title: Eye opening and PSD95 are required for long-term potentiation in developing superior colliculus.
abstract: The only major glutamate receptor membrane-associated guanylate kinase scaffolds expressed in the young superficial superior colliculus (SC) are synapse-associated protein 102 (SAP102) and postsynaptic density protein 95 (PSD95). In this, as in all visual brain regions examined, synaptic PSD95 increases rapidly following simultaneous eyelid opening (EO). We show that EO and PSD95 are necessary for SC NMDA receptor (NMDAR)-dependent long-term potentiation (LTP) and this LTP is eliminated or reinstated by manipulating EO. PSD95 knockdown (KD) in vivo blocks this LTP, but not long-term depression, and reduces frequencies of miniature AMPA receptor and NMDAR currents with no change in presynaptic release. Furthermore, miniature NMDAR currents after PSD95 KD show an activity-triggered calcineurin sensitivity that is normally only found in the pre-EO period when SAP102 binds mixed GluN2A/GluN2B NMDARs. These data indicate that young SC LTP arises from PSD95 unsilencing of silent synapses, that unsilencing is labile in young brain, and that even though SAP102 and PSD95 can bind the same NMDARs, only PSD95 enables SC synaptic maturation.
authors.affiliation: McGovern Institute for Brain Research and Department of Brain and Cognitive Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. jpzhao@mit.edu
authors.forename: Jian-Ping
authors.initials: JP
authors.lastname: Zhao
authors.forename: Yasunobu
authors.initials: Y
authors.lastname: Murata
authors.forename: Martha
authors.initials: M
authors.lastname: Constantine-Paton
mesh_terms: D000367:Age Factors; D000818:Animals; D015153:Blotting, Western; D019703:Calcineurin / Q000378:metabolism; D017931:DNA Primers / Q000235:genetics; D000076122:Disks Large Homolog 4 Protein; D019706:Excitatory Postsynaptic Potentials; D005143:Eyelids / Q000502:physiology*; D005822:Genetic Vectors / Q000235:genetics; D057809:HEK293 Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D016086:Lentivirus; D017774:Long-Term Potentiation / Q000502:physiology*; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D009479:Neuropeptides / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D013477:Superior Colliculi / Q000502:physiology*; D013569:Synapses / Q000378:metabolism
chemical_list: D017931:DNA Primers; D000076122:Disks Large Homolog 4 Protein; C101195:Dlg3 protein, rat; C501449:Dlg4 protein, rat; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D009479:Neuropeptides; D016194:Receptors, N-Methyl-D-Aspartate; D019703:Calcineurin