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R Nitsch

Publications and source records attributed to R Nitsch.

At least 91 records · Page 5Linked to original sources
PubMed1994

Long lasting functional alterations in the rat dentate gyrus following entorhinal cortex lesion: a current source density analysis.

The functional consequences of lesions of the entorhinal cortex of rats were studied by analysing laminar distributions of stimulus induced field potentials in the dentate gyrus with a subsequent current source density analysis. Stimulation of the inner molecular layer elicits large excitatory postsynaptic potentials with small if any population spikes in the stratum granulare both in normal and lesioned animals. In lesioned animals middle molecular layer stimulation causes large excitatory sinks in the stratum moleculare without generation of population spikes in stratum granulare, while the same stimulation in slices from normal animals readily induces population spikes. The current source density analysis revealed a shift of current sinks induced by stimulation of either the inner or the middle molecular layer to common site. The N-methyl-D-aspartate receptor contribution to the current sink and source was found to be more prominent after middle molecular layer stimulation in comparison to inner molecular layers stimulation in the control group, while such a distinction could not be made in the lesioned group. Activation of mossy fibers did not reveal any significant differences between normal and lesioned animals. Following entorhinal cortex lesion sprouting of remaining afferents (e.g. commissural fibers) into the termination zones of the degenerated perforant path has been reported suggesting a compensatory replacement of excitatory synaptic input. However, persistent transneuronal dendritic alterations of neurons in the dentate gyrus have been observed which might result in altered dentate gyrus function. Our findings suggest that the reorganization process after entorhinal cortex lesion does not lead to full functional compensation of the lost perforant path input, resulting in an altered balance between excitation and inhibition.

Animals↗
PubMed1994

Morphological evidence that hypothalamic substance P-containing afferents are capable of filtering the signal flow in the monkey hippocampal formation.

This study in the African green monkey (Cercopithecus aethiops) was designed to characterize the neurochemical features of hippocampal nonpyramidal neurons that are specific synaptic targets of substance P-containing projective neurons located in the supramammillary nucleus. Our previous studies provided evidence for an excitatory nature to this hypothalamo-hippocampal pathway and described the mode of termination of these afferents on hippocampal principal neurons. The present correlated light and electron microscopic immunocytochemical analysis, using the nickel-diaminobenzidine/diaminobenzidine double-labeling technique, revealed that this hippocampal afferent system establishes multiple, exclusively asymmetric synapses with three specific subpopulations of nonpyramidal cells: (1) a small portion of parvalbumin-containing basket cells located periodically in or adjacent to the granule cell layer of the dentate gyrus, which therefore inhibit only a subpopulation of granule cells; (2) some of the calbindin-immunoreactive local circuit neurons located in the hilar area; and (3) calbindin-positive cells occurring exclusively in the stratum molecular of the middle portion of the CA3 subfield. Postembedding studies revealed that the aforementioned calbindin-containing cells are GABAergic inhibitory neurons. Our studies indicate that hypothalamic afferents can effectively filter the information flow at different levels of the excitatory signal loop in the monkey hippocampal formation. Dentate granule cells, which are only stimulated by hypothalamic afferents, will transfer excitatory signals differently than those that are controlled by a feedforward inhibitory mechanism initiated by these fibers. In the CA3 subfield, the signal flow can again be depressed by those pyramidal neurons that are inhibited by calbindin-containing cells receiving an excitatory hypothalamic input.

Animals↗
PubMed1993

Transneuronal changes in dendrites of GABAergic parvalbumin-containing neurons of the rat fascia dentata following entorhinal lesion.

The perforant path fibers from the entorhinal cortex form synapses with both granule cells and GABAergic, parvalbumin-containing (PARV) nongranule cells. The authors recently reported a persistent reduction of PARV-positive dendrites in the termination zones of entorhinal fibers in the hippocampus proper and fascia dentata after lesion of the entorhinal cortex. In the present study the authors analyzed the effects of de-entorhination on the ultrastructure of postsynaptic PARV-positive dendrites in the molecular layer of the fascia dentata. PARV immunocytochemistry was performed 2, 8, 55, and 360 days after an ipsilateral entorhinal lesion and, for comparison, 10 days after an ipsilateral fimbria-fornix transection that disconnects the hippocampus from its septal and commissural afferents. Two days after entorhinal lesion, the authors observed swelling of the tissue close to the hippocampal fissure. Adjacent distal dendritic tips of PARV-positive dentate neurons appeared bloated and reduced in number. Reduction of PARV-positive dendrites in the former perforant path termination zone persisted 55 days after entorhinal lesion and could still observed after postlesional survival times for 1 year. Degenerating axon terminals were still present 55 days following lesion and PARV-positive dendrites exhibited abnormal invaginations. Fimbria transection did not result in similar dendritic changes in PARV-positive neurons. The results indicate a long-lasting process of reorganization in the molecular layer of the fascia dentata following entorhinal lesion and persisting changes in the morphology of PARV-immunoreactive dendrites. Entorhinal fibers seem to play a specific role for the maintenance of these dendrites, since similar changes did not occur following removal of septal and commissural fibers.

Animals↗
PubMed1993

Calretinin immunoreactivity in the monkey hippocampal formation--I. Light and electron microscopic characteristics and co-localization with other calcium-binding proteins.

Calretinin-containing neurons were visualized by immunocytochemistry in the monkey hippocampal formation, subicular complex, and entorhinal cortex. Calretinin-immunoreactivity was present exclusively in non-granule cells of the dentate gyrus and in non-pyramidal cells of Ammon's horn, subiculum and entorhinal cortex. Most frequently, calretinin-positive neurons were found at the hilar border of the dentate granule cell layer and in the stratum radiatum of CA1-3 areas. In the subicular complex, immunoreactive neurons were evenly distributed in all layers, whereas in the entorhinal cortex, they were accumulated in external layers above the lamina dissecans. Distinct bands of calretinin-positive fibers occupied the supragranular zone of the molecular layer in dentate gyrus, the pyramidal cell layer of the CA2 area in Ammon's horn and the upper two layers of presubiculum. The majority of calretinin-immunoreactive neurons were small, bipolar or fusiform neurons with a dendritic tree oriented parallel to the dendrites of principal cells (granule cells in dentate gyrus and pyramidal neurons elsewhere). Dendrites were smooth or sparsely spiny, displaying small spines of conventional type. Co-existence studies showed that these neurons were completely devoid of other calcium-binding proteins, parvalbumin and calbindin. Electron microscopic analysis revealed somata of immunoreactive neurons which contained a large nucleus and a small cytoplasmic rim, which contained only few organelles. The nucleus displayed deep infoldings and intranuclear rods. Input synapses of immunoreactive neurons were rare both on somata and dendrites and large surface areas were frequently apposed by glial processes. This was very prominent in the dentate gyrus and Ammon's horn. Axons of calretinin-positive neurons were thin, arborized in all layers and had small varicosities. Their terminals formed symmetric synaptic contacts mainly with dendrites and less frequently with somata of principal cells. Axon terminals of calretinin-immunoreactive fiber bundles in the supragranular layer, as well as in the pyramidal layer of the CA2 area, formed asymmetric synaptic contacts with dendritic shafts. In addition, they established asymmetric axospinous and axosomatic synaptic contacts with granule cells of the dentate gyrus. In the presubiculum, the calretinin-positive axon bundle included a large number of immunoreactive myelinated axons, as well as axon terminals. The characteristic location and features of synapses suggests that these fibers derive from extra-hippocampal afferents (Nitsch, R. and Leranth C. (1993) Neuroscience 55, 797-812) and not from the calretinin-immunoreactive neurons of the hippocampal formation.

Animals↗
PubMed1993

Calretinin immunoreactivity in the monkey hippocampal formation--II. Intrinsic GABAergic and hypothalamic non-GABAergic systems: an experimental tracing and co-existence study.

Our light and electron microscopic studies (Seress L., Nitsch R. and Leranth C. (1993) Neuroscience 55, 775-796.) indicated that in the hippocampus of the African Green monkey, calretinin is exclusively present in non-pyramidal cells. Calretinin-positive axons formed a prominent band at the border of the dentate molecular and granule cell layers and in the pyramidal layer of CA2, and established asymmetric synapses with different postsynaptic targets. The goal of this study is to determine the cells of origin of this presumably extrinsic innervation, and subsequently, the characterization of their neurochemical features. We were able to demonstrate that calretinin-immunoreactive axon terminals in the inner molecular layer of the dentate gyrus and in the pyramidal layer of CA2 disappear 10 days after fimbria-fornix transection. Retrograde tracing revealed their cells of origin to be in the supramammillary nucleus. Co-localization studies employing the cryostat consecutive, semithin section technique provided evidence that these large projecting neurons contained both calretinin and substance-P but lack GABA as an inhibitory transmitter. In contrast, co-localization studies revealed that almost all of the intrinsic calretinin-positive neurons in different areas of the primate hippocampus contained GAD or GABA. These results suggest that there are two separate calretinin-containing systems in the primate hippocampus, i.e. an intrinsic inhibitory and an extrinsic excitatory one, the latter deriving from the supramammillary nucleus of the hypothalamus.

Animals↗
PubMed1992

Reduction of posttraumatic transneuronal "early gene" activation and dendritic atrophy by the N-methyl-D-aspartate receptor antagonist MK-801.

The removal of a major hippocampal afferent system, the glutamatergic fibers from the entorhinal cortex, results in transneuronal changes in postsynaptic inhibitory neurons using gamma-aminobutyric acid (GABA) as a neurotransmitter. This study shows that these transneuronal alterations are reduced by the selective N-methyl-D-aspartate (NMDA) receptor antagonist (+)-MK-801. Thus, systemic injection of (+)-MK-801 prior to and after entorhinal lesion abolishes the retraction of distal dendrites from the termination zones of degenerating entorhinal fibers and reduces the swelling of their distal segments. Also, entorhinal lesion results in the appearance of c-fos protein-like immunoreactivity in hippocampal neurons and glial cells, which again is blocked by (+)-MK-801 administration. These data suggest that NMDA receptor-mediated neurotoxicity due to postlesional glutamate elevation results in early gene expression and in transneuronal dendritic changes. Similar processes may play a role in Alzheimer's disease, since there is a severe degeneration of the glutamatergic entorhino-hippocampal projection in this neurodegenerative disorder.

Afferent Pathways↗
PubMed1992

Parvalbumin-containing nonpyramidal neurons in intracortical transplants of rat hippocampal and neocortical tissue: a light and electron microscopic immunocytochemical study.

Previous immunocytochemical studies have shown that GABAergic nonpyramidal neurons of the rat hippocampus survive in intracerebral transplants. However, information is still lacking about the dendritic organization and the input synapses of these cells as well as their capacity to express the calcium-binding protein parvalbumin (PARV) under transplant conditions. In the present study, a monoclonal antibody against PARV was used to examine the dendritic morphology and the synaptic organization of parvalbumin-containing GABAergic neurons in hippocampal and dentate transplants. In addition, parvalbumin-containing nonpyramidal neurons were studied in neocortical transplants to compare the differentiation of grafted allocortical and neocortical nonpyramidal neurons. Tissue blocks of hippocampus and fascia dentata and of the parietal neocortex were taken from late embryonic rats (E 21 and E 16, respectively) and were transplanted into a cavity in the somatosensory cortex of young adult rats. After 3.5 or 7 months survival, the recipient brains were fixed by perfusion and immunostained for PARV. As in the hippocampal formation in situ, PARV-containing neurons in the hippocampal transplants were observed within and in the vicinity of the pyramidal and granule cell layer. In neocortical transplants, PARV-immunoreactive cells were distributed in all parts of the transplant with dendrites extending in various directions. In both hippocampal and neocortical transplants, immunoreactive dendrites were smooth and displayed the characteristic regular varicosities known from in situ studies of these cells. Numerous unlabeled terminals as well as a few immunoreactive boutons established synapses on the immunoreactive dendrites. PARV-positive terminals formed the typical pericellular baskets around the immunonegative cell bodies of pyramidal neurons and granule cells in the transplants. They established symmetric synapses with cell bodies and proximal dendrites. Synapses on axon initial segments were absent or rare. Our results demonstrate that allocortical as well as neocortical nonpyramidal neurons transplanted to the neocortex of adult recipients survive transplantation, express the calcium-binding protein parvalbumin, and develop a cell-specific morphology.

Animals↗
PubMed1992

Reorganization of input synapses of parvalbumin-containing neurons in the rat fascia dentata following entorhinal lesion.

Removal of ipsilateral entorhinal afferents to the fascia dentata results in a retraction of postsynaptic parvalbumin (PARV)-containing dendrites of GABAergic neurons from the outer molecular layer. This study analyzes the reorganization of input synapses of these identified neurons following deafferentation. The density of synaptic input (total length of synaptic membrane specializations) of PARV-immunostained dendrites increased by 34% in the outer molecular layer of the fascia dentata 8 days, and by 21% 55 days following lesion when compared with unoperated controls. Eight days postlesion this increase was mainly due to an enlargement of synaptic membrane specializations of single terminals whereas 55 days after the lesion there was an increase in the number of synapses on the identified dendrites. Our results suggest expansion of terminals of remaining afferent systems (i.e. commissural fibers) in the early postlesional period and reactive synaptogenesis (i.e. de novo formation of synaptic contacts) on PARV-positive dendrites after long survival time. This increased innervation may be of functional importance as it might compensate for the reduction of the receptive field of the PARV-positive, supposedly inhibitory neurons in the postlesional dentate gyrus.

Animals↗
PubMed1992

Nerve growth factor and choline acetyltransferase activity levels in the rat brain following experimental impairment of cerebral glucose and energy metabolism.

Intracerebroventricular (ICV) injection of streptozotocin (STZ) has been reported to impair cerebral glucose utilization and energy metabolism (Nitsch and Hoyer: Neurosci Lett, 128:199-202, 1991) and also to prejudice passive avoidance learning in adult rats (Mayer et al.: Brain Res 532:95-100, 1990). It is well established that the forebrain cholinergic system, whose integrity is essential for learning and memory functions, depends on the target-derived retrograde messenger nerve growth factor (NGF). Therefore, we measured NGF and choline acetyltransferase (ChAT) activity levels in the forebrain cholinergic system in adult rats that had received a single injection of either STZ or artificial cerebrospinal fluid into the left ventricle 1 or 3 weeks prior to sacrifice. One week after ICV STZ treatment, NGF content was significantly decreased (-32%) in the septal region, where NGF-responsive cell bodies are located and NGF exerts its neurotrophic action after retrograde transport from NGF-producing targets. In contrast, NGF levels in the cortex and hippocampus, which are target regions for the basal forebrain cholinergic neurons, and in the brainstem and cerebellum were increased (+12% to +47%) within 3 weeks after ICV STZ treatment. The alterations in NGF levels were not related to changes in ChAT activity that decreased in the hippocampus by only 15%. This might be due to masking effects exerted by compensatory NGF-mediated stimulation of ChAT activity in remaining functional neurons. It is suggested that impaired behavior which has been observed after STZ-induced impairment of cerebral glucose and energy metabolism may be at least partially related to a diminished capacity of central NGF-responsive neurons to bind and/or transport NGF.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Changes in brain monoaminergic neurotransmitter concentrations in rat after intracerebroventricular injection of streptozotocin.

The tissue concentrations of the monoaminergic neurotransmitters noradrenaline (NA), dopamine, and serotonin (5-HT) and of their major metabolites were measured by HPLC and electrochemical detection in several rat brain areas after intracerebroventricular injection of streptozotocin (STZ). NA levels were found to be decreased in the frontal cortex by 14%, in the entorhinal cortex by 18%, and in the striatum by 38%. In the entorhinal cortex, 5-HT levels were decreased by 19% and the 5-HT turnover rate, measured as the 5-hydroxyindoleacetic acid/5-HT ratio, was found to be increased by 48%. These results may be indicative of a distinct susceptibility of some neurotransmitters in certain brain areas after a more general impairment of brain metabolism by means of intracerebroventricular application of the diabetogenic compound STZ.

Animals↗
PubMed1992

Synaptic connections of seizure-sensitive neurons in the dentate gyrus.

A selective loss of somatostatin- and neuropeptide Y-immunoreactive neurons has been reported in the dentate gyrus of rats with cerebral ischemia, following sustained electric stimulation, and in patients with non-tumor-related temporal lobe epilepsy. Three theoretical possibilities were tested that may explain why these neurons are more vulnerable than others, such as the cholecystokinin- and calcium-binding protein-containing cells: (1) the seizure-sensitive neurons are more involved in specific excitatory circuitry than are the seizure-resistant cells; (2) the somatostatin- and neuropeptide Y-immunoreactive neurons are less protected by inhibitory GABAergic inputs than cells immunoreactive for cholecystokinin; and (3) the seizure-sensitive neurons do not contain calcium-binding proteins. The present results of light and electron microscopic, single and double, immunostaining experiments and co-localization studies performed on the hippocampal formations of rats and non-human primates, support the idea that the calcium-binding protein content of a neuron defines its seizure sensitivity.

Animals↗
PubMed1992

Identification of neuronal connections by means of electron microscopic immunocytochemistry.

For many years neuroanatomical research has focused on the tracing of connections between populations of neurons in the central nervous system. With the development of immunocytochemical procedures employing antibodies against transmitters, transmitter-synthesizing enzymes and various neuropeptides, it has become possible to study the chemical characteristics of nerve cells. By combining tracer techniques and immunocytochemical approaches the transmitter identity of a projection can be determined. Moreover, electron microscopic double-labeling procedures allow the identification of the target cells of immunocytochemically characterized presynaptic terminals. This way, by the immunocytochemical identification of transmitters or neuropeptides in defined projection neurons, a more functional interpretation of neuroanatomical data has become possible. In the present report, these combinations of techniques are demonstrated by describing recent studies of cholinergic septohippocampal projection neurons.

Animals↗
PubMed1991

Dose-dependent stimulation of adenylate cyclase in rat hippocampal tissue by isoprenaline, Gpp(NH)p and forskolin: lack of circadian phase-dependency.

In rat hippocampal tissue the basal as well as drug-stimulated adenylate cyclase (AC) activity was studied after sacrificing the animals at 9 different circadian times (01.00, 04.00, 07.00, 10.00, 13.00, 16.00, 19.00, 22.00, 01.00 h). The AC was stimulated in vitro either via the beta-adrenoceptor by isoprenaline (IPN, 0.01-100 mumol/l plus GTP 0.005-50 mumol/l, via the GTP-binding protein by Gpp(NH)p (0.03-100 mumol/l) or via the catalytic unit of the AC by forskolin (0.1-600 mumol/l). For each drug dose-response curves could be constituted in single hippocampal tissues at each of the time points of sacrifice. Whereas maximal stimulation by forskolin was not achieved with the highest dose used (600 mumol/l, EC50-, Emax-values and Hill-coefficients could be calculated for both IPN and Gpp(NH)p, respectively. Thus, the rank order of drug stimulated AC activity was forskolin > Gpp(NH)p > IPN. However, no circadian phase-dependency in basal as well as drug-stimulated AC activity was found.

Adenylyl Cyclases↗
PubMed1991

Neuropeptide Y (NPY)-immunoreactive neurons in the primate fascia dentata; occasional coexistence with calcium-binding proteins: a light and electron microscopic study.

Neuropeptide Y (NPY)-containing neurons are known to be highly vulnerable following sustained electrical stimulation in rats and in humans suffering from temporal lobe epilepsy. This has been related to a strong excitatory input. In contrast, there is evidence that neurons containing calcium-binding proteins exhibit a high resistance under experimental seizure and hypoxia conditions. The aim of this study was to determine the coexistence of NPY and calcium-binding proteins in inhibitory neurons of the primate fascia dentata and their synaptic connections. Vibratome sections of hippocampi of African green monkeys (Cercopithecus aethiops) were immunostained with antibodies against NPY, PARV, and CB. A quantitative coexistence study was performed for NPY and PARV on consecutive semithin sections. In contrast to the rodent hippocampus, NPY-immunoreactive neurons were found exclusively in the hilus of fascia dentata with horizontally oriented dendrites which did not extend into the granular and molecular layer. Conversely, PARV-immunoreactive neurons were also present in the granular and inner molecular layer and extended their dendrites far out in the molecular layer and the hilus. Axon terminals immunoreactive for NPY were mostly concentrated in the middle and outer molecular layer and the hilar region and were rare in the granular layer. PARV-immunoreactive boutons were basically restricted to the granular layer where they formed typical baskets. The antibody against calbindin stained almost exclusively granule cells. Coexistence of NPY- and PARV-immunoreactivity was found only in hilar neurons and was rare (9 out of 152 cells analyzed). These results suggest that most NPY-immunoreactive neurons do not contain calcium-binding proteins. NPY-containing neurons exhibited ultrastructural characteristics as described for inhibitory neurons. Their dendrites were only sparsely contacted by mostly asymmetric synaptic terminals, including a very small number of mossy fiber axon terminals. In turn, numerous NPY-immunoreactive axon terminals formed symmetric synapses with spines and dendritic shafts of unlabeled neurons in the middle and outer molecular layer, whereas no contact with granule cell bodies was evident. Thus, we conclude that the vulnerability of NPY-containing inhibitory neurons may be due more to the lack of calcium-binding proteins than to a strong excitatory innervation. As their axons may contribute to the inhibitory control of the major excitatory input from the entorhinal cortex, their loss following overstimulation may play a role in perpetuating hippocampal seizure activity.

Animals↗
PubMed1991

Local action of the diabetogenic drug, streptozotocin, on glucose and energy metabolism in rat brain cortex.

Glucose is the principal source for energy production in the brain, and undisturbed glucose metabolism is pivotally significant for normal function of this organ. Peripheral glucose metabolism is impaired by streptozotocin (STZ), which induces diabetes mellitus. In this investigation, we have studied the local effects of intracerebroventricular (i.c.v.) STZ on glucose and energy metabolism in cerebral cortex. Three weeks after one single i.c.v. administration of STZ, ATP and phosphocreatine (CrP) concentrations as well as the ATP/ADP ratio and the energy charge potential were decreased, while the concentrations of glucose and ADP were increased, in cerebral cortex. Arterial blood glucose levels were not altered by i.c.v. STZ. It is concluded that brain energy metabolism is locally impaired by i.c.v. STZ. We propose that the disturbance of brain energy metabolism by i.c.v. STZ administration may provide a model for the study of prolonged metabolic neuronal stress.

Adenosine Diphosphate↗
PubMed1991

Maintenance of peripheral dendrites of GABAergic neurons requires specific input.

This study demonstrates that the removal of a major hippocampal afferent system, the fibers from the entorhinal cortex, results in transneuronal changes in postsynaptic GABAergic inhibitory neurons. Following swelling of their distal segments, the peripheral dendrites of these cells retract from the termination zones of degenerating entorhinal fibers in the outer molecular layer of the fascia dentata and in stratum lacunosum-moleculare of the hippocampus proper. These dendritic alterations are long-lasting and do not seem to be restored by sprouting of other intact afferents. Persisting transneuronal changes in GABAergic hippocampal neurons following the removal of their entorhinal afferents may play a role in Alzheimer's disease since there is a severe degeneration of the entorhino-hippocampal projection in this neurodegenerative disorder.

Afferent Pathways↗