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Z I Bashir

Publications and source records attributed to Z I Bashir.

29 records · Page 2Linked to original sources
PubMed1994

Motor deficit and impairment of synaptic plasticity in mice lacking mGluR1.

Metabotropic glutamate receptor 1 (mGluR1) is a member of a large family of G-protein-coupled glutamate receptors, the physiological functions of which are largely unknown. Mice deficient in mGluR1 have severe motor coordination and spatial learning deficits. They have no gross anatomical or basic electrophysiological abnormalities in either the cerebellum or hippocampus, but they show impaired cerebellar long-term depression and hippocampal mossy fibre long-term potentiation. mGluR1-deficient mice should therefore be valuable models for studying synaptic plasticity.

Animals↗
PubMed1994

A molecular switch activated by metabotropic glutamate receptors regulates induction of long-term potentiation.

Pharmacological studies of long-term potentiation (LTP) in the hippocampus are starting to provide a molecular understanding of synaptic plastic processes which are believed to be important for learning and memory in vertebrates. In the CA1 region of the hippocampus, the synaptic activation of glutamate receptors of the N-methyl-D-aspartate (NMDA) subtype is necessary for the induction of LTP under most experimental conditions. The synaptic activation of metabotropic glutamate receptors (mGluRs) is also needed for the induction of LTP. We now show that the role of mGluRs in the induction of LTP is fundamentally different from that of NMDA receptors. NMDA receptors initiate a molecular event that needs to be triggered each time a tetanus is delivered to induce LTP. In contrast, mGluRs activate a molecular switch which then negates the need for mGluR stimulation during the induction of LTP. This mGluR-activated switch is input-specific and can be turned off by a train of low-frequency stimulation. The molecular switch is a new feature of LTP which has fundamental consequences for our understanding of synaptic plastic mechanisms.

Animals↗
PubMed1994

An investigation of depotentiation of long-term potentiation in the CA1 region of the hippocampus.

We have investigated long-term synaptic depression in the CA1 region of rat hippocampal slices. Prolonged low-frequency stimulation (LFS; 900 stimuli delivered at 2 Hz) of the Schaffer collateral-commissural pathway in naïve slices did not induce long-term depression (LTD) of synaptic transmission. However, if long-term potentiation (LTP) was firstly induced in the pathway then LFS generated an LTD-like effect (i.e. depotentiation of LTP). Depotentiation could be induced 2 h (the longest time studied) after the induction of LTP and was stable for the duration of the experiment (followed for up to 40 min). The induction of depotentiation was not blocked by the N-methyl-D-aspartate receptor antagonist D-2-amino-5-phosphonopentanoate, the L-type voltage-gated Ca2+ channel blocker nimodipine or the nitric oxide synthase inhibitor N omega-nitro-L-arginine. However, the magnitude of depotentiation was reversibly reduced, in a stereoselective manner, by the specific metabotropic glutamate receptor (mGluR) antagonist (+)-alpha-methyl-4-carboxyphenylglycine. These results show that prolonged low frequency stimulation can result in an mGluR-dependent depotentiation of LTP.

2-Amino-5-phosphonovalerate↗
PubMed1993

Induction of LTP in the hippocampus needs synaptic activation of glutamate metabotropic receptors.

Understanding the mechanisms of long-term potentiation (LTP) should provide insights into the molecular basis of learning and memory in vertebrates. Ionotropic glutamate receptors play a central role in LTP; AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate) receptors and NMDA (N-methyl-D-aspartate) receptors mediate synaptic responses that are enhanced in LTP and, in addition, NMDA receptors are necessary for the induction of LTP in most pathways. There is also circumstantial evidence that metabotropic glutamate receptors (mGluRs) may be involved in LTP because the specific mGluR agonist aminocyclopentane dicarboxylate can augment tetanus-induced LTP2 and, under certain circumstances, can itself induce a slow-onset potentiation. But the absence of any effective mGluR antagonist has prevented the determination of whether mGluRs are involved in the induction of tetanus-induced LTP. We report here that (RS)-alpha-methyl-4-carboxyphenylglycine is a specific mGluR antagonist in the hippocampus and have used this compound to examine the nature of the involvement of mGluRs in LTP. We show that synaptic activation of mGluRs is necessary for the induction of both NMDA receptor-dependent and NMDA receptor-independent forms of LTP in the hippocampus.

Action Potentials↗
PubMed1993

Phases in the development of a penicillin epileptiform focus in rat neocortex.

Somatosensory evoked potentials and potentials evoked by direct cortical stimulation were recorded from layer IV of the somatosensory area of the cerebral cortex in urethane anaesthetised rats. Penicillin was expelled electrophoretically from the tip of a drug-filled micropipette at constant rates into layer IV. Small fluxes of penicillin (with electrophoretic currents of -50 to -90 nA) resulted in the appearance, after a delay of 1-2 min, of an enhancement of amplitude in the voltage of both types of evoked potential, unaccompanied by any prolongation of the waveform or spontaneous focal epileptiform discharges. The amplitude of the enhanced evoked potential exhibited a strength-response curve which was a scaled-up version of the curve before penicillin, the scaling factor reflecting the enhancement of amplitude. As the interval between a pair of stimuli was increased, the magnitude of the response to the second stimulus recovered, following a time course similar to that before penicillin. With larger fluxes of penicillin (with electrophoretic currents of -250 to -1000 nA) the amplitude of evoked potentials rose more rapidly and to a higher level; as the concentration of penicillin rose, this enhancement of amplitude led into a second phase, in which there was additionally an increase in the duration of the evoked potentials and the appearance of spontaneous epileptiform discharges. The evoked potentials in this situation showed physiological properties different from those before penicillin application. The strength-response curve exhibited a discontinuity, indicating the evoked potential to be the sum of a physiological response and an epileptiform discharge, the former being graded with stimulus strength and the latter being all or none.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Long-term potentiation of NMDA receptor-mediated synaptic transmission in the hippocampus.

Neurotransmission at most excitatory synapses in the brain operates through two types of glutamate receptor termed alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) and N-methyl-D-aspartate (NMDA) receptors; these mediate the fast and slow components of excitatory postsynaptic potentials respectively. Activation of NMDA receptors can also lead to a long-lasting modification in synaptic efficiency at glutamatergic synapses; this is exemplified in the CA1 region of the hippocampus, where NMDA receptors mediate the induction of long-term potentiation (LTP). It is believed that in this region LTP is maintained by a specific increase in the AMPA receptor-mediated component of synaptic transmission. We now report, however, that a pharmacologically isolated NMDA receptor-mediated synaptic response can undergo robust, synapse-specific LTP. This finding has implications for neuropathologies such as epilepsy and neurodegeneration, in which excessive NMDA receptor activation has been implicated. It adds fundamentally to theories of synaptic plasticity because NMDA receptor activation may, in addition to causing increased synaptic efficiency, directly alter the plasticity of synapses.

Animals↗
PubMed1991

Involvement of excitatory amino acid receptors in long-term potentiation in the Schaffer collateral-commissural pathway of rat hippocampal slices.

The present article reviews studies from our laboratory, which have shown that excitatory amino acids receptors of the N-methyl-D-aspartate type are involved in the induction of long-term potentiation in the Schaffer collateral-commissural pathway of rat hippocampal slices. The nature of the excitatory amino acid receptors that mediate the response that is modified by the induction of long-term potentiation is also considered. The mechanism of induction of long-term potentiation is discussed, as are some possible stages that are required for the maintenance of this process. Some new data are presented concerning the ability of N-methyl-D-aspartate to potentiate synaptic transmission and to depress the amplitude of the presynaptic fibre volley. Concerning the potentiation, it is shown that brief (1-2 min) perfusion of slices with N-methyl-D-aspartate is sufficient to potentiate synaptic transmission for at least 3 h. The N-methyl-D-aspartate induced depression of the presynaptic fibre volley is shown to be transient and independent of synaptic transmission.

Animals↗
PubMed1990

Activation of the glycine site in the NMDA receptor is necessary for the induction of LTP.

The effects of 7-chlorokynurenate (7-C1KY) were examined on N-methyl-D-aspartate (NMDA) receptor-mediated synaptic mechanisms in the CA1 region of rat hippocampal slices. 7-C1KY depressed both the NMDA receptor-mediated component of synaptic transmission recorded in Mg2(+)-free medium and the induction of long-term potentiation (LTP) in Mg2(+)-containing medium. Both of these effects were reversed by D-serine, suggesting that the action of 7-C1KY was at the allosteric glycine site on the NMDA receptor.

Action Potentials↗