NMDA and non-NMDA glutamate receptors in auditory transmission in the barn owl inferior colliculus

Abstract

The pharmacology of auditory responses in the inferior colliculus (IC) of the barn owl was investigated by iontophoresis of excitatory amino acid receptor antagonists into two different functional subdivisions of the IC, the external nucleus (ICx) and the lateral shell of the central nucleus (lateral shell), both of which carry out important computations in the processing of auditory spatial information. Combined application of the NMDA receptor antagonist 2-amino-5-phosphonovaleric acid (AP5) and the non-NMDA receptor antagonist 6-cyano-5-nitroquinoxaline-2,3- dione (CNQX) significantly reduced auditory-evoked spikes at all sites in these two subdivisions, and completely eliminated responses at many locations. This suggests that excitatory amino acid receptors mediate the bulk, if not all, of auditory responses in the ICx and lateral shell. NMDA and non-NMDA receptors contributed differently to auditory responses in the two subdivisions. In the ICx, AP5 significantly reduced the number of auditory-evoked spikes at every site tested. On average, AP5 eliminated 55% of auditory-evoked spikes at multiunit sites and 64% at single-unit sites in this structure. In contrast, in the lateral shell, AP5 significantly reduced responses at less than half the sites tested, and, on average, AP5 eliminated only 19% of spikes at multiunit sites and 25% at single-unit sites. When the magnitude of response blockade produced by AP5 at individual multiunit sites was normalized to adjust for site-to-site differences in the efficacy of iontophoresed AP5 and CNQX, AP5 blockade was still significantly greater in the ICx than the lateral shell. CNQX application strongly reduced responses in both subdivisions. These data suggest that NMDA receptor currents make a major contribution to auditory responses in the ICx, while they make only a small contribution to auditory responses in the lateral shell. Non-NMDA receptor currents, on the other hand, contribute to auditory responses in both subdivisions, and mediate the bulk of auditory transmission in the lateral shell. The time course of the NMDA receptor contribution to ICx auditory responses and the dependence of this contribution on stimulus level were both examined in detail. AP5 preferentially blocked spikes late in ICx auditory responses, while CNQX blocked spikes equally throughout the responses. This pattern is consistent with a simple model in which slow NMDA receptor currents and faster non-NMDA receptor currents are both activated by auditory inputs to ICx neurons.

Contribution of NMDA and AMPA Receptors to Temporal Patterning of Auditory Responses in the Inferior Colliculus

“…First, NMDARs mediate excitatory responses of some IC neurons in the absence of AMPAR-mediated depolarization. This agrees closely with conclusions of previous in vivo iontophoretic studies in IC (Feldman and Knudsen, 1994;Zhang and Kelly, 2001). Furthermore, it supports in vitro IC studies showing that NMDARs conduct current at resting membrane potentials when AMPARs are blocked Sivaramakrishnan and Oliver, 2005).…”

“…In the inferior colliculus (IC), studied here, in vitro and in vivo studies generally reinforce the view that AMPARs and NMDARs mediate early and late elements, respectively, of temporal response patterns (Faingold et al, 1989;Feldman and Knudsen, 1994;Zhang and Kelly, 2001;Ma et al, 2002;Wu et al, 2004). However, in vivo blockade of AMPARs in IC does not always eliminate early spikes as expected (Feldman and Knudsen, 1994;Zhang and Kelly, 2001), and in vitro studies of other systems reveal fast postsynaptic responses mediated by NMDARs (D'Angelo et al, 1990;Wolszon et al, 1997).…”

“…The later excitatory response mediated by NMDARs contributes to synaptic plasticity by allowing Ca 2ϩ entry that activates signal transduction cascades. In some neurons (e.g., in sensory systems), NMDARs may contribute essentially to the pattern of action potentials that encodes information (Sillito et al, 1990;Feldman and Knudsen, 1994). Here, NMDARs play roles related to temporal integration and timing of neural discharges: AMPARs mediate precisely timed initial spikes, whereas NMDARs mediate later spikes in response to sensory input (Binns, 1999;Kelly and Zhang, 2002;Blitz and Regehr, 2003).…”

Glycinergic “Inhibition” Mediates Selective Excitatory Responses to Combinations of Sounds

“…NMDARs play a significant role in the excitatory response of IC neurons to simple stimuli (Feldman and Knudsen, 1994;Zhang and Kelly, 2001;Sanchez et al, 2007), but may also contribute to temporal integration and response enhancement to more complex signals. We tested the hypothesis that NMDARs contribute to the facilitatory interaction of combination-sensitive neurons by enhancing the excitatory response to multiple inputs.…”

Perceptron learning rule derived from spike-frequency adaptation and spike-time-dependent plasticity

“…Each time an input spike arrives, s(t) is incremented by 1. Between spikes, s(t) decays exponentially to zero according to τ s ds/dt = −s, with a time constant of τ s = 10 ms (39).…”