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PubMed2000

Cognitive impairment and synaptosomal choline uptake in rats following impact acceleration injury.

Traumatic brain injury is well known to cause deficits in learning and memory, which typically improve with time. Animal studies with fluid percussion or controlled cortical impact injury have identified transient disturbances in forebrain cholinergic innervation which may contribute to such cognitive problems. This study examines the extent to which water maze performance and forebrain synaptosomal choline uptake are affected one week after injury using the newly developed impact acceleration injury model. Injury or sham injury was delivered to adult male Sprague-Dawley rats under halothane anesthesia using a 500-g 2.1-m weight drop. Based on righting reflex, injured rats were divided into moderate (< or = 12 min) or severe (>12 min) groups. Water maze testing was performed on days 5-7 postinjury. On day 7, choline uptake was determined in synaptosomes from hippocampus, a parietal cortex, and entorhinal cortex. Maze learning was severely impaired in the severe injury group but not in the moderate injury group. Learning retention was slightly impaired in the moderate injury group and severely affected in the severe injury group. There was a very strong correlation between the severity of injury as determined by prolongation of righting times and disruption of maze learning at 1 week postinjury. There was no change in synaptosomal choline uptake in any of the forebrain regions in the severe injury group, but a slight (14%) decrease in the hippocampus and parietal cortex of the moderate injury group. Correlation analysis showed no relationship between synaptosomal choline uptake in any brain region and performance in either water maze learning or retention. This study shows that the impact acceleration model produces cognitive impairments equivalent to those seen with fluid percussion injury and controlled cortical impact. Compared with those models, the impact acceleration model does not produce a similar disruption of forebrain cholinergic nerve terminals.

Acceleration↗
PubMed1991

Hippocampal kindling in the rat is associated with time-dependent increases in the concentration of glial fibrillary acidic protein.

The effect of hippocampal kindling on the regional brain concentration of total glial fibrillary acidic protein (GFAP), a marker of reactive astrocytes, was studied in partially kindled rats, and in fully kindled rats after a post-kindling period of 24 h, 1 week, and 2 months. GFAP concentration was measured in arbitrary units by dot-blots. In the hippocampus, dentate gyrus, basolateral amygdala, pyriform cortex, and entorhinal cortex, limbic structures which are known to be involved in the kindling process, there was an increase in GFAP concentration which was maximal in the fully kindled animals studied after 24 h. In most brain areas, GFAP concentration was still elevated 1 week post-kindling, but had declined to control level 2 months post-kindling. A significant increase in GFAP was also found in septum, ventral pallidum/accumbens nucleus, and primary motor cortex of kindled rats with a post-kindling period of 24 h, whereas in several other brain regions GFAP was unchanged. These results suggest that astrocyte activation, indicative of degenerative changes in nearby neurons, is a transient and regional phenomenon in kindling occurring only during the development of the kindled state.

Animals↗
PubMed2005

Inspiratory phase-locked alpha oscillation in human olfaction: source generators estimated by a dipole tracing method.

Olfactory perception and related emotions are largely dependent on inspiration. We acquired simultaneous respiration and electroencephalographic recordings during pleasant odour and unpleasant odour stimulation. We sought to identify changes in respiratory pattern, inspiratory-related potentials and location of dipoles estimated from the potentials. Electroencephalographic recording was triggered by inspiration onset. Respiratory frequency decreased at pleasant odour recognition, and it increased at unpleasant odour detection and recognition. O2 consumption records showed that these changes were not due to metabolic demand. During olfactory stimulation, inspiratory phase-locked alpha oscillation (I-alpha) was found in the averaged potential triggered by inspiration onset. I-alpha was observed at both pleasant odour and unpleasant odour detection and recognition, but it was not seen in the inspiration-triggered potentials of normal air breathing. Electroencephalographic dipole tracing identified the location of dipoles from the I-alpha in the limbic area and the cortex; the entorhinal cortex, hippocampus, amygdala, premotor area and centroposterior orbitofrontal cortex subserve odour detection, and the rostromedial orbitofrontal cortex subserves odour recognition. We suggest that the I-alpha in our study originated from the olfactory cortex in the forebrain and was phase-locked to inspiration.

Action Potentials↗
PubMed1996

Effects of rhinal cortex lesions combined with hippocampectomy on visual recognition memory in rhesus monkeys.

1. We assessed the visual recognition abilities, as measured by delayed nonmatching-to-sample with trial-unique objects, of rhesus monkeys with hippocampectomy (i.e., removal of the hippocampal formation plus parahippocampal gyrus) combined with ablations of the rhinal cortex (i.e., entorhinal cortex plus perirhinal cortex). 2. Relative to unoperated controls, monkeys with combined hippocampectomy and rhinal cortex ablation (H+Rh) were significantly impaired in visual recognition. 3. Comparison of the scores of the monkeys in the present H+Rh group, which sustained near-complete rhinal cortex damage, with the scores of monkeys in an earlier H+Rh group in which the rostral part of the rhinal cortex had been spared indicates that the magnitude of the impairment is greater in the group with the more complete rhinal cortex damage. This finding is consistent with the idea that the rhinal cortex is critical for visual recognition. 4. Comparison of the present results with those from an earlier study on visual recognition that employed lesions limited to the rhinal cortex (Rh group) shows, paradoxically, that adding removal of the hippocampal formation and parahippocampal gyrus to a rhinal cortex lesion significantly reduces the recognition impairment produced by rhinal cortex lesions alone. 5. Our findings do not fit the view that the hippocampal formation, parahippocampal gyrus, and rhinal cortex constitute parts of a single functional system, such that the greater the damage to the entire system, the more severe the impairment. Instead, the results are consistent with the view that there are multiple functional subdivisions within the medial temporal lobe.

Animals↗
PubMed1994

Hybridization histochemical localization of activin receptor subtypes in rat brain, pituitary, ovary, and testis.

We have studied the distribution of activin receptor gene expression in the brain, pituitary, ovary, and testis of the adult rat by in situ hybridization, using probes complementary to the mRNAs encoding the mouse activin receptor subtypes II and IIB (ActRII and ActRIIB). Throughout the brain, ActRII mRNA expression was stronger than that of ActRIIB, and the patterns of expression were similar, although not identical. The most intense sites of activin receptor gene expression were the hippocampal formation, especially the dentate gyrus (ActRII), taenia tecta, and induseum griseum; the amygdala, particularly the amygdaloid-hippocampal transition zone; and throughout the cortical mantle, including the primary olfactory cortex (piriform cortex and olfactory tubercle); other regions of the cortex showing lesser degrees of hybridization included the cingulate cortex, claustrum, entorhinal cortex, and subiculum. In addition, moderate levels of expression were observed in several hypothalamic areas involved in neuroendocrine regulation, such as the suprachiasmatic, supraoptic, paraventricular, and arcuate nuclei. Moreover, activin receptors were also expressed in regions with inputs to the hypothalamus, both in the forebrain (bed nucleus of the stria terminalis and medial preoptic area) and within the brainstem (nucleus of the solitary tract, dorsal motor nucleus of the vagus, locus coeruleus, and mesencephalic raphé system). ActRII mRNA was observed in the intermediate lobe of the pituitary and, less prominently, in the anterior lobe, whereas ActRIIB appeared to be weakly expressed throughout all three pituitary divisions. In both male and female gonads, activin receptor message was clearly present in germ cells, and ActRII was the predominant form. In the ovary, in addition to an intense signal in the oocyte, activin receptor was expressed in corpus luteum and granulosa cells during diestrous day 1. In the testis, there was a strong ActRII signal in rounded spermatids, and a moderate signal in pachytene spermatocytes. In contrast, ActRIIB was absent within tubules, but weakly expressed in interstitial and Leydig cells. This is the first report of the distribution of activin receptor message in adult mammalian tissues. Although consistent with some previously suggested functional associations of activin-containing pathways in the brain, this pattern of expression suggests a greater role for activin than was previously appreciated in cortical, limbic, and somatosensory pathways and in the maturation of germ cells in the gonads of both male and female rats.

Activin Receptors↗
PubMed2002

Binge ethanol exposure in adult rats causes necrotic cell death.

BACKGROUND: Although alcoholics show neurodegeneration after decades of drinking, recent studies with an animal model of binge drinking have found corticolimbic damage after as few as four days. Neurodegeneration can occur through apoptotic or necrotic mechanisms. The goal of this research is to characterize the time course of binge ethanol-induced neurodegeneration and to identify apoptotic or necrotic characteristics of this neurodegeneration. METHODS: Histologic methods (e.g., amino cupric silver staining, Fluoro-Jade B, hematoxylin and eosin, transmission electron microscopy) were used to quantify the time course of degeneration and to characterize the ultrastructural changes that occur with binge ethanol-induced neurodegeneration. RESULTS: After 2 days of binge ethanol, significant damage was evident in the olfactory bulb. After 4 days of binge ethanol, there was significant damage in the agranular insular cortex, anterior piriform cortex, perirhinal cortex, lateral entorhinal cortex, and the temporal dentate gyrus. Ultrastructural examination revealed shrunken soma, vacuolated cytoplasm, pyknotic nucleus, and irregularly clumped chromatin consistent with dark cell degeneration, a form of necrotic neuronal death. CONCLUSIONS: Binge drinking causes necrotic neurodegeneration after 2 days of exposure and increased damage after 4 days but does not increase during withdrawal. These studies indicate that binge drinking induced neurodegeneration is necrotic and occurs during ethanol intoxication and not as a result of ethanol withdrawal.

Aging↗
PubMed1992

Systematisation of the olfactory bulb efferent projections in a lemurian primate: Microcebus murinus.

In order to investigate a sensorial pathway essential in animal behavior, the efferent projections of the olfactory bulbs in Microcebus murinus were identified after transection of one olfactory peduncle and revelation of degenerating fibers by various silver staining methods. Total and partial sections have enabled the demonstration of the involvement in the olfactory projection areas of each olfactory tract: the lateral olfactory tract (LOT) and the intermediate olfactory tract (IOT), either via the medial forebrain bundle (MFB) or not. The IOT fibers innervate the cortex, the anterior olfactory nucleus, the caudate-putamen, the septum and the hippocampus on both sides. The LOT fibers reach the olfactory tubercle, the piriform cortex, the entorhinal cortex and the amygdala on both sides. Olfactory fibers could also be observed in the MFB innervating on both sides firstly the hypothalamic areas (the lateral hypothalamus, the suprachiasmatic, posterior supraoptic, mammillary nuclei and the median eminence), and then the mesencephalic structures (the locus coeruleus and the raphe nuclei). It may be concluded that the olfactory bulbs are not only connected with above-mentioned telencephalic areas, but are also directly related to the vegetative and integrative brain areas located in the hypothalamus and the brainstem and especially with the major nuclei which play an essential role in neurovegetative, neuroendocrine and behavioral regulation.

Animals↗
PubMed1977

Immunohistochemical studies on the localization and distribution of monoamine neuron systems in the rat brain II. Tyrosine hydroxylase in the telencephalon.

Extensive plexuses of TH-positive nerve terminals were found in many parts of the telencephalon, mainly confined to the subcortical and limbic cortical structures. Of special interest were the distinct networks of varying densities in the amygdaloid cortex, the entorhinal cortex, the prepiriform cortex, the anterior cingulate cortex and the (pre-)frontal cortex. Their distribution is identical with the patterns observed in recent studies on cortical dopamine nerve terminals using certain modifications of the Falck-Hillarp technique. The extremely dense TH innervations patterns of the caudate nucleus, nucleus accumbens, tuberculum olfactorium and the less dense basket-like innervation of the lateral septal nuclei could also be demonstrated. TH-positive cell bodies in a periglomerular position could be observed in the olfactory bulb. A few TH-positive cell bodies were observed in the area around the anterior commissure and in the cingulate cortex. In one area, the hippocampal formation, TH-positive dotlike structures were located in the position of the mossy fibres. In all probability they do not belong to monoamine neurons but may contain a cross-reacting protein. In general, the distribution and density of TH-positive terminals agrees well with extensive regional, biochemical studies on TH activity performed by other groups. Minor discrepancies are discussed. As stated in a parallel study on the distribution of TH in the mes- and diencephalon these findings indicate that TH activity is closely related to the amount of enzyme protein. The TH enzyme levels seem to be much higher in the DA than in the NA nerve terminals of the forebrain which would explain the preferential demonstration of DA terminals in the forebrain using TH antiserum and the high and low TH enzyme activity in DA and NA rich regions, respectively.

Animals↗
PubMed1991

Cortical and subcortical patterns of synaptophysinlike immunoreactivity in Alzheimer's disease.

Quantification of synaptophysinlike immunoreactivity is a valuable method for studying the presynaptic terminals in the normal and damaged nervous system. The present report shows that in the control brain, the predominant pattern of synaptic immunostaining in the neocortex was that of an evenly distributed densely granular immunolabeling of the neuropil, while in the paleocortex and in subcortical areas of the brain most of the presynaptic terminals were distributed along the dendritic arborizations or around the neuronal somata. The immunochemical and the immunohistochemical analysis of the Alzheimer's disease tissue showed that the frontal and parietal cortex presented the most severe and widespread loss, with a 45% loss in synaptophysin immunoreactivity. These areas showed an average 35% loss of large neurons. The visual cortex, hippocampus, entorhinal cortex, nucleus basalis of Meynert, and locus ceruleus displayed some degree of loss, but to a lesser extent. In addition to this loss, the basic patterns of organization of the presynaptic terminals were altered, with the presence of abundant, enlarged synaptophysin-labeled terminals. This study further supports the role of synaptic pathology in Alzheimer's disease.

Aged↗
PubMed1996

Subordination induced decrease in 5-hydroxytryptamine and dopamine levels in the frontal cortex--a study using worker-parasite relationship in rats as a model.

Competition for a limited resource appears to be an important factor in natural selection. Such competition when elicited experimentally, leads to the establishment of dominant-subordinate (D-S) relationship between the competitors. The present study was carried out to analyse the effect of D-S relationship on the levels of monoamines, namely, dopamine (DA), 5-hydroxytryptamine (5-HT) and norepinephrine (NE) in various brain regions. The model of D-S relationship selected for this work was a modified worker-parasite paradigm in adult male Wistar rats. The levels of monoamines were estimated in the frontal cortex, the entorhinal cortex, the hippocampus and the septum of the two competitors and a non-competitor control, using high pressure liquid chromatography (HPLC). Levels of DA and 5-HT, but not NE, were found to be lower (P < 0.05) only in the frontal cortex of the subordinate as compared to that of the dominant or the control. These findings are comparable with similar neurochemical changes reported to be caused by some of the known stressors.

Animals↗
PubMed1998

Immunohistochemical localization of metabotropic glutamate receptors, mGluR7a and mGluR7b, in the central nervous system of the adult rat and mouse: a light and electron microscopic study.

The distributions of two alternative splicing variants of metabotropic glutamate receptor mGluR7, mGluR7a and mGluR7b, were examined immunohistochemically in the rat and mouse by using variant-specific antibodies raised against C-terminal portions of rat mGluR7a and human mGluR7b. Many regions throughout the central nervous system (CNS) showed mGluR7-like immunoreactivities (LI). The distribution patterns of mGluR7-LI in the rat were substantially the same as those in the mouse, although some species differences were observed in a few regions. Intense mGluR7a-LI was seen in the main and accessory olfactory bulbs, anterior olfactory nucleus, islands of Calleja, superficial layers of the olfactory tubercle, piriform cortex and entorhinal cortex, periamygdaloid cortex, amygdalohippocampal area, hippocampus, layer I of the neocortical regions, globus pallidus, superficial layers of the superior colliculus, locus coeruleus, and superficial layers of the medullary and spinal dorsal horns. The distribution of mGluR7b was more restricted. It was intense in the islands of Calleja, substantia innominata, hippocampus, ventral pallidum, and globus pallidus. The medial habenular nucleus also showed intense mGluR7a-LI in the rat but not in the mouse. For both mGluR7a- and mGluR7b-LI, localization in the active zones of presynaptic axon terminals was confirmed electron microscopically at synapses of both the asymmetrical and symmetrical types. It is noteworthy that mGluR7a-LI is seen preferentially in relay nuclei of the sensory pathways and that both mGluR7a- and mGluR7b-LI are observed not only in presumed glutamatergic axon terminals, but also in non-glutamatergic axon terminals including presumed inhibitory ones. Thus, mGluR7 may play roles not only as an autoreceptor in glutamatergic axon terminals, but also as a presynaptic heteroreceptor in non-glutamatergic axon terminals in various CNS regions.

Amygdala↗
PubMed1998

The distribution of nitric oxide synthase-I and NADPH-diaphorase containing neurons in the cerebral cortex of different strains of mice and its association with learning and memory.

We investigated the distribution of nitric oxide synthase-I (NOS-I) containing neurons within the neocortex of inbred mice belonging to the Balb/c, NMRI and DBA/2 strains which differ in learning and memory performance. The NOS-I positive neurons were detected immunohistochemically with antibodies against NOS-I and enzyme histochemically using their NADPH-diaphorase (NADPH-d) activity. The qualitative and quantitative evaluation of cortical NADPH-d and NOS-I containing neurons revealed that more than 95% of these cells contained both enzymes. Therefore, we combined the NADPH-d with the WFA-staining to evaluate and parcellate at one section. The specific differences in learning and memory tasks of the three mouse strains have been tested in previous studies. Our investigation test the hypothesis that differences in various aspects of eight-arm radial maze learning are associated with differences in the density of NOS-I positive neurons in cytoarchitectonically and functionally identified cortical areas. We found an increased density of NADPH-d neurons within the whole neocortex in the DBA/2 strain, which reached a lower learning score than the Balb/c and NMRI strains. Significantly higher densities of NADPH-d neurons appeared in the areas of the gustatory cortex, the piriform cortex, the entorhinal cortex and in area 1 of the temporal cortex in DBA/2 mice. A negative correlation exists between the learning scores and the number of NADPH-d positive neurons. If NOS-I activity influences spatial learning as determined in the eight-arm radial maze, the areas with strongly elevated NADPH-d positive neurons may demarcate task-related cortical areas affected in mice with a reduced learning capacity.

Animals↗
PubMed2006

Stereologic analysis of microvascular morphology in the elderly: Alzheimer disease pathology and cognitive status.

The presence of microvascular changes has been documented both in brain aging and Alzheimer disease (AD), although the relationship between the morphometry of brain capillaries and cognitive impairment is still unknown. We performed an analysis of capillary morphometric parameters and AD-related pathology in 19 elderly individuals with variable degrees of cognitive decline. Cognitive status was assessed prospectively using the Clinical Dementia Rating (CDR) scale. Total capillary lengths and numbers as well as mean length-weighted diameter, total neurofibrillary tangle (NFT) and neuron numbers, and amyloid volume were estimated in entorhinal cortex and the CA1 field. Total capillary numbers and mean diameters explained almost 40% of the neuron number variability in both the CA1 and entorhinal cortex. Total capillary length and numbers in the CA1 and entorhinal cortex did not predict cognitive status. Mean capillary diameters in the CA1 and entorhinal cortex were significantly related to CDR scores, explaining 18.5% and 31.1% of the cognitive variability, respectively. This relationship persisted after controlling for NFT and neuron numbers in multivariate regression models. Consistent with the growing interest about microvascular pathology in brain aging, the present data indicate that changes in capillary morphometric parameters may represent independent predictors of AD-related neuronal depletion and cognitive decline.

Aged, 80 and over↗
PubMed1999

A quantitative autoradiographic study of [3H]cAMP binding to cytosolic and particulate protein kinase A in post-mortem brain staged for Alzheimer's disease neurofibrillary changes and amyloid deposits.

The cAMP-dependent protein kinase (PKA) has been implicated in the Alzheimer's disease pathology of abnormal tau phosphorylation leading to neurofibrillary tangle (NFT) formation, as well as in amyloid precursor protein alpha-secretase processing. In the present study, we determined whether [3H]cAMP binding to cytosolic and particulate PKA showed any relationship to the extent of Alzheimer's disease pathology at post-mortem. Autoradiographic [3H]cAMP binding to cytosolic and particulate PKA was measured in sections of entorhinal cortex/hippocampal formation from 23 cases that had been staged for Alzheimer's disease-related neurofibrillary changes and amyloid deposits according to Braak and Braak [H. Braak, E. Braak, Neuropathological staging of Alzheimer's-related changes, Acta Neuropathol. 82 (1991) 239-259]. [3H]cAMP binding to cytosolic PKA showed statistically significant reductions in the entorhinal cortex (P<0.01, ANOVA) with respect to neurofibrillary changes. Post-hoc analysis with Fisher's PLSD test showed significant reductions of [3H]cAMP binding to cytosolic PKA at the isocortical stages (V and VI), compared to the non-pathological (O) (by 55%, P<0.01), transentorhinal (I and II) (by 58%, P<0.001) and limbic (III and IV) (by 45%, P<0.05) stages. A significant reduction (by 25%, P<0.05) was also seen in the transentorhinal compared to the limbic stages. [3H]cAMP binding to cytosolic PKA showed no significant alterations with respect to neurofibrillary changes in either the subiculum, CA1-CA4 subfields of the hippocampus or the dentate gyrus. [3H]cAMP binding to cytosolic PKA also showed significant declines in the entorhinal cortex (P<0.01) and subiculum (P<0.05) with respect to staging for amyloid deposits. Post-hoc analysis with Fisher's PLSD test showed significant reductions of [3H]cAMP binding to cytosolic PKA in the entorhinal cortex at amyloid stage C compared to stages O (by 41%, P<0.01) and A (by 38%, P<0.01). In the subiculum, there were significant reductions of [3H]cAMP binding at stages C (by 41%, P<0.01) and B (by 40%, P<0.05), respectively, compared to stage O. [3H]cAMP binding to particulate PKA did not show significant relationships to staging for either neurofibrillary changes or amyloid deposits in either the entorhinal cortex or any of the hippocampal subregions. These findings suggest that whereas [3H]cAMP binding to cytosolic PKA in the entorhinal cortex is reduced with progression of neurofibrillary and amyloid pathology, other hippocampal regions show a preservation of cytosolic and particulate PKA even in late stage pathologies.

Aging↗
PubMed1997

Decreased expression of N-methyl-D-aspartate receptor 1 messenger RNA in select regions of Alzheimer brain.

An antisense oligonucleotide probe was used to examine the expression of gene encoding the obligatory NMDAR1 subunit of the N-methyl-D-aspartate receptor in the hippocampus and adjacent cortical areas (entorhinal and perirhinal cortices) of seven Alzheimer patients and in the same brain regions of seven control individuals. Both groups were matched according to age, sex, cause of death, post mortem delay, and tissue storage time. Densitometric analysis of in situ hybridization autoradiograms revealed a 34% (P<0.05) decrease in NMDAR1 messenger RNA levels in layer III of the entorhinal cortex in Alzheimer brains. Similar deficits. although statistically not significant, were observed in layers II and IV-VI of the entorhinal cortex, and in granule cells of the dentate gyrus. Reduced levels of NMDAR1 messenger RNA were also found in layers II-VI of the perirhinal cortex (41 53% decrease, P<0.02). There were no changes in NMDAR1 messenger RNA expression in the CA1, hilus, or subiculum. Both Alzheimer and control group show substantial intersubject variation in levels of NMDAR1 messenger RNA. The analysis of emulsion-dipped tissue revealed a trend toward a decrease in the number of silver grains overlying individual neurons in the CA1, entorhinal cortex, and granule cell layer of some Alzheimer patients. No significant relationship was detected between the levels of NMDAR1 messenger RNA and post mortem delay, tissue storage, age of the subjects, or mini mental state exam score either in control or Alzheimer individuals. In contrast, a strong inverse correlation between NMDAR1 expression and disease duration was found. These data suggest that reduction in expression of the NMDAR1 gene observed in certain regions of Alzheimer hippocampus and adjacent cortical regions is specific for the disease itself. We postulate that reduced transcript levels may reflect either regional cell loss or anomalies in glutamatergic input to the hippocampus and entorhinal cortex in Alzheimer's disease. When followed by changes at the receptor subunit protein level, altered expression of the NMDAR1 gene in Alzheimer brain may contribute, through the formation of N-methyl-D-aspartate receptors with different properties, to the previously reported modified N-methyl-D-aspartate receptor ligand binding, abnormal vulnerability of select neuronal populations to excitotoxic insult, and may also be involved in learning and memory deficits.

Aged↗
PubMed1999

Entorhinal but not hippocampal or subicular lesions disrupt latent inhibition in rats.

Latent inhibition (LI) is the deficit of conditioning resulting from repeated nonreinforced preexposure to a conditioned stimulus before its pairing with an unconditioned stimulus. There are cumulative data showing that large lesions of the hippocampal formation disrupt LI. However, the effects of selective lesions of the different components of the hippocampal formation have never been directly addressed in the same study and conditioning paradigm. The first experiment of the present study aimed at investigating the effects of excitotoxic lesions of the hippocampus, subiculum, or entorhinal cortex on LI in an "off-baseline"-conditioned emotional response procedure. Hippocampus or subiculum lesions had no effect on either LI or conditioning. In contrast, entorhinal cortex lesions disrupted LI without modifying conditioning. In Experiment 2, locomotor activity in a novel environment was assessed in the same rats. Whereas lesions of hippocampus increased locomotor activity, lesions of the subiculum or the entorhinal cortex were devoid of effect. Although both LI and habituation to novel environmental cues are thought to involve interactions between the hippocampal formation and the mesolimbic pathway, these results indicate a functional dissociation between the hippocampus and the entorhinal cortex.

Animals↗
PubMed1994

The organotypic entorhinal-hippocampal complex slice culture of adolescent rats. A model to study transcellular changes in a circuit particularly vulnerable in neurodegenerative disorders.

The entorhinal-hippocampal system is severely altered in many neurodegenerative disorders with mnemonic malfunction, e.g. Alzheimer's, Parkinson's and Huntington's disease. The present approach characterizes an organotypic complex slice culture comprising both the entorhinal cortex and the hippocampal formation in order to establish a tool for experimental studies of the entorhinal-hippocampal interaction and its presumed neurodegenerative alterations in vitro. Slices were obtained from rats at about postnatal day 15 and maintained in culture using the interface technique. Thus, also structures known to be developed gradually during the first weeks postnatally are in accord to structures seen in adult rats. After two-three weeks in vitro, slices in the culture dish still revealed the typical morphological features of the entorhinal-hippocampal formation as visible with the dissecting microscope. Biocytin, which is taken up by and transported within living cells, labeled typical cell bodies, dendrites and axons of stellate neurons in layer II and pyramidal cells in layer III when applied to the outer layers of the entorhinal cortex. Small injections of biocytin within the dentate gyrus displayed living granule cells and the maintenance of their projection to the pyramidal cells in CA3, i.e., a typical suprapyramidal plexus of mossy fibers. The presence of axons of entorhinal neurons traveling towards the hippocampus and growth cones traversing the deep layers of the entorhinal cortex indicate that both brain regions are still interacting. Immunocytochemistry for calbindin D-28K revealed labeled neurons in layer II of the entorhinal cortex and dentate granule cells which are known to contain this calcium-binding protein.

Alzheimer Disease↗
PubMed2005

Differential role of entorhinal and hippocampal nerve growth factor in short- and long-term memory modulation.

We studied the effects of infusion of nerve growth factor (NGF) into the hippocampus and entorhinal cortex of male Wistar rats (250-300 g, N = 11-13 per group) on inhibitory avoidance retention. In order to evaluate the modulation of entorhinal and hippocampal NGF in short- and long-term memory, animals were implanted with cannulae in the CA1 area of the dorsal hippocampus or entorhinal cortex and trained in one-trial step-down inhibitory avoidance (foot shock, 0.4 mA). Retention tests were carried out 1.5 h or 24 h after training to measure short- and long-term memory, respectively. Immediately after training, rats received 5 microl NGF (0.05, 0.5 or 5.0 ng) or saline per side into the CA1 area and entorhinal cortex. The correct position of the cannulae was confirmed by histological analysis. The highest dose of NGF (5.0 ng) into the hippocampus blocked short-term memory (P < 0.05), whereas the doses of 0.5 (P < 0.05) and 5.0 ng (P < 0.01) NGF enhanced long-term memory. NGF administration into the entorhinal cortex improved long-term memory at the dose of 5.0 ng (P < 0.05) and did not alter short-term memory. Taken as a whole, our results suggest a differential modulation by entorhinal and hippocampal NGF of short- and long-term memory.

Animals↗