The role of GABAergic inhibition in shaping the response size and duration selectivity of bat inferior collicular neurons to sound pulses in rapid sequences

Abstract

Natural sounds, such as vocal communication sounds of many animal species typically occur as sequential sound pulses. Therefore, the response size of auditory neurons to a sound pulse would be inevitably affected when the sound pulse is preceded and succeeded by another sound pulse (i.e., forward and backward masking). The present study presents data to show that increasing strength of GABAergic inhibition relative to excitation contributes to decreasing response size and sharpening of duration selectivity of bat inferior collicular (IC) neurons to sound pulses in rapid sequences. The response size in number of impulses and duration selectivity of IC neurons were studied with a pulse train containing 9 sound pulses. A family of duration tuning curves was plotted for IC neurons using the number of impulses discharged to each presented sound pulse against pulse duration. Our data show that the response size of IC neurons progressively decreased and duration selectivity increased when determined with sequentially presented sound pulses. This variation in the response size and duration selectivity of IC neurons with sequentially presented sound pulses was abolished or reduced during bicuculline and GABA application. Bicuculline application increased the response size and broadened the duration tuning curve of IC neurons while GABA application produced opposite results. Possible mechanisms underlying increasing strength of GABAergic inhibition with sequentially presented sound pulses are presented. Biological significance of these findings in relation to acoustic signal processing is also discussed.

Introduction

In auditory physiology, the processing of auditory signals has traditionally been explained by excitatory and inhibitory interactions of divergent and convergent projections within the auditory system (Suga, 1997, Suga et al., 1998). For example, in the auditory pathway, the central nucleus of the inferior colliculus (IC) receives and integrates excitatory and inhibitory inputs from many lower auditory nuclei as well as from the auditory cortex (Adams, 1979, Casseday and Covey, 1995, Herbert et al., 1991, Huffman and Henson, 1990, Oliver et al., 1994, Pollak and Casseday, 1989, Saldana et al., 1996, Shneiderman and Oliver, 1989, Winer et al., 1998). The inhibitory inputs to the IC are glycinergic, which originates extrinsically, and GABAergic, which originates extrinsically and intrinsically (Fubara et al., 1996, Oliver and Shneiderman, 1991, Roberts and Ribak, 1987). Many studies have shown that the interplay between excitation and GABAergic and/or glycinergic inhibition shapes auditory response properties and multi-parametric selectivity of IC neurons (e.g., duration, frequency, amplitude, direction, etc.) (Casseday et al., 1994, Casseday et al., 2000, Fuzessery and Hall, 1996, Jen and Feng, 1999, Jen and Zhang, 2000, Jen and Zhou, 1999, Jen et al., 2001, Jen et al., 2002, Klug et al., 1995, Koch and Grothe, 1998, LeBeau et al., 1996, LeBeau et al., 2001, Lu and Jen, 2001). Furthermore, two recent studies have shown that inhibitory inputs with stronger intensity and longer duration are more effective in producing inhibition of auditory response of IC neurons than inhibitory inputs with weaker intensity and shorter duration (Lu and Jen, 2002, Lu and Jen, 2003).

In the real world, natural sounds such as vocal communication sounds of many animal species typically occur as sequential sound pulses. Therefore, the response size of auditory neurons to a sound pulse would be affected when the sound pulse is preceded and succeeded by other sound pulses (i.e., forward and backward masking). As evident in a previous study, the response size of IC neurons is often larger when stimulated with a single sound pulse than when stimulated with the same sound pulse presented in pulse trains (Moriyama et al., 1994). Furthermore, the response size of IC neurons progressively decreased with sequentially presented sound pulses (Jen and Zhou, 1999, Jen et al., 2001, Lu et al., 1997, Lu et al., 1998, Moriyama et al., 1994, Pinheiro et al., 1991, Wu and Jen, 1995, Zhou and Jen, 2002). What might be the neural mechanisms underlying these observations?

During synaptic transmission, excitatory and inhibitory signals arrive repetitively at a neuron would produce temporal facilitation of opposite postsynaptic potentials (IPSP vs EPSP). However, at higher repetition rates, temporal depression occurs due to depletion of neurotransmitters resulting in decreasing postsynaptic potentials (Wu and Betz, 1998, Zucker, 1989). A previous study on the rat pyramidal neurons showed that excitatory synaptic currents displayed stronger depression than inhibitory synaptic currents in response to sustained activation at high stimulus repetition rates (Galarreta and Hestrin, 1998). This study indicates that the time course of temporal facilitation and depression may differ between the two opposing postsynaptic potentials.

In the present study, we hypothesize that increasing strength of inhibition over excitation contributes to variation in auditory sensitivity of IC neurons to rapidly presented sound pulses. To test this hypothesis, we studied the variation in the response size and duration selectivity of IC neurons in relation to increasing strength of GABAergic inhibition with sequentially presented sound pulses. Specifically, we obtained the number of impulses and duration tuning curves of IC neurons for each presented sound pulse before and during application of bicuculline (an antagonist for GABA-A receptors, Bormann, 1988, Cooper et al., 1982) and GABA. Variation in the number of impulses and duration selectivity of IC neurons with sequentially presented sound pulses was then quantitatively determined and statistically compared.