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PubMed1987

The entorhinal cortex of the monkey: I. Cytoarchitectonic organization.

As an essential preliminary to a series of experimental studies of the afferent and efferent connections of the monkey entorhinal cortex, we have carried out a detailed analysis of its cytoarchitectonic organization. Primarily on the basis of features observed in Nissl- and fiber-stained preparations, supplemented with Golgi-stained material and preparations stained for heavy metals by Timm's method and histochemically for acetylcholinesterase, the entorhinal cortex has been divided into seven fields that are named according to their rostrocaudal and mediolateral positions except for one rostrally located field that is named for the prominent input that it receives from the olfactory bulb. At rostral levels, the entorhinal cortex is marked by a number of morphological inhomogeneities. The neurons tend to be organized in patches that are surrounded by large, thick, radially oriented bundles of fibers. At caudal levels, the entorhinal cortex has a more distinctly laminated appearance, reminiscent of that in the neocortex, and most of the neurons and fiber fascicles are arranged in discrete radial columns. The cortical region adjoining the entorhinal cortex laterally, which is commonly known as the "perirhinal cortex," is in fact composed of two separate fields corresponding to areas 35 and 36 of Brodmann. Area 35 occupies the fundus and part of the lateral aspect of the rhinal sulcus. Area 36 extends from the lateral bank of the rhinal sulcus into the inferior temporal gyrus, where it borders fields TA and TE rostrally, and field TF of the parahippocampal gyrus caudally. The surface extents of each of the entorhinal fields have been determined by making "unfolded" two-dimensional maps of the region and measuring the areas with a computerized digitizing system.

Acetylcholinesterase↗

PubMed1994

The effects of lesions of the entorhinal cortex and the horizontal nucleus of the diagonal band of broca upon performance of a spatial location recognition task.

The effects of lesions of the horizontal nucleus of the diagonal band of Broca (HNDB) and the entorhinal cortex (ENTO) upon performance of a spatial location recognition task were assessed. Two hypotheses of entorhinal cortex function were considered in interpretation of the data. The first hypothesis assumes that the anatomical proximity and interconnections between the hippocampus and the entorhinal cortex are indicative of a functional similarity. The second hypothesis recognizes the interconnections of the hippocampus and the entorhinal cortex, but posits that the two structures have distinct functions. The hippocampus receives input primarily from the medial septum (MS), whereas the entorhinal cortex receives input from the HNDB and the MS. The study attempted to assess the function of the ENTO and the HNDB in a spatial location recognition task with the intent of comparing the findings to previous research of the hippocampus and MS. Performance of animals with HNDB lesions and the ENTO lesions was at chance levels for all serial positions. Results indicated that there are functional differences between the HNDB and other basal forebrain structures. Further, the performance deficit of the ENTO group does not differ from that observed following lesions of the hippocampus.

Animals↗

PubMed1993

Role of the amygdala, hippocampus and entorhinal cortex in memory consolidation and expression.

1. Experiments using localized microinfusions of specific agonists and antagonists of neurotransmitter receptors have shown that the amygdala, hippocampus, medial septum and entorhinal cortex are involved in memory consolidation, storage and expression. The data are consistent with observations derived from lesion studies suggesting a role for these structures in memory processes, but permit many additional conclusions concerning the mechanisms involved and their timing. 2. Memories are initially processed by glutamatergic N-methyl-D-aspartate (NMDA) receptors in amygdala, hippocampus and medial septum, which are sensitive to amino-phosphono valerate (AP5). Memory of inhibitory avoidance is processed by the three structures; memory of habituation to a novel environment is processed only by the hippocampus. At the time of consolidation, immediately after training, gamma-aminobutyrate type A (GABA-A) receptors, modulated by endogenous benzodiazepines, play an inhibitory role, and cholinergic muscarinic and beta-noradrenergic transmission play a modulatory role. 3. From 90 to 180 min after training, memories are blocked by cyano-nitro-quinoxalinedione (CNQX) given into the amygdala, septum and hippocampus. CNQX blocks non-NMDA glutamatergic receptors. Also between 90 and 180 min after training, memory of the habituation and inhibitory avoidance tasks is blocked by the infusion of AP5 or of the GABA-A agonist, muscimol, into the entorhinal cortex. This late post-training intervention of the entorhinal cortex is essential for the integration of successively acquired memories, and occurs in response to the simultaneous activation of CNQX-sensitive synapses in amygdala and hippocampus. 4. The expression of memory is blocked by the infusion of CNQX, at the time of testing, into the amygdala and hippocampus (inhibitory avoidance), into the hippocampus but not the amygdala (habituation), or into the entorhinal cortex (for the two tasks). Since consolidation is blocked by AP5 infused into these structures (see above), the data agree with the hypothesis that memories are mediated by (or actually consist of) long-term potentiation (LTP) in these areas of the brain. LTP induction is blocked by AP5 and LTP expression is blocked by CNQX. It is possible that, at the time of memory expression, the entorhinal cortex is an output of the amygdala and hippocampus.

2-Amino-5-phosphonovalerate↗

PubMed2002

Projections from the lateral, basal, and accessory basal nuclei of the amygdala to the entorhinal cortex in the macaque monkey.

We used the anterograde tracers Phaseolus vulgaris-leucoagglutinin (PHA-L) and biotinylated dextran amine (BDA) to examine the projections from the lateral, basal, and accessory basal nuclei of the amygdaloid complex to the entorhinal cortex in Macaca fascicularis monkeys. The heaviest amygdaloid projections originate in the lateral nucleus, which innervates the rostrally situated entorhinal fields but does not project to the caudal entorhinal cortex. The most extensive projections originate in the ventral division of the lateral nucleus. Injections in this subdivision lead to moderate to heavy fiber and terminal labeling in the entorhinal cortex, rostral levels of the rostral intermediate El (ER) and lateral fields, (ELr), and light labeling in the olfactory field EO. The projections from all portions of the lateral nucleus terminate most heavily in layer III. Layer II of EO and ER also receives a substantial input from the ventral division of the lateral nucleus. Layer II of ELr receives light innervation from all portions of the lateral nucleus that project to layer III. Projections from the basal nucleus arise mainly from the parvicellular division and are light to moderate in density. Fibers terminate predominantly in ELr, ER, EO, and the caudal portion of the lateral field (Elc); only the most rostral portion of El receives projections. While fibers from the basal nucleus innervate the same layers as the projections from the lateral nucleus, they tend to have a more vertical or radial orientation within the entorhinal cortex. Electron microscopic analysis of these fibers and terminals indicates that they overwhelmingly form asymmetrical synapses onto dendrites and dendritic spines. The accessory basal nucleus provides a light projection to the same regions of the entorhinal cortex innervated by the lateral and basal nuclei.

Amygdala↗

PubMed1997

Diet induced hyperammonemia decreases neuronal nuclear size in rat entorhinal cortex.

Hepatic encephalopathy is mainly caused by an excess of ammonium ions. Among other effects, glutamate transmission in the brain is impaired, and thereof, neuronal function in multiple systems is affected. We investigated in rats the effect of diet induced hyperammonemia in the entorhinal cortex, a well known glutamatergic pathway to the dentate gyrus, by measuring the neuronal nuclear area in two entorhinal cortex subfields (dorsolateral subfield (DLE) and dorsal intermediate subfield (DIE); [Insausti, R., Herrero, M.T. and Witter, M.P., Origin and distribution of cortical efferents from the entorhinal cortex in the rat, Hippocampus, 7 (1997) 146-183]) that project to separate septotemporal levels of the hippocampus. After 2, and more overtly, after 8 weeks of the ammonium enriched diet consumption, the neuronal nuclear size in layers II, III, V and VI of both entorhinal cortex subfields showed a significant reduction in size. We conclude that already at 2 weeks of treatment there is a decrease in neuronal nuclear size in all layers of the entorhinal cortex, which might have widespread functional effects on cortical and subcortical structures.

Acetates↗

PubMed2003

Olfactory learning and memory impairments following lesions to the hippocampus and perirhinal-entorhinal cortex.

The role of the hippocampus and perirhinal-entorhinal cortex was examined in an olfactory discrimination paradigm. Small neurotoxic lesions of the hippocampus (21% tissue damage) yielded relatively unimpaired olfactory retention across brief (30 s), intermediate (approximately 5 min), and 24-hr delays, whereas impairments were noted at 5-day retention intervals. Larger hippocampal lesions (63% tissue damage) spared memory at intermediate delays, with no impact at 8-day retention intervals. Aspiration lesions directed at the perirhinal-entorhinal cortex produced a variable performance pattern, with impairments noted at intermediate, 24-hr, and 5-day delays. Results suggest the hippocampus is not specifically involved in retaining olfactory information, with additional consideration given to the relationship between lesion size and memory impairment.

Animals↗

PubMed2004

Higher atrophy rate of entorhinal cortex than hippocampus in AD.

OBJECTIVES: To determine if atrophy rates were higher for entorhinal cortex (ERC) than for hippocampus in Alzheimer disease (AD), to determine the relationship between hippocampal atrophy rate and memory impairment, and to compare atrophy rates of ERC and hippocampus in differentiating between patients with AD and cognitively normal (CN) controls. METHODS: Twenty patients with AD and 25 CN subjects had MRI scans and clinical evaluations twice approximately 1.9 years apart. ERC volumes were measured manually and hippocampal volumes were measured semiautomatically on volumetric T1-weighted MR images. RESULTS: In AD, the atrophy rate of ERC (7.1 +/- 3.2%/year) was higher (p < 0.02) than that of hippocampus (5.9 +/- 2.4%/year). Furthermore, memory deficit in mild AD, measured with the Delayed List Verbal Recall test, correlated significantly with atrophy rates of both ERC (r = -0.61) and hippocampus (r = -0.59). Atrophy rates of ERC and hippocampus were comparable in differentiating between AD and CN. Using atrophy rates of ERC or hippocampus to detect a 20% treatment effect with 90% power (p < 0.05) would require about 100 completed patients per arm in a 2-year study. CONCLUSION: The finding in AD that the atrophy rate in the entorhinal cortex is higher than in the hippocampus is consistent with the view that AD pathology begins in the entorhinal cortex.

Aged↗

PubMed2005

Cognitive impact of neuronal pathology in the entorhinal cortex and CA1 field in Alzheimer's disease.

The relative contribution of Alzheimer's disease (AD) hippocampal neuronal pathology in cognitive decline is still a matter of debate. To address this issue, we performed a stereological analysis of layer II of the entorhinal cortex and the CA1 field of the hippocampus in 34 autopsy cases covering the whole spectrum of old age and Clinical Dementia Rating (CDR) scores. In both areas, the proportion of neurofibrillary tangle (NFT)-containing neurons increased steadily as a function of the CDR score. Questionable dementia was associated with a 1.9% neuronal loss in the entorhinal cortex and 26% in the CA1 field. NFT numbers predicted only 38% of the neuron number variability in the entorhinal cortex and 55% in the CA1 field. Neuron counts in the entorhinal cortex and both neuron and NFT counts in the CA1 field were significantly associated with cognitive status explaining 25% and 44% of the CDR variability, respectively. Our data reveal a dissociation between the patterns of progression of NFT and neuronal loss in the entorhinal cortex and CA1 field. Moreover, they show that less than 50% of the cognitive variability may be attributable to AD neuronal pathology in these areas.

Age Factors↗

PubMed1976

Electrophysiological analysis of the projection from the contralateral entorhinal cortex to the dentate gyrus in normal rats.

The projection from the contralateral entorhinal cortex to the dentate gyrus is shown to exert a monosynaptic excitatory action. Stimulation of the contralateral entorhinal cortex evokes unitary granule cell discharges in the dentate gyrus. This evoked activity is followed by a period of inhibition lasting about 50 msec. Laminar analyses of field potentials generated by contralateral medial entorhinal stimulation localize the synaptic activity to the middle portion of the granule cell dendrites. This localization is consistent with the termination site of the contralateral entorhinal projection as previously shown anatomically. Earlier studies have indicated that the entorhinal cortex excites only the ipsilateral dentate gyrus. These findings now demonstrate that the cortical input to the dentate gyrus is bilateral in normal rats. However, the contralateral projection appears to be much less efficacious than the ipsilateral input.

Animals↗

PubMed1997

Distribution of parvalbumin-, calretinin-, and calbindin-D28k-immunoreactive neurons and fibers in the human entorhinal cortex.

Parvalbumin, calretinin, and calbindin-D28k are calcium-binding proteins that are located in largely nonoverlapping neuronal populations in the brain. The authors studied the distribution of parvalbumin-, calretinin-, and calbindin-D28k-immunoreactive (ir) cells, fibers, terminals, and neuropil in the eight subfields of the human entorhinal cortex. The distribution of each of the three calcium-binding proteins largely followed the cytoarchitectonic borders of the eight entorhinal subfields, although the regional and laminar distributions of the three proteins were segregated rather than overlapping. The highest density of parvalbumin-ir neurons and terminals was found in the caudal and lateral subfields of the entorhinal cortex. Calretinin and calbindin-D28k immunoreactivities were high rostromedially, although a large number of calretinin and calbindin-D28k neurons were also found in the caudal subfields. All parvalbumin-ir cells had a morphological appearance of nonpyramidal neurons. Parvalbumin-ir terminals formed basket-like formations around unstained somata and cartridges, suggesting that parvalbumin neurons compose a subpopulation of gamma-aminobutyric acid (GABA)ergic basket cells and chandelier cells, respectively. Although calretinin and calbindin-D28k were also found in numerous nonpyramidal neurons, both were also located in pyramidal-shaped neurons in layers V and VI (calretinin) and in layers II and III (calbindin) of the entorhinal cortex, suggesting that they play roles in projection neurons as well. Moreover, the high density of nonpyramidal neurons containing calcium-binding proteins in layers II and III of the entorhinal cortex suggests that they form an integral component of a network that controls the entorhinal outputs to the hippocampus. Furthermore, the largely nonoverlapping distributions of the parvalbumin-, calretinin-, and calbindin-ir neuronal populations in the entorhinal cortex indicate that each of them may modulate a different subset of topographically organized entorhinal outputs.

Adult↗

PubMed1991

Excitotoxic lesions of the rat entorhinal cortex. Effects of selective neuronal damage on acquisition and retention of a non-spatial reference memory task.

The neurotoxin N-methyl-D-aspartate was used to induce selective bilateral neuronal loss in the entorhinal cortex, in order to model one aspect of the neurodegeneration observed in Alzheimer's disease, Down's syndrome and aging. Lesioned, sham-lesioned and intact control rats learned a reference memory task involving a brightness discrimination for water reward. Rats were trained over 1 week until reaching criteria and tested for retention after a 10-day interval. Lesioned rats showed impaired retention compared to shams and controls, but were able to reacquire the task. Anatomical analysis confirmed excitotoxic lesions of the entorhinal cortex, and showed collateral sprouting of acetylcholinesterase-stained fibers into the outer molecular layer of the dentate gyrus, indicating denervation plasticity in the hippocampus. This functional anatomical study of the entorhinal cortex demonstrates the importance of the entorhinal cortex in memory retention, and raises the possibility that functional deficits in certain neurodegenerative diseases may be modeled by partial neuronal loss in the entorhinal cortex.

Animals↗

PubMed1987

Effects of entorhinal lesions on trophic activities present in rat entorhinal cortex and hippocampus as studied using primary cultures of entorhinal and septal tissues.

The present study examined trophic activities in normal and injured brain which affect the survival and growth of central neurons in culture. Adult rats received bilateral lesions through the angular bundle, severing projections between the entorhinal cortex and the hippocampus. Ten days later, extracts were prepared from the entorhinal or hippocampal regions of the injured brains and compared with extract prepared from analogous regions of normal brains for trophic activities in cultures of either entorhinal or septal tissues. At least three activities were observed: (1) a trophic activity which bound to polylysine-treated wells, which was greater than 10,000 Da in size, heat labile, and sensitive to trypsin, and which supported the survival of both septal and entorhinal neurons in culture; (2) a trophic activity which did not bind to polylysine-treated wells, which was greater than 10,000 Da in size, heat labile, and sensitive to trypsin, and which, in the presence of polylysine-bindable material, facilitated the survival and growth of entorhinal cells in culture, and (3) an inhibitory activity which significantly reduced survival in entorhinal cultures when cells were plated in the presence of high concentrations of extract prepared from normal brain. These effects were not due to nonspecific effects of plating the cells in, or treating the wells with, large amounts of protein. A significant injury-related increase in non-polylysine-bindable trophic activity was also observed. Extracts prepared from either the hippocampus or the entorhinal area of the injured brains contained more non-polylysine-bindable trophic activity than extract prepared from normal brains. Injury-related changes in trophic activities were more prominent in entorhinal than in septal cultures. This increase in activity may account for the injury-related effects on the survival of entorhinal transplants reported previously [Gibbs and Cotman: Neuroscience (in press) 1987], and may represent an endogenous mechanism by which the brain attempts to selectively support the survival of injured cells following injury.

Animals↗

PubMed1994

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

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

Animals↗

PubMed1996

Layer-specific sprouting of commissural fibres to the rat fascia dentata after unilateral entorhinal cortex lesion: a Phaseolus vulgaris leucoagglutinin tracing study.

After unilateral entorhinal cortex lesion commissural fibres to the inner molecular layer of the rat fascia dentata are said to sprout into the former termination zone of entorhinal afferents. This sprouting process has not yet been demonstrated at the level of individual fibres. In the present study, Phaseolus vulgaris leucoagglutinin tracing was used to analyse the commissural projection to the inner molecular layer in rats with longstanding entorhinal cortex lesions. In comparison with controls, the commissural fibre plexus in the inner molecular layer had expanded by 20-45 microns outwards on the side of the entorhinal lesion. Unexpectedly, only a small number of axons arising from the bulk of commissural fibres in the inner molecular layer left the main fibre plexus and entered the outer molecular layer. Thus, there was still a clearly recognizable border between the Phaseolus vulgaris leucoagglutinin-labelled commissural fibre plexus in the inner molecular layer and the unstained outer molecular layer. The few commissural axons invading the outer molecular layer rarely branched but formed multiple en passant boutons, and occasionally exhibited growth cones. The data indicate that only few commissural fibres appear to be able to sprout beyond the border of their appropriate layer suggesting that the characteristic laminar specificity of hippocampal afferents is largely retained following deafferentation.

Animals↗

PubMed1998

Tachykinins may modify spontaneous epileptiform activity in the rat entorhinal cortex in vitro by activating GABAergic inhibition.

The effects of substance P and related tachykinins on intrinsic membrane properties and synaptic responses of neurons in cortical slices were determined. Substance P had no detectable effect on membrane properties of principal neurons in layer II or V of the rat medial entorhinal cortex or on neurons in either layer of the anterior cingulate cortex. Specific agonists at the neurokinin1-receptor were also without effect as were agonists at both neurokinin1- and neurokinin3-receptors. Substance P hyperpolarized a small number of principal neurons. These responses were weak and desensitized with repeated applications. Similar effects were seen with other neurokinin1-receptor agonists. Excitatory synaptic potentials mediated by either alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate- or N-methyl-D-aspartate-receptors in principal neurons of the entorhinal cortex were unaffected by substance P. Responses of entorhinal neurons to iontophoretically applied glutamate and N-methyl-D-aspartate were also unaffected. Inhibitory synaptic potentials mediated by either GABA(A)- or GABA(B)-receptors in entorhinal neurons were slightly but consistently enhanced by substance P. Neurons identified as interneurons on the basis of their firing characteristics were consistently depolarized by substance P. These responses also desensitized with repeated applications. Spontaneous epileptiform discharges evoked in entorhinal cortex by perfusion with a GABA(A)-receptor antagonist (bicuculline), were reduced in frequency and, sometimes, in duration by substance P. This effect was mimicked by other neurokinin1-receptor agonists and blocked by neurokinin1-receptor antagonists. It was also mimicked by neurokinin A but not by a specific neurokinin1-receptor agonist. The reduction in frequency of discharges was also mimicked by a GABA(B)-receptor agonist, L-baclofen, and blocked by the GABA(B)-receptor antagonist, CGP55845A. Neurokinin B, and a specific neurokinin1-receptor agonist (senktide), increased the frequency and (sometimes) duration of epileptiform discharges. Substance P could also increase frequency but this usually succeeded or preceded a decrease in frequency. The effect of neurokinin B was reduced by a metabotropic glutamate receptor antagonist. Substance P appears to have little direct effect on principal neurons of the entorhinal cortex but may hyperpolarize them indirectly by activating interneurons and releasing GABA. This indirect inhibition may be responsible for the ability of substance P to reduce the frequency of epileptiform discharges in the entorhinal cortex and may suggest that neurokinin1-receptor agonists have potential as anticonvulsant drugs.

Animals↗

PubMed2003

Gamma oscillations induced by kainate receptor activation in the entorhinal cortex in vitro.

Gamma frequency (30-80 Hz) oscillations are recordable from human and rodent entorhinal cortex. A number of mechanisms used by neuronal networks to generate such oscillations in the hippocampus have been characterized. However, it is as yet unclear as to whether these mechanisms apply to other anatomically disparate brain regions. Here we show that the medial entorhinal cortex (mEC) in isolation in vitro generates gamma frequency oscillations in response to kainate receptor agonists. Oscillations had the same horizontal and laminar spatiotemporal distribution as seen in vivo and in the isolated whole-brain preparation. Oscillations occurred in the absence of input from the hippocampal formation and did not spread to lateral entorhinal regions. Pharmacological similarities existed between oscillations in the hippocampus and mEC in that the latter were also sensitive to GABAA receptor blockade, barbiturates, AMPA receptor blockade, and reduction in gap junctional conductance. Stellate and pyramidal neuron recordings revealed a large GABAergic input consisting of gamma frequency IPSP trains. Fast spiking interneurons in the superficial mEC generated action potentials at gamma frequencies phase locked to the local field. Stellate cells also demonstrated a subthreshold membrane potential oscillation at theta frequencies that was temporally correlated with a theta-frequency modulation in field gamma power. Disruption in this stellate theta frequency oscillation by the hyperpolarisation activated current (Ih) blocker ZD7288 also disrupted theta modulation of field gamma frequency oscillations. We propose that similar cellular and network mechanisms to those seen in the hippocampus generate and modulate persistent gamma oscillations in the entorhinal cortex.

Action Potentials↗

PubMed1992

Agonist interactions with 5-HT3 receptor recognition sites in the rat entorhinal cortex labelled by structurally diverse radioligands.

1. The pharmacological properties of 5-HT3 receptor recognition sites labelled with [3H]-(S)-zacopride, [3H]-LY278,584, [3H]-granisetron and [3H]-GR67330 in membranes prepared from the rat entorhinal cortex were investigated to assess the presence of cooperativity within the 5-HT3 receptor complex. 2. In rat entorhinal cortex homogenates, [3H]-(S)-zacopride, [3H]-LY278,584, [3H]-granisetron and [3H]-GR67330 labelled homogeneous densities of recognition sites (defined by granisetron, 10 microM) with high affinity (Bmax = 75 +/- 5, 53 +/- 5, 92 +/- 6 and 79 +/- 6 fmol mg-1 protein, respectively; pKd = 9.41 +/- 0.04, 8.69 +/- 0.14, 8.81 +/- 0.06 and 10.14 +/- 0.04 for [3H]-(S)-zacopride, [3H]-LY278,584, [3H]-granisetron and [3H]-GR67330, respectively, n = 3-8). 3. Quipazine and granisetron competed for the binding of each of the radioligands in the rat entorhinal cortex preparation at low nanomolar concentrations (pIC50; quipazine 9.38-8.51, granisetron 8.62-8.03), whilst the agonists, 5-hydroxytryptamine (5-HT), phenylbiguanide (PBG) and 2-methyl-5-HT competed at sub-micromolar concentrations (pIC50; 5-HT 7.16-6.42, PBG 7.52-6.40, 2-methyl-5-HT 7.38-6.09). 4. Competition curves generated with increasing concentrations of quipazine, PBG, 5-HT and 2-methyl-5-HT displayed Hill coefficients greater than unity when the 5-HT3 receptor recognition sites in the entorhinal cortex preparation were labelled with [3H]-LY278,584, [3H]-granisetron and [3H]-GR67330. These competing compounds displayed Hill coefficients of around unity when the sites were labelled with [3H]-(S)-zacopride. Competition for the binding of [3H]-(S)-zacopride, [3H]-LY278,584, [3H]-granisetron and [3H]-GR67330 by granisetron generated Hill coefficients around unity.5. The nature of the interaction of competing compounds (quipazine, granisetron, PBG, 5-HT, 2-methyl-5-HT) for the [3H]-(S)-zacopride binding site in the rat entorhinal cortex preparation was not altered by the removal of the Krebs ions or the addition of the monoamine oxidase inhibitor, pargyline, to the HEPES/Krebs buffer.6. In conclusion, the present studies provide further evidence towards the presence of cooperativity within the 5-HT3 receptor macromolecule and indicate that either [3H]-(S)-zacopride labels a different site on the receptor complex from [3H]-LY278,584, [3H]-granisetron or [3H]-GR67330, or it binds in such a manner as to prevent the conformatory change in the receptor protein responsible for the cooperative binding of agonists (and quipazine).

Animals↗

PubMed1995

Electrophysiology and morphology of a new type of cell within layer II of the rat lateral entorhinal cortex in vitro.

Using a combination of intracellular recording and morphological techniques, we describe the properties of a new cell type within layer II of the lateral entorhinal cortex. A thick and bifurcating apical dendrite and thinner basal dendrites extended from the pyramidal shaped cell body. The axon ramified within all superficial layers of the lateral entorhinal cortex. These pyramidal-like cells exhibited 2 pronounced electrophysiological features; a high threshold for spike generation, and their prominent excitatory synaptic potentials with little inhibition following lateral entorhinal cortex stimulation. The electrophysiological properties and the axonal morphology suggest that this cell type has a local information processing role within the lateral entorhinal cortex.

2-Amino-5-phosphonovalerate↗