title: Identity of endogenous NMDAR glycine site agonist in amygdala is determined by synaptic activity level.
abstract: Mechanisms of N-methyl-D-aspartate receptor-dependent synaptic plasticity contribute to the acquisition and retention of conditioned fear memory. However, synaptic rules which may determine the extent of N-methyl-D-aspartate receptor activation in the amygdala, a key structure implicated in fear learning, remain unknown. Here we show that the identity of the N-methyl-D-aspartate receptor glycine site agonist at synapses in the lateral nucleus of the amygdala may depend on the level of synaptic activation. Tonic activation of N-methyl-D-aspartate receptors at synapses in the amygdala under low activity conditions is supported by ambient D-serine, whereas glycine may be released from astrocytes in response to afferent impulses. The release of glycine may decode the increases in afferent activity levels into enhanced N-methyl-D-aspartate receptor-mediated synaptic events, serving an essential function in the induction of N-methyl-D-aspartate receptor-dependent long-term potentiation in fear conditioning pathways.
authors.affiliation: Department of Psychiatry, McLean Hospital, Harvard Medical School, Belmont, Massachusetts 02478, USA.
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.forename: Silvia
authors.initials: S
authors.lastname: Sacchi
authors.forename: Loredano
authors.initials: L
authors.lastname: Pollegioni
authors.forename: Alo C
authors.initials: AC
authors.lastname: Basu
authors.forename: Joseph T
authors.initials: JT
authors.lastname: Coyle
authors.forename: Vadim Y
authors.initials: VY
authors.lastname: Bolshakov
mesh_terms: D000679:Amygdala / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism; D003605:D-Amino-Acid Oxidase / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D005260:Female; D005912:Gliotoxin / Q000633:toxicity; D005998:Glycine / Q000378:metabolism*; D066298:In Vitro Techniques; D017774:Long-Term Potentiation / Q000187:drug effects; D008297:Male; D051379:Mice; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000819:agonists* / Q000378:metabolism*; D012694:Serine / Q000378:metabolism; D013569:Synapses / Q000187:drug effects / Q000378:metabolism*
chemical_list: D016194:Receptors, N-Methyl-D-Aspartate; D012694:Serine; D005912:Gliotoxin; D003605:D-Amino-Acid Oxidase; D005998:Glycine