title: Developmental expression of Ca2+-permeable AMPA receptors underlies depolarization-induced long-term depression at mossy fiber CA3 pyramid synapses.
abstract: Many central excitatory synapses undergo developmental alterations in the molecular and biophysical characteristics of postsynaptic ionotropic glutamate receptors via changes in subunit composition. Concerning AMPA receptors (AMPARs), glutamate receptor 2 subunit (GluR2)-containing, Ca2+-impermeable AMPARs (CI-AMPARs) prevail at synapses between mature principal neurons; however, accumulating evidence indicates that GluR2-lacking, Ca2+-permeable AMPARs (CP-AMPARs) contribute at these synapses early in development. Here, we used a combination of imaging and electrophysiological recording techniques to investigate potential roles for CP-AMPARs at developing hippocampal mossy fiber-CA3 pyramidal cell (MF-PYR) synapses. We found that transmission at nascent MF-PYR synapses is mediated by a mixed population of CP- and CI-AMPARs as evidenced by polyamine-dependent inwardly rectifying current-voltage (I-V) relationships, and partial philanthotoxin sensitivity of synaptic events. CP-AMPAR expression at MF-PYR synapses is transient, being limited to the first 3 postnatal weeks. Moreover, the expression of CP-AMPARs is regulated by the PDZ (postsynaptic density-95/Discs large/zona occludens-1) domain-containing protein interacting with C kinase 1 (PICK1), because MF-PYR synapses in young PICK1 knock-out mice are philanthotoxin insensitive with linear I-V relationships. Strikingly, MF-PYR transmission via CP-AMPARs is selectively depressed during depolarization-induced long-term depression (DiLTD), a postsynaptic form of MF-PYR plasticity observed only at young MF-PYR synapses. The selective depression of CP-AMPARs during DiLTD was evident as a loss of postsynaptic CP-AMPAR-mediated Ca2+ transients in PYR spines and reduced rectification of MF-PYR synaptic currents. Preferential targeting of CP-AMPARs during DiLTD is further supported by a lack of DiLTD in young PICK1 knock-out mice. Together, these findings indicate that the transient participation of CP-AMPARs at young MF-PYR synapses dictates the developmental window to observe DiLTD.
authors.affiliation: National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: Michelle T-W
authors.initials: MT
authors.lastname: Ho
authors.forename: Kenneth A
authors.initials: KA
authors.lastname: Pelkey
authors.forename: Lisa
authors.initials: L
authors.lastname: Topolnik
authors.forename: Ronald S
authors.initials: RS
authors.lastname: Petralia
authors.forename: Kogo
authors.initials: K
authors.lastname: Takamiya
authors.forename: Jun
authors.initials: J
authors.lastname: Xia
authors.forename: Richard L
authors.initials: RL
authors.lastname: Huganir
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Lacaille
authors.forename: Chris J
authors.initials: CJ
authors.lastname: McBain
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002118:Calcium / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D036881:Long-Term Synaptic Depression / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D019599:Mossy Fibers, Hippocampal / Q000254:growth & development* / Q000378:metabolism; D009474:Neurons / Q000502:physiology; D017966:Pyramidal Cells / Q000254:growth & development / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D013569:Synapses / Q000502:physiology*; D009435:Synaptic Transmission / Q000502:physiology
chemical_list: D018091:Receptors, AMPA; D002118:Calcium