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 397 records · Page 22Linked to original sources
PubMed1997

Persistent short term memory deficits in Hebb-Williams maze performance are shown by rats with unilateral entorhinal cortex lesions.

The spatial abilities of adult, male Sprague-Dawley rats in the Hebb-Williams maze were examined at 6 months after unilateral electrolytic entorhinal cortex lesions. Compared with sham-operated rats, their performance was impaired in both initial entry and repeat entry errors over 12 consecutive problems, using immediate starting replacement for the 6 trials per problem. The configurations of the 12 maze problems are independent, and deficits were seen over the entire course of the testing. This study indicates that Hebb-Williams maze performance deficits after unilateral entorhinal cortex lesion are persistent and can be seen up to 6 months after injury.

Animals↗
PubMed1999

Retigabine strongly reduces repetitive firing in rat entorhinal cortex.

Retigabine (D-23129) [N-(2-amino-4-(4-fluorobenzylamino)phenyl) carbamic acid ethyl ester] is a novel antiepileptic drug. The compound was shown to possess anticonvulsant properties both in vivo and in vitro. We investigated the effects of retigabine on neurones in the rat medial entorhinal cortex using conventional intracellular recordings in combined hippocampal-entorhinal cortex slices. Retigabine strongly reduced the number of action potentials elicited by 1 s long depolarising current injections. Both the amplitudes of monosynaptic inhibitory postsynaptic potentials/currents (IPSP/Cs) and the amplitudes of excitatory postsynaptic potentials (EPSPs) remained unaffected. The drug increased outward rectification and induced a membrane-potential hyperpolarisation in most of the tested neurones. The findings suggest that retigabine exerts its anticonvulsant effects by activation of a K(+)conductance, however it cannot be excluded from our experiments that other mechanisms may be involved in the effect of retigabine on membrane properties.

Animals↗
PubMed1995

Characterization of histamine H3 receptors regulating acetylcholine release in rat entorhinal cortex.

1. The pharmacological properties and location of H3 receptors modulating acetylcholine release have been investigated in non-superfused slices and synaptosomes of rat entorhinal cortex preloaded with [3H]-choline. 2. (R)alpha-methylhistamine, an H3-receptor agonist, potently inhibited the K(+)-evoked tritium release from slices, an effect antagonized by thioperamide, an H3-receptor antagonist, with nanomolar potency. 3. The K(+)-evoked tritium release from synaptosomes remained unaltered in the presence of the potent and selective H3-receptor agonists, imetit and (R)alpha-methylhistamine, suggesting that H3 receptors modulating acetylcholine release are not presynaptically located on cholinergic nerve terminals. 4. Phenylbutanoylhistamine and phenylpropylhistamine, two H3-receptor antagonists of moderate potency, failed to antagonize the inhibitory effects of (R)alpha-methylhistamine observed in slices. Unexpectedly, both compounds when used alone, inhibited tritium release from slices and synaptosomes with micromolar potency and to the same extent (by approximately 50% when added at a final concentration of 200 microM). This inhibitory effect did not involve H1, H2 or H3 receptors and was not mediated by an unknown histamine receptor site, since histamine used at a high concentration neither reproduced nor antagonized the effect of phenylbutanoylhistamine. It remained unaltered in the presence of scopolamine and was neither mimicked nor antagonized by vasoactive intestinal peptide, previously shown to be colocalized with acetylcholine in some neurones. 5. It is concluded that acetylcholine release in rat entorhinal cortex is modulated by H3 receptors presumably not located on cholinergic axon terminals. It remains to be established whether these H3 receptors belong to a receptor subtype different from those previously described since the potency ofphenylbutanoylhistamine and phenylpropylhistamine as H3-receptor antagonists was probably greatly underestimated by additional properties of both drugs.

Acetylcholine↗
PubMed1986

The organization of the reciprocal connections between the subiculum and the entorhinal cortex in the cat: I. A neuroanatomical tracing study.

The connections between the subiculum (SUB) and the entorhinal cortex (EC) were studied in the cat with retrograde and anterograde tracing techniques. Injections of the retrogradely transported tracer WGA-HRP at different levels along the septotemporal axis of the subiculum result in labeled neurons predominantly in the medial entorhinal cortex (MEA) in the superficial layers II and III. In the deep layers labeled cells are found more widespread over the EC. The superficially located labeled EC neurons are topographically distributed in a lateromedial gradient, which corresponds to a septotemporal gradient along the longitudinal axis of the subiculum. This organization of the EC-SUB projection system could be substantiated by the use of injections anterogradely transported radioactively labeled amino acids in EC. The SUB to EC projections were investigated with the anterograde transport of WGA-HRP and with radioactively labeled amino acids that were injected at different levels along the septotemporal axis of the subiculum. This results in a patch of anterogradely labeled fibers and terminals in MEA, predominantly in layers II and III, with a wider band of label in the deep layers. Again, a topographical distribution along the lateromedial axis of the EC corresponding to the septotemporal axis of the SUB was observed. Contralateral reciprocal connections between EC and SUB are also present, and exhibit a similar topographical organization.

Amino Acids↗
PubMed1998

GM1-Ganglioside Suppresses Septodentate Sprouting and Enhances Recovery from Entorhinal Cortex Lesions on DRL Perfomance and Locomotor Behavior in Rats.

Administration of gangliosides accelerates recovery of function after entorhinal cortex lesions on open field activity and learned spatial alternation tasks. In the present study, we examined whether GM1 ganglioside might enhance recovery from bilateral entorhinal cortex lesions on a differential reinforcement of low-rate responding tak with a 20 sec delay (DRL-20) as well as on open field activity. Optical densitometry measurements were taken to assess sprouting by the acetylcholinesterase-containing septodentate pathway. Eighteen rats were assigned to sham/GM1, lesion/GM1, or lesion/saline conditions. After preoperative training and testing, the rats received surgery and were then tested post-operatively for thirty days. GM1 injections (20 mg/kg) were given beginning the day before surgery through day 5 postsurgery and then on alternating days. Relative to the lesion/saline group, rats in the lesion/GM1 group showed enhanced recovery on the DRL-20 and the open field tasks. The lesion/GM1 group had significantly less septodentate sprouting than the lesion group treated with saline. GM1 treatment may be facilitating recovery from bilateral entorhinal lesions by reducing the trauma of injury and denervation, reducing heterologous sprouting, or both.

Journal Article↗
PubMed1998

Participation of GABAA-mediated inhibition in ictallike discharges in the rat entorhinal cortex.

The spontaneous, synchronous activity induced by 4-aminopyridine (4AP, 50 microM) in the adult rat entorhinal cortex was analyzed with simultaneous field potential and intracellular recordings in an in vitro slice preparation. Four-AP induced isolated negative-going field potentials (interval of occurrence = 27.6 +/- 9.9 (SD) s; n = 27 slices) that corresponded to intracellular long-lasting depolarizations (LLDs), and ictallike epileptiform discharges (interval of occurrence = 10.4 +/- 5.7 min; n = 27 slices) that were initiated by the negative field potentials. LLDs recorded with K-acetate-filled microelectrodes triggered few action potentials of variable amplitude and had a duration of 1.7 +/- 0.8 s (n = 26 neurons), a peak amplitude of 11.8 +/- 5.0 mV (n = 26 neurons) and a reversal potential of -66.2 +/- 3.9 mV (n = 17 neurons). The ictal discharges studied with K-acetate microelectrodes consisted of prolonged depolarizations (duration = 72.9 +/- 44.3 s; peak amplitude = 29.2 +/- 11.4 mV; n = 25 neurons) with action-potential firing during both the tonic and the clonic phase. These depolarizations had a reversal potential of -45.3 +/- 3.8 mV (n = 4 neurons). Intracellular Cl- diffusion from KCl-filled microelectrodes made both LLDs and ictal depolarizations increase in amplitude (30.5 +/- 8.2 mV, n = 8 and 41.8 +/- 9.8 mV, n = 6 neurons, respectively). LLDs recorded with KCl and 2-(trimethyl-amino)N-(2, 6-dimethylphenyl)-acetamide (QX-314) microelectrodesreached an amplitude of 36.3 +/- 5.2 mV, lasted 12.5 +/- 6.5 s, and had a reversal potential of -31.3 +/- 2.5 mV (n = 4 neurons); under these recording procedures the ictal discharge amplitude was 41.5 +/- 5.0 mV and the reversal potential -24.0 +/- 7.0 mV (n = 4 neurons). The N-methyl-D-aspartate (NMDA) receptor antagonist 3,3-(2-carboxy-piperazine-4-yl)-pro-pyl-l-phosphonate (10 microM, n = 5 neurons) alone or concomitant with the nonNMDA receptor antagonist 6-cyano-7-nitro-quinoxaline-2,3-dione (10 microM, n = 4 neurons) abolished ictal discharges, without influencing LLDs. LLDs were blocked by the gamma-aminobutyric acid-A (GABAA) receptor antagonist bicuculline methiodide (BMI, 10 microM, n = 6 neurons) or the mu-opioid receptor agonist (-Ala2-N-Me-Phe, Gly-ol) enkephalin (DAGO, 10 microM, n = 2 neurons). Application of BMI (n = 4 neurons) or DAGO (n = 2 neurons) to control the medium abolished LLDs and ictal discharges but disclosed a novel type of epileptiform depolarization that lasted 3.5 +/- 1.2 s and occurred every 5.2 +/- 2.6 s (n = 6 neurons). Our data indicate that 4AP induces in the rat entorhinal cortex a synchronous, GABA-mediated potential that is instrumental in initiating NMDA-dependent, ictal discharges. Moreover we present evidence for an active role played by GABAA-mediated potentials in the maintenance and termination of these prolonged epileptiform events.

4-Aminopyridine↗
PubMed2001

Involvement of the entorhinal cortex in a process of attentional modulation: evidence from a novel variant of an IDS/EDS procedure.

Novel behavioral assays were used to assess the role of the entorhinal cortex in modulating attention to components of stimulus compounds. In Stage 1, rats received discrimination training with compounds constructed from 3 dimensions (auditory, visual, and tactile); in each compound the combination of components from 2 dimensions (e.g., auditory and visual) were relevant to the solution of the discrimination, and the remaining dimension (e.g., tactile) was irrelevant. In Stage 2, rats received a different discrimination in which the relevant dimensions were either congruent (auditory and visual) or incongruent (auditory and tactile) with those that were relevant in Stage 1. Sham-operated rats acquired the congruent discrimination more rapidly than the incongruent discrimination--a finding indicative of a process of attentional modulation--whereas rats with excitotoxic lesions of the entorhinal cortex acquired both discriminations equally readily.

Animals↗
PubMed2000

Trajectory encoding in the hippocampus and entorhinal cortex.

We recorded from single neurons in the hippocampus and entorhinal cortex (EC) of rats to investigate the role of these structures in navigation and memory representation. Our results revealed two novel phenomena: first, many cells in CA1 and the EC fired at significantly different rates when the animal was in the same position depending on where the animal had come from or where it was going. Second, cells in deep layers of the EC, the targets of hippocampal outputs, appeared to represent the similarities between locations on spatially distinct trajectories through the environment. Our findings suggest that the hippocampus represents the animal's position in the context of a trajectory through space and that the EC represents regularities across different trajectories that could allow for generalization across experiences.

Algorithms↗
PubMed2006

A spin glass model of path integration in rat medial entorhinal cortex.

Electrophysiological recording studies in the dorsocaudal region of medial entorhinal cortex (dMEC) of the rat reveal cells whose spatial firing fields show a remarkably regular hexagonal grid pattern (Fyhn et al., 2004; Hafting et al., 2005). We describe a symmetric, locally connected neural network, or spin glass model, that spontaneously produces a hexagonal grid of activity bumps on a two-dimensional sheet of units. The spatial firing fields of the simulated cells closely resemble those of dMEC cells. A collection of grids with different scales and/or orientations forms a basis set for encoding position. Simulations show that the animal's location can easily be determined from the population activity pattern. Introducing an asymmetry in the model allows the activity bumps to be shifted in any direction, at a rate proportional to velocity, to achieve path integration. Furthermore, information about the structure of the environment can be superimposed on the spatial position signal by modulation of the bump activity levels without significantly interfering with the hexagonal periodicity of firing fields. Our results support the conjecture of Hafting et al. (2005) that an attractor network in dMEC may be the source of path integration information afferent to hippocampus.

Animals↗
PubMed2004

Glutamate transporters and metabotropic receptors regulate excitatory neurotransmission in the medial entorhinal cortex of the rat.

In layer III of the medial entorhinal cortex (mEC), a region that is especially prone to cell damage in Alzheimer's disease, schizophrenia and epilepsy, effects of blocking glutamate uptake on excitatory synaptic transmission were studied. Two competitive glutamate transporter antagonists, TBOA and tPDC, reduced the amplitude of pharmacologically isolated AMPAR and NMDAR mediated EPSPs/EPSCs without changing the time course of the events. This effect was mimicked by tACPD, an agonist of groups I and II metabotropic glutamate receptors (mGluRs). The competitive groups I and II mGluR antagonist MCPG blocked the depression of the EPSC amplitude induced by tACPD and also prevented the effect of either TBOA or tPDC. Furthermore, EGLU, which selectively antagonizes group II mGluRs, blocked the effect of tPDC and LY3414965, a specific group I mGluR antagonist, abolished the reduction of amplitude caused by TBOA. Additionally, application of TBOA increased the paired-pulse index, suggesting a presynaptic mechanism for the depression of EPSP/EPSC amplitude. The present data suggest that glutamate transporters and group I/II mGluRs regulate excitatory synaptic transmission in the mEC. Presynaptic mGluRs may limit excessive glutamate accumulation if uptake becomes compromised.

Amino Acid Transport System X-AG↗
PubMed1999

Morphological study of the entorhinal cortex, hippocampal formation, and basal ganglia in Rett syndrome patients.

Entorhinal cortex (EC), fascia dentata (FD), hippocampus (HP), and basal ganglia (BG) were studied in Rett syndrome (RS) cases and compared with control brains and an autism case. Kluver-Barrera and Golgi methods were used. In RS most of the areas of EC, HP, and FD showed severe cell hypochromia. In the EC all cells of layer II and most in layer III were in a state of total chromatolysis or were "ghost" cells, but the cells of layers V and VI were preserved and moderately hyperchromic. In FD and HP the majority of the granular cells and cells of CA3 and CA4 fields were severely hypochromic, whereas in the CA1 field most cells were normal or slightly hypercaryochromic. In BG mostly mild or moderate aberration from normal cell structure was observed: in striatum, mild hypercaryochromia of small neurons and more expressive hyperchromia of large neurons were found; and in pallidum, mild or moderate hypercaryochromia to severe hyperchromia in pallidum internum was found. Degeneration of thick myelinated fibers was evident in pallidum. Large striatal and pallidal neurons showed signs of constructive changes in Golgi slices. These data allow the determination of the cause of the main symptoms of RS. The motor disorders, including specific stereotyped movements, could be related to the enhanced activity of BG cells due to their deafferentation from the side of the neocortex and to supposed hyperactivity of the EC-striatal pathway; the mental retardation and epileptic seizures could be due to FD-HP involvement.

Adolescent↗
PubMed1997

Muscarinic modulation of the oscillatory and repetitive firing properties of entorhinal cortex layer II neurons.

Neurons in layer II of the entorhinal cortex (EC) are key elements in the temporal lobe memory system because they integrate and transfer into the hippocampal formation convergent sensory input from the entire cortical mantle. EC layer II also receives a profuse cholinergic innervation from the basal forebrain that promotes oscillatory dynamics in the EC network and may also implement memory function. To understand the cellular basis of cholinergic actions in EC, we investigated by intracellular recording in an in vitro rat brain slice preparation the muscarinic modulation of the electroresponsive properties of the two distinct classes of medial EC layer II projection neurons, the stellate cells (SCs) and non-SCs. In both SCs and non-SCs, muscarinic receptor activation with carbachol (CCh, 10-50 microM) caused atropine-sensitive (300 nM) membrane depolarization. In SCs, the CCh-induced membrane depolarization was associated with subthreshold membrane potential oscillations and "spike cluster" discharge, which are typically expressed by these cells on depolarization. CCh, however, caused a decrease of the dominant frequency of the membrane potential oscillations from 9.2 +/- 1.1 (SD) Hz to 6.3 +/- 1.1 Hz, as well as a decrease of the intracluster firing frequency from 18.1 +/- 1.7 Hz to 13.6 +/- 1.3 Hz. In addition, spike cluster discharge was less robust, and the cells tended to shift into tonic firing during CCh. In contrast to SCs, in non-SCs, CCh drastically affected firing behavior by promoting the development of voltage-dependent, long-duration (1-5 s) slow bursts of action potentials that could repeat rhythmically at slow frequencies (0.2-0.5 Hz). Concomitantly, the slow afterhyperpolarization (sAHP) was replaced by long-lasting plateau postdepolarizations. In both SCs and non-SCs, CCh also produced conspicuous changes on the action potential waveform and its afterpotentials. Notably, CCh significantly decreased spike amplitude and rate of rise, which suggests muscarinic modulation of a voltage-dependent Na+ conductance. Finally, we also observed that whereas CCh abolished the sAHP in both SCs and non-SCs, the membrane-permeant analogues of adenosine 3',5'-cyclic monophosphate, 8-(4-chlorophenylthio)-adenosine-cyclic monophosphate and 8-bromo-adenosine-cyclic-monophosphate, abolished the sAHP in SCs but not in non-SCs. The data demonstrate that cholinergic modulation further differentiates the intrinsic electroresponsiveness of SCs and non-SCs, and add support to the presence of two parallel processing systems in medial EC layer II that could thereby differentially influence their hippocampal targets. The results also indicate an important role for the cholinergic system in tuning the oscillatory dynamics of entorhinal neurons.

Action Potentials↗
PubMed1996

Profound loss of layer II entorhinal cortex neurons occurs in very mild Alzheimer's disease.

The entorhinal cortex (EC) plays a crucial role as a gateway connecting the neocortex and the hippocampal formation. Layer II of the EC gives rise to the perforant pathway, the major source of the excitatory input to the hippocampus, and layer IV receives a major hippocampal efferent projection. The EC is affected severely in Alzheimer disease (AD), likely contributing to memory impairment. We applied stereological principles of neuron counting to determine whether neuronal loss occurs in the EC in the very early stages of AD. We studied 20 individuals who at death had a Clinical Dementia Rating (CDR) score of 0 (cognitively normal), 0.5 (very mild), 1 (mild), or 3 (severe cognitive impairment). Lamina-specific neuronal counts were carried out on sections representing the entire EC. In the cognitively normal (CDR = 0) individuals, there were approximately 650,000 neurons in layer II, 1 million neurons in layer IV, and 7 million neurons in the entire EC. The number of neurons remained constant between 60 and 90 years of age. The group with the mildest clinically detectable dementia (CDR = 0.5), all of whom had sufficient neurofibrillary tangles (NFTs) and senile plaques for the neuropathological diagnosis of AD, had 32% fewer EC neurons than controls. Decreases in individual lamina were even more dramatic, with the number of neurons in layer II decreasing by 60% and in layer IV by 40% compared with controls. In the severe dementia cases (CDR = 3), the number of neurons in layer II decreased by approximately 90%, and the number of neurons in layer IV decreased by approximately 70% compared with controls. Neuronal number in AD was inversely proportional to NFT formation and neuritic plaques, but was not related significantly to diffuse plaques or to total plaques. These results support the conclusion that a marked decrement of layer II neurons distinguishes even very mild AD from nondemented aging.

Aged↗
PubMed1991

Cloning of hippocampal poly(A) RNA sequences that increase after entorhinal cortex lesion in adult rat.

Evidence is given for altered gene expression in the hippocampus in response to entorhinal cortex lesioning. Three RNA markers encoding glial fibrillary acidic protein, apolipoprotein E and alpha-tubulin were isolated from a rat hippocampal cDNA library by differential screening with cDNA probes from entorhinal cortex lesioned and control rat hippocampus RNA. By Northern blot analysis, mRNA for apolipoprotein E and alpha-tubulin increased to peak around 6 days after the lesion and returned to near control level at 30 days. The increased synthesis of both mRNAs coincides with the acute phase of synaptogenesis, protein synthesis, and polyribosomes accumulation in the deafferented hippocampal area.

Animals↗
PubMed2006

Tonic facilitation of glutamate release by presynaptic NR2B-containing NMDA receptors is increased in the entorhinal cortex of chronically epileptic rats.

We have shown previously that when postsynaptic NMDA receptors are blocked, the frequency, but not amplitude, of spontaneous EPSCs (sEPSCs) at synapses in the entorhinal cortex is reduced by NMDA receptor antagonists, demonstrating that glutamate release is tonically facilitated by presynaptic NMDA autoreceptors. In the present study, we recorded sEPSCs using whole-cell voltage clamp in neurons in layer V in slices of the rat entorhinal cortex. Using specific antagonists for NR2A [(R)-[(S)-1-(4-bromo-phenyl)-ethylamino]-(2,3-dioxo-1,2,3,4-tetrahydroquinoxalin-5-yl)-methyl]-phosphonic acid] and NR2B [(alphaR, betaS)-alpha-(4-hydroxyphenyl)-beta-methyl-4-(phenylmethyl)-1-piperidinepropanol hydrochloride (Ro 25-6981)] subunit-containing receptors, we confirmed that in slices from juvenile rats (4-6 weeks of age), the autoreceptor is predominantly of the NR1-NR2B subtype. In older (4-6 months of age) control animals, the effect of the NR2B antagonist was less marked, suggesting a decline in autoreceptor function with development. In slices from rats (aged 4-6 months) exhibiting spontaneous recurrent seizures induced with a lithium-pilocarpine protocol, Ro 25-6981 again robustly reduced sEPSC frequency. The effect was equal to or greater than that seen in the juvenile slices and much more pronounced than that seen in the age-matched control animals. In all three groups, the NR2A antagonist was without effect on sEPSCs. These results suggest that there is a developmental decrease in NMDA autoreceptor function, which is reversed in a chronic epileptic condition. The enhanced autoreceptor function may contribute to seizure susceptibility and epileptogenesis in temporal lobe structures.

Age Factors↗
PubMed1999

Effects of retigabine (D-23129) on different patterns of epileptiform activity induced by 4-aminopyridine in rat entorhinal cortex hippocampal slices.

The purpose of this study was to evaluate the effects of the new anticonvulsant drug N-(2-amino-4-[fluorobenzylaminol-phenyl) carbamic acid ethyl ester (retigabine, D-23129, ASTA Medica, Dresden, Germany) on different patterns of epileptiform activity induced by 4-aminopyridine (4AP) in rat entorhinal cortex hippocampal slices. Application of 4AP (100 microM) induced in entorhinal cortex two different types of epileptiform activities; seizure-like events (SLE) and interictal epileptiform discharges (IED). Bicuculline (10 microM) changed 4AP-induced SLE and IED to recurrent epileptiform discharges (RED). IED were isolated after blockade of the SLE by glutamate receptor antagonists for alpha-amino-3-hydroxy-5-methylisoxazole4-proprionic acid (AMPA) and N-methyl-D-aspartate (NMDA) receptors, i.e. 1,2,3,4 tetrahydro-6-nitro-2,3-dioxo-benzolflquinoxaline-7-sulfonamide (NBQX, 10 microM) and 2-amino-5-phosphonovaleric acid (APV, 30 microM). Anticonvulsant properties of retigabine were evaluated as effect on the frequency and amplitude of SLE, IED and RED. Retigabine suppressed all types of epileptiform events in a dose dependent and reversible manner. SLE were suppressed in 71.4 and 100% of slices by 5 and 10 microM, respectively. The frequency of IED was significantly reduced by 20 microM retigabine (40.9+/-24.5%) and IED were blocked completely by 50 microM retigabine. When IED were isolated by application of glutamate antagonists 20 microM retigabine was sufficient to block this activity completely. RED induced by combined application of bicuculline and 4AP were blocked in 71.4% of the tested slices with 100 microM retigabine. The frequency of the RED in the remaining slices was reduced by 96.1+/-6.1%. We conclude that retigabine acts on a large variety of different epileptiform activities in temporal lobe structures that are known to develop readily pharmacoresistant seizures.

4-Aminopyridine↗
PubMed1993

Interactions of dopamine with glutamate- and GABA-mediated synaptic transmission in the rat entorhinal cortex in vitro.

We have studied the interactions between dopamine and glutamate-mediated transmission in the entorhinal cortex using intracellular recording in a slice preparation from the rat brain. High concentrations (0.1-1 mM) of dopamine had weak, direct effects on the membrane potential with predominantly hyperpolarizing responses in layer II neurons and depolarizing responses in layer V. Studies with the dopamine antagonists sulpiride (D2 antagonist, 10-50 microM) and SCH-23390 (D1 antagonist, 50 microM) indicated that the hyperpolarization by dopamine could be mediated by D2 receptors, although the pharmacology was not clear-cut. The depolarizing response was not affected by either D1 or D2 antagonists. Synaptic responses of layer II and layer V cells were complex, consisting of both inhibitory and excitatory potentials. In untreated slices, dopamine reduced all components of the synaptic responses. However, when components of the responses were pharmacologically isolated, only the excitatory, glutamate-mediated potentials were consistently affected and the GABAergic inhibitory potentials were more resistant to reduction by dopamine. Excitatory potentials mediated by both N-methyl-D-aspartate and alpha-amino-3-hydroxy-5-methyl-isoxazolepropionic acid receptors were reduced by dopamine, but the former were more strongly affected. Studies with antagonists suggested that the D1 receptor is more likely to be involved in the decrement of glutamate transmission. Thus, dopamine appears to modulate glutamate-mediated synaptic transmission in the entorhinal cortex, and it is conceivable that a disturbance in this interaction could be involved in the aetiology of schizophrenia.

Animals↗
PubMed1997

NMDA receptor 2C subunit is selectively decreased by MK-801 in the entorhinal cortex.

Administration of the non-competitive NMDA receptor antagonist MK-801 (5-methyl-10,11-dihydro-5H-dibenzo[1,d]cyclohepten-5,10-imine) produces paradoxical neurotoxicity in limbic cortical regions which includes the entorhinal cortex. The expression of NMDAR-2C but not -2A, -2B or -2D subunits was significantly decreased in rat entorhinal cortex layer III following MK-801 administration. These results suggest an important role for the NMDAR-2C subunit in the response to MK-801-induced neurotoxicity in brain regions highly vulnerable to injury.

Animals↗