title: Experience-dependent regulation of presynaptic NMDARs enhances neurotransmitter release at neocortical synapses.
abstract: Sensory experience can selectively alter excitatory synaptic strength at neocortical synapses. The rapid increase in synaptic strength induced by selective whisker stimulation (single-row experience/SRE, where all but one row of whiskers has been removed from the mouse face) is due, at least in part, to the trafficking of AMPA receptors (AMPARs) to the post-synaptic membrane, and is developmentally regulated. How enhanced sensory experience can alter presynaptic release properties in the developing neocortex has not been investigated. Using paired-pulse stimulation at layer 4-2/3 synapses in acute brain slices, we found that presynaptic release probability progressively increases in the spared-whisker barrel column over the first 24 h of SRE. Enhanced release probability can be at least partly attributed to presynaptic NMDA receptors (NMDARs). We find that the influence of presynaptic NMDARs in enhancing EPSC amplitude markedly increases during SRE. This occurs at the same time when recently potentiated synapses become highly susceptible to a NMDAR-dependent form of synaptic depression, during the labile phase of plasticity. Thus, these data show that augmented sensory stimulation can enhance release probability at layer 4-2/3 synapses and enhance the function of presynaptic NMDARs. Because presynaptic NMDARs have been linked to synaptic depression at layer 4-2/3 synapses, we propose that SRE-dependent up-regulation of presynaptic NMDARs is responsible for enhanced synaptic depression during the labile stage of plasticity.
authors.affiliation: Department of Biological Sciences and Center for the Neural Basis of Cognition, Carnegie Mellon University, Pittsburgh, Pennsylvania 15213, USA.
authors.forename: Joanna
authors.initials: J
authors.lastname: Urban-Ciecko
authors.affiliation: Department of Biological Sciences and Center for the Neural Basis of Cognition, Carnegie Mellon University, Pittsburgh, Pennsylvania 15213, USA.
authors.forename: Jing A
authors.initials: JA
authors.lastname: Wen
authors.affiliation: Center for Neuroscience at the University of Pittsburgh, Department of Psychiatry, Pittsburgh, Pennsylvania 15219, USA.
authors.forename: Puja K
authors.initials: PK
authors.lastname: Parekh
authors.affiliation: Department of Biological Sciences and Center for the Neural Basis of Cognition, Carnegie Mellon University, Pittsburgh, Pennsylvania 15213, USA barth@cmu.edu.
authors.forename: Alison L
authors.initials: AL
authors.lastname: Barth
mesh_terms: D000818:Animals; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D008810:Mice, Inbred C57BL; D019579:Neocortex / Q000187:drug effects / Q000254:growth & development / Q000502:physiology*; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology*; D018408:Patch-Clamp Techniques; D010812:Physical Stimulation; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000378:metabolism*; D017661:Receptors, Presynaptic / Q000037:antagonists & inhibitors / Q000378:metabolism*; D012683:Sensory Deprivation / Q000502:physiology; D013569:Synapses / Q000187:drug effects / Q000502:physiology; D046509:Tissue Culture Techniques; D055698:Touch Perception / Q000502:physiology*; D015854:Up-Regulation; D014738:Vibrissae / Q000502:physiology
chemical_list: D016194:Receptors, N-Methyl-D-Aspartate; D017661:Receptors, Presynaptic