title: Sequential changes in AMPA receptor targeting in the developing neocortical excitatory circuit.
abstract: Many principal neurons undergo an early developmental switch from GluR2-lacking to GluR2-containing synaptic glutamate receptors. We tested the generality and timing of the GluR2 switch in excitatory neurons of rat somatosensory cortex. Previous studies show that the switch occurs between postnatal day 14 (P14) and P16 in layer 5 pyramidal neurons. We show, using sensitivity to intracellular spermine, that a similar switch occurs between P12 and P14 in layer 2/3 pyramidal cells and between P7 and P8 in layer 4 stellate cells. The presence of GluR2-lacking receptors in layer 2/3 pyramidal cells before P12 was confirmed by demonstrating sensitivity to blockade by 1-naphthyl-acetyl-spermine and large single-channel conductances. GluR2 and the postsynaptic protein PSD95 show progressive colocalization in tissue from P10, P14, and P24 rats, mirroring electrophysiological developments. To distinguish whether changes in GluR2 expression or targeting underlie the switch, we characterized dendritic AMPA receptor responses using focal photolysis of caged glutamate. Contrary to synaptic responses, dendritic responses at all ages studied (P6-P40) were characteristic of GluR2-containing receptors. In addition, dendritically and synaptically evoked responses showed a corresponding decrease in NMDA/AMPA ratios in pyramidal cells, suggesting parallel mechanisms that regulate neuronal calcium levels. These data suggest that the GluR2 switch results from changes in AMPA receptor targeting during early postnatal development, and that rather than following the laminar sequence of cortical development, it proceeds sequentially from layer 4 to layer 2/3 and finally to layer 5b.
authors.affiliation: Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, California 94305, USA.
authors.forename: Julia
authors.initials: J
authors.lastname: Brill
authors.forename: John R
authors.initials: JR
authors.lastname: Huguenard
mesh_terms: D000375:Aging / Q000378:metabolism; D000818:Animals; D003712:Dendrites / Q000378:metabolism; D000076122:Disks Large Homolog 4 Protein; D004558:Electric Stimulation; D019706:Excitatory Postsynaptic Potentials; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D019579:Neocortex / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism*; D009924:Organ Culture Techniques; D018408:Patch-Clamp Techniques; D017966:Pyramidal Cells / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D013569:Synapses / Q000378:metabolism; D013997:Time Factors
chemical_list: D000076122:Disks Large Homolog 4 Protein; C501449:Dlg4 protein, rat; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate; C104722:glutamate receptor ionotropic, AMPA 2