Biomedical subjects

C E Ribak

Publications and source records attributed to C E Ribak.

At least 37 records · Page 2Linked to original sources

PubMed1998

Increased expression of GABA transporters, GAT-1 and GAT-3, in the deafferented superior colliculus of the rat.

GABA transporters (GATs) play a critical role in the translemmal transport of GABA in neurons and glial cells. Two major brain GATs, GAT-1 and GAT-3, are found in astrocytes in the adult brain. Astroglia demonstrate morphological and molecular changes in response to brain injury and deafferentation. The present study was designed to determine whether the expression of GATs changes after nerve deafferentation using the rat superior colliculus (SC) as a model. The immunoreactivity for GAT-1 and GAT-3, as well as GABA and glutamic acid decarboxylase (GAD)-65 and GAD-67, was studied in the SC of control rats and rats with unilateral optic nerve transections. Immunolabeling for both GAT-1 and GAT-3 was increased in the neuropil of the denervated SC as compared to that for the SC of control rats or for the unaffected SC of experimental rats. In contrast, immunoreactivity for GABA, GAD-65 and GAD-67 was not altered. The change in the immunolabeling of GAT-1 and GAT-3 was detectable at 1 day postlesion and became more evident between 3-30 days postlesion. At the electron microscopic level, immunoreactivity for both GAT-1 and GAT-3 in the unaffected SC was localized to astrocytic processes, whereas GAT-1 immunolabeling was also present in synaptic terminals. In the deafferented SC, immunolabeling for both GATs was elevated in the somata and processes of hypertrophied astrocytes as compared to that in the unaffected SC, whereas GAT-1 labeling in neuronal profiles was largely unchanged. A substantial increase of GAT-1 and GAT-3 in astrocytes following optic nerve transection suggests that these cells play a role in modulating GABA's action in the deafferented SC.

Afferent Pathways↗

PubMed1998

Corticotropin-releasing hormone (CRH)-containing neurons in the immature rat hippocampal formation: light and electron microscopic features and colocalization with glutamate decarboxylase and parvalbumin.

Corticotropin-releasing hormone (CRH) excites hippocampal neurons and induces death of selected CA3 pyramidal cells in immature rats. These actions of CRH require activation of specific receptors that are abundant in CA3 during early postnatal development. Given the dramatic effects of CRH on hippocampal neurons and the absence of CRH-containing afferents to this region, we hypothesized that a significant population of CRHergic neurons exists in developing rat hippocampus. This study defined and characterized hippocampal CRH-containing cells by using immunocytochemistry, ultrastructural examination, and colocalization with gamma-aminobutyric acid (GABA)-synthesizing enzyme and calcium-binding proteins. Numerous, large CRH-immunoreactive (ir) neurons were demonstrated in CA3 strata pyramidale and oriens, fewer were observed in the corresponding layers of CA1, and smaller CRH-ir cells were found in stratum lacunosum-moleculare of Ammon's horn. In the dentate gyrus, CRH-ir somata resided in the granule cell layer and hilus. Ultrastructurally, CRH-ir neurons had aspiny dendrites and were postsynaptic to both asymmetric and symmetric synapses. CRH-ir axon terminals formed axosomatic and axodendritic symmetric synapses with pyramidal and granule cells. Other CRH-ir terminals synapsed on axon initial segments of principal neurons. Most CRH-ir neurons were coimmunolabeled for glutamate decarboxylase (GAD)-65 and GAD-67 and the majority also contained parvalbumin, but none were labeled for calbindin. These results confirm the identity of hippocampal CRH-ir cells as GABAergic interneurons. Further, a subpopulation of neurons immunoreactive for both CRH and parvalbumin and located within and adjacent to the principal cell layers consists of basket and chandelier cells. Thus, axon terminals of CRH-ir interneurons are strategically positioned to influence the excitability of the principal hippocampal neurons via release of both CRH and GABA.

Animals↗

PubMed1998

Co-localization of corticotropin-releasing hormone with glutamate decarboxylase and calcium-binding proteins in infant rat neocortical interneurons.

Corticotropin releasing hormone (CRH) has been localized to interneurons of the mammalian cerebral cortex, but these neurons have not been fully characterized. The present study determined the extent of co-localization of CRH with glutamate decarboxylase (GAD) and calcium-binding proteins in the infant rat neocortex using immunocytochemistry. CRH-immunoreactive (ir) neurons were classified into two major groups. The first group was larger and consisted of densely CRH-immunostained small bipolar cells, predominantly localized to layers II and III. The second group of CRH-ir cells was lightly labeled and included multipolar neurons mainly found in deep cortical layers. Co-localization studies indicated that the vast majority of CRH-ir neurons, including both bipolar and multipolar types, was co-immunolabeled for GAD-65 and GAD-67. Most multipolar, but only some bipolar, CRH-ir neurons also contained parvalbumin, while CRH-ir neurons rarely contained calbindin or calretinin. These results indicate that virtually all CRH-ir neurons in the rat cerebral cortex are GABAergic. Furthermore, since parvalbumin is expressed by cortical basket and chandelier cells, the co-localization of CRH and parvalbumin suggests that some cortical CRH-ir neurons may belong to these two cell types.

Animals↗

PubMed1998

Dentate granule cells form novel basal dendrites in a rat model of temporal lobe epilepsy.

Mossy fibre sprouting and re-organization in the inner molecular layer of the dentate gyrus is a characteristic of many models of temporal lobe epilepsy including that induced by perforant-path stimulation. However, neuroplastic changes on the dendrites of granule cells have been less-well studied. Basal dendrites are a transient morphological feature of rodent granule cells during development. The goal of the present study was to examine whether granule cell basal dendrites are generated in rats with epilepsy induced by perforant-path stimulation. Adult Wistar rats were stimulated for 24 h at 2 Hz and with intermittent (1/min) trains (10 s duration) of single stimuli at 20 Hz (20 V, 0.1 ms) delivered 1/min via an electrode placed in the angular bundle. The brains of these experimental rats and age- and litter-matched control animals were processed for the rapid Golgi method. All rats with perforant-path stimulation displayed basal dendrites on many Golgi-impregnated granule cells. These basal dendrites mainly originated from their somata at the hilar side and then extended into the hilus. Quantitative analysis of more than 800 granule cells in the experimental and matched control brains showed that 6-15% (mean=8.7%) of the impregnated granule cells have spiny basal dendrites on the stimulated side, as well as the contralateral side (mean=3.1%, range=2.9-3.9%) of experimental rats, whereas no basal dendrites were observed in the dentate gyrus from control animals. The formation of basal dendrites appears to be an adaptive morphological change for granule cells in addition to the previously described mossy fibre sprouting, as well as dendritic and somatic spine formation observed in the dentate gyrus of animal and human epileptic brains. The presence of these dendrites in the subgranular region of the hilus suggests that they may be postsynaptic targets of the mossy fibre collaterals.

Animals↗

PubMed1997

Immunocytochemical localization of AMPA receptors in the rat inferior colliculus.

Immunocytochemistry was used to study the distribution of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor subtypes in the inferior colliculus (IC) of genetically epilepsy-prone rats (GEPR-9s) and normal Sprague-Dawley (SD) rats. The analysis was conducted using 3 antibodies specific for glutamate receptor subtypes, GluR 1, GluR 2/3, and GluR 4. Light microscopy showed that immunostaining of the IC was most dense with the GluR 2/3 antibody for both strains of animals. The amount of GluR 2/3 immunolabeling was similar for sound-stimulated GEPR-9s, seizure-naive GEPR-9s, and SD rats. The electron microscopy of GluR 2/3 in the IC revealed immunoreaction products associated with the postsynaptic densities of asymmetric synapses. The thin sections had comparable amounts of reaction product in dendrites or dendritic spines for both strains. Since the distribution and quantity of AMPA receptors in the IC of GEPR-9s and SD rats are similar, our results indicate that altered AMPA receptors are probably not the primary cause of seizure initiation in GEPR-9s.

Animals↗

PubMed1997

Suppression of cathepsins B and L causes a proliferation of lysosomes and the formation of meganeurites in hippocampus.

Cultured hippocampal slices exhibited prominent ultrastructural features of brain aging after exposure to an inhibitor of cathepsins B and L. Six days of treatment with N-CBZ-L-phenylalanyl-L-alanine-diazomethylketone (ZPAD) resulted in a dramatic increase in the number of lysosomes in the perikarya of neurons and glial cells throughout the slices. Furthermore, lysosomes in CA1 and CA3 pyramidal cells were not restricted to the soma but instead were located throughout dendritic processes. Clusters of lysosomes were commonly found within bulging segments of proximal dendrites that were notable for an absence of microtubules and neurofilaments. Although pyknotic nuclei were sometimes encountered, most of the cells in slices exposed to ZPAD for 6 d appeared relatively normal. Slices given 7 d of recovery contained several unique features, compared with those processed immediately after incubation with the inhibitor. Cell bodies of CA1 neurons were largely cleared of the excess lysosomes but had gained fusiform, somatic extensions that were filled with fused lysosomes and related complex, dense bodies. These appendages, similar in form and content to structures previously referred to as "meganeurites," were not observed in CA3 neurons or granule cells. Because meganeurites were often interposed between cell body and axon, they have the potential to interfere with processes requiring axonal transport. It is suggested that inactivation of cathepsins B and L results in a proliferation of lysosomes and that meganeurite generation provides a means of storing residual catabolic organelles. The accumulated material could be eliminated by pinching off the meganeurite but, at least in some cases, this action would result in axotomy. Reduced cathepsin L activity, increased numbers of lysosomes, and the formation of meganeurites are all reported to occur during brain aging; thus, it is possible that the infusion of ZPAD into cultured slices sets in motion a greatly accelerated gerontological sequence.

Animals↗

PubMed1997

Immunoreactivity for GABA plasma membrane transporter, GAT-1, in the developing rat cerebral cortex: transient presence in the somata of neocortical and hippocampal neurons.

The immunoreactivity for a gamma-aminobutyric acid (GABA) membrane transporter, GAT-1, was examined in the neocortex and hippocampal formation of developing rats from the day of birth (postnatal day 0, P0) to the adult stage. The immunolabeling was mainly localized to the neuropil, but was also in a select population of cell bodies during a limited time period. Layers I and VIb of neocortex exhibited relatively high reactivity at birth, but diminished their staining with development. In contrast, GAT-1 immunoreactivity in the neuropil in the cortical plate and its derivatives was light at birth, but increased rapidly during the first 2-3 postnatal weeks in an inside-out order. An adult pattern with immunoreactive puncta more densely distributed in layers II to IV than the deeper layers was completed by P30-45. The neuropil reactivity in the hippocampal formation at P0 was greater than that in the neocortex, densely localized in a supragranular band, and less densely in the hilus of the dentate gyrus and the strata radiatum and oriens of the hippocampus. This pattern was basically maintained at later stages except that the immunoreactivity in the supragranular band diminished, whereas that in the subgranular zone was enhanced. A population of cell bodies morphologically characteristic of cortical and hippocampal interneurons was substantially immunolabeled for GAT-1 by P5 and remained until P30. At the electron microscopic level, GAT-1 immunoreactivity was localized mainly to axon terminals and astrocytes between P5 and P45, but was also found in neuronal somata and their dendrites between P5 and P30. Our data show a differential postnatal development of GAT-1 immunoreactivity in the rat cerebral cortex, including a transient presence of immunoreactivity in the somata of a subpopulation of cerebral interneurons and a developmental downregulation of GAT-1 expression in the earliest generated cortical elements (layers 1 and VIb). The findings in the present study suggest that GAT-1 expression in the neocortex and hippocampus may relate to the functional maturation of the GABAergic system.

Animals↗

PubMed1997

Prenatal development of nicotinamide adenine dinucleotide phosphate-diaphorase activity in the human hippocampal formation.

Nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) histochemistry was used to study the development of the neurons metabolizing nitric oxide in the prenatal human hippocampal formation. Strongly reactive non-pyramidal neurons appeared in small numbers in the subplate at 15 weeks, and rapidly increased in this layer, as well as the cortical plate-derived layers between 17 and 24 weeks. The marginal zone also had a few NADPH-d cells at 15 weeks. The pattern of these darkly reactive cells stabilized by 28 weeks, with the somata distributed mostly at the border of the cortex and white matter in the entorhinal cortex and subiculum, or the alveus in Ammon's horn. Moderately stained non-pyramidal neurons appeared in the dentate gyrus by 17 weeks, and increased in this region and Ammon's horn up to 28 weeks. Small, lightly reactive non-pyramidal neurons were first seen by 32 weeks and increased in number by term. They were mainly distributed in layers II/III of the entorhinal cortex and stratum pyramidale of the subiculum and Ammon's horn. NADPH-d positive fibers in the marginal zone were mostly thin and developed between 20 and 28 weeks. In other cortical layers, thick processes from the darkly stained NADPH-d neurons appeared first, then fine fibers appeared more numerous, especially after 28 weeks. NADPH-d processes that arose from non-pyramidal cells were frequently apposed to blood vessels, including those in the hippocampal fissure. In addition, NADPH-d reactivity was also present in pyramidal and granule cells, but this staining was most pronounced between 15 and 24 weeks. The results show three types of distinctly stained NADPH-d interneurons in the fetal human hippocampal formation with different developmental courses and morphology. Also, hippocampal principal neurons transiently express NADPH-d at early fetal ages. Our data correlated with other findings suggest that nitric oxide may play a role in neuronal development in the hippocampal formation by modulating neuronal differentiation and maturation, and regulating blood supply.

Dentate Gyrus↗

PubMed1997

Calcitonin gene-related peptide immunoreactivity selectively labels accessory optic nuclei and pathways of the rat visual system.

The present study shows the distribution of calcitonin gene-related peptide (CGRP)-immunolabeled neuronal somata and fibers in the accessory optic system of adult rats. CGRP-immunoreactive cell bodies were small to medium-sized and mostly fusiform or oval-shaped. Both immunolabeled somata and fibers were found in the dorsal and lateral terminal nuclei as well as in the interstitial nucleus of the superior fasciculus (posterior fibers); whereas only immunoreactive fibers were found in the ventral division of the medial terminal nucleus, particularly its rostral portion. These results indicate that CGRP-containing neurons are present in all nuclear components of the accessory optic system and suggest that this neuropeptide may play a neuromodulative role in eye movements.

Animals↗

PubMed1997

In situ hybridization for c-fos mRNA reveals the involvement of the superior colliculus in the propagation of seizure activity in genetically epilepsy-prone rats.

Previous work showed that bilateral lesions made between the inferior and superior colliculi reduced the severity of audiogenic seizures in genetically epilepsy-prone rats (GEPR-9s), and indicated that the connections between these two structures are vital for the propagation of seizure activity. To determine the involvement of the superior colliculus (SC) in seizure propagation, GEPR-9s were given four audiogenic seizures within 1 h by ringing a loud bell, and their brains were processed 30 min later for in situ hybridization for c-fos mRNA. Brain sections from such rats showed dense labeling in both the dorsal cortex and external nucleus of the inferior colliculus. Labeling continued rostrally into the intermediate and deep layers of the SC and the periaqueductal gray region. In addition, other brain regions such as the amygdala, piriform cortex and dorsal endopiriform nucleus showed dense labeling for c-fos mRNA. Comparable increases were not observed in the brains of Sprague-Dawley (SD) rats receiving auditory stimulation or in unstimulated GEPR-9s and SD rats, thereby indicating that increases in stimulated GEPR-9s are seizure-specific. This study provides further evidence that the SC is involved in the propagation of seizure activity in GEPR-9s, and also demonstrates the activation of other brain regions by audiogenic seizures.

Acoustic Stimulation↗

PubMed1997

A common morphological response of astrocytes to various injuries: "dark" astrocytes. A light and electron microscopic analysis.

Our previous studies showed that neurons became argyrophilic following different kinds of brain injuries. In the present study we demonstrated that astrocytes could also become argyrophilic following compressive or concussive head injuries and following intraperitoneal administration of pentylenetetrazole or kainic acid. Furthermore the soma, nucleus and processes of these argyrophilic astrocytes were shown in other preparations to be hyper-basophilic with the light microscope, and hyper-electron dense and shrunken at the ultrastructural level. When the head injuries were inflicted either at the 15th min. of perfusion-fixation or at the 30th min. of transcardial perfusion with chilled physiological saline, several astrocytes also became argyrophilic, hyper-basophilic, shrunken and hyper-electron dense. These data indicate that (i) the intracellular pathological event in these astrocytes is similar to that of "dark" neurons or "dark" cells of non-neural tissues, (ii) the formation of "dark" astrocytes can be independent of the actual state of metabolism, and (iii) the "dark" morphological state of astrocytes might have a role in neuropathological processes.

Animals↗

PubMed1996

Cultured basal forebrain cholinergic neurons in contact with cortical cells display synapses, enhanced morphological features, and decreased dependence on nerve growth factor.

Prior studies examining the dependence of basal forebrain cholinergic neurons (BFCNs) on nerve growth factor (NGF) for survival have reached differing conclusions depending on the experimental paradigm employed, suggesting the importance of environmental and developmental variables. The present study examined the NGF dependence of BFCNs and modulatory effects of target (cortical) neurons under the controlled conditions of dissociated cell cultures. Initial experiments found BFCNs (identified by using choline acetyltransferase immunocytochemistry) in pure basal forebrain (BF) cultures to be dependent on NGF between the 2nd and 4th week in vitro. During that developmental period, NGF deprivation for 3 days, induced by application of anti-NGF antibody, resulted in degeneration of over 80% of BFCNs, whereas at earlier or later times, BFCNs were largely resistant to NGF deprivation. When BF neurons were plated together with cortical neurons (as dissociated co-cultures), the BFCNs grew neuritic processes (labeled with acetylcholinesterase histochemistry) that appeared to specifically target cortical neurons; electron microscopy revealed that synapses formed between these cells. BFCNs in co-cultures were more resistant to NGF deprivation, were larger, and had much more extensive neuritic growth than BFCNs in pure BF cultures. The resistance of BFCNs to NGF deprivation provided by cortical neurons could be largely reproduced by addition of other trophic factors (brain-derived neurotrophic factor, BDNF; neurotrophin 3, NT3; neurotrophin 4/5, NT4/5; or glial-derived neurotrophic factor, GDNF) during NGF deprivation in pure BF cultures. These results suggest that developing BFCNs undergo a critical period requiring trophic influences that may be provided by NGF or other trophic factors, as well as unknown factors derived from cortical neurons.

Acetylcholinesterase↗

PubMed1996

GABA plasma membrane transporters, GAT-1 and GAT-3, display different distributions in the rat hippocampus.

This study evaluates the distribution of two high affinity gamma-aminobutyric acid (GABA) transporters (GAT-1 and GAT-3) in the rat hippocampus using immunocytochemistry and affinity purified antibodies. GAT-1 immunoreactivity was prominent in punctate structures and axons in all layers of the dentate gyrus. In Ammon's horn, immunoreactive processes were concentrated around the somata of pyramidal cells, particularly at their basal regions. The apical and basal dendritic fields of pyramidal cells also displayed numerous GAT-1 immunoreactive punctate structures and axons. The zone of termination of the mossy fibers that includes both the hilus of the dentate gyrus and stratum lucidum of the CA3 area was the lightest immunolabeled region of the hippocampal complex. Electron microscopic preparations demonstrated that GAT-1 immunoreactive axon terminals form symmetric synapses with somata, axon initial segments, and dendrites of granule and pyramidal cells in the dentate gyrus and Ammon's horn, respectively. Immunoreactivity was localized to the plasma membrane and the cytoplasm of axon terminals. The somata of previously described local circuit neurons in the dentate gyrus and Ammon's horn contained GAT-1 immunoreactivity associated with the Golgi complex. Light, diffuse GAT-3 immunoreactivity was present throughout the hippocampal formation. Thin, astrocytic glial processes displayed GAT-1 and GAT-3 immunoreactivity. This localization of GAT-1 and GAT-3 indicates that they are involved in the uptake of GABA from the extracellular space into GABAergic axon terminals and astrocytes.

Animals↗

PubMed1996

Selective death of hippocampal CA3 pyramidal cells with mossy fiber afferents after CRH-induced status epilepticus in infant rats.

Previous studies of CRH-induced status epilepticus in infant rats demonstrated neuronal loss in several limbic structures, including the CA3 region of the hippocampus. The goal of the present study was to identify the neurons affected by CRH-induced seizures and determine whether they formed synapses with afferent axon terminals. Clusters of neurons in the CA3 region of the hippocampus were osmiophilic when viewed in thick sections. Semi-thin 2-microns sections of the pyramidal cell layer contained dark, shrunken neurons with apical and basal dendrites among normal appearing pyramidal cells. Electron microscopy revealed degenerating pyramidal cells with intact cell membranes and electron dense nuclei and cytoplasm. The shrunken dendrites of these cells had spines and were postsynaptic to large immature-appearing mossy fibers. Thus, CA3 pyramidal neurons that are linked via mossy fibers to the tri-synaptic excitatory hippocampal circuit die subsequent to CRH-induced status epilepticus. The shrunken appearance and selective loss of these neurons are incompatible with necrosis as the mechanism of degeneration.

Afferent Pathways↗

PubMed1996

Astrocytic processes compensate for the apparent lack of GABA transporters in the axon terminals of cerebellar Purkinje cells.

The aim of the present study was to evaluate the expression of two high affinity GABA transporters (GAT-1 and GAT-3) in the rat cerebellum using immunocytochemistry and affinity purified antibodies. GAT-1 immunoreactivity was prominent in punctate structures and axons in all layers of the cerebellar cortex, and was especially prominent around the somata of Purkinje cells. In contrast, the deep cerebellar nuclei showed few if any GAT-1 immunoreactive puncta. Weak GAT-3 immunoreactive processes were present in the cerebellar cortex, whereas GAT-3 immunostaining was prominent around the somata of neurons in the deep cerebellar nuclei. Electron microscopic preparations of the cerebellar cortex demonstrated that GAT-1 immunoreactive axon terminals formed symmetric synapses with somata, axon initial segments and dendrites of Purkinje cells and the dendrites of granule cells. Astrocytic processes in the cerebellar cortex were also immunolabeled for GAT-1. However, Purkinje cell axon terminals that formed symmetric synapses with neurons in the deep cerebellar nuclei lacked GAT-1 immunoreactivity. Instead, weak GAT-1 and strong GAT-3 immunoreactivities were expressed by astrocytic processes that enveloped the Purkinje cell axon terminals. In addition, GAT-3-immunoreactivity appeared in astrocytic processes in the cerebellar cortex. These observations demonstrate that GAT-1 is localized to axon terminals of three of the four neuronal types that were previously established as being GABAergic, i.e. basket, stellate and Golgi cells. GAT-1 and GAT-3 are expressed by astrocytes. The failure to identify a GABA transporter in Purkinje cells is consistent with previous data that indicated that Purkinje cells lacked terminal uptake mechanisms for GABA. The individual glial envelopment of Purkinje cell axon terminals in the deep cerebellar nuclei and the dense immunostaining of GAT-3, and to a lesser extent GAT-1, expressed by astrocytic processes provide a compensatory mechanism for the removal of GABA from the synaptic cleft of synapses formed by Purkinje cell axon terminals.

Animals↗

PubMed1995

Electron microscopy of cell islands in layer II of the primate entorhinal cortex.

An electron microscopic analysis of cell islands in layer II of the entorhinal cortex from rhesus monkeys was made to determine the ultrastructural features of these unique neuronal clusters. The rostral, intermediate, and caudal divisions of the entorhinal cortex were selected for electron microscopic examination. In the rostral division, neurons were grouped together in prominent clusters, often with 10 or more contiguous somata. Somatic and dendrosomatic appositions were frequent, without intervening cellular processes or specialized junctions. Somata were relatively small, typically 10-15 microns in diameter, with oval or circular nuclei that were euchromatic and contained nucleoli. Small nuclear infoldings were commonly seen. A thin shell of perikaryal cytoplasm contained numerous organelles. Axosomatic synapses were infrequent, with a mean of only 1.0 synapse per neuron per thin section. The neuropil contained numerous synapses, and myelinated axons were seen infrequently. In the intermediate division, somatic appositions were rarely observed. Somata were relatively large, typically 15-20 microns in diameter, and displayed a moderate amount of cytoplasm. Axosomatic synapses were relatively common, with a mean of 3.3 synapses per neuron per thin section. In the caudal division, neurons were typically grouped in clusters of two to three contiguous somata. Neurons were about 15 microns in diameter and displayed a moderate amount of cytoplasm. Axosomatic synapses were of moderate frequency, with a mean of 2.5 synapses per neuron per thin section. The neuropil in the caudal division displayed a relatively high frequency of myelinated axons. Our analysis of three regions of the entorhinal cortex revealed significant differences in the frequency of somatic appositions and axosomatic synapses, and in certain ultrastructural features of the somata and neuropil. These results showed that cell islands in layer II of the entorhinal cortex display regional morphologic differences. The paucity of symmetric axosomatic synapses in the rostral division may correlate with this region's vulnerability in certain diseases.

Animals↗

PubMed1995

Postnatal development and synaptic connections of hilar mossy cells in the hippocampal dentate gyrus of rhesus monkeys.

Mossy cells of the hippocampal dentate gyrus were analyzed through postnatal development. At birth, a few thorny excrescences were found on the proximal dendrites of mossy cells, whereas distal dendrites displayed pedunculate spines. Thorny excrescences increased in number and complexity until the third month. After that age, the complexity of thorny excrescences is so great that an increase in spine density can be seen only in electron microscopic preparations. An increase in the number of pedunculate spines per unit length of distal dendrite was detected via light microscopy during the first 9 postnatal months. The somata and dendrites of mossy cells displayed adult-like characteristics after the ninth postnatal month. Mossy fiber terminals at birth frequently displayed immature ultrastructural characteristics and formed synapses with dendritic shafts and spines. At later postnatal ages and in adults, axospinous synapses were found almost exclusively. This is consistent with the postnatal development of the complex spines of the mossy cells. Axons of mossy cells were generally confined to the hilus in our 150-microns-thick sections, where they gave rise to several collaterals. The axon terminals from these collaterals formed asymmetric synapses with dendrites and dendritic spines in the hilar region of the dentate gyrus. These data provide the first anatomical evidence that hilar mossy cells of the primate dentate gyrus have excitatory projections similar to their equivalent cell type in subprimates. The present study indicates that mossy cells of the dentate gyrus are in a more advanced stage of development at birth and mature faster than similar neurons of the human hippocampus. This may represent a faster maturation of hippocampal circuitry in nonhuman primates compared to that in the human.

Animals↗

PubMed1995

Peptide-induced infant status epilepticus causes neuronal death and synaptic reorganization.

Status epilepticus (SE) produced by excitatory amino acids is a well established model in adult rodents. Limbic neuronal degeneration and synaptic reorganization observed after, for example, kainic acid-induced SE are considered relevant to human epilepsy. Kainic acid also produces severe seizures in infant rats, but neuronal injury and sprouting have not been demonstrated. The results of the present study show that corticotropin releasing hormone (CRH)-induced SE causes limbic neuronal death and reorganization in infant rats. In adults, CRH produced seizures at much higher doses, and no neuronal degeneration. As a modulator of the CNS stress response, CRH is activated in various 'stressful' circumstances. Its age-dependent ability to kill neurons represents a unique form of cell death potentially important in human medicine.

Animals↗