Analysis of the Role of Inhibition in Shaping Responses to Sinusoidally Amplitude-Modulated Signals in the Inferior Colliculus

Abstract

Burger, R. Michael and George D. Pollak. Analysis of the role of inhibition in shaping responses to sinusoidally amplitude-modulated signals in the inferior colliculus. J. Neurophysiol. 80: 1686–1701, 1998. Neurons in the central nucleus of the inferior colliculus (ICc) typically respond with phase-locked discharges to low rates of sinusoidal amplitude-modulated (SAM) signals and fail to phase-lock to higher SAM rates. Previous studies have shown that comparable phase-locking to SAM occurs in the dorsal nucleus of the lateral lemniscus (DNLL) and medial superior olive (MSO) of the mustache bat. The studies of MSO and DNLL also showed that the restricted phase-locking to low SAM rates is created by the coincidence of phase-locked excitatory and inhibitory inputs that have slightly different latencies. Here we tested the hypothesis that responses to SAM in the mustache bat IC are shaped by the same mechanism that shapes responses to SAM in the two lower nuclei. We recorded responses from ICc neurons evoked by SAM signals before and during the iontophoretic application of several pharmacological agents: bicuculline, a competitive antagonist for γ-aminobutyric acid-A (GABAA) receptors; strychnine, a competitive antagonist for glycine receptors; the GABAB receptor blocker, phaclofen, and the N-methyl-d-aspartate (NMDA) receptor blocker, (−)-2-amino-5-phosphonopentanoic acid (AP5). The hypothesis that inhibition shapes responses to SAM signals in the ICc was not confirmed. In >90% of the ICc neurons tested, the range of SAM rates to which they phase-locked was unchanged after blocking inhibition with bicuculline, strychnine or phaclofen, applied either individually or in combination. We also considered the possibility that faster α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptors follow high temporal rates of incoming excitation but that the slower NMDA receptors could follow only lower rates. Thus at higher SAM rates, NMDA receptors might generate a sustained excitation that “smears” the phase-locked excitation generated by the AMPA receptors. The NMDA hypothesis, like the inhibition hypothesis, was also not confirmed. In none of the cells that we tested did the application of AP5 by itself, or in combination with bicuculline, cause an increase in the range of SAM rates that evoked phase-locking. These results illustrate that the same response property, phase-locking restricted to low SAM rates, is formed in more than one way in the auditory brain stem. In the MSO and DNLL, the mechanism is coincidence of phase-locked excitation and inhibition, whereas in ICc the same response feature is formed by a different but unknown mechanism.