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Long-Term Potentiation in the Hippocampal CA1 Region Does Not Require Insertion and Activation of GluR2-Lacking AMPA Receptors

¹Interdepartmental Ph.D. Program for Neuroscience and ²Department of Physiology, David Geffen School of Medicine at University of California, Los Angeles, California; and ³Neuroscience Program, Garvan Institute of Medical Research, Darlinghurst, New South Wales, Australia

Submitted 26 April 2007; accepted in final form 16 July 2007

Activity-dependent insertion of AMPA-type glutamate receptors is thought to underlie long-term potentiation (LTP) at Schaffer collateral fiber synapses on pyramidal cells in the hippocampal CA1 region. Although it is widely accepted that the AMPA receptors at these synapses contain glutamate receptor type 2 (GluR2) subunits, recent findings suggest that LTP in hippocampal slices obtained from 2- to 3-wk-old rodents is dependent on the transient postsynaptic insertion and activation of Ca²⁺-permeable, GluR2-lacking AMPA receptors. Here we examined whether LTP in slices prepared from adult animals exhibits similar properties. In contrast to previously reported findings, pausing synaptic stimulation for as long as 30 min post LTP induction had no effect on LTP maintenance in slices from 2- to 3-mo-old mice. LTP was also not disrupted by postinduction application of a selective blocker of GluR2-lacking AMPA receptors or the broad-spectrum glutamate receptor antagonist kynurenate. Although these results suggest that the role of GluR2-lacking AMPA receptors in LTP might be regulated during postnatal development, LTP in slices obtained from 15- to 21-day-old mice also did not require postinduction synaptic stimulation or activation of GluR2-lacking AMPA receptors. Thus the insertion and activation of GluR2-lacking AMPA receptors do not appear to be fundamental processes involved in LTP at excitatory synapses in the hippocampal CA1 region.

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