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“Neuronal activity controls the strength of excitatory synapses by mechanisms that include changes in the postsynaptic responses mediated by AMPA receptors. These receptors account for most fast responses at excitatory synapses of the CNS, and their activity is regulated by various signaling pathways which control the electrophysiological
properties of AMPA receptors and their interaction with numerous intracellular WZB117 supplier regulatory proteins. AMPA receptor phosphorylation/dephosphorylation and interaction with other proteins control their recycling and localization to defined postsynaptic sites, thereby regulating the strength of the synapse. This review focuses on recent advances in the understanding of the molecular mechanisms of regulation of
AMPA receptors, and the implications in synaptic plasticity. (C) 2009 IBRO. Published by Elsevier Ltd. All rights reserved.”
“Endocannabinoids are critically involved in the extinction of fear memory. check details Here we examined the effects of repeated cannabinoid administration on the extinction of fear memory in rats and on inhibitory synaptic transmission in medial prefrontal cortex (mPFC) slices. Rats were treated with the CB1 receptor agonist WIN55212-2 (WIN 10 mg/kg, i.p.) once per day for 7 d. On day 8, the rats were submitted to a standard fear conditioning procedure, and retention of memory was measured with potentiated startle paradigm. We found that (1) WIN-pretreated rats exhibited much less extinction to cue alone presentations; (2) the reduction of fear-potentiated startle normally seen when the CB1 receptor agonists were infused into the mPFC was absent in the WIN-pretreated rats; (3) WIN-induced inhibition of GABAergic however transmission was significantly less in slices from the WIN-pretreated rats than that from the vehicle-pretreated control; (4) WIN failed to induce extracellular signal-regulated kinases (ERKs) phosphorylation in the WIN-pretreated rats; and (5) the level of
CB1 receptor in the WIN-pretreated rats was lower than that of vehicle-pretreated rats. These results suggest that endocannabinoids within the mPFC play an important role in the extinction of conditioned fear. However, long-term marijuana use may limit its clinical efficacy for the treatment of anxiety disorders.”
“It has long been known that the mammalian forebrain contains a subset of glutamatergic neurons that sequester zinc in their synaptic vesicles. This zinc may be released into the synaptic cleft upon neuronal activity. Extra-cellular zinc has the potential to interact with and modulate many different synaptic targets, including glutamate receptors and transporters.