title: Developmental changes in structural and functional properties of hippocampal AMPARs parallels the emergence of deliberative spatial navigation in juvenile rats.
abstract: The neural mechanisms that support the late postnatal development of spatial navigation are currently unknown. We investigated this in rats and found that an increase in the duration of AMPAR-mediated synaptic responses in the hippocampus was related to the emergence of spatial navigation. More specifically, spontaneous alternation rate, a behavioral indicator of hippocampal integrity, increased at the end of the third postnatal week in association with increases in AMPAR response duration at SC-CA1 synapses and synaptically driven postsynaptic discharge of CA1 pyramidal neurons. Pharmacological prolongation of glutamatergic synaptic transmission in juveniles increased the spontaneous alternation rate and CA1 postsynaptic discharge and reduced the threshold for the induction of activity-dependent synaptic plasticity at SC-CA1 synapses. A decrease in GluA1 and increases in GluA3 subunit and transmembrane AMPAR regulatory protein (TARP) expression at the end of the third postnatal week provide a molecular explanation for the increase in AMPAR response duration and reduced efficacy of AMPAR modulators with increasing age. A shift in the composition of AMPARs and increased association with AMPAR protein complex accessory proteins at the end of the third postnatal week likely "turns on" the hippocampus by increasing AMPAR response duration and postsynaptic excitability and reducing the threshold for activity-dependent synaptic potentiation.
authors.affiliation: Molecular Neuroscience Department, Krasnow Institute for Advanced Study, George Mason University, Fairfax, Virginia 22030, USA.
authors.forename: Margaret G
authors.initials: MG
authors.lastname: Blair
authors.forename: Nhu N-Q
authors.initials: NN
authors.lastname: Nguyen
authors.forename: Sarah H
authors.initials: SH
authors.lastname: Albani
authors.forename: Matthew M
authors.initials: MM
authors.lastname: L'Etoile
authors.forename: Marina M
authors.initials: MM
authors.lastname: Andrawis
authors.forename: Leanna M
authors.initials: LM
authors.lastname: Owen
authors.forename: Rodrigo F
authors.initials: RF
authors.lastname: Oliveira
authors.forename: Matthew W
authors.initials: MW
authors.lastname: Johnson
authors.forename: Dianna L
authors.initials: DL
authors.lastname: Purvis
authors.forename: Erin M
authors.initials: EM
authors.lastname: Sanders
authors.forename: Emily T
authors.initials: ET
authors.lastname: Stoneham
authors.forename: Huaying
authors.initials: H
authors.lastname: Xu
authors.forename: Theodore C
authors.initials: TC
authors.lastname: Dumas
mesh_terms: D000367:Age Factors; D000818:Animals; D056547:CA1 Region, Hippocampal / Q000254:growth & development* / Q000502:physiology*; D015220:Calcium Channels / Q000502:physiology; D004594:Electrophysiology; D005071:Evoked Potentials / Q000502:physiology; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D005260:Female; D008297:Male; D018782:Maze Learning / Q000502:physiology*; D009473:Neuronal Plasticity / Q000502:physiology; D009924:Organ Culture Techniques; D010078:Oxazines / Q000494:pharmacology; D051381:Rats; D020318:Rats, Long-Evans; D018091:Receptors, AMPA / Q000819:agonists / Q000502:physiology*; D013028:Space Perception / Q000502:physiology*; D013569:Synapses / Q000502:physiology
chemical_list: D015220:Calcium Channels; D010078:Oxazines; D018091:Receptors, AMPA; C491911:Cacng2 protein, rat; C104723:glutamate receptor ionotropic, AMPA 3; C414782:2H,3H,6aH-pyrrolidino(2'',1''-3',2')1,3-oxazino(6',5'-5,4)benzo(e)1, 4-dioxan-10-one