title: Synapse-specific control of experience-dependent plasticity by presynaptic NMDA receptors.
abstract: Sensory experience orchestrates the development of cortical circuitry by adaptively modifying neurotransmission and synaptic connectivity. However, the mechanisms underlying these experience-dependent modifications remain elusive. Here we demonstrate that visual experience suppresses a presynaptic NMDA receptor (preNMDAR)-mediated form of timing-dependent long-term depression (tLTD) at visual cortex layer (L) 4-2/3 synapses. This tLTD can be maintained during development, or reinstated in adulthood, by sensory deprivation. The changes in tLTD are mirrored by changes in glutamate release; visual deprivation enhances both tLTD and glutamate release. These effects require the GluN3A NMDAR subunit, the levels of which are increased by visual deprivation. Further, by coupling the pathway-specific optogenetic induction of tLTD with cell-type-specific NMDAR deletion, we find that visual experience modifies preNMDAR-mediated plasticity specifically at L4-L2/3 synapses.
authors.affiliation: Department of Cell Biology and Physiology, University of North Carolina, Chapel Hill, NC 27599, USA.
authors.forename: Rylan S
authors.initials: RS
authors.lastname: Larsen
authors.affiliation: UNC Neuroscience Center, University of North Carolina, Chapel Hill, NC 27599, USA.
authors.forename: Ikuko T
authors.initials: IT
authors.lastname: Smith
authors.affiliation: Department of Cell Biology and Physiology, University of North Carolina, Chapel Hill, NC 27599, USA.
authors.forename: Jayalakshmi
authors.initials: J
authors.lastname: Miriyala
authors.affiliation: Department of Cell Biology and Physiology, University of North Carolina, Chapel Hill, NC 27599, USA.
authors.forename: Ji Eun
authors.initials: JE
authors.lastname: Han
authors.affiliation: Neurobiology Curriculum, University of North Carolina, Chapel Hill, NC 27599, USA.
authors.forename: Rebekah J
authors.initials: RJ
authors.lastname: Corlew
authors.affiliation: Department of Cell Biology and Physiology, University of North Carolina, Chapel Hill, NC 27599, USA; Neurobiology Curriculum, University of North Carolina, Chapel Hill, NC 27599, USA; UNC Neuroscience Center, University of North Carolina, Chapel Hill, NC 27599, USA; Carolina Institute for Developmental Disabilities, University of North Carolina, Chapel Hill, NC 27599, USA.
authors.forename: Spencer L
authors.initials: SL
authors.lastname: Smith
authors.affiliation: Department of Cell Biology and Physiology, University of North Carolina, Chapel Hill, NC 27599, USA; Neurobiology Curriculum, University of North Carolina, Chapel Hill, NC 27599, USA; UNC Neuroscience Center, University of North Carolina, Chapel Hill, NC 27599, USA; Carolina Institute for Developmental Disabilities, University of North Carolina, Chapel Hill, NC 27599, USA. Electronic address: bphilpot@med.unc.edu.
authors.forename: Benjamin D
authors.initials: BD
authors.lastname: Philpot
mesh_terms: D000818:Animals; D018698:Glutamic Acid / Q000378:metabolism; D036881:Long-Term Synaptic Depression / Q000502:physiology; D051379:Mice; D009473:Neuronal Plasticity / Q000502:physiology*; D062308:Optogenetics; D010775:Photic Stimulation; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics / Q000502:physiology*; D017661:Receptors, Presynaptic / Q000502:physiology*; D012683:Sensory Deprivation / Q000502:physiology; D013569:Synapses / Q000502:physiology*; D014793:Visual Cortex / Q000378:metabolism / Q000502:physiology; D014796:Visual Perception / Q000502:physiology
chemical_list: C584082:GluN3A protein, mouse; D016194:Receptors, N-Methyl-D-Aspartate; D017661:Receptors, Presynaptic; D018698:Glutamic Acid