Voltage-Controlled Plasticity at GluR2-Deficient Synapses Onto Hippocampal Interneurons

Abstract

Laezza, Fernanda and Raymond Dingledine. Voltage-controlled plasticity at GluR2-deficient synapses onto hippocampal interneurons. J Neurophysiol 92: 3575-3581, 2004; doi:10.1152/jn.00425.2004. High-frequency stimulation of pyramidal cell inputs to developing (P9-12) hippocampal stratum radiatum interneurons expressing GluR2-lacking, Ca 2ϩ -permeable AMPA receptors produces longterm depression of synaptic transmission, if N-methyl-D-aspartate (NMDA) receptors are blocked. Here we show that these same synapses display a remarkably versatile signal integration if postsynaptic NMDA receptors are activated. At synapses expressing GluR2-deficient AMPA receptors, tetanic stimulation that activates NMDA receptors triggered long-term potentiation or depression (LTP or LTD) depending on membrane potential. LTP was elicited at most synapses when the interneuron was held at -30 mV during the stimulus train but was typically prevented by postsynaptic hyperpolarization to -70 mV, by strong depolarization to 0 mV, by D-2-amino-5-phosphonovaleric acid, or by postsynaptic injection of the Ca 2ϩ chelator bis-(o-aminophenoxy)-N,N,NЈ,NЈ-tetraacetic acid. At synapses with predominantly GluR2-containing AMPA receptors, repetitive stimulation did not change synaptic strength regardless of whether NMDA receptors were activated. The interactions among GluR2 expression, NMDA receptor expression, and membrane potential thus confer on hippocampal interneurons a distinctive means for differential decoding of high-frequency inputs, resulting in enhanced or depressed transmission depending on the functional state of the interneuron. I N T R O D U C T I O NThe expression of distinct synaptic receptors and voltagegated ion channels on a heterogeneous population of interneurons underlies their different integrative roles in the hippocampal circuit (Jonas et al. 2004). Long-term potentiation (LTP) and long-term depression (LTD) of excitatory synaptic strength are activity-dependent forms of synaptic plasticity triggered by Ca 2ϩ entry through postsynaptic N-methyl-D-aspartate (NMDA) receptors (Bliss and Collingridge 1993). High-frequency afferent stimulation can depress excitatory transmission to hippocampal GABAergic interneurons (Laezza et al. 1999; McBain 2002, 2004;Maccaferri et al. 1998;McMahon and Kauer 1997). An NMDA receptor-independent LTD mechanism involves Ca 2ϩ entry through postsynaptic Ca 2ϩ -permeable AMPA receptors (Laezza et al. 1999; McBain 2002, 2004) and, in stratum radiatum interneurons, activation of presynaptic mGluR7 receptors (Laezza et al. 1999). High-frequency stimulation can also potentiate synaptic inputs to interneurons via an mGluR1-dependent mechanism (Perez et al. 2001) High-frequency stimulation of pyramidal cell afferents to s. radiatum interneurons induces LTD at GluR2-deficient, but not GluR2-replete, synapses (Laezza et al. 1999). LTD occurs in the presence of NMDA receptor antagonists and is triggered by Ca 2ϩ entry through AMPA receptors. Type II EPSCs are therefore both heterogeneous in terms of NMDA re...

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