GABA_ASynapses Shape Neuronal Responses to Sound Intensity in the Inferior Colliculus

Abstract

Neurons in the inferior colliculus (IC) change their firing rates with sound pressure level. Some neurons maintain monotonic increases in firing rate over a wide range of sound intensities, whereas other neurons are monotonic over limited intensity ranges. We examined the conditions necessary for monotonicity in this nucleus in vitro in rat brain slices and in vivo in the unanesthetized rabbit. Our in vitro recordings indicate that concurrent activation of GABA A synapses with excitatory inputs facilitates monotonic increases in firing rate with increases in stimulus strength. In the absence of synaptic inhibition, excitatory input to IC neurons causes large depolarizations that result in firing block and nonmonotonicity. In vivo, although GABA A synapses decrease the firing rate in all IC neurons, they can have opposing effects on rate-level functions. GABAergic inputs activated by all sound intensities maintain monotonicity by keeping the postsynaptic potential below the level at which depolarization block occurs. When these inputs are blocked, firing block can occur and rate-level functions become nonmonotonic. High-threshold GABAergic inputs, in contrast, cause nonmonotonic responses by decreasing the firing rate at high intensities. Our results suggest that a dynamic regulation of the postsynaptic membrane potential by synaptic inhibition is necessary to allow neurons to respond monotonically to a wide range of sound intensities.

Role of GABAergic Inhibition in the Coding of Interaural Time Differences of Low-Frequency Sounds in the Inferior Colliculus

“…We rarely tested the limits of this effect because, in many cases, even after a short exposure, action potentials began to systematically decrease in height and finally abort as if the neuron were going into depolarization block. In the brain slice, all IC neurons display depolarization block to lemniscal shock when GABA A receptors are blocked and a similar pattern is observed in the responses of IC neurons in the unanesthetized rabbit to tone bursts under iontophoresis of GABA A antagonists (Sivaramakrishnan et al 2004). A similar observation was made by McAlpine and Palmer (2002).…”

Reorganization of receptive fields following hearing loss in inferior colliculus neurons

“…Further, it has been shown that iontophoresis of GABA can change a unit's tone RIF from nonmonotonic to monotonic, while blocking GABA with bicuculline could decrease monotonicity in some units (Faingold et al, 1991, Sivaramakrishnan et al, 2004. Their results highlight the complexity of inhibitory effects on responses, even when such effects are limited to local IC synapses.…”

“…However, the spontaneous rates were not affected (Le Beau et al, 1996), and the FRA bandwidth was rarely increased (Palombi and Caspary, 1996a). Thus, local inhibitory influences appear to be primarily on-CF, and truncating the high frequency side of an FRA could alter the on-CF inhibitory/excitatory balance, so that the "inhibitory/excitatory balance" explanation and the "truncated FRA" explanations of plasticity may not be entirely independent hypotheses.Further, it has been shown that iontophoresis of GABA can change a unit's tone RIF from nonmonotonic to monotonic, while blocking GABA with bicuculline could decrease monotonicity in some units (Faingold et al, 1991, Sivaramakrishnan et al, 2004. Their results highlight the complexity of inhibitory effects on responses, even when such effects are limited to local IC synapses.…”

Neuronal Responses to Lemniscal Stimulation in Laminar Brain Slices of the Inferior Colliculus

“…The PSP evoked in bicuculline in the presence of a partial block of NMDA-Rs by 50 mM APV had a lower peak amplitude than in bicuculline alone, thus the first spike latency was longer. A decrease in first spike latency in ICC in the presence of bicuculline has been shown to occur during sound stimulation in vivo (Pollak and Park 1993; Sivaramakrishnan et al 2004).…”

“…The activation of excitatory and inhibitory synapses on ICC neurons during sound stimulation has been demonstrated by a few intracellular and wholecell recordings from ICC neurons in vivo (Torterolo et al 1995;Covey et al 1996;Kuwada et al 1997;Pedemonte et al 1997); however, most studies on excitation and inhibition in ICC have relied on extracellular recording techniques (Faingold et al 1993;Park and Pollak 1993a, b;Le Beau et al 1996; Palombi and Caspary 1996; Casseday et al 2000; Sivaramakrishnan et al 2004). Experiments in brain slices offer a controlled environment for the activation of synaptic inputs to ICC neurons and have allowed the pharmacological isolation and identification of specific synaptic currents (Moore et al 1998;Ma et al 2002a, b;Wu et al 2002Wu et al , 2004.…”