Differences in lesion-induced hippocampal plasticity between mice and rats

We studied the differences between mice and rats in lesion-induced sprouting in the hippocampus. The entorhinal cortex was unilaterally lesioned with ibotenic acid in adult, female mice and rats. Four weeks later the subsequent axonal sprouting in the dentate gyrus was analysed, by measuring the density of the synaptophysin immunohistochemical and acetylcholinesterase histochemical staining in the termination area of the entorhinal cortex axons. The data demonstrate that both mice and rats display a significantly increased density of staining for synaptophysin and acetylcholinesterase in the molecular layer of the dentate gyrus, indicative of axonal sprouting. Both species also show an upregulation in the density of staining for acetylcholinesterase in the molecular layer of the dentate gyrus. Further, rats, but not mice, show a significant upregulation of synaptophysin staining in stratum lacunosum moleculare of CA1 following the lesions. However, whereas rats show significant shrinkage of the molecular layer of the dentate gyrus, mice do not show any shrinkage of that layer following entorhinal cortex lesions. Taken together, these data indicate that whereas the process of reinnervation in the hippocampus is similar between the mouse and the rat, the hippocampal response to denervation shows clear differences between these two species.     

Monoclonal antibodies reveal molecular differences between terminal fields in the rat dentate gyrus.

We have derived a number of monoclonal antibodies which detect molecular differences correlating with the afferent inputs to the molecular layer of the adult rat hippocampal dentate gyrus. One group, dubbed OM-1 to OM-4, strongly stain the outer zone of the molecular layer, which receives its major innervation from the ipsilateral entorhinal cortex. A second group, IM-1 and IM-2, show a complementary pattern and preferentially stain the inner molecular layer, which receives inputs from the ipsilateral and contralateral hippocampus. These antigens are not, however, restricted to these layers, being found outside the hippocampus in several other areas of neuropil in the adult brain. In the developing brain the IM-1 antigen appears ubiquitously from the earliest age studied, embryonic day 12. Within the dentate gyrus, its restriction to the inner terminal field of the molecular layer only occurs during the second postnatal week. In contrast, OM staining appears only sparsely and late in the prenatal brain, appearing in developing cortical white matter between embryonic days 18 and 20. The outer dentate molecular layer becomes OM-positive from birth onwards, corresponding to the time of arrival of entorhinal axons during the first postnatal week. These two groups of monoclonal antibodies recognize a number of different glycoproteins. Ultrastructural immunohistochemistry shows they are cell surface molecules, and as such may be involved in the recognition events required for the establishment of specific patterns of neuronal connectivity.     

Similarities and differences between cholinergic systems in the superior colliculus of guinea pig and rat

Summary We studied the distribution of acetylcholinesterase activity and choline acetyltransferase immunoreactivity in the superior colliculus of the guinea pig and the albino rat, using enzyme histochemical and immunohistochemical methods. Choline acetyltransferase-like immunoreactivity was localized in the neuropil throughout the colliculi, but the density of the immunoreactive neuropil varied among layers as well as between species. In the intermediate collicular layers the pattern of choline acetyltransferase immunoreactivity was closely matched by the distribution of acetylcholinesterase activity in guinea pig and rat, confirming our previous findings in the cat. Furthermore, in the guinea pig, but not in the rat, choline acetyltransferase-like immunoreactivity was localized in a prominent population of perikarya of the superficial gray layer.     

Acetylcholinesterase stain intensity variation in the rat dentate gyrus: a quantitative description based on digital image analysis

Three-dimensional patterns of variation in the intensity of acetylcholinesterase histochemical staining and the width of stain-defined subregions were quantified for the dentate gyrus of the adult male Long-Evans rat. Matched tissue sections sampled through the central hippocampal formation of five rats were measured with a digital image analysis computer system. The width and stain intensity were determined for defined portions of the dentate gyrus related to gross acetylcholinesterase staining patterns and the known distribution of dentate afferents. Normalized values reflecting stain intensity at defined positions within this standardized sampling array were examined to investigate regional differences in acetylcholinesterase distribution along the primary dendritic axis of dentate granule neurons. The data illustrate quantitative differences in the partitioning of acetylcholinesterase as a function of intrahippocampal position. The variation is more pronounced in the septal-temporal axis than the granule cell layer crest-tip axis. Furthermore, the septal-temporal variations in acetylcholinesterase intensity demonstrate some independence according to proximal-distal location within the molecular layer. The results suggest that acetylcholinesterase distribution within the dentate gyrus may reflect local physiological characteristics of those afferent systems related to this enzyme, including but not necessarily limited to those that are specifically cholinergic.     

Development of somatostatin-like immunoreactivity in the hippocampal formation of normal and reeler mice

Using antisera directed against somatostatin-28 or somatostatin-28(1-12), the development of somatostatin-like immunoreactivity (SS-LI) was examined in the hippocampal formation of normal and reeler mice. As early as postnatal day 5, SS-labeled neurons exhibit the adult pattern of distribution in the normal hippocampal formation, these neurons being situated predominantly in the stratum oriens of the hippocampus and the hilus of the dentate gyrus. In contrast, SS-labeled neurons in the reeler hippocampal formation are dispersed throughout the various layers, reflecting the disrupted laminar organization of the hippocampus in this mutant. In both the normal and reeler hippocampal formation, SS-labeled fibers are most abundant in the stratum lacunosum moleculare. However, in the reeler, there appears to be increase in the density of SS-LI fibers, not only in the stratum lacunosum moleculare but also in the stratum oriens, stratum radiatum and pyramidal cell layer of the hippocampus.     

Cell formation in the human hippocampal formation from mid-gestation to the late postnatal period

In the present study cell formation was studied in the human hippocampal formation from the 24th gestational week until the end of the first postnatal year. Proliferating cells were detected with the monoclonal antibody MIB-1.The cytoarchitectonic layers of Ammon's horn are formed before the 24th gestational week. In harmony with this observation, cell proliferation in the hippocampal ventricular zone is minimal after the 24th week. In addition, local cell multiplication in Ammon's horn is occasional and the proliferating cells are glial or endothelial cells. In contrast, cell formation continues in the hilar region of the dentate gyrus even after birth. Immature cells accumulate in the hilus, and at the border between the hilus and the granule cell layer throughout the first eight postnatal months. The subgranular zone of the dentate gyrus becomes a cell sparse area at about the 11th postnatal month, indicating that immature cells from the hilus have already migrated to the granule cell layer and differentiated into granule cells. There is an increase in glial cell proliferation both in Ammon's horn and the dentate gyrus at the 11.5th postnatal month suggesting the onset of myelination by the end of the first year.Our findings indicate that most pyramidal neurons of Ammon's horn are generated in the first half of pregnancy and no pyramidal neurons are formed after the 24th gestational week. In contrast, granule cells of the dentate gyrus proliferate in a decreasing rate during the second half of pregnancy and after birth. Proliferating neuronal precursors occur in a low percentage in the dentate gyrus of 3-, 5- and 11.5-month-old children.     

Regional heterogeneity in the distribution of neurotransmitter markers in the rat hippocampus.

A detailed neurochemical analysis of the distribution of markers for the most relevant neurotransmitter systems within the rat hippocampal formation has been performed. The hippocampi, obtained from unfrozen brains of male Sprague-Dawley rats were subdissected into tissue parts containing mainly CA1, CA3 or the dentate gyrus, respectively. Each part was further divided into ventral and dorsal halves. In these six hippocampal subregions the concentrations of noradrenaline, dopamine, serotonin, 3-methoxy-4-hydroxyphenylglycol, 5-hydroxyindoleacetic acid and the putative neurotransmitter amino acids glutamate, aspartate, GABA, glycine and taurine, and the levels of somatostatin and neuropeptide Y and the activities of choline acetyltransferase, acetylcholinesterase and glutamate decarboxylase were measured. A marked heterogeneity in the subregional distribution of markers for various neurotransmitter systems within the hippocampal formation was observed. Each neuronal marker was characterized by an individual pattern of distribution. Most of the markers showed a concentration-gradient, increasing from dorsal to ventral; only taurine was more abundant in the dorsal than in the ventral parts and no dorsoventral difference was seen for aspartate, glycine and neuropeptide Y. The highest molar ratios of total 3-methoxy-4-hydroxyphenylglycol to noradrenaline and 5-hydroxyindoleacetic acid to serotonin were found in the dorsal hippocampus. The levels of noradrenaline, GABA and glutamate decarboxylase activity were highest in the dentate gyrus and lowest in CA1. The concentrations of somatostatin were highest in CA1; those of serotonin were highest in CA3. Highest activities of choline acetyltransferase and acetylcholinesterase were found in the dentate gyrus; lowest activities were found in CA3. In CA3 the lowest values of glutamate, aspartate, taurine and somatostatin were also found. The heterogeneity in the distribution of individual neurochemical markers allows insights into possible functional differences of hippocampal subregions and provides a relevant basis for future neurochemical investigations in this brain area.     

Transient expression of phospholipase D1 in developing rat hippocampus

We investigated the distribution of phospholipase D1 (PLD1) protein in the developing rat hippocampus using an affinity-purified peptide antibody against PLD1. Immunoreactivity for PLD1 was first seen in some scattered cells in the hippocampus at embryonic day 18. At postnatal day 1 (P1), many PLD1 immunoreactive cells were observed in the CA1 and CA3 sectors, subiculum and the hilus of the dentate gyrus. During the first postnatal week, there was an abrupt increase of immunoreactive neurons in the hippocampus, and their number and intensity peaked at P7. During the second postnatal week, there was an abrupt decrease in the number of immunoreactive hippocampal neurons. By P14, no significant labeling was found in the hippocampus. These results corresponded well with those from Western blot analysis, suggesting that PLD1 may regulate the developmental processes of hippocampal neurons.     

Localization of CD226 in the mouse hippocampus and cerebellum during adulthood and postnatal development

CD226, a member of cell adhesion molecules, has been widely studied in the immune system; however, its expression in the CNS remains unknown. In our present study, we detected CD226 mRNA and protein in the mouse hippocampus and cerebellum by RT-PCR and Western blotting, respectively. Immunohistochemical studies found that CD226 is primarily located in the hilus of the dentate gyrus and stratum lucidum aligned along the pyramidal cells in the hippocampal CA3 area, the interspaces of granular cells and the somata of the Purkinje cells in the cerebellar cortex during adulthood. Double-staining results revealed that CD226 co-localized well with synaptic marker proteins including synaptophysin, syntaxin and PSD-95. During postnatal development, CD226 could not be detected at its adult locations until postnatal day 12; however, it was temporally expressed in the somata of neighboring or distant nuclei associated with its adult location. These results showed the diverse localization of CD226 in the mouse hippocampus and cerebellum for the first time and suggested its potential role in the CNS.     

Cholinergic innervation of ferret visual system

The distribution of acetylcholinesterase and choline acetyltransferase in primary visual areas of adult pigmented ferret was determined with cholinesterase histochemistry and choline acetyltransferase immunohistochemistry. In all visual areas the distribution of acetylcholinesterase in the neuropil closely matches that of choline acetyltransferase. In the cerebral cortex acetylcholinesterase and choline acetyltransferase are associated with axons found in every cortical layer and in the white matter. Area 17, identified by Nissl architectonics and cytochrome oxidase histochemistry, is distinguished by having a relatively low density of choline acetyltransferase- and acetylcholinesterase-stained axons in layer IV. Certain cortical non-pyramidal cell types show moderate staining for acetylcholinesterase after relatively long incubations, but no choline acetyltransferase-positive cells are observed in the cortex. In the lateral geniculate nucleus and superior colliculus the levels of choline acetyltransferase and acetylcholinesterase are considerably higher than in cerebral cortex, and choline acetyltransferase-stained axons there display prominent varicosities. The distribution of choline acetyltransferase and acetylcholinesterase in the neuropil of lateral geniculate nucleus and superior colliculus of ferret shows marked laminar variation. For instance, in the lateral geniculate nucleus, the levels of acetylcholinesterase and choline acetyltransferase in the "On" sublaminae of laminae A and A1 are higher than the "Off" sublaminae. In the superficial layers of the superior colliculus the levels of choline acetyltransferase and acetylcholinesterase are highest in the stratum zonale and lowest in the stratum opticum; in the intermediate gray layer of the superior colliculus acetylcholinesterase- and choline acetyltransferase-stained fibres are distributed into dense patches. As in cortex, choline acetyltransferase-positive cell bodies are not found in the lateral geniculate nucleus or superior colliculus, and acetylcholinesterase-stained cell bodies are visible only after long incubations. Cell bodies staining positively for choline acetyltransferase are found in a satellite of the superior colliculus, the parabigeminal nucleus.     

Cholecystokinin in the mouse hippocampus: localization in the mossy fiber and dentate commissural systems

Summary The distribution and source of cholecystokinin-like immunoreactivity (CCK-I) in the hippocampus of the Swiss Webster mouse was analyzed using light microscopic immunocytochemical techniques. In agreement with what has been observed in other animals, CCK-I was localized within sparsely scattered neurons throughout the hippocampus proper, in axons that arborize within and around stratum pyramidale, and in fine axons and puncta in stratum lacunosum-moleculare of region CA1. In contrast to other animals, CCK-I was also localized within the mossy fiber system (including dentate gyrus granule cells), within a dense band which occupied the full septo-temporal extent of the dentate gyrus inner molecular layer, and within polymorph neurons of the central hilus. The presence of CCK-I within the latter two areas suggested localization within the dentate gyrus commissural system. This was verified by the combined use of retrograde fluorescent dye transport and CCK immunocytochemistry. Virtually all of the dyelabeled dentate commissural neurons within the hilus were CCK-I. These data demonstrate that while there is little change in the distribution of CCK-I within hippocampal local circuit neurons across animals, there are substantial interspecies differences in the localization of CCK-I within major axonal projections in the hippocampal formation.     

Effect of canonical Wnt inhibition in the neurogenic cortex, hippocampus, and premigratory dentate gyrus progenitor pool.

Canonical Wnt signaling is crucial for the correct development of both cortical and hippocampal structures in the dorsal telencephalon. In this study, we examined the role of the canonical Wnt signaling in the dorsal telencephalon of mouse embryos at defined time periods by inhibition of the pathway with ectopic expression of Dkk1. Transgenic mice with the D6-driven Dkk1 gene exhibited reduced canonical Wnt signaling in the cortex and hippocampus. As a result, all hippocampal fields were reduced in size. Neurogenesis in the dentate gyrus was severely reduced both in the premigratory and migratory progenitor pool. The lower number of progenitors in the dentate gyrus was not rescued after migration to the subgranular zone and thus the dentate gyrus lacked the entire internal blade and a part of the external blade from postnatal to adult stages.     

树内侧隔核—斜角带复合体向腹侧海马的胆碱能和非胆碱能投射

本研究运用 WGA-HRP逆行追踪结合胆碱乙酰化酶免疫组织化学法研究了树鼠句内侧隔核 -斜角带复合体向腹侧海马的投射。结果表明 ,(1)树鼠句腹侧海马接受内侧隔核 -斜角带复合体的投射有三种形式 ,即来自内侧隔核 ,内侧隔核 -斜角带垂直部的外侧部和内侧隔核 -斜角带垂直部的后部。(2 )腹侧海马来自内侧隔核和斜角带垂直部的投射主要是非胆碱能的 ,其非胆碱能和胆碱能均主要来自内侧隔核。 (3 )腹侧海马各亚区 (CA1、CA2 /CA3和齿状回门区或 CA4)都主要接受内侧隔核的纤维传入 ,但胆碱能和非胆碱能比例不同 ,CA1、CA2 /CA3和 CA4来自内侧隔核 -斜角带垂直部的投射均主要是非胆碱能的 ,且主要来自内侧隔核 ,其胆碱能几乎等量来自内侧隔核和斜角带垂直部。内侧隔核 -斜角带复合体—腹侧海马亚区胆碱能和非胆碱能投射比例的不同 ,为认识内侧隔核 -斜角带复合体—海马通路对记忆环路中的海马调节机制 ,提供了新的形态学依据     

Ephrin-A5 modulates the topographic mapping and connectivity of commissural axons in murine hippocampus

Entorhinal and commissural/associational projections show a non-overlapping distribution in the hippocampus proper and the dentate gyrus. The expression of Ephrins and their Eph receptors in the developing hippocampus indicates that this family of axonal guidance molecules may modulate the formation of these connections. Here we focused on the role of the ephrin-A5 ligand in the development of the main hippocampal afferents. In situ hybridization showed that ephrin-A5 mRNA was detected mainly in the principal cells of the hippocampus proper and in the dentate gyrus throughout postnatal development. Immunocytochemical analyses revealed prominent expression of the EphA3 receptor, a putative receptor for ephrin-A5, in the main cells and the neuropil of the developing hippocampus. Tracing experiments in ephrin-A5(-/-) mice showed that commissural projections were transiently altered in the hippocampus proper at P5, but they were mistargeted throughout the postnatal development in the dentate gyrus. Immunocytochemistry with anti-calbindin antibodies revealed that the dentate mossy fiber projection was not altered in ephrin-A5(-/-) mice. Electron microscopy studies showed alterations in the density of synapses and spines in commissural/associational layers, but not in entorhinal layers, and in the mossy fibers in these animals. Taken together, these findings indicate that ephrin-A5 signaling is involved in the formation and maturation of synapses in the hippocampus.     

Shift of adenosine kinase expression from neurons to astrocytes during postnatal development suggests dual functionality of the enzyme

Adenosine is a potent modulator of excitatory neurotransmission, especially in seizure-prone regions such as the hippocampal formation. In adult brain ambient levels of adenosine are controlled by adenosine kinase (ADK), the major adenosine-metabolizing enzyme, expressed most strongly in astrocytes. Since ontogeny of the adenosine system is largely unknown, we investigated ADK expression and cellular localization during postnatal development of the mouse brain, using immunofluorescence staining with cell-type specific markers. At early postnatal stages ADK immunoreactivity was prominent in neurons, notably in cerebral cortex and hippocampus. Thereafter, as seen best in hippocampus, ADK gradually disappeared from neurons and appeared in newly developed nestin- and glial fibrillary acidic protein (GFAP)-positive astrocytes. Furthermore, the region-specific downregulation of neuronal ADK coincided with the onset of myelination, as visualized by myelin basic protein staining. After postnatal day 14 (P14), the transition from neuronal to astrocytic ADK expression was complete, except in a subset of neurons that retained ADK until adulthood in specific regions, such as striatum. Moreover, neuronal progenitors in the adult dentate gyrus lacked ADK. Finally, recordings of excitatory field potentials in acute slice preparations revealed a reduced adenosinergic inhibition in P14 hippocampus compared with adult. These findings suggest distinct roles for adenosine in the developing and adult brain. First, ADK expression in young neurons may provide a salvage pathway to utilize adenosine in nucleic acid synthesis, thus supporting differentiation and plasticity and influencing myelination; and second, adult ADK expression in astrocytes may offer a mechanism to regulate adenosine levels as a function of metabolic needs and synaptic activity, thus contributing to the differential resistance of young and adult animals to seizures.     

Heterogeneous expression of the cholecystokinin-like immunoreactivity in the mouse hippocampus, with special reference to the dorsoventral difference

The neuropeptide cholecystokinin (CCK) is widely distributed in the CNS. We herein investigated the immunocytochemical localization of CCK in the glutamatergic excitatory pathways in the mouse hippocampus, with particular reference to the dorsoventral difference. The intense CCK-like immunoreactivity (CCK-LI) was found in the mossy fiber pathway (stratum lucidum and dentate hilus) and in the inner molecular layer of the dentate gyrus. In the mossy fiber pathway, the CCK-LI was more intense at the ventral level than at the dorsal level. On the other hand, the CCK-LI in the stratum lucidum was more intense in the distal portion than in the proximal portion, both at the dorsal and ventral levels. High-resolution three-dimensional image analysis revealed the coexpression of CCK and synaptoporin (SPO) in the single mossy terminal, where they were spatially segregated but adjacent to each other. Quantitative image analysis indicated the difference in the amount of CCK within the mossy terminals along the dorsoventral and transverse axes of the hippocampus. On the other hand, in the inner molecular layer, CCK- and SPO-positive elements appeared to have little relation to each other. We also examined the postnatal development of the CCK-LI in the mouse hippocampus. The CCK-LI was detected in the inner molecular layer of the ventral dentate gyrus at postnatal day (P) 7. In the mossy fiber pathway, the CCK-LI was first evident at P 14, but it was restricted to the distal portion of the stratum lucidum in the ventral hippocampus. Interestingly, the distributions of the SPO immunoreactivity at P 7 were already similar to those of adult mice. The patterns of expression of CCK-LI at P 28 were almost similar to those of adult mice. The present data demonstrate the heterogeneous expression of CCK-LI in the mouse hippocampus, and provide a baseline to understand the role of CCK in the mouse brain.     

Activity-dependent changes in synaptophysin immunoreactivity in hippocampus,piriform cortex,and entorhinal cortex of the rat

Synaptophysin, an integral membrane glycoprotein of synaptic vesicles, has been widely used to investigate synaptogenesis in both animal models and human patients. Kindling is an experimental model of complex partial seizures with secondary generalization, and a useful model for studying activation-induced neural growth in adult systems. Many studies using Timm staining have shown that kindling promotes sprouting in the mossy fiber pathway of the dentate gyrus. In the present study, we used synaptophysin immunohistochemistry to demonstrate activation-induced neural sprouting in non-mossy fiber cortical pathways in the adult rat. We found a significant kindling-induced increase in synaptophysin immunoreactivity in the stratum radiatum of CA1 and stratum lucidum/radiatum of CA3, the hilus, the inner molecular layer of the dentate gyrus, and layer II/III of the piriform cortex, but no significant change in layer II/III of the entorhinal cortex, 4 weeks after the last kindling stimulation. We also found that synaptophysin immunoreactivity was lowest in CA3 near the hilus and increased with increasing distance from the hilus, a reverse pattern to that seen with Timm stains in stratum oriens following kindling. Furthermore, synaptophysin immunoreactivity was lowest in dorsal and greatest in ventral sections of both CA3 and dentate gyrus in both kindled and non-kindled animals. This demonstrates that different populations of sprouting axons are labeled by these two techniques, and suggests that activation-induced sprouting extends well beyond the hippocampal mossy fiber system.     

Microanatomical and electrophysiological changes of the rat dentate gyrus caused by lesions of the nucleus basalis magnocellularis

The effect of unilateral or bilateral lesions of the nucleus basalis magnocellularis (NBM) on the dentate gyrus of the hippocampus were assessed using microanatomical and electrophysiological techniques. NBM is the main cholinergic basal forebrain nucleus that supplies the fronto-parietal cortex. Lesions were induced using the neurotoxin ibotenic acid or a radio-frequency system and did not affect glutamic acid decarboxylase activity both in the frontal cortex and in the hippocampus. At 4 weeks after lesioning, a loss of choline acetyltransferase (ChAT) activity and of ChAT-immunoreactive fibres was observed in the frontal cortex but not in the hippocampus and no changes in the density of granule neurons of the dentate gyrus or in the hippocampal long-term potentiation (LTP) were noticeable. At 8 weeks after lesioning the loss of both ChAT activity and of ChAT-immunoreactive fibres persisted in the frontal cortex of NBM-lesioned rats. Moreover, at this time a significant decrease in the density of granule neurons in the dentate gyrus accompanied by a reduced probability of dentate LTP induction were observed in both ibotenic acid- and radio-frequency-lesioned rats. These findings have shown that although NBM does not send direct cholinergic projections to the hippocampus, lesions of this cholinergic nucleus are accompanied by delayed neurodegenerative changes involving the dentate gyrus. This suggests the occurrence of indirect connections between NBM and the hippocampus, the functional relevance of which should be explored.     

Chronic continuous infusion of nicotine increases the disappearance of choline acetyltranferase immunoreactivity in the cholinergic cell bodies of the medial septal nucleus following a partial unilateral transection of the fimbria fornix

Previous studies have demonstrated that chronic continuous nicotine treatment via minipumps partially protects against mechanically induced degeneration of the nigrostriatal dopamine neurons in the male Sprague-Dawley rat. In the present study we investigated how a 4-week continuous infusion with (–)-nicotine via minipumps implanted subcutaneously in the male Sprague-Dawley rat (0.125 mg/kg^–1 h^–1) influences the anterograde and retrograde changes occurring in the septohippocampal cholinergic neurons following a unilateral transection of the fimbria fornix. Choline acetyltransferase and acetylcholinesterase immunocytochemistry was performed in combination with computer-assisted morphometry and microdensitometry. Measurements of choline acetyltransferase enzyme activity was performed in the dorsal hippocampus. The chronic nicotine infusion significantly increased the disappearance of the choline acetyltransferase immunoreactive nerve cell area within the medial septal nucleus of the lesioned side. However, the disappearance of the acetylcholinesterase immunoreactive nerve terminals within the dentate gyrus (molecular layer) and of choline acetyltransferase enzyme activity within the dorsal hippocampus was not found to be influenced by the chronic nicotine infusion. Thus, chronic infusion of (–)-nicotine does not appear to exert any protective activity on mechanically injured septohippocampal cholinergic neurons but may instead increase their dysfunction. In comparison with the dopaminergic neurons it may therefore be that the continuous chronic nicotine exposure does not lead to sufficient desensitization of the nicotinic cholinoceptors of the cholinergic neurons to reduce the chronic influx of sodium and calcium ions via the nicotinic ion channels and thus intraneuronal calcium levels and energy demands. Interactions between the high-affinity tyrosine kinase receptors for the neurotrophins and other growth factors and the nicotinic receptors may also be different from those taking place within the nigral dopaminergic neurons. Thus, heterogeneities may exist among central neuronal systems with regard to their trophic responses to chronic continuous nicotine treatment.Abbreviations AChF acetylcholinesterase - ChAT choline acetyltranferase - DA dopamine - ir immunoreactive - IR immunoreactivity - spMGV specific mean gray value     

The persistent expression of a highly polysialylated NCAM in the dentate gyrus of the adult rat.

The expression of a highly polysialylated form of the neural cell adhesion molecule (NCAM-H), often termed 'embryonic NCAM', has been investigated in the hippocampal formation of developing and adult rats. To determine the immunohistochemical localization of NCAM-H, a monoclonal antibody that reacts with the polysialic acid portion of NCAM-H was used. In the late embryonic and early postnatal periods, immunoreactivity for NCAM-H was found throughout the hippocampal formation, except for the ventricular layer. Thereafter, the immunoreactivity gradually decreased and almost vanished in most parts in the adult. However, a strong immunoreactivity remained on a number of cells in the dentate gyrus of adult rats, particularly in the deepest part of the granular layer. The immunoreactive arborized dendrites, mostly arising from the primary apical pole of the granule cells, were found to enter the molecular layer. The mossy fibers also were positive. Electron-microscopic examination of the hilus portion showed that the immunoreactivity was detected on the plasma membrane of some axons in the mossy fiber bundles. Since postnatal neurogenesis is known to continue into adulthood in the deepest part of the granule cell layer of the dentate gyrus, these results suggest that, in the adult dentate gyrus, NCAM-H is expressed by newly generated granule cells, and that the NCAM-H-expressing new cells may participate in the formation of new neural circuits.