Cerebellar Nuclei: Key Roles for Strategically Located Structures
With the exception of vestibular information, cerebellar nuclei represent the unique source of output of the cerebellar circuitry. The fastigial (FN), globose/emboliform (interpositus, IN), and dentate (DN) nuclei receive inhibitory GABAergic signals from Purkinje neurons and send back fibers to the cerebellar cortex. The numerous GABAA inhibitory synapses between cerebellar cortex and cerebellar nuclei allow responses to high-frequency Purkinje cell firing [1]. Cerebellar nuclei receive excitatory collaterals of mossy fibers and climbing fibers, especially via AMPA and NMDA receptors [2]. A subset of small neurons in cerebellar nuclei project to the inferior olivary complex, providing a feedback to the inferior olive. Cerebellar nuclei thus integrate the converging excitatory and inhibitory signals to provide the final output of the cerebellar circuits. Each cerebellar nucleus has a separate somatotopic representation of the body [3]. The projections to different cerebral cortical areas originate from distinct areas of cerebellar nuclei. In particular, the DN is spatially divided into a motor and nonmotor zone, with a closed loop from the nucleus to the cerebral cortex and back to the nucleus. Cerebellar nuclei control differentially the medial and lateral motor systems and their functions [4]. The vestibular and FN are concerned with the control of eye movements, control of head orientation, stance, and gait. FN can be functionally divided into rostral and caudal components [4, 5]. The rostral portion is involved in the control of somatic musculature, head orientation, and eye-gaze shifts [4]. The caudal FN plays key roles in saccade generation and smooth pursuit [6]. The IN is particularly active during the modulation of various reflexes and sensory feedback [7]. The eyeblink responses are typically associated with a modulation of activity in behaving animals [8]. The intermediate cortex and the IN fire in relation to the antagonist muscle group [9, 10], in agreement with a role in damping the limb oscillations and compensation of errors [11]. The IN participates in the excitability of the stretch reflexes [12]. The DN is especially concerned with voluntary movements of the extremities, including reaching and grasping. Dentate neurons preferentially fire at the onset of movement triggered by mental associations [4]. An influential theory is that cerebellar nuclei constitute temporal pattern generators that can contribute to the precise temporal control of motor or cognitive events [13, 14]. The plasticity of Purkinje neurons–cerebellar nuclei synapses is based upon synaptically driven changes in excitability and LTP/LTD [15–17]. In conjunction with the LTP/LTD in cerebellar cortex and the adaptations occurring in mossy/ climbing fibers, such plasticity allows for reshaping of patterns of activities in cerebellar nuclei. On the basis of GABA decarboxylase isoform 67 (GAD67) expression and electrophysiological properties, three types of cerebellar nuclei neurons have been described [18]: the large non-GABAergic neurons (“GADnL”; putatively corresponding to the glutamatergic projection neurons) and two classes of smaller neurons, one M. Manto :N. Oulad Ben Taib Service de Neurologie et Neurochirurgie, ULB Erasme, Brussels, Belgium