Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Entorhinal Cortex”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 649 records · Page 36Linked to original sources

Prenatal ethanol effects on NGF level, NPY and ChAT immunoreactivity in mouse entorhinal cortex: a preliminary study.

It has been reported that maternal ethanol consumption leads to deficits in the limbic areas involved in cognitive functions and interferes with synthesis and utilization of neurotrophins. In the present study, it was hypothesized that prenatal alcohol intake might induce neuroanatomical alterations in the entorhinal cortex (EC). We also investigated the possible EC involvement of brain nerve growth factor (NGF), the first neurotrophin to be isolated, during such pathological events. To test this hypothesis, we used pregnant mice exposed to ethanol during EC neurogenesis (starting about gestational day 8). Our data show that prenatal alcohol intake in male mice alters the EC neuronal growth and differentiation. These morphological alterations are accompanied by an altered NGF level in the EC of prenatal alcohol-treated mice. We also found a decrease in choline acetyltransferase- and neuropeptide Y-immunopositive neurons in the EC of alcohol-exposed mice. However, the relationship between neuronal damage induced in the EC by ethanol, low presence of NGF, and the possible functional and behavioral consequences remains to be elucidated.

Animals↗

Neurotensin receptor binding abnormalities in the entorhinal cortex in schizophrenia and affective disorders.

BACKGROUND: Convergent evidence from in vivo and in vitro studies of schizophrenia have implicated the mesial temporal lobe as a primary site of pathological change in this disorder. We have previously reported decreased neurotensin receptor density in layer II of the intermediate entorhinal cortex (ERC) in schizophrenia, a finding seen elsewhere but not seen in more caudal ERC. METHODS: To study neuroanatomic and diagnostic specificity, we measured the density of neurotensin receptors in the intermediate and caudal ERC and hippocampal formation of schizophrenic, affective disorder control subjects, and normal control subjects. Slide-based radioligand binding was used to perform these studies. RESULTS: Not only schizophrenic but also affective disorder subjects had decreased neurotensin receptor density in layer II of the intermediate ERC. Affective disorder subjects had significantly decreased neurotensin receptor density in layers V/VI of the intermediate ERC, and schizophrenic subjects trended in the same direction. CONCLUSIONS: These findings demonstrate region-specific changes in neurotensin receptor binding levels in the mesial temporal lobe; however, there is no clear diagnostic specificity for these changes, because they were seen to varying degrees in both schizophrenia and affective disorders.

Adult↗

Large-scale expression study of human mesial temporal lobe epilepsy: evidence for dysregulation of the neurotransmission and complement systems in the entorhinal cortex.

Human mesial temporal lobe epilepsies (MTLE) are the most frequent form of partial epilepsies and display frequent pharmacoresistance. The molecular alterations underlying human MTLE remain poorly understood. A two-step transcriptional analysis consisting in cDNA microarray experiments followed by quantitative RT-PCR validations was performed. Because the entorhinal cortex (EC) plays an important role in the pathophysiology of the MTLE and usually discloses no detectable or little cell loss, resected EC and each corresponding lateral temporal neocortex (LTC) of MTLE patients were used as the source of disease-associated and control RNAs, respectively. Six genes encoding (i) a serotonin receptor (HTR2A) and a neuropeptide Y receptor type 1 (NPY1R), (ii) a protein (FHL2) associating with the KCNE1 (minK) potassium channel subunit and with presenilin-2 and (iii) three immune system-related proteins (C3, HLA-DR-gamma and CD99), were found consistently downregulated or upregulated in the EC of MTLE patients as compared with non-epileptic autopsy controls. Quantitative western blot analyses confirmed decreased expression of NPY1R in all eight MTLE patients tested. Immunohistochemistry experiments revealed the existence of a perivascular infiltration of C3 positive leucocytes and/or detected membrane attack complexes on a subset of neurons, within the EC of nine out of eleven MTLE patients. To summarize, a large-scale microarray expression study on the EC of MTLE patients led to the identification of six candidate genes for human MTLE pathophysiology. Altered expression of NPY1R and C3 was also demonstrated at the protein level. Overall, our data indicate that local dysregulation of the neurotransmission and complement systems in the EC is a frequent event in human MTLE.

Adult↗

Generation of theta rhythm in medial entorhinal cortex of freely moving rats.

A regular slow wave theta rhythm can be recorded in the medial entorhinal cortex (MEC) of freely moving rats during voluntary behaviors and paradoxical sleep. Electrode penetrations normal to the cortical layers proceeding from the deeper to the more superficial layers reveal a continuous theta rhythm in layers IV-III (deep MEC theta rhythm) with an amplitude maximum in layer III, a null between the outer one-third of layer III and the inner one-half of layer I, and a continuous phase-reversed theta rhythm in layers II-I (superficial MEC theta rhythm) with an amplitude maximum there. Deep MEC theta rhythm is similar in phase and wave shape to CA1 theta rhythm; superficial MEC theta rhythm is similar in phase to DG theta rhythm. Laminar profiles throughout MEC show that the theta rhythm is generated there; it is not volume conducted from hippocampus.

Animals↗

Late post-learning participation of entorhinal cortex in memory processes.

Mice of the BALB/c strain were bilaterally implanted with electrodes in the lateral entorhinal cortex (EC) in order to study the influence of post-trial EC stimulation on memory. The learning task was a food reinforced operant conditioning. At one of several time intervals after a first learning session, the experimental groups were stimulated for 80 s with subseizure current intensity. Testing was carried out 24 h later. In the first experiment, a continuous reinforcement schedule was used. EC stimulation had no effect when applied at the 30-s or 3-h intervals, but surprisingly a 30-min delayed stimulation greatly improved retention compared to performance of non-stimulated animals. In the second experiment, the same paradigm was used in a discriminative operant conditioning task. The same facilitation on retention was observed only with the 30-min delayed stimulation. Compared to previous data with hippocampal or hypothalamic stimulation, the present results reveal that EC is lately involved in memory processes.

Animals↗

Basket-like interneurones in layer II of the entorhinal cortex exhibit a powerful NMDA-mediated synaptic excitation.

Spiny stellate neurones of layer II of the entorhinal cortex (EC) provide the perforant path input to the dentate gyrus. Previous studies have shown that synaptic responses of these neurones are dominated by GABAergic inhibition. The present study describes intracellular recordings from 'fast-spiking' interneurones in layer II which may be the basis of the synaptic inhibition. Lucifer yellow fills of fast-spiking cells revealed neurones with a widespread axonal arborization forming basket-like complexes around unlabelled cells in layer II. Synaptic activation of the fast-spiking cells evoked long duration excitations which were mediated largely by NMDA receptors. A fast AMPA/kainate EPSP was also detectable. These neurones have morphological and physiological properties which make them well-suited to exert a widespread inhibitory control over the efferent output of layer II to the dentate gyrus.

Animals↗

Preferential neuronal loss in layer III of the entorhinal cortex in patients with temporal lobe epilepsy.

We report a characteristic pattern of neuropathological change in the entorhinal cortex (EC) from four patients with temporal lobe epilepsy. Specimens of the EC were obtained during the surgical treatment of intractable partial seizures and were studied by light microscopy in Nissl-stained sections. A distinct loss of neurons was observed in the anterior portion of the medial EC in the absence of apparent damage to temporal neocortical gyri. Cell loss was most pronounced in layer III, but also noticed in layer II, particularly in the rostral field. A similar pattern of neurodegeneration in the EC was found in all specimens examined though the degree of neuronal loss varied between cases. These observations provide neuropathological evidence for an involvement of the EC in temporal lobe epilepsy. Since the EC occupies a pivotal position in gating hippocampal input and output, our results further support previous suggestions that dysfunction of this region may contribute, either independently or in concert with Ammon's horn sclerosis, to epileptogenesis in humans.

Adult↗

Functional interactions of the entorhinal cortex: an 18F-FDG PET study on normal aging and Alzheimer's disease.

UNLABELLED: Alzheimer's disease (AD) is a brain disorder characterized by reduced cerebral glucose metabolism (CMRgl) in several cortical regions. Evidence from neuropathology studies, animal models of AD, and (18)F-FDG PET studies on cognitive impairment suggest that disrupted connections with the entorhinal cortex (EC) could be implicated in the emergence of the cortical hypometabolism. This (18)F-FDG PET study assessed the functional interactions-that is, the intercorrelations between the EC and the whole brain in vivo-in normal aging and AD. METHODS: Eighty-seven consecutive clinical AD patients underwent (18)F-FDG PET scanning at rest. Thirty-five sex- and age-matched healthy elderly subjects were studied as controls (NC). A voxel-based correlation analysis was performed with statistical parametric mapping to assess significant correlations between relative CMRgl (rCMRgl) in the EC and the rest of the brain, for NC and AD patients. Results were considered significant at P < 0.001. RESULTS: The pattern of EC functional interactions varies between normal aging and AD patients. In NC, the left and right EC were bilaterally correlated with several cortical and limbic regions, in accord with the major anatomic pathways identified in nonhuman primates. Alternatively, in AD patients, the EC correlations with the contralateral hemisphere were entirely lost, whereas those within the ipsilateral hemisphere were preserved only with the inferior temporooccipital (T-O) areas. CONCLUSION: This (18)F-FDG PET correlation study indicates that AD-related processes lead to an altered functional relationship between the EC and several cortical and limbic regions, with respect to normal aging. Our results suggest that the assessment of coupled rCMRgl reductions between the EC and the ipsilateral T-O cortex, besides the typical pattern of cortical reduction, could increase (18)F-FDG PET diagnostic sensitivity and further motivate its inclusion in the clinical assessment of AD.

Aged↗

Transient upregulation of NCAM mRNA in astrocytes in response to entorhinal cortex lesions and ischemia.

Axonal sprouting and synaptic reorganization play an important role in the adaptation of the CNS to injury. However, the molecular mechanisms underlying this neuronal plasticity are poorly understood. In the present study we used in situ hybridization to examine the expression of NCAM mRNA in normal hippocampus, and in response to entorhinal cortex (EC) lesions and transient global ischemia. Both neurons and astrocytes were labeled by digoxygenin-tagged cRNA probes which recognize all three major NCAM isoforms of the adult CNS. In contrast, NCAM180-specific probes labeled only neurons in the hippocampus. After unilateral EC lesion, a transient and anatomically restricted upregulation of NCAM120/140 mRNA in reactive astrocytes in the denervated molecular layer of the dentate gyrus was observed. This increase was only present 2-4 days after the lesion whereas the GFAP mRNA increase was present up to 30 days postlesion. Following global ischemia a similar, transient increase of NCAM120/140 mRNA labeling of reactive astrocytes was observed; this increase was anatomically restricted to CA1, where neuronal loss occurred. Results suggest that the transient upregulation of NCAM120/140 mRNA in reactive astrocytes shortly after injury might be an important molecular mechanism in the cascade of events underlying neuronal plasticity in the adult CNS.

Animals↗

Neural correlates of social odor recognition and the representation of individual distinctive social odors within entorhinal cortex and ventral subiculum.

Recognition of individual conspecifics is important for social behavior and requires the formation of memories for individually distinctive social signals. Individual recognition is often mediated by olfactory cues in mammals, especially nocturnal rodents such as golden hamsters. In hamsters, this form of recognition requires main olfactory system input to the lateral entorhinal cortex (LEnt). Here, we tested whether neurons in LEnt and the nearby ventral subiculum (VS) would show cellular correlates of this natural form of recognition memory. Two hundred ninety single neurons were recorded from both superficial (SE) and deep layers of LEnt (DE) and VS while male hamsters investigated volatile odorants from female vaginal secretions. Many neurons encoded differences between female's odors with many discriminating between odors from different individual females but not between different odor samples from the same female. Other neurons discriminated between odor samples from one female and generalized across collections from other females. LEnt and VS neurons showed enhanced or suppressed cellular activity during investigation of previously presented odors and in response to novel odors. A majority of SE neurons decreased firing to odor repetition and increased activity to novel odors. In contrast, DE neurons often showed suppressed activity in response to novel odors. Thus, neurons in LEnt and VS of male hamsters encode information that is critical for the identification and recognition of individual females by odor cues. This study reveals cellular mechanisms in LEnt and VS that may mediate a natural form of recognition memory in hamsters. These neuronal responses were similar to those observed in rats and monkeys during performance in standard recognition memory tasks. Consequently, the present data extend our understanding of the cellular basis for recognition memory and suggest that individual recognition requires similar neural mechanisms as those employed in laboratory tests of recognition memory.

Action Potentials↗

5-HT3 receptor ligands lack modulatory influence on acetylcholine release in rat entorhinal cortex.

The objective of this study was to explore the role of 5-HT3 receptors in modulating potassium (K+)-evoked release of [3H]-acetylcholine ([3H]-ACh) from superfused slices of rat entorhinal cortex previously loaded with [3H]-choline. Rat entorhinal cortices were cross-chopped into 300 microns slices, superfused with oxygenated Krebs buffer containing 2.5 mmol/l Ca2+ and stimulated with two consecutive exposures of 20 mmol/l K+ for 4 min (S1 and S2, respectively). Compounds were added 20 min before S2 stimulation and remained in the superfusion buffer for the duration of the experiment. The S2/S1 ratio was then calculated. Stimulated release of [3H]-ACh was dependent on extracellular Ca2+ and K+ concentration. In Sprague Dawley rats, 2-methyl-5-HT (10(-9)-10(-6) mol/l), in the presence of 1 mumol/l ritanserin or 1 mumol/l ondansetron, had no influence on K(+)-evoked release of [3H]-ACh. In slices prepared from Hooded Lister rats, 2 mumol/l 5-HT but not 2-Me-5-HT significantly (P < 0.05) inhibited K(+)-evoked [3H]-ACh release only 17% in the presence of 1 mumol/l ritanserin. However, 2 mumol/l 2-Me-5-HT plus 1 nmol/l ondansetron had no effect. High performance liquid chromatography coupled to electrochemical detection (HPLC-ECD) was used to monitor endogenous release of ACh in the above conditions to confirm data from the radiolabelled experiments. No significant inhibition or increase in K(+)-evoked ACh release was observed with either 5-HT3 receptor agonists or antagonists.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗

Functional interaction between entorhinal cortex and basolateral amygdala during trace conditioning of odor aversion in the rat.

In rats, conditioned odor aversion (COA) occurs only if the time interval separating the odor from the subsequent intoxication is very short suggesting that the memory trace of the odor is subject to rapid decay. Recent results from our laboratory have found that lesion of the entorhinal cortex (EC), and activation of the basolateral nucleus of the amygdala (BLA) rendered COA tolerant to long interstimulus interval. The present study examined whether the odor memory trace depends on the interaction between the EC and the BLA. Rats lesioned in the EC received infusions of muscimol (a GABA(A) receptor agonist) into the BLA immediately after the odor presentation during acquisition of COA. Injection of muscimol into BLA prevented tolerance of COA to long interstimulus interval induced by EC lesions. This suggests that EC modulates the short-term memory trace of the odor by controlling the GABAergic activity of the BLA during acquisition of COA.

Amygdala↗

Tolerogenic effect of fiber tract injury: reduced EAE severity following entorhinal cortex lesion.

Despite transient, myelin-directed adaptive immune responses in regions of fiber tract degeneration, none of the current models of fiber tract injuries evokes disseminated demyelination, implying effective mechanisms maintaining or re-establishing immune tolerance. In fact, we have recently detected CD95L upregulation accompanied by apoptosis of leukocytes in zones of axonal degeneration induced by entorhinal cortex lesion (ECL), a model of layer-specific axonal degeneration. Moreover, infiltrating monocytes readily transformed into ramified microglia exhibiting a phenotype of immature (CD86+/CD80-) antigen-presenting cells. We now report the appearance of the axonal antigen neurofilament-light along with increased T cell apoptosis and enhanced expression of the pro-apoptotic gene Bad in cervical lymph nodes after ECL. In order to test the functional significance of such local and systemic depletory/regulatory mechanisms on subsequent immunity to central nervous system antigens, experimental autoimmune encephalomyelitis was induced by proteolipid protein immunization 30 days after ECL. In three independent experiments, we found significantly diminished disease scores and infiltrates in lesioned compared to sham-operated SJL mice. This is consistent with a previous meta-statistical analysis (Goodin et al. in Neurology 52:1737-1745, 1999) rejecting the O-hypothesis that brain trauma causes or exacerbates multiple sclerosis. Conversely, brain injuries may involve long-term tolerogenic effects towards brain antigens.

Animals↗

Neuritic pathology is lacking in the entorhinal cortex, subiculum and hippocampus in middle-aged adults with schizophrenia, bipolar disorder or unipolar depression.

Earlier reports have provided conflicting results regarding the association between Alzheimer's disease (AD) and mental disorders. Using a well-characterized postmortem series of 40 middle-aged human brains, we have performed quantitative analysis of neurofibrillary tangles and senile plaques in the entorhinal cortex, subiculum and rostral hippocampus in 9 subjects with schizophrenia, 8 with bipolar disorder, 12 with depression, and 11 age- and sex-matched controls. No significant differences were found among the four groups. Our study indicates that the Alzheimer-type changes, which might be related to the likelihood of AD development later in life, are not increased in middle-aged subjects with mental illness. The result also supports the more recent reports that have demonstrated no increased incidence of AD in mentally ill patients.

Adult↗

Effects of post-training infusions of a mitogen-activated protein kinase kinase inhibitor into the hippocampus or entorhinal cortex on short- and long-term retention of inhibitory avoidance.

We recently demonstrated the time-dependent impairment of long-term retention of a step-down inhibitory avoidance task in rats induced by post-training infusion of the specific MAPKK (mitogen-activated protein kinase kinase) inhibitor PD 098059 into the hippocampus (HIP), amygdala (AMY), entorhinal cortex (EC) and posterior parietal cortex (PPC). Here we investigate the role of the MAPK cascade in the HIP and the EC on both short- and long-term retention of inhibitory avoidance in rats, using three different doses of the MAPKK inhibitor PD 098059. Adult male Wistar rats were trained and tested in inhibitory avoidance and given an infusion of PD 098059 (0.5, 5.0 or 50.0 microM) at 0, 30, 90, 120, 180, 270 or 360 min after training. A retention test session was carried out at 90, 180 or 270 min after training (short-term memory, STM) and/ or 24 h after training (long-term memory, LTM). When infused into the HIP at 0 min, but not at 30, 90, 120 or 180 min after training, PD 098059 impaired STM. Intrahippocampal PD 098059 impaired LTM when infused at 180 min, but not at 0, 30, 90, 120 or 270 min after training. When infused into the EC, PD 098059 enhanced STM when given at 0 min after training and had no effect when given at 30, 90, 120 or 180 min after training. In this structure, PD 098059 impaired LTM when given at 180 or 270 min, but not at 30, 90, 120 or 360 min after training. All effects were dose-dependent. These findings indicate that the MAPK cascade in the HIP and EC is differentially involved in short- and long-term retention of inhibitory avoidance in rats.

Animals↗

Neuronal sources of theta rhythm in the entorhinal cortex of the rat. II. Phase relations between unit discharges and theta field potentials.

The discharge patterns and layer distribution of entorhinal cortex (EC) units were investigated in paralysed and locally anesthetized rats injected with physostigmine in order to induce theta (theta) rhythm. Entorhinal unit activity and field potentials were recorded simultaneously with the same micropipette. Hippocampal CA1 theta rhythm was used as reference. Statistical analysis included auto- and cross-correlations and interval histograms. Results showed: a. the existence of rhythmic and non-rhythmic cells, both tending to fire in a constant phase relationship with theta rhythm; b. in all EC subdivisions, most rhythmic cells were located in superficial cell layers (II-III); c. on the average, rhythmic cells from the medial EC fired synchronously; d. non-rhythmic cells tended also to fire synchronously but with an opposite phase relationship with respect to rhythmic neurons. Although a complex organization in the rhythmicity of EC units is revealed, it is concluded that the neuronal sources of theta activity in the EC are located in superficial cell layers, and it is strongly suggested that the EC output through the perforant path may rhythmically modulate the discharge pattern of hippocampal pyramidal and dentate granule cells.

Action Potentials↗

Functional role of entorhinal cortex in working memory processing.

Our learning and memory system has the challenge to work in a world where items to learn are dispersed in space and time. From the information extracted by the perceptual systems, the learning system must select and combine information. Both these operations may require a temporary storage where significance and correlations could be assessed. This work builds on the common hypothesis that hippocampus and subicular, entorhinal and parahippocampal/postrhinal areas are essential for the above-mentioned functions. We bring up two examples of models; the first one is modeling of in vivo and in vitro data from entorhinal cortex layer II of delayed match-to-sample working memory experiments, the second one studying mechanisms in theta rhythmicity in EC. In both cases, we discuss how cationic currents might be involved and relate their kinetics and pharmacology to behavioral and cellular experimental results.

Animals↗

Modulations of EEG activity in the entorhinal cortex and forebrain olfactory areas during odour sampling.

With the aim of determining a possible role of the entorhinal cortex (EC) in the processing of olfactory information, its electrical activity was recorded during different types of odour sampling behaviour. The EC spontaneous field potentials (EEGs) were related to those recorded simultaneously from the more rostrally lying olfactory bulb (OB) and prepiriform cortex (PPC), using coherence functions. The coherence values are measures of coupling between two neuronal populations. Auto- and coherence spectra were characterized by a peak in the beta-band (35-36 Hz) and another in the 16-20 Hz band. For the beta-peak of the PPC-EC coherence it was shown that both the maximal values and the median frequency decrease during the first 0.5-1.0 s of a trial in a two-choice odour discrimination task. These transients differed significantly for CS+ and CS- trials. However, no such difference was observed during exploratory sniffing at the same pair of odorants. It was concluded that during sniffing the degree of coupling of the EC with the PPC depends on the behavioural context but not on the quality of the odorants. As regards the 16-20 Hz components it was shown, using bispectral analysis, that these components represent the 1/2 subharmonic of the beta-components. The subharmonic components were enhanced during the initiation of sniffing. This means that the neural networks of OB, PPC and EC have non-linear dynamic properties. These networks show different modes of oscillatory behaviour, characteristic of the restful state and of the active sniffing state. Theoretical implications of these experimental results are discussed. In conclusion, it was demonstrated that modulations with sniffing behaviour are present in the beta-EEG components and their subharmonics in the olfactory brain areas including the EC. This indicates that the latter is involved in processes of the evaluation of olfactory cues in relation to the animal's behaviour.

Animals↗