei to intricately folded sheets. This
nucleus and the nucleus of Darkschewitsch in the central grey, and in may indicate the presence of a detailed topical localization in the cor
the thalamic nuclei that project to motor, premotor, prefrontal and ticonuclear and climbing fibre afferent connections in the D2 zone, but
posterior parietal cortical areas and the frontal and parietal eye fields almost nothing is known about its intrinsic organization.


Cerebellar circuitry
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Premotor cortex
Accessory eye field Parietal eye field
M1
Prefrontal cortex
Posterior parietal cortex
Frontal eye field
Premotor cortex
Parietal eye field
M1 S1 Thalamus
Accessory eye field
Superior colliculus
Prefrontal cortex
Globose nucleus
Darkschewitsch
nucleus
Frontal eye field C2 zone
Medial tegmental tract
Posterior parietal cortex
Rostral Dorsal
A B MAO M1
face
Inferior olive
Motor M1
AIP
M1 arm
PMV
Accessory eye field Parietal eye field SMA Leg Posterior M1 leg arm
Prefrontal cortex SP Mr Ae hand Arm AIP p coa rri te et xal SMA hand 7b
Premotor cortex 9I 46d F PE MF VFace 7b 46d FEF
Frontal eye field arm Pre SMA
9I Ventral
Dorsomedial Non-motor
subnucleus Thalamus Thalamus Rostral Caudal
E
Superior colliculus
C2
Rostral
D1
Caudal dentate
Lateral
dentate D2
subnucleus
Parvocellular Parvocellular
red nucleus D1 zone red nucleus D2 zone
Medial tegmental tract Central tegmental tract
Ventral lamina PO Dorsal lamina PO
Inferior olive Inferior olive
C D F
Fig. 22.18 A, Cortical areas targeted by the cerebellothalamic pathways of the posterior interposed and dentate nuclei. The primary motor area (M1) with
the primary sensory area (S1), the premotor cortex with the posterior parietal areas and the frontal and parietal eye fields constitute interconnected
networks. B, The connections of the globose (posterior interposed) nucleus. C, The connections of the caudal pole of the dentate nucleus. D, The
connections of the rostral dentate nucleus. E, The subdivision of the rostral dentate into rostral motor and caudal non-motor divisions, showing the
location of neurones retrogradely labelled from injection sites indicated in the diagram of the cerebral cortex in D. F, The flattened cerebellar cortex


showing localization of the C2, D1 and D2 zones. Abbreviations: AIP, anterior intraparietal area; FEF, frontal eye field; PMV, ventral premotor cortex;
PO, principal olive; rostral MAO, rostral medial accessory olive; SMA, supplementary motor area; 7b, 46d, 9l, cortical areas. (D, Modified with permission
from Strick PL, Dum RP, Fiez JA 2009 Cerebellum and nonmotor function. Annu Rev Neurosci 32:413–434.)
Mossy fibre systems share several common features. Individual
AFFERENT MOSSY FIBRE CONNECTIONS
mossy fibres distribute bilaterally and give off collaterals at specific
OF THE CEREBELLUM mediolateral positions that terminate in longitudinal aggregates of
mossy fibre rosettes (see Fig. 22.11). Entire mossy fibre systems termi
Mossy fibre systems take their origin from multiple sites in the spinal nate as multiple, bilaterally distributed bands of mossy fibre terminals
cord and the brainstem. The pontocerebellar pathway is the major (Fig. 22.20A). These bands are not continuous, but are often restricted
mossy fibre system in primates. Although mossy fibre systems have to either the apices or the bases of the folia. Exteroceptive components
rarely been traced with experimental methods in primates, fMRI has of mossy fibre systems terminate superficially, whereas proprioceptive
provided information on their organization in the human cerebellum. systems terminate in the bases of the folia (Ekerot and Larson 1972)


Cerebellum
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Abducens nerve (Fig. 22.20B). The mossy fibre aggregates are not as distinct as the
Central tegmental tract Genu of facial nerve climbing fibre zones and often merge in the bases of the fissures. Mossy
fibre aggregates of different systems interdigitate or overlap; precise
information is lacking.
The termination of the spinocerebellar, reticulocerebellar, cuneocere
bellar and trigeminocerebellar tracts is restricted to the anterior and
posterior motor regions of the cerebellum, i.e. to the anterior lobe, the
simplex lobule (VI and HVI), lobule VIII and the paramedian lobule
(gracile HVIIB and biventral HVIII lobules). These lobules also receive
primary and secondary vestibulocerebellar inputs and pontocerebellar
mossy fibres relaying information from cortical motor areas. Many of
these mossy fibre systems terminate according to a somatotopical
pattern (Fig. 22.20C). A very similar somatotopical organization occurs
in the C1, C3 and Y climbing fibre zones that are restricted to the
hemisphere of the same lobules (see Fig. 22.16).
Pontine nuclei Spinocerebellar, trigeminocerebellar,
NRTP reticulocerebellar and
Descending tracts vestibulocerebellar fibres
(corticospinal etc.)
Medial lemniscus
The spinal cord is connected to the cerebellum through the spinocere
Fig. 22.19 A lithograph of a transverse section through the pons, showing
bellar and cuneocerebellar tracts, and through indirect mossy fibre
the localization of the central tegmental tract in the pontine tegmentum.
pathways relayed by the lateral reticular nucleus in the medulla oblon
Abbreviation: NRTP, nucleus reticularis tegmenti pontis. (Reproduced
gata. These pathways are all excitatory in nature. Some of them give
from Stilling B 1846 Untersuchungen über den Bau und die Verrichtungen
collaterals to the cerebellar nuclei before ending on cortical granule


des Gehirns. I. Über den Bau des Hirnknotens oder der Varolischen
cells.
Brücke. Jena, Druck und Verlag von Friedrich Make.)
Trigeminocerebellar tract
Cuneocerebellar tract
Sensory nuclei of trigeminal nerve Reticulocerebellar tract
Central cervical spinocerebellar tract
G CI CE
Dorsal column nuclei
A
DV
Exteroceptive
Lateral reticular nucleus
Proprioceptive
Anterior lobe Simplex lobule
NRL
Central cervical
nucleus C1
Central cervical
Rostral nucleus
spinocerebellar
tract
VIII
Dorsal C4-T1
spinocerebellar
B tract
Anterior lobe Intermediate
grey
Ventral
Dorsal horn
spinocerebellar
tract
Posterior thoracic
Simplex lobule T2-12
nucleus column
Paramedian lobule
L1-S2
Spinal border cells
C D
Fig. 22.20 A, The termination of spinocerebellar fibres as multiple sagittal bands in the anterior lobe of Tupaia glis. B, A sagittal section through the
cerebellum showing the termination of exteroceptive mossy fibre systems in the apices of the lobules of the anterior lobe, the simplex lobule and lobule
VIII (pyramis), and of proprioceptive systems in the bases of the fissures. C, The somatotopic organization of the termination of the exteroceptive
components of the spinocerebellar, cuneocerebellar and trigeminocerebellar tracts in the hemisphere of the anterior lobe, the simplex lobule and the
paramedian (biventral) lobule. D, The origin of the spinocerebellar, cuneocerebellar and reticulocerebellar tracts. Abbreviations: CE, external cuneate
nucleus; CI, internal cuneate nucleus; DV, nucleus of the spinal tract of the trigeminal nerve; G, gracile nucleus; NRL, lateral reticular nucleus.


Cerebellar circuitry
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The dorsal spinocerebellar tract transmits information from the ipsi Trigeminocerebellar mossy fibres stem from the ipsilateral principal
lateral lower limb (Ch. 20). It contains proprioceptive fibres that arise sensory nucleus and the nucleus of the spinal tract of the trigeminal
from neurones in the posterior thoracic nucleus (Clarke’s column) in nerve, and terminate in the hemisphere in the anterior and posterior
the thoracic and upper lumbar spinal cord, and exteroceptive fibres face regions (simplex lobule – HVI – and gracile lobule – HVIIB).
from the thoracic and lumbar dorsal horns. It enters the cerebellum in The distinct somatotopic organization of the anterior and posterior
the inferior cerebellar peduncle to terminate bilaterally in the vermis motor regions of the hemispheres is reflected in the termination of the
and hemisphere of the anterior and posterior lower limb regions. exteroceptive components of the dorsal spinocerebellar, cuneocerebel
The cuneocerebellar tract is considered as the upper limb equivalent lar and trigeminocerebellar tracts. It is much less distinct for propriocep
of the dorsal spinocerebellar tract (Ch. 20). It takes its origin from the tive systems, such as the central cervical spinocerebellar tract.
dorsal column nuclei, the exteroceptive component from the internal Reticulocerebellar mossy fibres stem from the lateral and paramed
cuneate and gracile nuclei, and the proprioceptive component from the ian reticular nuclei of the medulla oblongata (Ch. 21). The lateral
external cuneate nucleus. Both components terminate in the anterior reticular nucleus supplies major collateral projections to the cerebellar
and posterior upper limb regions: the proprioceptive component bilat nuclei. Spinoreticular fibres terminate in a somatotopical pattern within
erally in the bases of the fissures, and the exteroceptive component the ventral lateral reticular nucleus, which projects bilaterally, mainly
ipsilaterally in the apices of the lobules of the hemisphere. The extero to the vermis. Spinoreticular fibres from the cervical cord overlap with


ceptive component has been shown to terminate in multiple longitu collaterals from the rubrospinal tract and a projection from the cerebral
dinal zones congruent with the climbing fibre zones of this region; cortex, and all terminate in the dorsal part of the nucleus, which projects
these zones share the same detailed somatotopical organization as the to forelimb regions of the ipsilateral hemisphere. The cerebellar cortical
C1, C3 and the Y climbing fibre zones (Ekerot and Larson 1980). projection of the paramedian reticular nucleus is very similar to that of
The ventral spinocerebellar tract is a composite pathway. It informs the ventral lateral reticular nucleus.
the cerebellum about the state of activity of spinal reflex arcs related to Primary vestibulocerebellar mossy fibres enter the cerebellum with
the lower limb and lower trunk. Its fibres originate in the intermediate the ascending branch of the vestibular nerve, pass through the superior
grey matter and the spinal border cells of the lumbar and sacral seg vestibular nucleus and juxtarestiform body, and terminate, mainly ipsi
ments of the spinal cord, cross near their origin, and ascend close to laterally, in the granular layer of the nodule, caudal part of the uvula,
the surface as far as the lower midbrain before looping around the ventral part of the anterior lobe and bases of the deep fissures of the
entrance of the trigeminal nerve to join the superior cerebellar pedun vermis (Fig. 22.21A). Secondary vestibulocerebellar mossy fibres arise
cle. Most of these fibres cross again in the cerebellar white matter. from the superior vestibular nucleus and the caudal portions of the
The rostral spinocerebellar tract originates from cell groups of the medial and inferior vestibular nuclei, and terminate bilaterally,
intermediate zone and horn of the contralateral cervical enlargement. not only in the same regions that receive primary vestibulocerebellar
Although considered to be the upper limb and upper trunk equivalent fibres, but also in the flocculus and the adjacent ventral paraflocculus
of the ventral spinocerebellar tract, most of its fibres remain ipsilateral (the access ory paraflocculus of the human cerebellum), which lack


throughout their course. They enter the cerebellum through both the a primary vestibulocerebellar projection (Fig. 22.21B). Some of the
superior and the inferior cerebellar peduncles and terminate in the mossy fibres from the medial and inferior vestibular nuclei are
anterior and posterior vermis. cholinergic.
An upper (central) cervical spinocerebellar tract originates from a
central cervical nucleus at high cervical levels (C1–C4). The tract termi
nates bilaterally in the bases of the fissures of the entire cerebellum, CORTICOPONTOCEREBELLAR PROJECTION
lacks a somatotopical organization and conveys labyrinthine informa
tion and proprioception from neck muscles (Matsushita and Tanami The cerebral cortex is the largest single source of fibres that project
1987). to the pontine nuclei (Fig. 22.22). The fibres traverse the cerebral
Hemisphere Vermis
Primary fissure Primary fissure
Anterior lobe Simple
Folium
Culmen
Simple
Folium Tuber
Tuber
Pyramis Central lobule
Pyramis
Biventral Uvula Lingula
lobule
Nodule
Uvula
Tonsil C Nodule
Flocculus
Superior
Vestibular nerve
Lateral
Vestibular nuclei
Medial
Inferior
Vestibular ganglion
A B
Fig. 22.21 Vestibulocerebellar mossy fibre projections. A, Primary vestibulocerebellar projections from the bipolar neurones of the vestibular ganglion.
B, Secondary vestibulocerebellar projections from the vestibular nuclei. C, A sagittal section showing the distribution of both sets of afferents.


Cerebellum
346
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NOITCeS
peduncle: those from the frontal lobe occupy the medial part of the via the crossed descending branch of the superior cerebellar peduncle.
peduncle; corticonuclear and corticospinal fibres occupy its central part; The medial, visuomotor, division of the nucleus reticularis tegmenti
and fibres from the parietal, occipital and temporal lobes occupy its pontis receives visuomotor afferents from the frontal eye fields, the
lateral part. The mediolateral sequence of the fibres in the cerebral contralateral superior colliculus (the tectopontine tract) and other
peduncle is approximately maintained in their termination in the visuomotor centres in the brainstem, and targets lobule VII, the visual
pontine nuclei. Prefrontopontine fibres and the frontal eye fields vermis and the adjacent crus I, the flocculus and the adjacent ventral
project medially and rostrally; motor and premotor projections termi paraflocculus. The bilateral projection of its lateral, motor, portion
nate centrally and caudally; and parietal, occipital and temporal fibres overlaps with similar projections from the pontine nuclei. Mossy fibres
terminate in the lateral pontine nuclei (Schmahmann and Pandya from the nucleus reticularis tegmenti pontis provide the cerebellar
1997). Motor and premotor projections are somatotopically organized, nuclei with a collateral innervation complementary to that of the lateral
such that the face is represented rostrally and the hindlimb caudally in reticular nucleus. An uncrossed component of the tectopontine tract
the nuclei. In monkeys, the majority of the corticopontine fibres stem terminates in the dorsolateral corner of the pontine nuclei, where it
from motor, premotor and parietal areas. The prefrontal, general overlaps extrastriatal visual afferents.
sensory and visual projections are relatively minor (Glickstein et al
1985). A prefrontal projection from the dorsal prefrontal cortex has
been confirmed for humans (Beck 1950). Many corticopontine fibres ‘OCULOMOTOR CEREBELLUM’
are collaterals of axons that project to other targets in the brainstem


and spinal cord (Ugolini and Kuypers 1986). The pontocerebellar pro Traditionally, the flocculus and the nodulus are known as the ‘vestib
jection is almost completely crossed. Fibres from the pontine nuclei ulocerebellum’ because they maintain afferent and efferent connec
access the cerebellum via the middle cerebellar peduncle and terminate tions with the vestibular system. They also belong to the functionally
throughout the entire cerebellar cortex, with the exception of lobule X more comprehensive oculomotor division of the cerebellum, which
(nodulus). Visual cortical mossy fibre input is found in the paraflocc includes lobule VII (visual vermis), the adjacent ansiform lobule,
ulus (tonsil, HIX). The pontocerebellar projection is still incompletely dorsal lobule IX (uvula), the ventral paraflocculus (the human acces
known; the relevant literature has been reviewed by Nieuwenhuys et al sory paraflocculus) and the dorsal paraflocculus (the human tonsil).
(2008) and by Voogd and Ruigrok (2012). Figure 22.22C is a simplified The mossy fibre projection of the nucleus prepositus hypoglossi, a key
version of this projection (Glickstein et al 1985). element in the saccadeproducing system (Ch. 41), outlines the entire
The nucleus reticularis tegmenti pontis (tegmental reticular nucleus oculomotor cerebellum, with the exception of the dorsal paraflocculus
of the pons) is located along the midline, dorsal to the pontine nuclei (Belknap and McCrea 1988) (Fig. 22.23B). The function of lobule X
(see Fig. 22.22C). It gives rise to bilateral components of the middle (nodulus) is not an exclusive oculomotor one because it also influences
cerebellar peduncle and receives a projection from the cerebellar nuclei labyrinthine and postural reflexes and vegetative systems.
Extrastriatal cortex
Extrastriatal
Vestibular/optokinetic
Posterior parietal cortex
Extrastriatal cortex
NRTP
Cerebral peduncle


Fig. 22.22 The corticopontocerebellar system. A, The origin of corticopontine fibres from the cerebral cortex in the monkey (macaque). B, The relative
proportions of corticopontine neurones in different areas of the cerebral cortex of the monkey, indicated in panel A. C, A transverse section through the
pons showing the distribution of corticopontine fibres in the pontine nuclei and the nucleus reticularis tegmenti pontis (NRTP). D, The flattened cortex
of the monkey cerebellum showing the distribution of pontocerebellar mossy fibres. (B, Modified from Glickstein M, May JG, 3rd, Mercier BE 1985
Corticopontine projection in the macaque: the distribution of labelled cortical cells after large injections of horseradish peroxidase in the pontine nuclei.
J Comp Neurol 235:343–359.)
2mm
rep
sllec
dellebal
fo
rebmuN
Cingulate premotor areas
20
18
Prefrontal
16
Frontal eye fields
14
12 Premotor
10 Sensory–motor
8 Posterior parietal
25 19 6
9 24 23 4
6
M1 S1 5 2
11 10 9 8 6 25 23 4 3 5 7 19 18 17 13 22 Areas
Prefrontal cortex Frontal Premotor cortex B 24 2 14
eye fields 1
M1 S1 5
9 8 1,2,3 7
10 11 4 22 19 17 Anterior lobe
6
18 Simplex
lobule
I-V
Crus I
A
Crus II VI
VII
VIII
Ventral paraflocculus
IX
Flocculus X
Dorsal paraflocculus
Paramedian lobe
C D


Cerebellar circuitry
347
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reTPAHC
Lobules I and II
Anterior lobe
SI
Simplex lobule
Ansiform lobule VII
ANS
Paramedian lobe VII
VIII
PETR
Dorsal paraflocculus PMD
IX IX
Ventral paraflocculus
X
X PFLV
Flocculus
PFLD
FL
A B Contralateral Ipsilateral
Fig. 22.23 A, A flattened map of the cerebellar cortex of the mammalian cerebellum showing the distribution of vestibulocerebellar mossy fibres in
orange. The hatched lobules belong to the oculomotor cerebellum. B, The distribution of mossy fibres originating from the nucleus prepositus hypoglossi
outlines the oculomotor cerebellum of the squirrel monkey, with the exception of the dorsal paraflocculus (PFLD). Other abbreviations: ANS, ansiform
lobule; FL, flocculus; PETR, petrosal lobule; PFLV, ventral paraflocculus; PMD, paramedian lobule; SI, simplex lobule; VII–X, lobules VII–X. (Reproduced
with permission from Belknap DB, McCrea RA 1988 Anatomical connections of the prepositus and abducens nuclei in the squirrel monkey. J Comp
Neurol 268:13–28.)
The oculomotor cerebellum is involved in longterm adaptation of nerve, known as the accessory optic tract. These nuclei project to the
saccades, ocular stabilization reflexes and smooth pursuit (reviewed in ventrolateral outgrowth of the inferior olive, located immediately rostral
Voogd et al (2012)). The role of the flocculus and the adjacent ventral to the dorsal cap (see Fig. 22.15). The ventrolateral outgrowth innervates
paraflocculus in longterm adaptation of the vestibuloocular reflex the F1 and F3 zones. Repeated simultaneous activation of the vestibular
(VOR) has been extensively studied. It is one of the few instances where mossy fibreparallel fibre input and the climbing fibres, relaying retinal


the function of the cerebellum is clearly understood. slip, induces plastic changes in the Purkinje cell output that compen
sates for the retinal slip. Combinations of the horizontal and anterior
Vestibulo-ocular reflex canal systems ensure compensation of retinal slip in all possible planes.
Knowledge of this system has been instrumental in the concept that
climbing fibres are carriers of error signals, used in cerebellar learning
The VOR is an ancient reflex, being present in agnatha and fishes. It
(Marr 1969, Ito 1982).
stabilizes the position of the retina in space, during movements of the
head, by rotating the eyeball in the opposite direction. The VOR is an
open reflex; there is no time for a feedback connection that would
NEUROIMAGING AND THE FUNCTIONAL DIVISIONS
compensate for inaccuracies in the execution of the reflex. This function
is taken over by the longterm adaptation of the reflex by the flocculus. OF THE CEREBELLUM
The circuitry of the flocculus, similar to the VOR, is organized on the
coordinate system of the semicircular canals (Simpson and Graf 1981, Mossy fibre projections have been studied in the human brain using
van der Steen et al 1994). The VOR consists of different components. fMRI. In the cerebellum, activity in climbing fibres and Purkinje cells
One component connects the lateral (horizontal) semicircular canal, is overwhelmed by the massive activity of the mossy fibres (Diedrich
via oculomotor neurones in the vestibular nuclei, with the oculogyric sen et al 2010), which means that the modular organization of the
muscles that move the eyes in a plane colinear with the plane of the cerebellum therefore cannot be visualized with this method. The divi
lateral canal (Fig. 22.24). The anterior semicircular canal influences the sion of the human cerebellum into anterior and posterior motor and
ipsilateral superior oblique and the contralateral inferior oblique intermed iate nonmotor portions has been observed in numerous
muscles that move the eye in the plane of this canal. (For further details, neuroimaging studies (reviewed by Stoodley and Schmahmann


see Chs 38 and 41.) (2009)). The somatotopical localization in each hemisphere of the
Five Purkinje cell zones are present in the cortex of the flocculus and anterior lobe and the simplex and biventral lobules in the posterior
the adjacent ventral paraflocculus. Apart from the C2 zone, located most lobe has been confirmed with fMRI (Grodd et al 2001, Buckner et al
medially, two pairs of zones occupy its lateral portion. Zones F1 and 2011, Yeo et al 2011). A systematic somatotopical gradient has been
F3 connect with the oculomotor neurones in the vestibular nuclei, reported for the digits of the hand in the hemisphere of lobule V
subserving the anterior canal VOR. The F2 and F4 zones connect with (Wiestler et al 2011).
oculomotor neurones of the horizontal canal VOR. The flocculus and The crura of the ansiform lobule (HVII) are activated during the
ventral paraflocculus receive vestibular mossy fibre input, relaying an execution of cognitive tasks. More recently, restingstate functional con
efferent copy of the output of the vestibulooculomotor neurones. They nectivity fMRI has been used to map topographical correlations between
also receive climbing fibre input, signalling retinal slip that occurs when remote, functionally coupled regions in the cerebral cortex and the
the stabilization of the retina by the VOR is incomplete. Retinal slip is cerebellum. Several functional networks in the cerebral cortex have been
perceived by two groups of neurones in the mesencephalon. In the identified with this method (Yeo et al 2011) (Fig. 22.25). However, it
horizontal plane, it is relayed by the nucleus of the optic tract. This does not provide information on the anatomical connections or the
nucleus, located in the pretectum, receives fibres of the contralateral excitatory or inhibitory nature of the constituent areas of each of these
optic nerve via the optic tract and projects to the dorsal cap of the systems; connections between the cerebrum and the cerebellum could
inferior olive, located dorsomedial to the caudal medial accessory olive be indirect, e.g. through cortical association systems or brainstem nuclei


(see Fig. 22.15). The dorsal cap provides the F2 and F4 zones with other than the pontine nuclei. The networks are distributed in a mir
climbing fibres. Retinal slip in the plane of the anterior canal is conveyed rored fashion in the anterior and posterior cerebellum. The default
by the lateral and medial nuclei of the accessory system, which belong mode network, a network of brain regions that are active when an
to a group of nuclei located on the periphery of the rostral mesen individual is not focused on the outside world (Buckner et al 2008;
cephalon, receiving optic nerve fibres from an offshoot of the optic Commentary 3.1), occupies a central position.


Cerebellum
348
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NOITCeS
Left eye Right eye Fig. 22.24 The circuitry used by the
flocculus in long-term adaptation of the
Retinal slip in the vestibulo-ocular reflex (VOR). The
horizontal and system is organized in the planes of the
vertical planes semicircular canals. For an explanation,
see the text. Abbreviations: C2, C2
Purkinje cell zone; DC, dorsal cap;
F1–F4, floccular Purkinje cell zones
F1–F4; VLO, ventrolateral outgrowth.
(Modified with permission from Voogd J
Medial rectus
et al 2012 Visuomotor cerebellum in
and contralateral
human and nonhuman primates.
lateral rectus
Superior rectus Cerebellum 11:392–410.)
and contralateral
inferior oblique
Optic tract
Vestibular nuclei nucleus
and group Y
Accessory
Anterior semicircular canal optic system
C2 F1 F2 F3 F4
DC
VLO
Left labyrinth
Lateral semicircular canal
FEF
M1
S1
Parietal
Frontal
Primary
fissure
V
Posterior
superior
IV
Temporal fissure
A Occipital B
VI
Posterior superior fissure
VI
IV Primary
fissure VII Intercrural fissure
V
Posterior
VI superior
VIII
fissure
VII
C D Ansoparamedian fissure
Tonsil Prebiventral fissure
Somatomotor Dorsal association Default Ventral association Frontoparietal Visual
Fig. 22.25 A map of the topographical correlations between remote, functionally coupled regions in the human cerebral cortex and the cerebellum using
resting state functional connectivity fMRI. A, Networks distinguished in the cerebral cortex. B, An anterior view of the human cerebellum showing regions
that are functionally coupled to the different cerebral networks. C, A dorsal view of the human cerebellum. D, A caudal view of the human cerebellum.
Abbreviation: FEF, frontal eye field. (A, Redrawn from Yeo BTT, Krienen FM, Sepulere J 2011 The organization of the human cerebral cortex estimated


by intrinsic functional connectivity. J Neurophysiol 106:1125–1165; B–D, Reconstructions based on the transverse sections illustrated in Buckner RJ,
Krienen FM, Castellanos A 2011 The organization of the human cerebellum estimated by functional connectivity. J Neurophysiol 106:2322–2345.)


349
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Key references
KEY REFERENCES
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ment in somaticvisceral integration. Brain Res Rev 52:93–106.


CHAPTER
23
Diencephalon
The diencephalon is part of the prosencephalon (forebrain), which contralateral thalamus by an interthalamic adhesion (Fig. 18.10). The
develops from the foremost primary cerebral vesicle and differentiates boundary with the hypothalamus is marked by a faint hypothalamic
into a caudal diencephalon and rostral telencephalon. The cerebral sulcus, which curves from the upper end of the cerebral aqueduct to the
hemisphere develops from the side of the telencephalon, containing a interventricular foramen. The thalamus is continuous with the mid-
lateral ventricle. The sites of evagination become the interventricular brain tegmentum, the subthalamus and the hypothalamus.
foramina, through which the two lateral ventricles and midline third Internally, the greater part of the thalamus is divided into anterior,
ventricle communicate. The diencephalon corresponds largely to the medial and lateral nuclear groups by a vertical Y-shaped sheet of white
structures that develop lateral to the third ventricle. The lateral walls of matter, the internal medullary lamina (Figs 23.3–23.4; Table 23.2). In
the diencephalon form the epithalamus most superiorly, the thalamus addition, intralaminar nuclei lie embedded within the internal medul-
centrally, and the subthalamus and hypothalamus inferiorly. lary lamina and midline nuclei abut the lateral walls of the third ven-
tricle. The reticular nucleus forms a shell-like lateral covering to the
main nuclear mass, separated from it by an external medullary lamina
THALAMUS
of nerve fibres.
In general, thalamic nuclei both project to and receive fibres from
The thalamus plays a crucial role in many brain functions, serving as a the cerebral cortex (Jones 1985, Macchi and Jones 1997) (see Fig. 23.4).
processing and distribution centre, relaying and regulating information The whole cerebral cortex, including neocortex, paleocortex of the piri-
from the outside world and the internal milieu to the cerebral cortex form lobe and archicortex of the hippocampal formation, is reciprocally


and vice versa. It is involved in multiple activities, including conscious- connected with the thalamus. The thalamus is the major route by which
ness, sleep, memory and sensory and motor functions. Our increasing subcortical neuronal activity influences the cerebral cortex, and the
understanding of the role of the thalamus is providing insights into greatest input to most thalamic nuclei comes from the cerebral cortex.
pathological disorders of the brain and is opening up the possibility of The projection to the thalamus from the cortex is precisely recipro-
targeting its various constituent nuclei to treat a variety of disorders, cal; each cortical area projects in a topographically organized manner
including epilepsy, Parkinson’s disease, pain and psychiatric disorders to all sites in the thalamus from which it receives an input (see Table
(Table 23.1; see Fig. 23.5) (For review, see Lozano and Lipsman 2013.) 23.2). Thalamocortical fibres terminate predominantly in layer IV of
Morphologically, the thalamus is a large ovoid nuclear mass, about the cortex. Corticothalamic fibres that reciprocate ‘specific’ thalamocor-
4 cm long, which borders the dorsal part of the third ventricle (Figs tical pathways arise from modified pyramidal cells of layer VI, whereas
23.1–23.2). Its narrow anterior pole lies close to the midline and forms those reciprocating ‘non-specific’ inputs arise from typical pyramidal
the posterior boundary of the interventricular foramen. Posteriorly, an cells of layer V, and may in part be axon collaterals of other cortico-
expansion, the pulvinar, extends beyond the third ventricle to overhang subcortical pathways.
the superior colliculus (see Fig. 21.5). The brachium of the superior It is customary to consider thalamic nuclei as either ‘specific’ nuclei,
colliculus (superior quadrigeminal brachium) separates the pulvinar which mediate finely organized and precisely transmitted sensory infor-
above from the medial geniculate body below. A small oval elevation, mation to discrete cortical sensory areas, or as ‘non-specific’ nuclei, with
the lateral geniculate body, lies lateral to the medial geniculate. less precisely defined functions.


The superior (dorsal) surface of the thalamus is covered by a thin The specific nuclei are further subdivided into relay nuclei and asso-
layer of white matter, the stratum zonale. This curved surface is sepa- ciation nuclei. However, many nuclei classified as specific may also send
rated from the overlying body of the fornix by the choroid fissure with non-specific projections to widespread cortical areas. Similarly, the divi-
the tela choroidea within it. More laterally, it forms part of the floor of sion of thalamic nuclei into relay and association groups rests on the
the lateral ventricle. The lateral border of the superior surface of the assumption that relay nuclei receive a major subcortical pathway,
thalamus is marked by the stria terminalis and overlying thalamostriate whereas association nuclei are reciprocally connected to cortical areas
vein, which separate the thalamus from the body of the caudate nucleus. that are traditionally referred to as association areas and which receive
Laterally, a slender sheet of white matter, the external medullary lamina, their principal non-cortical input from other subcortical structures.
separates the main body of the thalamus from the reticular nucleus.
Lateral to this, the thick posterior limb of the internal capsule lies
between the thalamus and the lentiform complex.
The medial surface of the thalamus is the superior (dorsal) part of
the lateral wall of the third ventricle. It is usually connected to the
Table 23.1 Thalamic deep brain stimulation targets
Corpus callosum
Indication Target References
Left thalamus
Pain VPl/VPm, PVG Boccard et al 2013
Tremor VL (Vim) Benabid et al 1991, Hubble et al 1996
Epilepsy Anterior thalamus Hodaie et al 2002 Third ventricle
Obsessive–compulsive Inferior thalamic Jiménez et al 2013
Left hippocampus
disorder peduncle
Minimally conscious state CM (central thalamus) Giacino et al 2012 Left inner ear vestibular
Tourette’s syndrome CM Piedad et al 2012 apparatus (semicircular canals)


Dystonia VL (Voa/Vop), VL (Vim) Cooper 1976, Tasker et al 1988
Myoclonus–dystonia Vim Gruber et al 2010
Abbreviations: CM, centromedian nucleus of thalamus; PVG, periventricular grey; Vim, ventral intermediate Fig. 23.1 A coronal T2-weighted magnetic resonance image at the level
nucleus of thalamus (nucleus ventrointermedius); VL, ventral lateral thalamic nucleus (nucleus of the thalamus and third ventricle. (Courtesy of Professor Alan Jackson,
ventrolateralis); Voa, nucleus ventro-oralis anterior; Vop, nucleus ventro-oralis posterior; VPl, ventral Wolfson Molecular Imaging Centre, The University of Manchester,
350 posterolateral nucleus; VPm, ventral posteromedial nucleus. Manchester, UK.)


Thalamus
351
32
RETPAHC
Choroid plexus Thalamus Fig. 23.2 The principal parts of the diencephalon and
Corpus callosum Caudate nucleus (head) basal ganglia, coronal section.
Body of fornix Internal capsule
Claustrum
Insula
Putamen
Globus
pallidus
Cornu ammonis
Inferior horn Caudate nucleus (tail)
of lateral ventricle Optic tract
Hippocampus Subthalamic nucleus
Third ventricle Crus cerebri
Interpeduncular fossa Red nucleus
Ventral part of pons Substantia nigra
Table 23.2 Main thalamic nuclei and their major afferent and efferent connections The anterior nuclei are the principal recipients of the mammil-
lothalamic tract, which arises from the mammillary nuclei of the
Group Nucleus Major subcortical Major cortical System
hypothalamus.
connection connections
The mammillary nuclei receive fibres from the hippocampal forma-
Anterior Anterior Mammillary bodies Cingulate and Relay limbic tion via the fornix. The medial mammillary nucleus projects to the
(MTT) parahippocampal
ipsilateral anteroventral and anteromedial thalamic nuclei, and the
gyrus
lateral mammillary nucleus projects bilaterally to the anterodorsal
Medial Dorsomedial Amygdala, thalamic Prefrontal cortex Association
nuclei. The nuclei of the anterior group also receive a prominent cholin-
nuclei
ergic input from the basal forebrain and the brainstem.
Lateral
Ventral VA GPi, SNr Premotor cortex Relay motor The cortical targets of efferent fibres from the anterior nuclei of the
VL Ipsilateral GPi, Supplementary and Relay motor thalamus lie largely on the medial surface of the hemisphere. They
contralateral primary motor include the anterior limbic area (in front of and inferior to the corpus
cerebellum cortex
callosum), the cingulate gyrus and the parahippocampal gyrus (includ-
VPl, VPm STT to VPl, TTT to Somatosensory Relay sensory
ing the medial entorhinal cortex and the presubiculum and parasubicu-


VPm, MLT to cortex, insula
anterior surface lum). There also appear to be minor connections between the anterior
LGB Optic tract Visual cortex Visual nuclei and the dorsolateral prefrontal and posterior areas of neocortex.
MGB Auditory pathway Auditory cortex Auditory The anterior thalamic nuclei are believed to be involved in the regula-
(inferior brachium)
tion of alertness and attention and in the acquisition of memory.
Dorsal Pulvinar – LP Superior colliculus Parieto-occipito- Association
temporal
LD Pretectum and Cingulate,
superior colliculus parahippocampus MEDIAL THALAMIC NUCLEI
Intralaminar CM GPi, cerebellum Striatum, motor
cortex The single component of this thalamic region is the mediodorsal or
Reticular Widespread Widespread dorsomedial nucleus, which is particularly large in humans. Laterally,
connections connections it is limited by the internal medullary lamina and intralaminar nuclei.
Medially, it abuts the midline parataenial and reuniens (medioventral)
Abbreviations: CM, centromedian nucleus of thalamus; GPi, internal segment of globus pallidus; LD, lateral nuclei. It is divided into anteromedial magnocellular and posterolateral
dorsal nucleus of thalamus; LGB, lateral geniculate body; LP, lateral posterior nucleus of thalamus; MGB,
parvocellular parts.
medial geniculate body; MLT, medial lemniscal tract; MTT, mammillothalamic tract; SNr, substantia nigra
The smaller magnocellular division receives olfactory input from
pars reticularis; STT, spinothalamic tract; TTT, trigeminothalamic tract; VA, ventral anterior nucleus;
VL, ventral lateral nucleus; VPl, ventral posterolateral nucleus; VPm, ventral posteromedial nucleus. the piriform and adjacent cortex, the ventral pallidum, and the
amygdala.
The mediobasal amygdaloid nucleus projects to the dorsal part of
the anteromedial magnocellular nucleus, and the lateral nuclei project


There is little evidence of significant intrathalamic connectivity, but to the more central and anteroventral regions. The anteromedial mag-
there are increasing indications of non-cortical afferent pathways linked nocellular nucleus projects to the anterior and medial prefrontal cortex,
to so-called association nuclei; the extensive connectivity between the notably to the lateral posterior and central posterior olfactory areas on
reticular nucleus and other thalamic nuclei is a notable exception. the orbital surface of the frontal lobe. In addition, fibres pass to the
ventromedial cingulate cortex and some to the inferior parietal cortex
and anterior insula. These cortical connections are reciprocal.
ANTERIOR THALAMIC NUCLEI The larger, posterolateral parvocellular division connects reciprocally
with the dorsolateral and dorsomedial prefrontal cortex, the anterior
The anterior group of nuclei lie between the arms of the Y-shaped cingulate gyrus and the supplementary motor area. In addition, efferent
internal medullary lamina, and underlie the anterior thalamic tubercle fibres pass to the posterior parietal cortex.
(see Figs 21.5, 23.4). Three subdivisions are recognized: the largest The mediodorsal nucleus appears to be involved in a wide variety of
is the anteroventral nucleus, the others being the anteromedial and higher functions. Damage may lead to a decrease in anxiety, tension,
anterodorsal nuclei. aggression or obsessive thinking. There may also be transient amnesia,


DiEnCEPHAlon
352
3
noiTCES
A (VApc) and a magnocellular part (VAmc). The subcortical connections
Paraventricular nucleus Caudate nucleus
to this region are largely ipsilateral from the internal pallidum and the
Mediodorsal nucleus pars reticularis of the substantia nigra. The terminal fields from these
origins do not overlap. Fibres from the globus pallidus end in the prin-
cipal part of the ventral anterior nuclear complex. The substantia nigra
Lateral posterior
Habenular nuclei nucleus projects to the magnocellular part of the ventral anterior nuclear
complex. Corticothalamic fibres from the premotor cortex (area 6)
Reticular nucleus
Parataenial nucleus terminate in the principal part and fibres from the frontal eye field (area
8) terminate in the magnocellular part. The ventral anterior thalamus
Centromedian does not appear to receive fibres directly from the motor cortex. The
Parafascicular nucleus nucleus efferent projections from the ventral anterior nuclear complex are
incompletely known. Some pass to intralaminar thalamic nuclei and
Ventral postero-
Posterior lateral nucleus others project to widespread regions of the frontal lobe and to the
hypothalamic
anterior parietal cortex. Their functions are unclear. The ventral anterior
nucleus Ventral posteromedial
thalamus appears to play a central role in the transmission of the corti-
nucleus
cal ‘recruiting response’, a phenomenon in which stimulation of the
Zona incerta
thalamus can initiate long-lasting, high-voltage, repetitive negative elec-
trical waves over much of the cerebral cortex.
Subthalamic nucleus
Medial
Ventral lateral nucleus
mammillary nucleus Red nucleus
The ventral lateral (VL) nucleus consists of two major divisions with
distinctly different connections and functions. The anterior division, or
B Paracentral nucleus pars oralis (VLo), receives topographically organized fibres from the
Anterior nuclei Lateral dorsal nucleus ipsilateral internal pallidum. The posterior division, or pars caudalis
(VLc), receives topographically organized fibres from the contralateral
Paraventricular nucleus Caudate nucleus deep cerebellar nuclei. Additional subcortical projections have been


reported from the spinothalamic tract and the vestibular nuclei. Numer-
Mediodorsal
ous cortical afferents to both the pars oralis and the pars caudalis origi-
nucleus
nate from precentral motor cortical areas, including both area 4 and
Parataenial area 6.
nucleus The pars oralis of the ventral lateral nucleus sends efferent fibres to
the supplementary motor cortex on the medial surface of the hemi-
Reuniens sphere and to the lateral premotor cortex. The pars caudalis of the
nucleus
ventral lateral nucleus projects efferent fibres to the primary motor
Nucleus submedius Ventral lateral cortex, where they end in a topographically arranged fashion. The head
nucleus
region of area 4 receives fibres from the medial part of pars caudalis,
and the leg region receives fibres from the lateral pars caudalis.
Mammillothalamic Nucleus of
Approximately 70% of ventral lateral neurones are large relay neu-
tract prerubral field
rones, and the other 30% are local circuit interneurones. Responses can
be recorded in ventral lateral thalamic neurones during both passive
Fornix
Subthalamic and active movement of the contralateral body. The topography of its
Ventromedial nucleus connections, and recordings made within the nucleus, suggest that the
hypothalamic
pars caudalis contains a body representation comparable to that in the
nuclei
ventral posterior nucleus. In patients with tremor, clusters of ventral
lateral neurones fire in bursts that are synchronous with peripheral
Lateral tuberal nucleus
tremor: these cells have been designated as ‘tremor cells’.
Stereotaxic surgery of the ventral lateral nucleus is sometimes used
Infundibular nucleus
in the treatment of essential tremor (see Table 23.1; Fig. 23.5). In the
Fig. 23.3 The main nuclear aggregations of cell bodies in the past, thalamotomy was used extensively for the treatment of Parkinson’s
diencephalon, coronal sections. A, At the level of the mammillary bodies.
disease. The internal pallidum and the subthalamic nucleus are now
B, At the level of the tuber cinereum. Note the variations in cell size,


the preferred neurosurgical targets for Parkinson’s disease.
shape and packing density, which characterize the nuclear masses of the
thalamus, subthalamus and hypothalamus at these levels.
Ventral posterior nucleus
with confusion developing particularly over the passage of time. Much The ventral posterior (VP) nucleus is the principal thalamic relay for
of the neuropsychology of medial nuclear damage reflects defects in the somatosensory pathways. It is thought to consist of two major divi-
functions similar to those performed by the prefrontal cortex, with sions: the ventral posterolateral (VPl) and ventral posteromedial (VPm)
which it is closely linked. The effects of ablation of the mediodorsal nuclei. The ventral posterolateral nucleus receives the medial lemniscal
nuclei parallel, in part, the results of prefrontal lobotomy. and spinothalamic pathways, and the ventral posteromedial nucleus
receives the trigeminothalamic pathway. Connections from the vestibu-
lar nuclei and lemniscal fibres terminate along the ventral surface of the
LATERAL THALAMIC NUCLEI
ventral posterior nucleus.
There is a well-ordered topographic representation of the body in
The lateral nuclear complex, lying lateral to the internal medullary the ventral posterior nucleus. The ventral posterolateral nucleus is
lamina, is the largest division of the thalamus. It is divided into dorsal organized so that sacral segments are represented laterally and cervical
and ventral tiers of nuclei. The lateral dorsal nucleus, lateral posterior segments medially. The latter abut the face area of representation
nucleus and the pulvinar all lie dorsally. The lateral and medial genicu- (trigeminal territory) in the ventral posteromedial nucleus. Taste fibres
late nuclei lie inferior to the pulvinar near the posterior pole of the synapse most anteriorly and ventromedially within the ventral postero-
thalamus. The ventral-tier nuclei are the ventral anterior, ventral lateral lateral nucleus.
and ventral posterior nuclei. At a more detailed level, single body regions are represented as
curved lamellae of neurones, parallel to the lateral border of the VP
Ventral anterior nucleus
nucleus, such that there is a continuous overlapping progression of


adjacent receptive fields from dorsolateral to ventromedial. Consider-
The ventral anterior (VA) nuclear complex lies at the anterior pole of ably less change in location of receptive field on the body is seen when
the ventral nuclear group. It is limited anteriorly by the reticular nucleus passing anteroposteriorly through the nucleus. While not precisely der-
and posteriorly by the ventral lateral nucleus, and lies between the matomal in nature, these curvilinear lamellae of cells probably derive
external and internal medullary laminae. It consists of a principal part from afferents related to a few adjacent spinal segments. There is


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A B
D
C
Fig. 23.5 Magnetic resonance images from four different patients with neurological or psychiatric disorders, showing the position of deep brain-
stimulating (DBS) electrodes. A, Bilateral anterior thalamic DBS for epilepsy. B, Left thalamic DBS for pain, with electrodes in the sensory relay nucleus
(ventral caudal nucleus of the thalamus) laterally and the periventricular grey medially. C, DBS electrode in the ventral intermediate nucleus of the
thalamus in a patient with essential tremor. D, Bilateral inferior thalamic peduncle DBS electrodes in a patient with obsessive–compulsive disorder.


Thalamus
353
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Superolateral surface of hemisphere Medial surface of hemisphere
Mediodorsal nucleus
Nuclei of the midline
Anterior nuclear group
Interthalamic adhesion
Reticular nucleus
Ventral anterior nucleus
Pulvinar
Ventral lateral nucleus
Centromedian nucleus
Medial geniculate body
Dorsal lateral nucleus
Ventral posterolateral nucleus
Lateral geniculate body Lateral posterior nucleus
Intralaminar nuclei
Ventral posteromedial nucleus
Fig. 23.4 The main nuclear masses of the thalamus (viewed from the lateral aspect in the lower illustration), colour-coded to indicate the areas of
cerebral neocortex with which they are interconnected. The lack of colour in the centromedian, intralaminar and reticular nuclei and in areas of the frontal
and temporal lobes is not related to the colour code. The reticular nucleus lies lateral to the main mass of the thalamus. Only the anterior pole of the
reticular nucleus is shown, its posterior extent being depicted by the heavy interrupted line.
considerable distortion of the body map within the nucleus, reflecting pale-staining cells, which are less densely packed than those of the
the differences in the density of peripheral innervation that occur in lateral nucleus. The ventral nucleus receives fibres from the central
different body regions, e.g. many more neurones respond to stimula- nucleus of the ipsilateral inferior colliculus via the inferior quadrigemi-
tion of the hand than of the trunk. Within a single lamella, neurones nal brachium and also from the contralateral inferior colliculus. The
in the anterodorsal part of the nucleus respond to deep stimuli, includ- nucleus contains a complete tonotopic representation. Low-pitched
ing movement of joints, tendon stretch, and manipulation of muscles. sounds are represented laterally, and progressively higher-pitched
Most ventrally, neurones once again respond to deep stimuli, particu- sounds are encountered as the nucleus is traversed from lateral to
larly tapping. Intervening cells within a single lamella respond only to medial. The dorsal nucleus receives afferents from the pericentral
cutaneous stimuli. This organization has been confirmed by recordings nucleus of the inferior colliculus and from other brainstem nuclei of


made in the human ventral posterior nucleus. the auditory pathway. A tonotopic representation has not been described
The ventral posterior nucleus projects to the primary somatic sensory in this subdivision and cells within the dorsal nucleus respond to a
cortex (SI) of the postcentral gyrus and to the second somatic sensory broad range of frequencies. The magnocellular medial nucleus receives
area (SII) in the parietal operculum. The posterior part of the ventral fibres from the inferior colliculus and from the deep layers of the
posteromedial nucleus projects to the insular cortex. Within the primary superior colliculus. Neurones within the magnocellular subdivision
sensory cortex, the central cutaneous core of the ventral posterior may respond to modalities other than sound. However, many cells
nucleus projects solely to area 3b; dorsal and ventral to this, a narrow respond to auditory stimuli, usually to a wider range of frequencies
band of cells projects to both area 3b and area 1. The most dorsal and than neurones in the ventral nucleus. Many units show evidence of
ventral deep stimulus receptive cells project to areas 3a and 2. The binaural interaction, with the leading effect arising from stimuli in the
whole nucleus projects to the second somatic sensory area. contralateral cochlea. The ventral nucleus projects primarily to the
primary auditory cortex. The dorsal nucleus projects to auditory areas
Medial geniculate nucleus surrounding the primary auditory cortex. The magnocellular division
projects diffusely to auditory areas of the cortex and to adjacent insular
and opercular fields.
The medial geniculate nucleus, which is a part of the auditory pathway,
is located within the medial geniculate body, a rounded elevation situ-
Lateral geniculate nucleus
ated posteriorly on the ventrolateral surface of the thalamus, and sepa-
rated from the pulvinar by the superior quadrigeminal brachium. It
receives fibres travelling in the inferior quadrigeminal brachium. Three The lateral geniculate body, which is part of the visual pathway, is a
major subnuclei – medial, ventral and dorsal – are recognized within small, ovoid, ventral projection from the posterior thalamus (see Figs


it. The inferior brachium separates the medial (magnocellular) nucleus, 21.5, 23.4). The superior quadrigeminal brachium enters the postero-
which consists of sparse, deeply staining neurones, from the lateral medial part of the lateral geniculate body dorsally, lying between the
nucleus, which is made up of medium-sized, densely packed and darkly medial geniculate body and the pulvinar.
staining cells. The dorsal nucleus overlies the ventral nucleus and The lateral geniculate nucleus is an inverted, somewhat flattened,
expands posteriorly; it is, therefore, sometimes known as the posterior U-shaped nucleus and is laminated (Fig. 23.6A). Its internal organiza-
nucleus of the medial geniculate. It contains small- to medium-sized, tion is usually described on the basis of six laminae, although seven or


Diencephalon
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Single lemniscal axons have an extended anteroposterior terminal
zone within the nucleus. Rods of cells running the length of the antero-
posterior, dorsoventrally orientated, lamellae respond with closely
similar receptive field properties and locations, derived from a small
bundle of lemniscal afferents. It appears, therefore, that each lamella
contains the complete representation of a single body part, e.g. a finger.
Lamellae consist of multiple narrow rods of neurones, orientated
anteroposteriorly, each of which receives input from the same small
region of the body that is represented within the lamella, and from the
same type of receptors. These thalamic ‘rods’ form the basis for both
place- and modality-specific input to columns of cells in the somatic
sensory cortex. Spinothalamic tract afferents to the ventral posterola-
teral nucleus terminate throughout the nucleus. The neurones from
which these axons originate appear to be mainly of the ‘wide-dynamic-
range’ class, responding to both low-threshold mechanoreceptors and
high-threshold nociceptors; a smaller proportion of neurones respond
exclusively to high-threshold nociceptors. Some neurones respond to
temperature changes. There is evidence that spinothalamic tract neu-
rones carrying nociceptive and thermal information terminate in a
distinct nuclear area, identified as the posterior part of the ventral
medial nucleus (VMpo).


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A Lateral geniculate nucleus Substantia nigra eight may be present. The laminae are numbered 1–6, from the inner-
most ventral to the outermost dorsal (Fig. 23.6BC). Laminae 1 and 2
consist of large cells, the magnocellular layers, whereas layers 4–6 have
smaller neurones, the parvocellular laminae. The apparent gaps between
laminae are called the interlaminar zones. Most ventrally, an additional
superficial, or S, lamina is recognized.
The lateral geniculate nucleus receives a major afferent input from
the retina. The contralateral nasal hemiretina projects to laminae 1, 4
and 6, whereas the ipsilateral temporal hemiretina projects to laminae
2, 3 and 5. The parvocellular laminae receive axons predominantly of
X-type retinal ganglion cells, i.e. more slowly conducting cells with
sustained responses to visual stimuli. The faster-conducting, rapidly
adapting Y-type retinal ganglion cells project mainly to the magnocel-
lular laminae 1 and 2, and give off axonal branches to the superior
colliculus. A third type of retinal ganglion cell, the W cells, which have
large receptive fields and slow responses, project to both the superior
colliculus and the lateral geniculate nucleus, where they terminate par-
ticularly in the interlaminar zones and in the S lamina.
The lateral geniculate nucleus is organized in a visuotopic manner
and it contains a precise map of the contralateral visual field. The verti-
cal meridian is represented posteriorly, the peripheral anteriorly, the
upper field laterally, and the lower field medially. Similar precise, point-
to-point representation is also found in the projection of the lateral
geniculate nucleus to the visual cortex. Radially arranged inverted pyra-
mids of neurones in all laminae respond to a single small area of the
contralateral visual field and project to a circumscribed area of cortex.
Hippocampus Optic tract Crus cerebri
The termination of geniculocortical axons in the visual cortex is con-


sidered in detail elsewhere.
B Central region The efferent fibres of the lateral geniculate nucleus pass principally
to the primary visual cortex (area 17) in the banks of the calcarine
Pregeniculate nucleus sulcus. It is possible that additional small projections pass to extrastriate
visual areas in the occipital lobe, possibly arising primarily in the inter-
laminar zones. For further reading on processing in the lateral genicu-
late nucleus, see Casagrande and Ichida (2011).
6
Lateral dorsal nucleus
5
The lateral dorsal nucleus is the most anterior of the dorsal tier of lateral
4
nuclei. Its anterior pole lies within a splitting of the internal medullary
L 3 M lamina, and posteriorly it merges with the lateral posterior nucleus.
Subcortical afferents to the lateral dorsal nucleus are from the pretectum
2 and superior colliculus. It is connected with the cingulate, retrosplenial
and posterior parahippocampal cortices, the presubiculum of the hip-
pocampal formation, and the parietal cortex.
1
Lateral posterior nucleus
Hilus The lateral posterior nucleus, which lies dorsal to the ventral posterior
nucleus, receives its subcortical afferents from the superior colliculus.
C Posterior pole It is reciprocally connected with the superior parietal lobe. Additional
connections have been reported with the inferior parietal, cingulate and
Parvocellular Magnocellular
medial parahippocampal cortex.
Pulvinar
The pulvinar corresponds to the posterior expansion of the thalamus,
which overhangs the superior colliculus (see Fig. 21.5). It has three
major subdivisions, which are the medial, lateral and inferior pulvinar
L M nuclei. The medial pulvinar nucleus is dorsomedial and consists of
compact, evenly spaced neurones. The inferior pulvinar nucleus lies
6 3 2 1 laterally and inferiorly, and is traversed by bundles of axons in the
mediolateral plane, an arrangement that confers a fragmented appear-
ance of horizontal cords or sheets of cells separated by fibre bundles.
The inferior pulvinar nucleus lies most inferiorly and laterally, and is a
more homogeneous collection of cells.


The subcortical afferents to the pulvinar are uncertain. Medial and
L: lateral
lateral pulvinar nuclei may receive fibres from the superior colliculus.
M: medial
It has been suggested that the inferior pulvinar nucleus receives fibres
1–6: cell laminae
both from the superior colliculus and directly from the retina, and that
Fig. 23.6 A, A coronal section showing the lateral geniculate nucleus. it contains a complete retinotopic representation.
B–C, Coronal sections through the lateral geniculate nucleus illustrating The cortical targets of efferent fibres from the pulvinar are wide-
the laminar arrangement of neurones (B) near its central region and (C) spread. In essence, the medial pulvinar nucleus projects to association
near its posterior pole. (A, Photograph by Kevin Fitzpatrick, London.) areas of the parietotemporal cortex, whereas lateral and inferior pulvi-
nar nuclei project to visual areas in the occipital and posterior tempo-
ral lobes. Thus, the inferior pulvinar nucleus connects with the striate
and extrastriate cortex in the occipital lobe, and with visual association
areas in the posterior part of the temporal lobe. The lateral pulvinar
nucleus connects with extrastriate areas of the occipital cortex, with


Diencephalon
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Aside from retinal afferents, the lateral geniculate nucleus receives a
major corticothalamic projection, the axons of which ramify densely in
the interlaminar zones. The major part of this projection arises from
the primary visual cortex, Brodmann’s area 17, but smaller projections
from extrastriate visual areas pass to the magnocellular and S laminae.
Other afferents include: fibres from the superficial layer of the superior
colliculus (which terminate in the interlaminar zone between laminae
1 and 2, and 2 and 3, and around lamina S); noradrenergic fibres from
the locus coeruleus; serotoninergic afferents from the midbrain raphe
nuclei; and cholinergic fibres from the pontine and mesencephalic
reticular formation.


Hypothalamus
355
32
RETPAHC
posterior parts of the temporal association cortex and with the parietal intralaminar nuclei may contribute to thalamic neglect, i.e. the unilat-
cortex. The medial pulvinar nucleus connects with the inferior parietal eral neglect of stimuli originating from the contralateral body or extra-
cortex, with the posterior cingulate gyrus and with the widespread personal space. This may arise particularly from unilateral damage to
areas of the temporal lobe, including the posterior parahippocampal the centromedian–parafascicular complex. The latter has been targeted
gyrus and perirhinal and entorhinal cortex. It also has extensive con- in humans for the neurosurgical control of pain and epilepsy. Bilateral
nections with prefrontal and orbitofrontal cortices. Similarly, the injury to the posterior intralaminar nuclei leads to a kinetic mutism
lateral pulvinar nucleus may also connect with the rostromedial pre- with apathy and loss of motivation. A second syndrome associated with
frontal cortex. damage involving the intralaminar nuclei is that of unilateral motor
Little is known of the functions of the pulvinar. The inferior pulvinar neglect, in which there is contralateral paucity of spontaneous move-
nucleus contains a complete retinotopic representation, and lateral and ment and motor activity.
medial pulvinar nuclei also contain visually responsive cells. However,
the latter nucleus, at least, is not purely visual – other modality responses
can be recorded and some cells may be polysensory. Given the complex- MIDLINE NUCLEI
ity of functions of the association areas to which they project, particu-
larly in the temporal lobe (e.g. perception, cognition and memory), it There is considerable divergence between different authors as to which
is likely that the role of the pulvinar in modulating these functions is elements of the medial diencephalon constitute the nuclei of the
equally complex. midline thalamic group. In the present account, the midline group of
Anteriorly, the major subdivisions of the pulvinar blend into a nuclei includes those medial thalamic structures ventral to the central
poorly differentiated region, within which several nuclear components medial nucleus, i.e. the rhomboid and reuniens nuclei, together with


have been recognized, including the anterior or oral pulvinar, the supra- the parataenial nuclei more dorsolaterally.
geniculate limitans nucleus and the posterior nuclei. The connectivity The midline nuclei receive subcortical afferent fibres from the
of this complex is also not well understood. It is recognized that differ- hypothalamus, the periaqueductal grey matter of the midbrain, the
ent components receive subcortical afferents from the spinothalamic spinothalamic tract and the medullary and pontine reticular formation.
tract and the superior and inferior colliculi. Cortical connections centre They are the major thalamic target of ascending noradrenergic and
primarily on the insula and adjacent parts of the parietal operculum serotoninergic axons from the locus coeruleus and raphe nuclei respec-
posteriorly. Stimulation of this region has been reported to elicit pain, tively, and they also receive a cholinergic input from the midbrain.
and large lesions may alleviate painful conditions. Similarly, excision Efferents from the midline nuclei pass to the hippocampal formation,
of its cortical target in the parietal operculum, or small infarcts in this the amygdala and the nucleus accumbens. Additional thalamocortical
cortical region, may result in hypoalgesia. axons reach the cingulate, and possibly orbitofrontal, cortex. The dual
cortical and basal nuclear relationship of these nuclei has often led to
their being considered a part of the intralaminar system. The cortical
INTRALAMINAR NUCLEI projections are reciprocal. The relationships of the midline nuclei
clearly identify them as part of the limbic system. There is some evi-
The term intralaminar nuclei refers to collections of neurones within dence that they may play a role in memory and arousal, and, pathologi-
the internal medullary lamina of the thalamus (see Fig. 23.4). Two cally, may be important in the regulation of seizure activity.
groups of nuclei are recognized. The anterior (rostral) group is subdi-
vided into central medial, paracentral and central lateral nuclei. The
RETICULAR NUCLEUS


posterior (caudal) intralaminar group consists of the centromedian and
parafascicular nuclei. The designations central medial and centrome-
dian are open to confusion; however, they are an accepted part of the The reticular nucleus is a curved lamella of large, deeply staining fusi-
terminology of thalamic nuclei in common usage. The centromedian form cells that wraps around the lateral margin of the thalamus, sepa-
nucleus is much larger, is considerably expanded in humans in com- rated from it by the external medullary lamina. Anteriorly, it curves
parison with other species, and is importantly related to the globus around the rostral pole of the thalamus to lie between it and the pre-
pallidus, deep cerebellar nuclei and motor cortex. Anteriorly, the inter- thalamic nuclei, notably the bed nucleus of the stria terminalis. The
nal medullary lamina separates the mediodorsal nucleus from the nucleus is so named because it is criss-crossed by bundles of fibres that,
ventral lateral complex. It is occupied by the paracentral nucleus later- as they pass between thalamus and cortex, produce a reticular
ally, and the central medial nucleus ventromedially, as the two laminae appearance.
converge towards the midline. A little more posteriorly, the central The nucleus is thought to receive collateral branches of corticotha-
lateral nucleus appears dorsally in the lamina as the latter splits to lamic, thalamocortical and probably thalamostriatal and pallidotha-
enclose the lateral dorsal nucleus. More posteriorly, at the level of lamic fibres as they traverse it. It receives an additional, probably
the ventral posterior nucleus, the lamina splits to enclose the ovoid cholinergic, afferent pathway from the nucleus cuneiformis of the mid-
centromedian nucleus. The smaller parafascicular nucleus lies more brain. Broadly speaking, the afferents from the cortex and thalamus
medially. are topographically arranged. The reticular nucleus contains visual,
The anterior intralaminar nuclei, i.e. central medial, paracentral and somatic and auditory regions, each with a crude topographic represen-


central lateral, have reciprocal connections with widespread cortical tation of the sensorium concerned. Cells within these regions respond
areas. There is some evidence of areal preference: the central lateral to visual, somatic or auditory stimuli with a latency, suggesting that
nucleus projects mainly to parietal and temporal association areas; the these properties arise from activation by thalamocortical axon collater-
paracentral nucleus to occipitotemporal and prefrontal cortex; and the als. Only in areas where representations abut do cells show modality
central medial nucleus to orbitofrontal and prefrontal cortex and to the convergence.
cortex on the medial surface. In contrast, the posterior nuclei, i.e. cen- The efferent fibres from the reticular nucleus pass into the body of
tromedian and parafascicular nuclei, have more restricted connections, the thalamus and are GABAergic. The projections into the main tha-
principally with the motor, premotor and supplementary motor areas. lamic nuclei broadly, but not entirely, reciprocate the thalamoreticular
Both anterior and posterior intralaminar nuclei also project to the connections. There may also be projections to the contralateral dorsal
striatum. Many cells throughout the anterior nuclei have branched thalamus. The reticular nucleus is believed to function in gating infor-
axons, which pass to both the cortex and the striatum. Dual projections mation relayed through the thalamus.
are less frequent in the posterior nuclei. The thalamostriate projection
is topographically organized. The posterior intralaminar nuclei receive
HYPOTHALAMUS
a major input from the internal pallidum. Additional afferents come
from the pars reticularis of the substantia nigra, the deep cerebellar
nuclei, the pedunculopontine nucleus of the midbrain, and possibly The hypothalamus consists of only 4 cm3 of neural tissue, or 0.3% of
the spinothalamic tract. The anterior nuclei have widespread subcortical the total brain. Nevertheless, it contains the integrative systems that, via
afferents. The central lateral nucleus receives afferents from the spi- the autonomic and endocrine effector systems, control fluid and elec-


nothalamic tract, and all component nuclei receive fibres from the trolyte balance, food ingestion and energy balance, reproduction, ther-
brainstem reticular formation, the superior colliculus and several pre- moregulation, and immune and many emotional responses.
tectal nuclei. Afferents to all intralaminar nuclei from the brainstem The hypothalamus extends from the lamina terminalis to a vertical
reticular formation include a prominent cholinergic pathway. plane posterior to the mammillary bodies, and from the hypothalamic
The precise functional role of the intralaminar nuclei is unclear. They sulcus to the base of the brain beneath the third ventricle. It lies beneath
appear to mediate cortical activation from the brainstem reticular for- the thalamus (see Fig. 16.6) and anterior to the tegmental part of
mation and to play a part in sensory–motor integration. Damage to the the subthalamus and the mesencephalic tegmentum. Laterally, it is


DiEnCEPHAlon
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and spinal cord. Damage to the anterior hypothalamus, e.g. during
surgery for suprasellar extensions of pituitary tumours, can result in an
Gyri recti of the frontal lobe uncontrollable rise in body temperature. Projections to the ventrome-
dial hypothalamus conjointly regulate food intake; damage to these
Olfactory tract structures during surgery for hypothalamic lesions (e.g. craniopharyn-
Optic nerve gioma) can result in uncontrolled eating and consequent obesity. Stim-
Optic chiasma ulation in the posterior part of the hypothalamus induces sympathetic
Anterior perforated arousal, which produces vasoconstriction, piloerection, shivering and
substance increased metabolic heat production. Circuitry mediating shivering is
Optic tract located in the dorsomedial posterior hypothalamus. However, this does
not imply the existence of discrete parasympathetic and sympathetic
Tuber cinereum with
‘centres’. Stimuli in many different parts of the hypothalamus can cause
attached infundibular stem
(pituitary stalk) profound changes in heart rate, cardiac output, vasomotor tone, periph-
eral resistance, differential blood flow in organs and limbs, the fre-
Mammillary body quency and depth of respiration, motility and secretion in the alimentary
Crus cerebri tract, erection and ejaculation.
Posterior perforated
substance
(in interpeduncular fossa) HYPOTHALAMIC NUCLEI
Trochlear nerve
Oculomotor nerve
The hypothalamus contains a number of neuronal groups that have
Pons been classified on phylogenetic, developmental, cytoarchitectonic, syn-
Trigeminal nerve aptic and histochemical grounds into named nuclei, many of which are
not very clearly delimited, especially in the adult. While the hypotha-
Fig. 23.7 The inferior aspect of the hypothalamus and surrounding lamus contains a few large myelinated tracts, many of the connections
structures. The cut end of the trochlear nerve on the left side has folded are diffuse and unmyelinated, and the precise paths of many afferent,
during processing. (Photograph by Kevin Fitzpatrick, London.) efferent and intrinsic connections are uncertain.


The hypothalamus can be divided anteroposteriorly into chiasmatic
(supraoptic), tuberal (infundibulotuberal) and posterior (mammillary)
bordered by the anterior part of the subthalamus, internal capsule and regions, and mediolaterally into periventricular, intermediate (medial)
optic tract. Structures in the floor of the third ventricle reach the pial and lateral zones. Between the intermediate and lateral zones is a para-
surface in the interpeduncular fossa. From anterior to posterior they are median plane, which contains the prominent myelinated fibres of the
the optic chiasma, the tuber cinereum, the median eminence and the column of the fornix, the mammillothalamic tract and the fasciculus
infundibular stalk, the mammillary bodies and the posterior perforated retroflexus. For this reason, some authors group the periventricular and
substance (Fig. 23.7). The latter lies in the interval between the diverg- intermediate zones as a single medial zone. These divisions are artificial
ing crura cerebri, and is pierced by small central branches of the poste- and functional systems cross them. The main nuclear groups and myeli-
rior cerebral arteries. It contains the small interpeduncular nucleus, nated tracts are illustrated in Figures 23.8 and 23.9 and are summarized
which receives terminals of the fasciculus retroflexus (habenulo- in Table 23.3.
interpeduncular tract) of both sides, and has other connections with The periventricular zone of the hypothalamus borders the third
the mesencephalic reticular formation and mammillary bodies. ventricle. In the anterior wall of the ventricle is the vascular organ
The mammillary bodies are smooth, hemispherical, pea-sized emi- of the lamina terminalis (OVLT, organum vasculosum), which is con-
nences, lying side by side, anterior to the posterior perforated substance, tinuous dorsally with the median preoptic nucleus and subfornical
each with nuclei enclosed in fascicles of fibres derived largely from the organ. On each side in the chiasmatic region are part of the preoptic


fornix. The tuber cinereum, between the mammillary bodies and the nucleus, the small, sexually dimorphic suprachiasmatic nucleus and
optic chiasma, is a convex mass of grey matter. From it, the median, periventricular neurones, which are medial to, and blend with, the
conical, hollow infundibulum becomes continuous ventrally with the paraventricular nucleus. In the tuberal region, the periventricular cell
posterior lobe of the pituitary. Around the base of the infundibulum is group expands around the base of the third ventricle to form the arcuate
the median eminence, which is demarcated by a shallow tubero- nucleus, which overlies the median eminence. In the posterior region,
infundibular sulcus. the narrow periventricular zone is continuous laterally with the poste-
Hypothalamic lesions have long been linked with widespread and rior hypothalamic area and behind that with midbrain periaqueductal
bizarre endocrine syndromes and with metabolic, visceral, motor and grey matter. The periventricular zone also contains a prominent peri-
emotional disturbances. The hypothalamus has major interactions with ventricular fibre system.
the neuroendocrine system and the autonomic nervous system, inte-
Suprachiasmatic nucleus
grating responses to both internal and external afferent stimuli with the
complex analysis of the world provided by the cerebral cortex.
The hypothalamus controls the endocrine system in a variety of Although it contains only a few thousand neurones, the suprachias-
ways: through magnocellular neurosecretory projections to the poste- matic nucleus is a remarkable structure. Sometimes called the master
rior pituitary; through parvocellular neurosecretory projections to the circadian pacemaker in mammals, it appears to be the neural substrate
median eminence (these control the endocrine output of the anterior for day–night cycles in motor activity, body temperature, plasma con-
pituitary and thereby the peripheral endocrine organs); and via the centration of many hormones, renal secretion, sleeping and waking,
autonomic nervous system (Nieuwenhuys 1985). The posterior pitui- and many other variables. Lesions of the suprachiasmatic region lead


tary neurohormones, vasopressin and oxytocin, are primarily involved to a disordered sleep–wake cycle. (For further reading, see Mohawk and
in the control of osmotic homeostasis and various aspects of reproduc- Takahashi (2011).)
tive function, respectively. Through its effects on the anterior pituitary, The suprachiasmatic nucleus has two principal subdivisions: ventro-
the hypothalamus influences the thyroid gland (thyroid-stimulating lateral and dorsomedial. Retinal fibres terminate in the ventrolateral
hormone, TSH), suprarenal cortex (adrenocorticotrophic hormone, subdivision, characterized by neurones immunoreactive for vasoactive
ACTH), gonads (luteinizing hormone, LH; follicle-stimulating hormone, intestinal polypeptide (VIP). This appears to be a general input zone,
FSH; prolactin), mammary gland (prolactin), and the processes of which also receives afferents from the midbrain raphe and parts of the
growth and metabolic homeostasis (growth hormone, GH). lateral geniculate nucleus of the thalamus. The dorsomedial subdivision
The hypothalamus influences both parasympathetic and sympa- has relatively sparse afferent innervation, and characteristically contains
thetic divisions of the autonomic nervous system. In general, parasym- parvocellular neurones immunoreactive for arginine vasopressin (AVP).
pathetic effects predominate when the anterior hypothalamus is Neurones within the suprachiasmatic nuclei that receive direct retinal
stimulated; sympathetic effects depend more on the posterior input do not respond to pattern, movement or colour. Instead, they
hypothalamus. operate as luminance detectors, responding to the onset and offset of
Stimulation of the anterior hypothalamus and paraventricular light, and their firing rates vary in proportion to light intensity, thereby
nucleus can cause decreased blood pressure and decreased heart synchronizing to the light–dark cycle.
rate. Stimulation in the anterior hypothalamus induces sweating and The suprachiasmatic nucleus receives glutamatergic afferents from
vasodilation (and thus heat loss) via projections that pass through retinal ganglion cells that entrain the rhythm to the light–dark cycle,


the medial forebrain bundle to autonomic centres in the brainstem but these are not essential for the production of the rhythm, which


Hypothalamus
357
32
RETPAHC
Lateral hypothalamic area (magenta)
Perifornical nucleus (red band)
Lateral preoptic area
Position of intermediate nucleus
Hypothalamic sulcus Interthalamic adhesion Fornix
Septum pellucidum
Tuberomammillary nucleus
Anterior commissure
Lateral tuberal nuclei
Lamina terminalis
A Supraoptic nucleus
Paraventricular nucleus
Posterior nucleus
Preoptic nucleus
Mammillothalamic tract
Dorsomedial nucleus
Lateral hypothalamic area (magenta) Ventromedial nucleus
Position of intermediate nucleus
Red nucleus
Pars dorsolateralis
Supraoptic
Pars dorsomedialis nucleus
Pars ventromedialis
Basis pedunculi
Oculomotor nerve Lateral tuberal nuclei
Optic tract
Pons Mammillary body Infundibular nucleus
B Infundibular stalk
Fig. 23.8 The hypothalamic region of the left cerebral hemisphere viewed from the medial aspect and dissected to display the major hypothalamic
nuclei. A, The medially placed nuclear groups have been removed. B, Both lateral and medial groups are included. Lateral to the fornix and the
mammillothalamic tract is the lateral hypothalamic region, in which the tuberomammillary nucleus is situated posteriorly and the lateral preoptic nucleus
rostrally. Surrounding the fornix is the perifornical nucleus, which joins the lateral hypothalamic area with the posterior hypothalamic nucleus. The
medially placed nuclei (yellow) fill in much of the region between the mammillothalamic tract and the lamina terminalis, but also project caudal to the
tract. The lateral tuberal nuclei are situated ventrally, largely in the lateral hypothalamic area. The supraoptic nucleus may form three rather separate
parts. The intermediate nuclei form three groups between the supraoptic and paraventricular nuclei. (Modified from Nauta WJH, Haymaker W 1969
Hypothalamic nuclei and fibre connections. In: Haymaker W, Anderson E, Nauta WJH (eds) The Hypothalamus, by permission of Charles C Thomas
Publisher, Ltd, Springfield, Illinois.)


persists in the blind. It contains many different neurotransmitters, lamina terminalis. LH and FSH are secreted by the adenohypophysis
including vasopressin, VIP, neuropeptide Y (NPY) and neurotensin. in circhoral (hourly) pulses, which are stimulated by GnRH, and are
Axons from the suprachiasmatic nucleus pass to many other hypotha- influenced by central monoamine and γ-aminobutyric acid (GABA),
lamic nuclei, including the paraventricular, ventromedial, dorsomedial by oestrogen and progesterone acting indirectly through other neu-
and arcuate nuclei. rones, by corticotrophin-releasing factor, and by endogenous opioids.
Neurones producing growth hormone-releasing hormone (GHRH) Gonadotrophin-inhibitory hormone (GnIH) is produced by neurones
are largely restricted to the arcuate nucleus. Some extend dorsally into located in the dorsomedial hypothalamic area that project to the
the periventricular nucleus and laterally into the retrochiasmatic area. median eminence. GnIH inhibits gonadotrophin synthesis and release
Their fibres run through the periventricular region to the neurovascular by decreasing the activity of GnRH neurones and also by acting directly
zone of the median eminence. The neurones receive afferent informa- on pituitary gonadotropes.
tion from glucose receptors in the ventromedial nucleus. Inputs from Corticotrophin-releasing hormone (CRH) is located primarily
the hippocampal–amygdala–septal complex could explain the release in parvocellular periventricular neurones. They are profoundly stimu-
of GH during stress. In humans, midline defects such as septo-optic lated by neurogenic (limbic input) and hypoglycaemic (ventromedial
dysplasia are associated with defective GH secretion. Dopamine has a nucleus) stress, and are also controlled by negative feedback by
stimulatory effect. cortisol.
Neurones producing somatostatin (growth hormone release- Thyrotrophin-releasing hormone (TRH) neurones are rather more
inhibiting hormone) are located in the periventricular nucleus. GHRH widely distributed in the periventricular, ventromedial and dorsomedial


and somatostatin are secreted in intermittent (3–5-hour) reciprocal nuclei. TRH release is influenced by core temperature, sensed in the
pulses but the origin of the pulses is unclear. A large pulse of GH is anterior hypothalamus, and by negative feedback of thyroid hormones.
secreted at the onset of slow-wave sleep. Somatostatin also inhibits It stimulates release of pituitary TSH and also acts to excite cold-sensitive
release of pituitary TSH. neurones in the preoptic area and to inhibit warm-sensitive ones.
Neurones producing gonadotrophin-releasing hormone (GnRH) Other tubero-infundibular arcuate neurones contain NPY and
and projecting to the median eminence are located in the periventricu- neurotensin. Arcuate neurones containing pro-opiomelanocortin pep-
lar and arcuate nuclei. Other GnRH neurones are found in the median tides project to the periventricular nucleus rather than the median
preoptic area, but these appear to project to the vascular organ of the eminence.