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 1,369 records · Page 76Linked to original sources

Autoradiographic distribution of [3H]nicotine binding in human cortex: relative abundance in subicular complex.

Distinct patterns of [3H]nicotine (3 nM) binding were apparent in various regions of adult human neo- and archicortex. Receptor binding was greatest in the subicular complex--particularly presubiculum--and entorhinal cortex, where it was prominent in the characteristic parvo- and magnocellular islands of these regions and in middle layers of entorhinal cortex. In somatosensory cortex (Brodmann areas 3, 1 and 2) and occipital (area 17) cortex binding was highest in the upper and lower layers, and relatively sparse in the sensory input, layer IV. In primary motor (area 4) and temporal (area 21) cortex, binding in the outer half of the cortical ribbon was denser than that in the inner half and a distinct band was apparent in temporal and cingulate (area 32) in the lower portion of layer III. In prefrontal association cortex the pattern of binding was less distinct although slightly higher in the lower architectonic layers. There was generally little binding in the hippocampus (areas CA1-4) and dentate gyrus with the exception of the stratum lacunosum moleculare in CA2-3 and, to a lesser extent, supra- and subgranule zones of the dentate. These patterns of reactivity, which are distinct from that of the major cortical cholinergic innervation, suggest that the nicotinic receptor, detected using nanomolar concentrations of [3H]nicotine, may primarily be associated with intracortical circuitry in the neocortex. The relatively high density in entorhinal and subicular regions may be related to the extensive phylogenetic development of these regions which has occurred in conjunction with the development of multimodal association circuitry in the human cortex.

Adolescent↗

Human medial temporal lobe in aging: anatomical basis of memory preservation.

The integrity of the hippocampal formation is necessary for the correct function of declarative memory for facts and events. Normal aging is associated with a widespread decrease in cortical volume, including the hippocampal formation and related cortical areas, although in many cases, memory is only minimally impaired. In the present study, we quantified the extent of the parahippocampal gyrus (entorhinal cortex, as well as the medial temporal lobe proisocortical areas related to memory function, such as temporopolar cortex, perirhinal cortex, and posterior parahippocampal cortex) in 42 control cases. After detailed cytoarchitectonic analysis (based on homology with the nonhuman primate medial temporal lobe), planimetric measurement (calculated area) of a two-dimensional reconstruction of the parahippocampal gyrus was performed, and cases older than 70 years were compared with cases younger than 70 years. All areas showed atrophy with aging (average, entorhinal cortex, 5%; perirhinal cortex, 4%; posterior parahippocampal cortex, 15%; temporal pole, not assessable). Both entorhinal and posterior parahippocampal cortices reached statistical significance. Our results suggest that cortical areas relevant in memory function, and anatomically linked to the hippocampus, present a small degree of atrophy with aging, thereby permitting the reciprocal flow of information between the hippocampus and the cerebral cortex necessary for memory encoding and retrieval.

Age Factors↗

Quantitative and cytoarchitectural studies of the entorhinal region and the hippocampus of New Zealand black mice.

New Zealand Black (NZB) mice were suggested as an animal model for human dementia. We performed quantitative and cytoarchitectural studies of the entorhinal region and the hippocampus of 10 NZB mice and compared the results with those for a control group of 10 Carworth Farm Webster (CFW) mice. No cytoarchitectural disturbances were observed in the entorhinal cortex and hippocampus of the NZB mice. We, however, found a reduced density of nerve cells in the entorhinal region as well as in the CA1 and CA3 regions of the Ammon's horn in NZB mice. Since the entorhinal region is an important link between sensory and association cortices and the limbic system which seems to play an important role in learning and memory, the present findings may be a cause of learning and/or memory deficits in the NZB mice. The undisturbed cytoachitecture of the entorhinal cortex suggests that the reduced cell sensity in NZB mice is rather an acquired lesion than a developmental malformation and, therefore, indicates therapeutic studies on memory and learning deficits in NZB mice.

Animals↗

Suprasellar cistern measures as a reflection of dementia in Alzheimer's disease but not Huntington's disease.

Four methods of measuring the suprasellar cistern (SSC), the SSC area ratio, the hexagonal area ratio, the width ratio, and perceptual rating, are described. All four are found to be reliable across raters, time, and procedure (light box vs. computer), and all are able to distinguish Alzheimer's Disease (AD) and Huntington's Disease (HD) patients from their respective age-matched controls. The width ratio, a measure of minimum distance between the two temporal lobes divided by brain width at the same level, was most effective in distinguishing HD from AD patients when age was used as a covariate. Because the width of the SSC measures separation of the temporal lobes at the level of the amygdala and entorhinal cortex, it is reasonable to expect this measure to distinguish between AD and HD, as the amygdala and entorhinal cortex are known to be particularly severely affected in AD, but not in HD, patients. The other measures of SSC were most highly correlated with cognitive status in AD patients. Several possible explanations for this finding are offered. No SSC measure was significantly correlated with cognitive status in HD. This suggests that atrophies of the frontal-temporal and basal forebrain areas are associated with cognitive decline in Alzheimer's Disease but not in Huntington's Disease.

Adolescent↗

Gonadal steroids regulate the expression of glial fibrillary acidic protein in the adult male rat hippocampus.

This study demonstrates that gonadal steroids (estradiol, testosterone, dihydrotestosterone) can regulate the expression of glial fibrillary acidic protein in the adult male rat brain. Previously, we showed that castration of adult male rats increased glial fibrillary acidic protein messenger RNA in the hippocampus and that this increase was additive with the increase induced by deafferenting entorhinal cortex lesions [Day et al. (1990) Molec. Endocr. 4, 1995-2002 . We extended these effects of castration and entorhinal cortex lesion to glial fibrillary acidic protein, using immunoassays. Furthermore, we found regional differences in responses to castration and inhibited by sex steroids. In contrast, hypothalamic glial fibrillary acidic protein expression was inhibited by castration. Similar regional differences were also shown for astrocyte glial fibrillary acidic protein distribution by immunocytochemistry. The regional specificity of glial fibrillary acidic protein expression after castration and sex steroid replacement is pertinent to the role of astrocytes in synaptic plasticity in unlesioned adults as well as in responses to lesions where the steroid milieu has been shown to influence sprouting.

Animals↗

Synthesis and biodistribution of [11C]R107474, a new radiolabeled alpha2-adrenoceptor antagonist.

R107474, 2-methyl-3-[2-(1,2,3,4-tetrahydrobenzo[4,5]furo[3,2-c]pyridin-2-yl)ethyl]-4H-pyrido[1,2-a]pyrimidin-4-one, was investigated using in vitro and in vivo receptor assays and proved to be a potent and relatively selective alpha(2)-adrenoceptor antagonist. Performed assays in vitro were inhibition of binding to a large number of neurotransmitter receptor sites, drug receptor binding sites, ion channel binding sites, peptide receptor binding sites, and the monoamine transporters in membrane preparations of brain tissue or of cells expressing the cloned human receptors. The compound has subnanomolar affinity for halpha(2A)- and halpha(2C)-adrenoceptors (K(i) = 0.13 and 0.15 nM, respectively) and showed nanomolar affinity for the halpha(2B)-adrenoceptors and 5-hydroxytryptamine(7) (h5-HT(7)) receptors (K(i) = 1 and 5 nM, respectively). R107474 interacted weakly (K(i) values ranging between 81 and 920 nM) with dopamine-hD(2L), -hD(3) and -hD(4), h5-HT(1D)-, h5-HT(1F)-, h5-HT(2A)-, h5-HT(2C)-, and h5-HT(5A) receptors. The compound, tested up to 10 microM, interacted only at micromolar concentrations or not at all with any of the other receptor or transporter binding sites tested in this study. In vivo alpha(2A)- and alpha(2C)-adrenoceptor occupancy was measured by ex vivo autoradiography 1h after subcutaneous (sc) administration of R107474. It was found that R107474 occupies the alpha(2A)- and alpha(2C)-adrenoceptors with an ED(50) (95% confidence limits) of 0.014 mg/kg sc (0.009-0.019) and 0.026 mg/kg sc (0.022-0.030), respectively. Radiolabeled 2-methyl-3-[2-([1-(11)C]-1,2,3,4-tetrahydrobenzo[4,5]furo[3,2-c]pyridin-2-yl)ethyl]-4H-pyrido[1,2-a]pyrimidin-4-one ([(11)C]R107474) was prepared and evaluated as a potential positron emission tomography (PET) ligand for studying central alpha(2)-adrenoceptors. [(11)C]R107474 was obtained via a Pictet-Spengler reaction with [(11)C]formaldehyde in 33 +/- 4% overall decay-corrected radiochemical yield. The total synthesis time was 55 min and the specific activity was 24-28 GBq/micromol. The biodistribution of [(11)C]R107474 in rats revealed that the uptake of [(11)C]R107474 after in vivo intravenous administration is very rapid; in most tissues (including the brain) it reaches maximum concentration at 5 min after tracer injection. In agreement with the known distribution of alpha(2)-adrenoceptors in the brain, highest uptake of radioactivity was observed in septum (3.54 +/- 0.52 ID/g, 5 min pi) and entorhinal cortex (1.57 +/- 0.10 ID/g, 5 min pi). Tissue/cerebellum concentration ratios for septum (5.38 +/- 0.45, 30 min pi) and entorhinal cortex (3.43+/-0.24, 30 min pi) increased with time due to rapid uptake followed by a slow washout. In vivo blocking experiments using the non-selective alpha(2)-adrenoceptor antagonist mirtazapine demonstrated specific inhibition of [(11)C]R107474 binding in selective brain areas. The receptor binding profile of mirtazapine is reported and the selectivity of inhibition of binding is discussed. These results suggest that [(11)C]R107474 deserves further investigation as a potential radioligand for studying alpha(2)-adrenoceptors using PET.

Adrenergic alpha-2 Receptor Antagonists↗

Pro-NGF from Alzheimer's disease and normal human brain displays distinctive abilities to induce processing and nuclear translocation of intracellular domain of p75NTR and apoptosis.

The pro form of neurotrophic growth factor (pro-NGF), purified by chromatography from human Alzheimer's disease (AD)-affected brains (ADhbi-pro-NGF), has been shown to induce apoptotic cell death in neuronal cell cultures through its interaction with the p75 neurotrophin receptor (p75NTR). In the present work, we report that ADhbi-pro-NGF stimulates processing of p75NTR with alpha- and gamma-secretases, yielding a 20-kd intracellular domain (p75(ICD)) that translocates to the nucleus. This process was accompanied by delayed apoptosis. In AD, p75(ICD) was significantly increased in human entorhinal cortex. Although human frontal cortex has been described as showing a higher pro-NGF increase in AD, the increase in the entorhinal cortex paralleled p75NTR processing in its intracellular domain. In addition, pro-NGF isolated from AD-affected brains differed functionally from pro-NGF isolated from comparably aged control brains, with pro-NGF isolated from control brains being unstable and undergoing degradation to NGF when added to cell culture. As p75(ICD) and pro-NGF are both mediators of apoptosis and are both found in increased levels in the cerebral cortex in AD, the present data have implications for understanding neuronal degeneration in AD.

3T3 Cells↗

L-4-chlorokynurenine attenuates kainate-induced seizures and lesions in the rat.

Blockade of the strychnine-insensitive glycine site of the NMDA receptor is considered an attractive strategy for the development of novel neuroprotective and anticonvulsive agents. 7-Cl-kynurenic acid (7-Cl-KYNA) is a potent, selective antagonist of the NMDA/glycine receptor but penetrates poorly through the blood-brain barrier. Its prodrug, L-4-Cl-kynurenine (4-Cl-KYN), readily enters the brain from the circulation and provides antiexcitotoxic neuroprotection after systemic application. We now examined the effect of 4-Cl-KYN on seizures and neuronal loss caused by the systemic administration of the chemoconvulsant kainate (KA). 4-Cl-KYN (50 mg/kg, ip) was given 10 min before and 30, 120, and 360 min after KA (10 mg/kg, sc). Microdialysis and tissue level measurements in 4-Cl-KYN-treated rats showed increases in the concentration of 7-Cl-KYNA in several limbic brain regions of KA-injected animals. Continuous EEG recording for 24 h revealed that 4-Cl-KYN significantly delayed seizure onset and reduced the total time spent in seizures. Repeated 4-Cl-KYN administration also prevented KA-induced lesions in the piriform cortex and provided protection of hippocampal pyramidal cells in area CA1. In contrast, neurons in the hilus and in layer III of the entorhinal cortex were not protected. Consistent with the in vivo results, in vitro application of 7-Cl-KYNA to brain slices containing hippocampus and entorhinal cortex preferentially blocked low Mg(2+)-induced seizure activity in hippocampal pyramidal cells. Taken together, these data suggest that a prodrug approach using 4-Cl-KYN might offer advantages in the treatment of temporal lobe epilepsy.

Animals↗

The neuropathology of Williams syndrome. Report of a 35-year-old man with presenile beta/A4 amyloid plaques and neurofibrillary tangles.

OBJECTIVE: To study neuropathologically Williams syndrome in a 35-year-old patient. METHODS: Sections from multiple regions of the brain were examined with luxol fast blue and hematoxylineosin staining, and selected sections were stained with the silver impregnation technique (Bielschowsky technique) and Congo red. In addition, immunohistochemistry with monoclonal antibodies against glial fibrillary acidic protein, beta/A4 amyloid, paired helical filaments, and phosphorylated tau protein was performed on cortical, hippocampal, amygdaloid, and basal ganglian sections. RESULTS: No specific macroscopic or microscopic abnormalities were recognized that are specific for Williams syndrome. The histopathologic examination did, however, demonstrate the presence of Alzheimer-type changes, including beta/A4 amyloid-containing senile plaques and scattered neurofibrillary tangles in neocortex and medial temporal lobe structures (entorhinal cortex, CA1 area of the hippocampus, and amygdala). Plaques were most numerous in the amygdala (7/mm2) and in the entorhinal cortex (4/mm2). Neurofibrillary tangles were less numerous (< 1/mm2), except in the hippocampus, where approximately 2/mm2 were found. CONCLUSIONS: To our knowledge, ours represents the first neuropathologic description of a patient with Williams syndrome. Although Williams syndrome is usually sporadic, familial cases have been reported along with candidate chromosomal loci. If our findings are confirmed in additional patients with Williams syndrome, they may provide clues to other factors that are important in the pathogenesis of senile plaques (with beta/A4 amyloid deposition) and neurofibrillary tangles.

Adult↗

Analyses of energy metabolism and mitochondrial genome in post-mortem brain from patients with Alzheimer's disease.

Biochemical and mitochondrial DNA analyses were performed in post-mortem brain tissue from seven patients with dementia of Alzheimer's type and age- and sex-matched controls. We analysed all complexes of the respiratory chain in four regions, i.e. temporal, parietal, entorhinal cortex and hippocampus. Although enzymes representing complex II, III and IV were reduced in activity, succinate cytochrome c reductase was significantly reduced only in the parietal and temporal cortex. However, Southern blot analyses with two restriction enzymes excluded any deletions larger than 500 bp in parietal and entorhinal cortex. It is concluded that there seems to be no specific respiratory chain defect in Alzheimer's disease.

Aged↗

Do recurrent seizures cause neuronal damage? A series of studies with MRI volumetry in adults with partial epilepsy.

Despite optimal treatment, 30% of epilepsy patients develop intractable epilepsy and continue to have recurrent seizures or other symptoms of epileptic syndrome restricting their ability to lead a full life. Hippocampal sclerosis is found in 60-70% of patients with intractable temporal lobe epilepsy (TLE). However, it is not known whether the damage in the hippocampus is the cause or the consequence of TLE. The purpose of the present series of studies was to investigate with magnetic resonance imaging (MRI) the appearance of medial temporal lobe damage during the course of partial epilepsy, and, particularly, to determine whether recurrent or prolonged seizures contribute to the damage. Altogether 259 partial epilepsy patients were investigated with quantitative MRI. High lifetime seizure number, complex febrile convulsions in the medical history, and early age at the onset of spontaneous seizures contributed to hippocampal damage in patients with TLE. The risk factors that predicted amygdaloid volume reduction were intracranial infection and complex febrile convulsions. Damage in the hippocampus or in the amygdala was rare at the time of first spontaneous seizures in TLE. In contrast, hippocampal damage was apparent in chronic TLE patients with years of frequent seizures. Chronic cryptogenic drug-resistant TLE patients had smaller mean hippocampal volumes ipsilateral to the seizure focus than controls. In all TLE patients, ipsilateral hippocampal volume correlated negatively with the lifetime seizure number. The mean amygdaloid volumes in chronic TLE patients did not differ from those in controls. However, about 20% of chronic patients had > or = 20% volume reduction in the amygdala. The mean volumes of the entorhinal cortex ipsilateral to the epileptic focus in cryptogenic TLE patients did not differ from those in controls. However, the entorhinal cortex was damaged in a subpopulation of TLE patients with associated hippocampal damage TLE. The findings of the present series of studies support the hypothesis that damage in the medial temporal lobe structures may be both the cause and consequence of TLE. The data provide evidence that in some patients hippocampal damage may progress as a function of repeated seizures, and argue for efficient drug therapy or early surgery to reach complete seizure control. Future research should address strategies for disease-modifying therapies and ultimately remission of the epileptic process.

Adolescent↗

A critical discussion of the role of neuroimaging in mild cognitive impairment.

OBJECTIVE: In this paper, the current neuroimaging literature is reviewed with regard to characteristic findings in mild cognitive impairment (MCI). Particular attention is drawn to the possible value of neuroimaging modalities in the prediction and early diagnosis of Alzheimer's disease (AD). METHODS: First, the potential contribution of neuroimaging to an early, preclinical diagnosis of degenerative disorders is discussed at the background of our knowledge about the pathogenesis of AD. Second, relevant neuroimaging studies focusing on MCI are explored and summarized. Neuroimaging studies were found through Medline search and by systematically checking through the bibliographies of relevant articles. RESULTS: Structural volumetric magnetic resonance imaging (MRI) and positron emission tomography (PET)/single photon emission tomography (SPECT) are currently the most commonly used neuroimaging modalities in studies focusing on MCI. There were considerable variations in demographical and clinical characteristics across studies. However, significant hippocampal and entorhinal cortex volume reductions were consistently found in subjects with MCI as compared with cognitively unimpaired controls. While hippocampal and entorhinal cortex atrophy in subjects with MCI are also well-established risk factors for the development of AD, these measures cannot be regarded as being of high predictive value in an individual case. Evidence for other typical neuroimaging changes in MCI is still scarce. In PET and SPECT studies, reduced blood flow and/or glucose metabolism in temporoparietal association areas, posterior cingulate and hippocampus were associated with a higher risk of progressive cognitive decline in MCI. In quantitative electroencephalogram (QEEG), low beta, high theta, low alpha and slowed mean frequency were associated with development of dementia. CONCLUSIONS: Existing studies suggest that neuroimaging measures have the potential to become valuable tools in the early diagnosis of AD. To establish their value in routine use, larger studies, preferably with long prospective follow-up are needed.

Alzheimer Disease↗

The topography of plaques and tangles in Down's syndrome patients of different ages.

The topographical distribution of senile plaques and neurofibrillary tangles has been investigated in 12 patients with Down's syndrome ranging from 31 to 65 years of age. No plaques or tangles whatsoever were seen in the brain of the 31-year-old patient. The nine patients over 53 years of age, showed a similar pathological picture in which there were numerous mature plaques in all areas of cerebral cortex, hippocampus and amygdala and numerous tangles in these areas and in subcortical structures such as nucleus basalis, locus caeruleus, dorsal raphe, ventral tegmental area, substantia nigra, olfactory bulb and tracts. In the other two patients aged 37 and 51 years, an intermediate pathological picture was seen in which primitive plaques predominated within the cortex, with numerous mature plaques in hippocampus and amygdala. In the 37-year-old patient, tangles were numerous in the entorhinal cortex, but much less common in hippocampus and amygdala, rare in cerebral cortex and absent in the subcortical areas, olfactory bulbs and tracts. A similar pattern was seen in the 51-year-old patient though here some cells in the subcortex were also affected. These observations suggest that the primary focus of plaque and tangle formation in Down's syndrome may be in amygdala, entorhinal cortex and hippocampus, with a 'spreading out' to subsequently involve all areas of cortex, certain subcortical regions and the olfactory bulbs and tracts. It appears unlikely that the olfactory bulbs and tracts provide a portal of entry for any pathogenic agent that may be responsible for inducing plaque and tangle formation within the rest of the brain.

Adult↗

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↗

Caspase gene expression in the brain as a function of the clinical progression of Alzheimer disease.

BACKGROUND: Caspase gene expression has previously been reported in terminal Alzheimer disease (AD) brain, but, currently, little is known about the temporal pattern of caspase gene expression relative to the onset and clinical progression of AD. OBJECTIVE: To derive a profile of caspase gene expression and proapoptotic indexes as a function of the clinical and neuropathologic progression of AD dementia. SETTING AND PATIENTS: Postmortem survey of nursing home patients characterized clinically by Clinical Dementia Rating (CDR) and neuropathologically by Consortium to Establish a Registry for Alzheimer's Disease criteria. DESIGN AND OUTCOME MEASURES: To assess messenger RNA expression of caspase-1, -2L, -2S, -3, -5, -6, -7, -8, and -9; apoptotic cell death by TUNEL assay; and poly (ADP-ribose) polymerase cleavage in postmortem brain tissue samples from cognitively normal (CDR 0), high risk of developing AD dementia (CDR 0.5), and severe dementia (CDR 5) cases. RESULTS: Compared with CDR 0 cases, elevated messenger RNA expression of caspase-1 and caspase-7 in the entorhinal cortex of CDR 0.5 cases coincided with increased poly (ADP-ribose) polymerase cleavage but not apoptotic cell injury. In the entorhinal cortex of CDR 5 cases, we found elevation of caspase-1, -2L, -3, -5, -6, -7, -8, and -9 and a greater than 4-fold increase in TUNEL-positive cells. Caspase messenger RNA expression was closely associated with neurofibrillary tangle and, to a lesser extent, neuritic plaque density. CONCLUSIONS: Proapoptotic mechanisms may be at play early in the onset of AD (before overt signs of apoptosis) and may be a conditional factor for later apoptotic cell injury or death. These data have relevance to potential therapeutic interventions for AD using selective caspase inhibitors.

Aged↗

Projection of the entorhinal layer II neurons in the rat as revealed by intracellular pressure-injection of neurobiotin.

A component of the perforant path, projection of the entorhinal layer II neurons, was investigated by recovering intracellularly labeled layer II neurons from the medial or intermediate entorhinal cortex in rats. The labeled layer II spiny stellate neurons had axon collaterals in layers I, II, and III of the entorhinal cortex as well as some axon collaterals in the subiculum. The stem axons gave rise to terminal axon branches that covered the entire extent (suprapyramidal blade, crest, and infrapyramidal blade) of the dentate gyrus and the CA2-3 fields in the transverse plane, forming a sheet-like formation. The axon arbor in the hippocampal formation spread up to 2 mm wide in a septotemporal direction. The sheet-like formation of the axon arbors was a narrow layer in the suprapyramidal blade and in the stratum lacunosum-moleculare of the CA2-3 fields. The layer became wider in the crest and infrapyramidal blade of the dentate gyrus. This study shows that the entorhinohippocampal circuit is not a simple circle from single cells level.

Animals↗

Adenosine acting via A1 receptors, controls the transition to status epilepticus-like behaviour in an in vitro model of epilepsy.

Adenosine has powerful inhibitory effects in the central nervous system. In this study, we aim to understand how adenosine controls the progression of seizure-like events (SLEs) in a seizure-prone region of the brain, the entorhinal cortex. We chose to use a low Mg(2+) model of epilepsy in an in vitro slice preparation where, in the entorhinal cortex, SLEs progress into a type of epileptiform activity called late recurrent discharges (LRDs) that bear resemblance to status epilepticus. Adenosine, acting via its A1 receptor, exerted powerful inhibitory effects to prevent the spontaneous progression to LRDs while the potent A1 receptor antagonist, DPCPX, accelerated the progression in a concentration dependent manner. The spontaneous progression from SLEs to LRDs was associated with a decline in total cellular ATP levels and studies with metabolic inhibitors indicated a key role for the production of endogenous adenosine from ATP. We therefore hypothesise that when ATP becomes rate limiting, extracellular adenosine levels fall, the normal inhibitory brake is removed and the progression from SLEs to LRDs or status epilepticus-like activity can ensue. Moreover, under these conditions, inhibition of the adenine nucleotide salvage pathways reversed the status epilepticus-like activity. Our findings suggest a powerful role for adenosine for the control of the progression to status epilepticus-like activity in an epilepsy model that is refractory to most anti-epileptic drugs. On this basis, manipulation of adenine nucleotide metabolism may represent a potential therapeutic approach for the treatment of status epilepticus.

Adenosine↗

Comparison of spatial and temporal characteristics of neuronal activity in sequential stages of hippocampal processing.

The activity of individual pyramidal cells in the CA1 and CA3 subfields of the rodent hippocampus exhibits a remarkable selectivity for specific locations and orientations of the rat within spatially-extended environments. These cells exhibit high rates of activity when the animal is present within restricted regions of space, referred to as place fields, and are extremely quiet when it is elsewhere. Although this phenomenon has been well studied in the CA fields of the hippocampus, relatively little is known about the spatial and temporal firing characteristics either of the entorhinal cortical inputs to the hippocampus, or of the subicular recipients of the output of hippocampal place cells. We report here on a comparison of spatial and temporal discharge characteristics among entorhinal cortex, CA3 and CA1, and the subiculum. CA3 complex spike cells were significantly more spatially specific than their CA1 counterparts. Neither entorhinal cortex nor subiculum exhibited the highly localized patterns of spatial firing observed in the CA fields. In addition, average discharge rates in these areas were substantially higher. However, particularly in subiculum, there was evidence for spatially consistent, but dispersed, firing in some cells, suggestive of the convergence of a number of CA1 place cells. The patterns observed are not consistent with the hypothesis that spatial selectivity is progressively refined at the various levels of hippocampal processing. Rather, hippocampal output appears to be expressed as a much more highly distributed spatial code than activity within the hippocampus proper. We suggest that the sparse coding used within the hippocampus itself represents a mechanism for increasing the storage capacity of a network whose function is to form associations rapidly.

Action Potentials↗