Connectivity and convergence of single corticostriatal axons

The distribution of synapses formed by corticostriatal neurons was measured to determine the average connectivity and degree of convergence of these neurons and to search for spatial inhomogeneities. Two kinds of axonal fields, focal and extended, and two striatal tissue compartments, the patch (striosome) and matrix, were analyzed separately. Electron microscopic examination revealed that both kinds of corticostriatal axons made synapses at varicosities that could be identified in the light microscope, and each varicosity made a single synapse. Thus, the distribution of varicosities was a good estimate of the spatial distribution of synapses. The distance between axonal varicosities was measured to determine the density of synaptic connections formed by one axon within the volume occupied by a striatal neuron. Intersynaptic distances were distributed exponentially, except that synapses were rarely located <4 microm apart. The mean distance between synapses was approximately 10 microm, so axons made a maximum of 40 synapses within the dendritic volume of a spiny neuron. There are approximately 2840 spiny neurons located within the volume of the dendrites of one spiny cell (Oorschot, 1996), so each axon must contact 相似文献   

A role for N-methyl-D-aspartate receptors in the regulation of synaptogenesis and expression of the polysialylated form of the neural cell adhesion molecule in the developing striatum

Striatal development proceeds during a protracted postnatal period in rats. In the dorsolateral striatum, the number of asymmetric synapses, formed mostly by glutamatergic afferents innervating the dendritic spines of medium-sized striatal neurons, increases during the 3rd postnatal week and then rapidly declines before reaching adult levels. The polysialylated form of the neural cell adhesion molecule (PSA-NCAM), which is widely expressed along neuronal membranes early in development, becomes progressively localized to synapses, and is no longer detectable in remaining synapses after synaptic pruning has occurred. Administration of MK-801, an antagonist of N-methyl-D-aspartate receptors, on day 20, either peripherally or locally into the striatum, decreases asymmetric synapse number by 30% and totally abolishes immunolabelling for PSA-NCAM in the dorsolateral striatum.     

Expression of different isoforms of nitric oxide synthase in experimentally denervated and reinnervated skeletal muscle

Denervated muscle fibers express enhanced levels of stress and apoptosis-associated proteins and undergo apoptosis. In experimentally denervated and reinnervated rat facial muscle, we now evaluate changes in the expression patterns of different isoforms of nitric oxide synthase (NOS)-generating nitric oxide (NO), which mediates oxidative stress and apoptosis. Physiological expression of NOS corresponds to a constant sarcolemmal staining pattern for neuronal NOS (nNOS) and a patchy sarcolemmal and weak sarcoplasmic labeling for the endothelial NOS-isoform, with no expression for inducible NOS (iNOS). Denervated muscle displayed distinct downregulation of nNOS with preserved expression of dystrophin. Also, denervated and immediately reinnervated muscle fibers showed decreased expression of nNOS. However, muscle fibers reinnervated for 10 weeks revealed a restored physiological expression of nNOS. There were no changes in the expression of endothelial and inducible NOS. As NO is known to induce growth arrest and collapse of neuronal growth cones, downregulation of NOS may contribute to promotion of axonal regeneration by aiding formation of new endplates. NO is upregulated in reinnervated muscle fibers and thus prevents polyneural hyperinnervation by extrajunctional synapses. Furthermore, downregulation of NOS during denervation is compatible with the finding that low levels of NO contribute to apoptosis instead of necrosis in disease states of oxidative stress.     

Pattern of expression of highly polysialylated neural cell adhesion molecule in the developing and adult rat striatum

In rats, morphological and synaptic maturation of the striatum, a brain area involved in the control of movement and in cognitive behaviour, proceeds for several weeks postnatally. Little is known, however, about the molecular events associated with the final maturation of the striatum. In particular, there is little information on molecules playing a role in cell adhesion, a phenomenon of particular importance for neuronal development. We have examined the time course and topography of expression of the highly polysialylated form of the neural cell adhesion molecule in the rat striatum during postnatal development and in the adult, and compared it to growth-associated protein-43, a marker of axonal growth. As earlier during development [Aaron L. I. and Chesselet M.-F. (1989) Neuroscience 28, 701-710], immunolabelling for polysialylated neural cell adhesion molecule was very intense in the entire striatum at postnatal days 17-19. At postnatal days 21 and 22, loss of polysialylated neural cell adhesion molecule immunoreactivity in the caudal part of the striatum contrasted with the persistence of immunoreactivity at more rostral levels. Most of the striatum was devoid of polysialylated neural cell adhesion molecule immunoreactivity by postnatal day 25. At this age, as well as in the striatum of adult rats, immunolabelling was only observed along the ventricular edge of the striatum. In contrast to polysialylated neural cell adhesion molecule immunoreactivity, immunolabelling for growth-associated protein-43 had reached its adult pattern by postnatal day 17, indicating that polysialylated neural cell adhesion molecule persists beyond the period of major axonal growth. In the adult, an area of stronger growth associated protein-43 immunoreactivity overlapped with the region which retained immunoreactivity to polysialylated neural cell adhesion molecule. The results indicate that, in the developing rat striatum, the neural cell adhesion molecule remains highly sialylated not only during the ingrowth of cortical and nigral inputs but also during the formation of dendritic spine and synaptogenesis. Loss of polysialyated neural cell adhesion molecule occurs at the time of emerging spontaneous activity in cerebral cortex, and precedes the development of mature responses to cortical stimulation and adult membrane properties in a majority of striatal neurons.     

Phenotype of striatal cells expressing c-Fos following amphetamine treatment of rats with intrastriatal dopaminergic grafts

Activation of the nigrostriatal dopaminergic system by psychostimulants such as amphetamine increases c-Fos expression in the striatum, mostly in the striatonigral substance P-ergic pathway. This effect is greatly reduced in the neostriatum deprived of dopaminergic afferents. Dopaminergic grafts implanted into the denervated neostriatum restore the reactivity of the striatum to amphetamine. However, the number of striatal neurons expressing c-Fos is greatly increased in the graft-bearing striatum compared with the normal striatum. We examined whether this increase in the number of c-Fos-expressing neurons corresponds to the recruitment of a new neuron population, or whether it reflects an increase in the proportion of substance P-ergic neurons exhibiting activation of c-Fos. Adult rats received a unilateral 6-hydroxydopamine lesion of the ascending dopaminergic mesotelencephalic pathway, and a suspension of embryonic mesencephalic neurons was subsequently implanted into the denervated neostriatum. Three months after implantation, animals were injected with d-amphetamine (5 mg/kg) and killed 2 h later. In the first experiment, striatal sections were processed to visualize both c-Fos protein, by immunohistochemistry, and preproenkephalin A or substance P, by in situ hybridization. In the second experiment, c-Fos and neuropeptide Y were visualized on the same sections. In addition, some sections incubated with anti-c-Fos antibody were counterstained with toluidine blue in order to determine whether cholinergic neurons were expressing c-Fos following amphetamine treatment. The density of neurons expressing c-Fos following amphetamine treatment was three-fold higher in the graft-bearing striata than in the striata of control animals. Approximately 75% of the c-Fos expressing cells were substance P-ergic in control animals whereas 6% were enkephalinergic and only a few were neuropeptide Y-ergic or cholinergic. Similar proportions were found in the graft-bearing striatum, signifying that the pattern of activation of c-fos following amphetamine administration is not changed by the graft. Thus, the increased expression of c-Fos predominantly reflects a graft-induced increase in the proportion of neurons expressing c-Fos within the same population of neurons which normally expresses c-Fos in the striatum, i.e. the striatonigral substance P-ergic neurons; there is no recruitment of a new neuronal population. This increased activation of the striatonigral substance P-ergic pathway may underlie the abnormal behavioural reactions brought about by amphetamine-induced stimulation of the implanted dopaminergic neurons.     

Activation of corticostriatal pathway leads to similar morphological changes observed following haloperidol treatment

Treatment with haloperidol, a dopamine receptor D-2 antagonist, for one month resulted in an increase in the mean percentage of asymmetric synapses containing a discontinuous, or perforated, postsynaptic density (PSD) [Meshul et al. (1994) Brain Res., 648:181-195] and a change in the density of striatal glutamate immunoreactivity within those presynaptic terminals [Meshul and Tan (1994) Synapse, 18:205-217]. We speculated that this haloperidol-induced change in glutamate density might be due to an activation of the corticostriatal pathway. To determine if activation of this pathway leads to similar morphological changes previously described following haloperidol treatment, GABA (10(-5) M, 0.5 microliters) was injected into the thalamic motor (VL/VM) nuclei daily for 3 weeks. This treatment resulted in an increase in the mean percentage of striatal asymmetric synapses containing a perforated PSD and an increase in the density of glutamate immunoreactivity within nerve terminals of asymmetric synapses containing a perforated or non-perforated PSD. Subchronic injections of GABA into the thalamic somatosensory nuclei (VPM/VPL) had no effect on the mean percentage of synapses with perforated PSDs but resulted in a small, but significant, increase in density of glutamate immunoreactivity. Using in vivo microdialysis, an acute injection of GABA (10(-5) M, 15 microliters) into VL/VM resulted in a prolonged rise in the extracellular level of striatal glutamate. The increase in asymmetric synapses with perforated PSDs and in glutamate immunoreactivity within nerve terminals of the striatum following either subchronic haloperidol treatment or GABA injections into VL/VM suggest that an increase in glutamate release may be a common factor in these two experiments. It is possible that the extrapyramidal side effects associated with haloperidol treatment may be due, in part, to an increase in release of glutamate within the corticostriatal pathway.     

Remodeling of neuronal circuitries in human temporal lobe epilepsy: increased expression of highly polysialylated neural cell adhesion molecule in the hippocampus and the entorhinal cortex

Neuronal loss and axonal sprouting are the most typical histopathological findings in the hippocampus of patients with drug-refractory temporal lobe epilepsy (TLE). It is under dispute, however, whether remodeling of neuronal circuits is a continuous process or whether it occurs only during epileptogenesis. Also, little is known about the plasticity outside of the hippocampus. We investigated the immunoreactivity of the highly polysialylated neural cell adhesion molecule (PSA-NCAM) in the surgically removed hippocampus and the entorhinal cortex of patients with drug-refractory TLE (n=25) and autopsy controls (n=7). Previous studies have shown that the expression of PSA-NCAM is associated with the induction of synaptic plasticity, neurite outgrowth, neuronal migration, and events requiring remodeling or repair of tissue. In patients with TLE, the optical density (OD) of punctate PSA-NCAM immunoreactivity was increased both in the inner and outer molecular layers of the dentate gyrus, compared with controls. The intensity of PSA-NCAM immunoreactivity in the inner molecular layer correlated with the duration of epilepsy, severity of hippocampal neuronal loss, density of mossy fiber sprouting, and astrogliosis. In TLE patients with only mild neuronal loss in the hippocampus, the density of infragranular immunopositive neurons was increased twofold compared with controls, whereas in TLE patients with severe neuronal loss, the infragranular PSA-NCAM-positive cells were not present. In the hilus, the somata and tortuous dendrites of some surviving neurons were intensely stained in TLE. PSA-NCAM immunoreactivity was also increased in CA1 and in layer II of the rostral entorhinal cortex, where immunopositive neurons were surrounded by PSA-NCAM-positive fibers and puncta. Our data provide evidence that synaptic reorganization is an active process in human drug-refractory TLE. Moreover, remodeling is not limited to the dentate gyrus, but also occurs in the CA1 subfield and the entorhinal cortex.     

Pigeon basal ganglia: insights into the neuroanatomy underlying telencephalic sensorimotor processes in birds

This paper reviews the organization of the avian and mammalian striatum. The striatum receives input from virtually the entire rostrocaudal and mediolateral expanse of the cerebral cortex. The corticostriatal projections appear to be glutamatergic, forming excitatory synapses in the striatum. Another major projection to the avian striatum that also appears to be glutamatergic stems from a set of nuclei in the dorsal zone of the avian thalamus that are comparable to the mammalian intralaminar, mediodorsal, and midline nuclei. Furthermore, the striatum receives a massive projection from dopaminergic neurons of the ventral tegmental area and substantia nigra in the midbrain tegmentum. In return, the midbrain tegmentum receives a direct GABAergic/substance P-ergic/ dynorphinergic projection from the striatum, as well as an indirect one formed by GABAergic/substance P-ergic/ dynorphinergic and GABA-ergic/enkephalinergic striatal neurons projecting to the pallidum in the first step, and pallidal GABAergic/LANT6/parvalbumin neurons projecting to the midbrain tegmentum in the second step. In addition to its projection neurons, the striatum possesses GABAergic and cholinergic interneurons. One motor output pathway of the striatum runs via the pallidum and dorsal thalamic ventral tier nulei to the motor cortex. In addition to this pathway, birds possess a major descending pathway from the basal ganglia to the tectum via the GABAergic nucleus spiriformis lateralis in the pretectum. On hodological and topological grounds, similar nuclei, although not GABAergic, can be found in mammals. Finally, an other striatal motor output is formed by a sequential GABAergic pathway from the basal ganglia via the substantia nigra to the tectum. In conclusion, it appears that the organization of the avian and mammalian basal ganglia is similar rather than different.     

Neurite outgrowth stimulated by L1 requires calcium influx into neurons but is not associated with changes in steady state levels of calcium in growth cones

L1, NCAM and N-cadherin are cell adhesion molecules (CAMs), present on neuronal growth cones, which promote cell-contact dependent axonal growth by activating a second messenger pathway in neurons that requires calcium influx through L- and N-type calcium channels. In the present study we show that two of these CAMs, (L1 and N-cadherin) can stimulate neurite regeneration from axotomised adult dorsal root ganglion (DRG) neurons cultured in vitro and that this response can be fully inhibited by agents that block or negate the effect of calcium influx into the neurons. However although the response required calcium influx into neurons, it was not associated with an increase in the steady state levels of calcium in neuronal growth cones. These results suggest that small localised changes, or increases in the rate of calcium cycling, in growth cones and/or filopodia, are more important for regulating axonal growth than changes in the steady-state level of calcium.     

Regulation of astroglial-derived dopaminergic neurotrophic factors by interleukin-1 beta in the striatum of young and middle-aged mice

Interleukin-1 beta (IL-1 beta) can induce dopaminergic axonal sprouting in the denervated striatum of parkinsonian animals. In order to determine whether IL-1 beta effects on dopaminergic axonal sprouting are mediated by the induction of astroglial-derived dopaminergic neurotrophic factors, effects of IL-1 beta treatment on acidic and basic fibroblast growth factor (aFGF and bFGF) and glial cell line-derived growth factor (GDNF) gene expression were examined in primary striatal astrocyte cultures and after in vivo administration. We found a selective induction of bFGF mRNA synthesis but not aFGF or GDNF mRNA after IL-1 beta treatment both in vitro and in vivo. This suggests that bFGF may be the putative endogenous dopaminergic neurotrophic factor mediating lesion-induced plasticity of dopamine neurons. In addition, to determine why recovery from injury becomes reduced with age, we examined whether there was an aging-associated decline in the ability of IL-1 beta to induce the synthesis of neurotrophic factors in middle-aged animals compared to young mice. Interestingly, IL-1 beta stimulated a greater induction in bFGF mRNA levels in the middle-aged mice compared to young mice. These results suggest that the regulation of bFGF and possibly its receptor signaling efficacy may vary as the brain ages.     

Early patterning of prelimbic cortical axons to the striatal patch compartment in the neonatal mouse

The striatum receives excitatory input from virtually the entire cerebral cortex. In the adult, this input is segregated into two functionally distinct compartments of the striatum, the patch (striosome) and matrix regions. This study determined whether the patterning of corticostriatal afferents from the prelimbic cortex to the striatal patch compartment develops during the early period of collateral formation or instead at the time of peak synaptogenesis. Initial formation of corticostriatal axon collaterals was observed by embryonic day (E) 19. Quantification of corticostriatal collaterals revealed a significant increase in the number and complexity of collateral branches at postnatal day 6 as compared to E19. Concomitant with the increase in collateral branching, a heterogeneous pattern of collateralization consisting of parallel rows of corticostriatal collaterals was observed in the medial striatum. In addition to the rows, clusters of corticostriatal axons occurred more laterally. These clusters colocalized with patches of dense tyrosine hydroxylase-positive fibers, a marker for the striatal patch compartment in the neonatal mouse. Together, these data indicate that corticostriatal patterning occurs during the period of early axon collateralization resulting in a segregation of corticostriatal axon collaterals from the prelimbic cortex to the striatal patch compartment.     

Decreased probability of neurotransmitter release underlies striatal long-term depression and postnatal development of corticostriatal synapses

Changes in synaptic efficacy are crucial for the development of appropriate neural circuits and brain information storage. We have investigated mechanisms underlying long-term depression (LTD) at glutamatergic synapses in the striatum, a brain region important in motor performance and cognition, and a target for Huntington and Parkinson diseases. Induction of striatal LTD is dependent on postsynaptic depolarization and calcium influx through L-type channels. Surprisingly, LTD maintenance appears to involve a decrease in the probability of neurotransmitter release from presynaptic terminals as evidenced by increases in paired-pulse facilitation and the coefficient of variation of synaptic responses that are tightly associated with LTD expression. Furthermore, both the apparent probability of neurotransmitter release and the magnitude of LTD decrease concomitantly during postnatal development, consistent with the idea that striatal LTD is involved in a developmental decrease in the probability of neurotransmitter release at corticostriatal synapses. The presynaptic changes that underlie striatal LTD may also be important for motor performance and certain forms of learning and memory.     

A possible mechanism for the aglycemia-induced depression of glutamatergic excitation in the striatum

We have studied the possible mechanisms underlying the decrease of excitatory transmission induced by glucose deprivation by using electrophysiological recordings in corticostriatal slices. Extracellular field potentials were recorded in the striatum after cortical stimulation; these potentials were progressively reduced by glucose deprivation. The reduction started 5 minutes after the onset of aglycemia. The field potential was fully suppressed after 40 minutes of glucose deprivation. After the washout of the aglycemic solution only a partial recovery was observed. Aglycemia also induced a delayed inward current during single-microelectrode voltage-clamp recordings from spiny neurons. This inward current was coupled with an increased membrane conductance. The A1 adenosine receptor antagonists, 8-cyclopentyl-1,3-dimethylxanthine (CPT, 1 micromol/L) and 1,3-dipropyl-8-cyclopentylxanthine (CPX, 300 nmol/L), significantly reduced the aglycemia-induced decrease of field potential amplitude. Moreover, in the presence of CPT and CPX, a full recovery of the field potential amplitude after the interruption of the aglycemic solution was observed. Conversely, these antagonists affected neither the inward current nor the underlying conductance increase produced by glucose deprivation. The ATP-sensitive potassium channel blockers glibenclamide (10 micromol/L) and glipizide (100 nmol/L) had no effect on the aglycemia-induced decrease of the field potential amplitude. We suggest that endogenous adenosine, but not ATP-dependent potassium channels, plays a significant role in the aglycemia-induced depression of excitatory transmission at corticostriatal synapses probably through a presynaptic mechanism. Moreover, adenosine is not involved in the postsynaptic changes induced by glucose deprivation in spiny striatal neurons.     

Semaphorins act as attractive and repulsive guidance signals during the development of cortical projections

Members of the semaphorin family have been implicated in mediating axonal guidance in the nervous system by their ability to collapse growth cones and to function as chemorepellents. The present findings show that recombinant Semaphorin D has similar effects on cortical axons and, in addition, inhibits axonal branching. In contrast, semaphorin E acts as an attractive guidance signal for cortical axons. Attractive effects were only observed when growth cones encountered increasing concentrations or a patterned distribution of Semaphorin E, but not when they are exposed to uniform concentrations of this molecule. Specific binding sites for Semaphorin D and Semaphorin E were present on cortical fibers both in vitro and in vivo at the time when corticofugal projections are established. In situ hybridization analysis revealed that the population of cortical neurons used in our experiments express neuropilin-1 and neuropilin-2, which are essential components of receptors for the class III semaphorins. Moreover, semD mRNA was detected in the ventricular zone of the neocortex whereas semE mRNA was restricted to the subventricular zone. Taken together, these results indicate that semaphorins are bifunctional molecules whose effects depend on their spatial distribution. The coordinated expression of different semaphorins, together with their specific activities on cortical axons, suggests that multiple guidance signals contribute to the formation of precise corticofugal pathways.     

Role of Leukotriene-degrading enzymes in pulmonary response to antigen infusion in sensitized guinea pigs in vivo

Although the expression of nerve growth factor (NGF) in the rat striatum is the highest at 2 postnatal weeks (P2w), the action of NGF at that age has not been studied in detail. We examined the effects of several neurotrophic factors, including NGF, on striatal cholinergic neurons cultured from P2w rats. We also examined the effects of a cyclic AMP (cAMP) analog and high K(+)-evoked depolarization. NGF specifically promoted the survival of choline acetyltransferase (ChAT)-positive neurons, and consequently increased the ChAT activity per well, whereas it did not induce the ChAT activity per cholinergic neuron. NGF-responsiveness was the highest in striatal cultures from P2w rats, but it was almost lost in cultures from P4w rats. Brain-derived neurotrophic factor (BDNF), neurotrophin-4/5 (NT-4/5), and a cAMP analog had survival-promoting effects on striatal total neurons including cholinergic neurons. On the other hand, high K+ hardly promoted the survival of striatal cholinergic neurons in cultures from P2w rats, although it increased the viable number of total striatal neurons. High K+ did not increase the ChAT activity in any tested cultures from postnatal 3- to 28-day-old rats. These results demonstrated that NGF prevented the death of striatal cholinergic neurons in cultures from P2w rats, but not from P4w rats, and that high K+ could not rescue these deaths. We propose that cholinergic neurons in the striatum are programmed to die at P2w, and that this programmed cell death can be restored by neurotrophins, but not by depolarization.     

Striatal mechanisms in Parkinson's disease: new insights from computer modeling

We review data and hypotheses concerning the functional anatomy of the striatum and the role of its corticostriatal and nigrostriatal afferents in Parkinson's disease (PD). Starting from molecular mechanisms of glutamatergic and dopaminergic actions in the striatum we have developed a compartmental model of striatal principal neurons that displays a significant degree of biological realism. Simulations of a network of striatal projection neurons under conditions likely to be found in healthy subjects as well as untreated and therapeutic situations of advanced PD provide clues concerning the dynamics of neuronal interactions and their possible effects on downstream motor structures in the generation of positive and negative motor symptoms. We present tentative biological explanations of the symptoms of rigidity and akinesia in PD leading to predictions concerning the origin of abnormal movements and the beneficial effects of dopaminergic treatment. Although these attempts are not yet sufficient to account for the complexity of clinical symptoms found in PD they can guide further empirical research and foster fruitful interactions between experimentalists, theoreticians, and clinicians in unraveling the functional anatomy of the basal ganglia.     

Interleukin-1beta and the interleukin-1 receptor antagonist act in the striatum to modify excitotoxic brain damage in the rat

The cytokine interleukin-1 (IL-1) has been implicated in ischaemic, traumatic and excitotoxic brain damage. The results presented here reveal novel actions of IL-1 in the striatum which markedly exacerbate cortical neuronal damage elicited by local excitotoxins in the striatum or cortex. Intrastriatal infusion of IL-1 receptor antagonist, IL-1ra, markedly inhibited striatal neuronal damage caused by N-methyl-D-aspartate (NMDA) or alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptor activation in the rat. In contrast, intracortical infusion of IL-1ra failed to inhibit NMDA or AMPA receptor-induced damage in the cortex. Intrastriatal co-infusion of IL-1 with the NMDA or AMPA receptor agonist did not affect local striatal damage induced by activation of either glutamate receptor subtype, but caused extensive cortical damage when administered into the striatum with AMPA. This secondary damage was significantly reduced by pretreatment with the NMDA receptor antagonist (MK-801), which did not affect local (striatal) damage caused by AMPA. Infusion of IL-1beta into the striatum (but not the cortex) markedly enhanced cortical damage caused by infusion of an NMDA or AMPA receptor agonist into the cortex. These data reveal selective actions of IL-1 and IL-1ra in the striatum, which influence cortical neuronal loss and suggest that IL-1 selectively enhances damage caused by AMPA receptor activation.     

Complex regulation of the expression of the polysialylated form of the neuronal cell adhesion molecule by glucocorticoids in the rat hippocampus

The gyrus dentatus is one of the few areas of the brain that continues to produce neurons after birth. The newborn cells differentiate into granule cells which project axons to their postsynaptic targets. This step is accompanied by the transient expression of the polysialylated isoforms of neuronal cell adhesion molecules (PSA-NCAM) by the developing neurons. Glucocorticoid hormones have been shown to inhibit neurogenesis. We noted a functional correlation between PSA-NCAM expression and glucocorticoid action after manipulation of corticosterone levels in the adrenalectomized rat. Adrenalectomy increased neurogenesis, evaluated from the incorporation of 5-bromo-2'-deoxyuridine in neuronal precursors, as well as PSA-NCAM expression. The increase in PSA-NCAM-immunoreactive (IR) cells in the gyrus dentatus, evidenced 72 h following adrenalectomy, persisted for at least a month. It was accompanied by enhanced dendritic arborization of PSA-NCAM-IR cells in the gyrus dentatus and by an increase in number of PSA-NCAM-IR fibres in the CA3 subfield. Neurogenesis was normalized by restitution of diurnal or nocturnal levels of corticosterone, whereas normalization of PSA-NCAM expression was only observed after simulation of the complete circadian fluctuation of the hormone. Our findings reveal the complex action of corticosterone in modulating the expression of PSA-NCAM in the gyrus dentatus of the hippocampal formation. They also highlight the importance of corticosterone fluctuations in the control of neurogenesis and plasticity in this structure.