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Zafar I Bashir

Publications and source records attributed to Zafar I Bashir.

13 recordsLinked to original sources
PubMed2006

Differential roles of NR2A and NR2B-containing NMDA receptors in LTP and LTD in the CA1 region of two-week old rat hippocampus.

The role of NMDA receptors in the induction of long-term potentiation (LTP) and long-term depression (LTD) is well established but which particular NR2 subunits are involved in these plasticity processes is still a matter of controversy. We have studied the effects of subtype selective NMDA receptor antagonists on LTP induced by high frequency stimulation (100 Hz for 1s) and LTD induced by low frequency stimulation (1 Hz for 15 min) in the CA1 region of hippocampal slices from 14 day old Wistar rats. Against recombinant receptors in HEK293 cells NVP-AAM077 (NVP) was approximately 14-fold selective for NR2A vs NR2B receptors, whilst Ro 25-6981 (Ro) was highly selective for NR2B receptors. On NMDA receptor-mediated EPSCs from Schaffer collaterals in CA1 neurones, NVP and Ro both reduced the amplitude but differentially affected the time constant of decay. The data are compatible with the selective effect of NVP (0.1 microM) and Ro (4 microM) on native NR2A and NBR2B receptors, respectively. NVP reduced both LTP and LTD whereas Ro reduced only LTP. Thus, LTP was reduced by 63% at 0.1 microM NVP and almost completely at 0.4 microM whereas 5 microM Ro reduced LTP by 45%. These data are consistent with a role for both NR2A and NR2B in the induction of LTP, under our experimental conditions. In comparison, LTD was unaffected by Ro (5 microM) even in the presence of a glutamate uptake inhibitor threo-beta-benzylaspartic acid (TBOA) to increase the concentration of glutamate at NR2B containing receptors. NVP (0.2-0.4 microM), however, produced a concentration dependent inhibition of LTD which was complete at 0.4 microM. The lack of effect of 0.1 microM NVP on LTD contrasts with its marked effect on LTP and raises the possibility that different NVP-sensitive NR2 subunit-containing NMDA receptors are required for LTP and LTD in this preparation.

Animals↗
PubMed2006

The different effects on recognition memory of perirhinal kainate and NMDA glutamate receptor antagonism: implications for underlying plasticity mechanisms.

To investigate the involvement of different types of glutamate receptors in recognition memory, selective antagonists of NMDA and kainate receptors were locally infused into the perirhinal cortex of the rat temporal lobe. Such infusion of a selective kainate receptor antagonist produced an unusual pattern of recognition memory impairment: amnesia after a short (20 min) but not a long (24 h) delay. In contrast, antagonism of perirhinal NMDA glutamate receptors by locally infused AP-5 (2-amino-5-phosphonopentanoic acid) impaired recognition memory after the long but not the short delay. For both drugs, impairment was found when the drug was present during acquisition but not when it was present during retrieval. Experiments in vitro indicate that selective antagonism of NMDA receptors containing NR2A subunits blocks perirhinal long-term potentiation (LTP), whereas antagonism of NMDA receptors containing NR2B subunits blocks long-term depression (LTD). However, recognition memory after a 24 h delay was impaired only when both an NR2A and an NR2B antagonist were infused together, not when either was infused separately. These results establish that kainate receptors have a role in recognition memory that is distinct from that of NMDA receptors, that there must be at least two independent underlying memory mechanisms in the infused region, that this region and no other is necessary for both short-term and long-term familiarity discrimination, and that perirhinal-dependent long-term recognition memory does not rely solely on processes used in NMDA-dependent LTP or LTD (although it might be independently supported by components of each type of process with one substituting for the other).

Animals↗
PubMed2006

Tyrosine phosphatases regulate AMPA receptor trafficking during metabotropic glutamate receptor-mediated long-term depression.

Two forms of long-term depression (LTD), triggered by activation of NMDA receptors (NMDARs) and metabotropic glutamate receptors (mGluRs), respectively, can be induced at CA1 synapses in the hippocampus. Compared with NMDAR-LTD, relatively little is known about mGluR-LTD. Here, we show that protein tyrosine phosphatase (PTP) inhibitors, orthovanadate and phenylarsine oxide, selectively block mGluR-LTD induced by application of the group I mGluR agonist (RS)-3,5-dihydroxyphenylglycine (DHPG-LTD), because NMDAR-LTD is unaffected by these inhibitors. Furthermore, DHPG-LTD measured using whole-cell recording is similarly blocked by either bath-applied or patch-loaded PTP inhibitors. These inhibitors also block the changes in paired-pulse facilitation and coefficient of variation that are associated with the expression of DHPG-LTD. DHPG treatment of hippocampal slices was associated with a decrease in the level of tyrosine phosphorylation of GluR2 AMPA receptor (AMPAR) subunits, an effect blocked by orthovanadate. Finally, in dissociated hippocampal neurons, orthovanadate blocked the ability of DHPG to reduce the number of AMPA receptor clusters on the surface of dendrites. Again, the effects of PTP blockade were selective, because NMDA-induced decreases in surface AMPAR clusters was unaffected by orthovanadate. Together, these data suggest that activation of postsynaptic PTP results in tyrosine dephosphorylation of AMPARs and their removal from the synapse.

Action Potentials↗
PubMed2006

Experience-dependent modification of mechanisms of long-term depression.

Mechanisms of long-term potentiation and depression (LTP and LTD) change considerably during development, but the importance of these changes and the factors that control them is not clear. We found that visual experience triggered a switch in mechanisms of LTD in rat perirhinal cortex, an area critical for visual recognition memory. Thus, changes in synaptic plasticity mechanisms were correlated with the changing physiological demands on the CNS.

Animals↗
PubMed2005

cAMP responsive element-binding protein phosphorylation is necessary for perirhinal long-term potentiation and recognition memory.

We established the importance of phosphorylation of cAMP responsive element-binding protein (CREB) to both the familiarity discrimination component of long-term recognition memory and plasticity within the perirhinal cortex of the temporal lobe. Adenoviral transduction of perirhinal cortex (and adjacent visual association cortex) with a dominant-negative inhibitor of CREB impaired the preferential exploration of novel over familiar objects at a long (24 h) but not a short (15 min) delay, disrupted the normal reduced activation of perirhinal neurons to familiar compared with novel pictures, and impaired long-term potentiation of synaptic transmission in perirhinal slices. The consistency of these effects across the behavioral, systems, and cellular levels of analysis provides strong evidence for involvement of CREB phosphorylation in synaptic plastic processes within perirhinal cortex necessary for long-term recognition memory.

Adenoviridae↗
PubMed2004

Differential roles of NR2A and NR2B-containing NMDA receptors in cortical long-term potentiation and long-term depression.

It is widely believed that long-term depression (LTD) and its counterpart, long-term potentiation (LTP), involve mechanisms that are crucial for learning and memory. However, LTD is difficult to induce in adult cortex for reasons that are not known. Here we show that LTD can be readily induced in adult cortex by the activation of NMDA receptors (NMDARs), after inhibition of glutamate uptake. Interestingly there is no need to activate synaptic NMDARs to induce this LTD, suggesting that LTD is triggered primarily by extrasynaptic NMDA receptors. We also find that de novo LTD requires the activation of NR2B-containing NMDAR, whereas LTP requires activation of NR2A-containing NMDARs. Surprisingly another form of LTD, depotentiation, requires activation of NR2A-containing NMDARs. Therefore, NMDARs with different synaptic locations and subunit compositions are involved in various forms of synaptic plasticity in adult cortex.

2-Amino-5-phosphonovalerate↗
PubMed2004

Metabotropic glutamate receptor signalling in perirhinal cortical neurons.

Long-term depression (LTD) induction relies upon receptor cross-talk between group I and group II metabotropic glutamate receptors (mGluRs) in perirhinal cortex. The molecular mechanism of this mGluR interplay is not clear. Here, we show that the mGluR subtypes postulated to be involved in this mechanism are developmentally regulated and mGluR2 has a preferential role over mGluR3 in the synergistic interaction with mGluR5. We have identified a >70% reduction in basal cAMP levels following mGluR2 stimulation, which could lead to increased mGluR5 function via reduced PKA mediated phosphorylation and decreased desensitisation of mGluR5. To further investigate the roles of mGluRs in downstream intracellular signalling, we have examined the effects of mGluRs on the phosphorylation state of cAMP response element-binding protein (CREB). Both group I and group II agonists increased the phosphorylation of CREB, which indicates a cAMP- and PKA-independent signalling mechanism. These results suggest a convergence of signalling mechanisms from surface mGluRs to CREB-mediated transcription.

Animals↗
PubMed2003

Cholinergic neurotransmission is essential for perirhinal cortical plasticity and recognition memory.

We establish the importance of cholinergic neurotransmission to both recognition memory and plasticity within the perirhinal cortex of the temporal lobe. The muscarinic receptor antagonist scopolamine impaired the preferential exploration of novel over familiar objects, disrupted the normal reduced activation of perirhinal neurones to familiar compared to novel pictures, and blocked production of long-term depression (LTD) but not long-term potentiation (LTP) of synaptic transmission in perirhinal slices. The consistency of these effects across the behavioral, systems, and cellular levels of analysis provides strong evidence for the involvement of cholinergic mechanisms in synaptic plastic processes within perirhinal cortex that are necessary for recognition memory.

Animals↗
PubMed2003

Regulation of kainate receptors by protein kinase C and metabotropic glutamate receptors.

Kainate receptors have recently been shown to be involved in synaptic transmission, to regulate transmitter release and to mediate synaptic plasticity in different regions of the CNS. However, very little is known about endogenous mechanisms that can control native kainate receptor signalling. In this study we have found that GluR5-containing kainate receptor-mediated actions can be modulated by activation of protein kinase C (PKC) but not protein kinase A (PKA). However, both PKA and PKC directly phosphorylate the GluR5 subunit of kainate receptors. Metabotropic glutamate (mGlu) receptors are well known to be involved in synaptic transmission, regulation of transmitter release and synaptic plasticity in a variety of brain regions. We now demonstrate that kainate receptor signalling is enhanced by activation of group I mGlu receptors, in a PKC-dependent manner. These data demonstrate for the first time that kainate receptor function can be modulated by activation of metabotropic glutamate receptors and have implications for understanding mechanisms of synaptic transmission, plasticity and disorders such as epilepsy.

Animals↗
PubMed2002

Tyrosine dephosphorylation underlies DHPG-induced LTD.

A form of long-term depression (LTD) of synaptic transmission can be induced by bath application of the group I metabotropic glutamate (mGlu) receptor agonist (RS)-3,5-dihydroxyphenylglycine (DHPG). The mechanisms responsible for the induction and expression of DHPG-induced LTD in the CA1 region of the hippocampus are currently the subject of intense investigation. Here we show that two protein tyrosine kinase (PTK) inhibitors (10 microM lavendustin A or 30 microM genistein) have little effect on DHPG-induced LTD. In contrast two protein tyrosine phosphatase (PTP) inhibitors (1 mM orthovanadate or 15 microM phenyl-arsine oxide) significantly inhibited DHPG-induced LTD. These data suggest that DHPG-induced LTD involves activation of a protein tyrosine phosphatase.

Animals↗
PubMed2002

Cooperation between mglu receptors: a depressing mechanism?

Recent findings from the perirhinal cortex have shed new light on the ways in which metabotropic glutamate receptors could be involved in synaptic plasticity, and in particular in long-term depression (LTD) of synaptic transmission. Importantly, these findings have also led to a greater understanding of mechanisms that could regulate mglu-receptor signalling and the ways in which mglu receptors interact with one another.

Animals↗
PubMed2002

Differences in GABAergic transmission between two inputs into the perirhinal cortex.

We have investigated properties of GABAergic synaptic transmission in perirhinal cortex evoked by stimulation of temporal and entorhinal cortex sides. GABAA IPSCs were isolated by blockade of glutamatergic transmission in slices of adult perirhinal cortex; IPSC decay was best fitted with two exponentials. Interestingly, temporal IPSCs had a larger slow component of decay (P < 0.05) compared to entorhinal IPSCs. Depression of IPSCs by the GABAB receptor agonist baclofen was greater (P < 0.05) in the temporal input (79 +/- 4% depression) than the entorhinal input (65 +/- 3% depression). Furthermore, baclofen abolished the slow component of IPSC decay in both inputs. Activity-dependent depression of IPSCs at 5 Hz was greater (P < 0.05) in the temporal input [paired pulse ratio (PPR) 0.5 +/- 0.04] compared to that in the entorhinal input (PPR 0.67 +/- 0.02, n = 10). The differences in paired pulse depression between the inputs were removed by the GABAB receptor antagonist CGP55845A. This study demonstrates several differences in GABA transmission between temporal and entorhinal inputs including the differential activation of presynaptic GABAB receptors and differential regulation of inhibitory synaptic transmission. These properties may be important in the control of neuronal activity within perirhinal cortex.

Afferent Pathways↗