bulb. cell bodies of mitral cells are located in a distinct layer deep in the olfactory glomeruli. each mitral cell extends a primary dendrite to a single glomerulus, where the dendrite gives rise to an elaborate tuft of branches onto which the primary olfactory axons synapse. each glomerulus in the mouse model, for example, contains approximately 25 mitral cells which receive innervation from approximately 25,000 olfactory receptor axons. the convergence increases the sensitivity of mitral cells to odor detection. general the most superficial layer of the cortex is the molecular or plexiform layer. it has a dense network of tangentially oriented fibers and cells made of axons of martinotti cells and stellate cells, as well as apical dendrites of pyramidal cells. apical dendrites from pyramidal cells in the external granular layer and more prominently the external pyramidal layer project into the molecular layer. there are also in the plexiform layer gabaergic synaptic connections between the apical dendrites of granular cells and the basal dendrites of the tufted cells and mitral cells. some of the apical dendrites from the pyramidal cells in the cerebral cortex may be up to 10μm in diameter. the apical dendrite of a large pyramidal neuron in the cerebral cortex may contain thousands of spines. spines in the cerebral cortex vary in size by several orders of magnitude from one region to another. smallest have a length of 0.2μm and a volume of about 0.04 cubic micrometres and the largest a length of 6.5μm and a volume of 2 cubic micrometres. neocortex pyramidal cells are the majority class of cells in the neocortex. they have high density of dendritic spines, prominent apical dendrites, and axons that project out of the cortex as well as locally within it. soma for these appear in all layers except i. spiny stellate cells are distinguished from pyramidal cells here by the absence of the apical dendrite and the fact that their axons also do not leave the cortex. these cells are thought to begin as pyramidal neurons and then retract their apical dendrites and axons. cerebellum a defining characteristic of purkinje cells in the cerebellum is the apical dendrite. development dendritic arbor formation for pyramidal neurons in the cortices occurs progressively beginning in late embryonic stages of development and extending well into post-natal periods. many dendrites of pyramidal neurons in deep layers branch and form connections in layer iv, while some extend to more superficial layers. pyramidal cell dendrites in layer iii branch to form arbors in layer i. thalamocortical afferents will make synaptic contact with dendrites in layer iv while myriad of other inputs will meet dendrites in layer i. the post-synaptic structure is driven in part by signals from incoming afferent fibers and through life there is plasticity in the synapses. the formation of these arbors is regulated by the strength of local signals during development. several patterns in activity control the development of the brain. action potential changes in the retina, hippocampus, cortex, and spinal cord provide activity-based signals both to the active neurons and their post-synaptic target cells. spontaneous activity originating within neuronal gap junctions, the cortex sub-plate, and sensory inputs are all involved in the cell signaling that regulates dendrite growth. useful models of dendritic arbor formation are the xenopus tadpoles, which are transparent in early stages of larval development and allow for dye-labeled neurons to be repeatedly imaged in the intact animal over several weeks. it has been observed from this and other models that there are rapid dendritic branch additions and retractions which lengthen the overall dendrite and accumulate more branches. this mirrors the development of axonal branches (both have a lifetime of approximately 10min). this activity decreases as neurons mature. signals including glutamate from axon branches may increase branch additions. within the xenopus tadpole model, several signaling systems have been studied. for example, in optical tectal neurons, dendrite arbor growth occurs approximately at the onset of retinal input. many on the caudal tectate have “silent” synapses which are modulated only by n-methyl-d-aspartate (nmda) receptors. as neurons mature, alpha-amino-3-hydroxy-5-methyl-4-isoxazole (ampa) receptors are added, increasing synaptic transmission. neuron and dendrite development are nmda dependent. rapidly growing dendrite arbors are more dynamic than slowly growing ones and dendrites themselves play an active role in their own development. it has been shown in studies that transport of hcn (hyperpolarization activated cyclic nucleotide) gated channel isoforms to dendritic fields of ca1 pyramidal neurons in the hippocampus occurs in an age-specific manner in the developing hippocampus. among the signals studied in this system is camkii a calcium/calmodulin-regulated serine/threonine kinase which is required for induction by not expression of long-term potentiation. camkii mrna is targeted to dendrites and both protein synthesis and enzyme activity are increased by strong synaptic input. expression in xenopus indicates that it is associated with the transition to slowed arbor growth. this suggests that activity promotes the reduction of dendrite branch growth and retraction, stabilizing the arbor configuration. the following pattern emerges for this system: branches with nmda-only receptors mature and recruit ampars, which stabilize the branches. these stable branches then add new branches with nmdar-only synapses which either stabilize through ampars or retract. ampar additions are present in adults and account for synaptic plasticity. camkii strengthening of signals results from the selective trafficking of glur1 ampars into synapses. in long term depression (ltd) the glur subunits of ampars undergo endocytosis. temporal differences in signaling over the course of neuron maturation suggest that the most promising studies of arbor development and synaptogenesis in the future are going to occur in intact brain systems. another model studied in apical dendrite development is the rat. injection of tetanus toxin into neonatal rats has shown that growth of apical dendrites occurs normally during signal deprivation while basal dendrite growth is restricted. this indicates that neural activity is critical to new dendrite formation. however, animal models may be insufficient to elucidate the complexity of these systems. pyramidal cells in ca1, for example, are 30 times as thick in humans as they are in rats. the entorhinal cortex is also subdivided into as few as 8 and as many as 27 sections in humans (depending on the system used), whereas there are only 2 in rats and 7 in monkeys. the connections of the dentate gyrus and entorhinal cortex are also more sophisticated in humans. in rats and cats, a very large reciprocal connection exists between the entorhinal cortex and the olfactory system. in primates this connection is absent and there are highly differentiated connections between the multimodal parasensory and paralimbic cortices and the ec which are not as evident in rats and cats. the increased size of the primate subiculum may proportionally enhance its effects on the entorhinal cortex. sexual dimorphism pyramidal cell dendritic arbor formation in the anterior cingulate cortex (layers 2/3) is more complex in males and, in contrast the orbital prefrontal regions, dendritic arborization is greater in females suggesting a fundamental difference in the prefrontal organization in males and females. in rats, for example, exposure to estrogen either exogenously or endogenously during proestrous leads to increases in ca1 spine densities. these differences may be due to the presence of gonadal hormones which have been demonstrated to influence cell structure in the hippocampus. treatment with testosterone has been shown to affect cortical neuron structure. pathology stress response and ptsd dendritic spines, post-synaptic structures receiving mainly excitatory input, are sensitive to experiences in development including stress episodes or drugs. studies have shown that prenatal stress reduces complexity, length, and spine frequency of layer ii/iii pyramidal apical dendrites in rat and primate models. dendritic atrophy has been described in hippocampal formation and prefrontal cortex in both models. chronic stress has been shown to reduce the arbor complexity and total dendritic length of apical dendrite trees of ca3 pyramidal neurons in the hippocampus as well. chronic stress-induced changes in behavior have usually been attributed to changes in the hippocampus which is a primary neural target of glucocorticoids and is involved in many of the behaviors altered by corticosteroid administration. both chronic stress and corticosteroid administration result in extensive atrophy of apical dendrites of pyramidal neurons in hippocampal area ca3, and these dendrites do not atrophy when cyanoketone (a corticosteroid blocker) is given. this dendrite atrophy is mediated by both glutaminergic and serotonergic systems (administration of either nmda receptor antagonist cgp 43487 or serotonin uptake inhibitor tianeptine prevents atrophy). cell death has been reported to prolonged treatment. stress hormones in small doses do not themselves cause damage but magnify effects of other dangerous agents, including excitotoxins, hypoglycemia, hypoxia and ischemia. damaging effects of stress in these neurons are thought to be related to expression of brain-derived neurotrophic factor (bdnf), the expression of which is reduced in stressed conditions and increased with the administration of anti-depressants. the prefrontal cortex is also a target for the glucocorticoids in stress (dexamethasone binds to receptors in frontal and prefrontal cortex at about 75% of concentration of hippocampus). endogenous regulation of corticosteroid receptors is indicated by altered binding of the previously mentioned compound in the prefrontal cortex with administration of corticosteroids. furthermore, regulation of stress activities involves the prefrontal cortex. lesions in rat prefrontal cortices impair spontaneous alternation, radial maze performance, and passive avoidance. in primates these impair inhibition of line-of-sight responses. chronic administration of corticosteroids decreases 5-ht1a receptor binding, 5-ht2 receptor binding, serotonin levels, and expression of neural cell adhesion molecule (a cell-surface macromolecule involved in regulating aspects of synapse stabilization). these changes indicate structural change follows stress hormone elevation. studies of dendritic morphological changes indicate that elevation of stress hormones in layer ii-iii of the prefrontal cortex causes no observable change in the structure or distribution of basal dendrites. the apical dendrites, however, show a significant redistribution in stress-hormone treated animal brains, which is measured using scholl analysis. scholl analysis estimates the amount and distributions of dendrite material by counting numbers of intersections of dendrites with an overlay of concentric rings centered at the soma. medial prefrontal cortex layer ii-iii pyramidal neurons showed significant reorganization with a 21% increase in proximal apical dendrite arbors and a decrease of 58% in distal apical dendrite arbors. these results are in contrast to the changes in the hippocampal ca3 dendritic arbors, in which only regressive changes were observed. one possible explanation proposed in these studies is that the atrophy of distal dendrites in ii-iii layer pyramidal neurons results directly from the loss of input from changed ca3 pyramidal neurons, as both ca1 and ca3 project directly into the medial prefrontal cortex. it has been determined from electrophysiological data that excitatory synapses on proximal apical dendrites of prefrontal cortex pyramidal neurons serve to amplify excitatory post-synaptic potential (epsp) signals generated in distal apical dendrites. this suggests that reduction in distal dendrite mass due to the stress hormone elevation may result in an increase in proximal apical dendrite complexity as the proximal apical dendrites attempt to offset the reduced distal apical dendrite signals. serotonergic alterations and alterations in glutamate release in the prefrontal cortex indicate that the neurochemical mechanisms altering structure in both the hippocampus and prefrontal cortex are similar. the division of management between extrinsic and intrinsic inputs to the dendrites in the piriform cortex (mentioned above) is also seen to a lesser degree in the medial prefrontal cortex. this indicates that stress-induced changes to apical dendrites increase the relative emphasis of intra-cortical signals at the expense of extra-cortical signals. in studies of hierarchical animals, it was observed that the dominant and subordinate animals show the same degree of dendritic reorganization, indicating that the dendritic atrophy with stress is not degree-dependent. metabolic disease in neurometabolic diseases, distended storage neurons are markedly swollen and pear shaped, with the nucleus and the nissl bodies displaced toward the apical dendrites. examples of neuron metabolic storage diseases are the sphingolipid storage diseases which typically involve malfunctioning hydrolases in the lysosomes responsible for the degradation of these lipids: type 2 and type 3 gaucher disease gm1 gangliosidosis and gm2 gangliosidosis this swelling is shown, for instance, in tay–sachs disease, a gm2 accumulation due to defective beta-hexosaminidase. visible in this disorder are large mega-neurite formations. cellular mechanisms it has been indicated that there is a "chicken and egg" issue in the study of models relating to epilepsy because on the one hand the