GABA_A receptors contribute more to rate than temporal coding in the IC of awake mice

Abstract

Speech is our most important form of communication, yet we have a poor understanding of how communication sounds are processed by the brain. Mice make great model organisms to study neural processing of communication sounds because of their rich repertoire of social vocalizations and because they have brain structures analogous to humans, such as the auditory midbrain nucleus inferior colliculus (IC). Although the combined roles of GABAergic and glycinergic inhibition on vocalization selectivity in the IC have been studied to a limited degree, the discrete contributions of GABAergic inhibition have only rarely been examined. In this study, we examined how GABAergic inhibition contributes to shaping responses to pure tones as well as selectivity to complex sounds in the IC of awake mice. In our set of long-latency neurons, we found that GABAergic inhibition extends the evoked firing rate range of IC neurons by lowering the baseline firing rate but maintaining the highest probability of firing rate. GABAergic inhibition also prevented IC neurons from bursting in a spontaneous state. Finally, we found that although GABAergic inhibition shaped the spectrotemporal response to vocalizations in a nonlinear fashion, it did not affect the neural code needed to discriminate vocalizations, based either on spiking patterns or on firing rate. Overall, our results emphasize that even if GABAergic inhibition generally decreases the firing rate, it does so while maintaining or extending the abilities of neurons in the IC to code the wide variety of sounds that mammals are exposed to in their daily lives. NEW & NOTEWORTHY GABAergic inhibition adds nonlinearity to neuronal response curves. This increases the neuronal range of evoked firing rate by reducing baseline firing. GABAergic inhibition prevents bursting responses from neurons in a spontaneous state, reducing noise in the temporal coding of the neuron. This could result in improved signal transmission to the cortex.

Noise-Induced Hearing Loss Alters Potassium-Chloride CoTransporter KCC2 and GABA Inhibition in the auditory centers

“…GBZ application in control animals is associated to a strong and expected increase in neural activity, broadly consistent with earlier studies and the well-known excitatory effect of GABA antagonist in IC 31 , 45 , 46 . The effect of GBZ in control animals depends on the characteristics of the rate-level function.…”

Absence of the Fragile X messenger ribonucleoprotein alters response patterns to sounds in the auditory midbrain

“…In previous studies classification of firing types in IC neurons was mostly based on the firing pattern to a single frequency and intensity, mostly at the CF (Nasimi and Rees, 2010;Gourévitch et al, 2020) or, as in other studies, by the shape of the excitatory and/or inhibitory frequency response areas (Palmer et al, 2013). With our approach, we included information on active inputs across the entire FRA into the classification scheme, by using the summed spiking activity to all presented frequencies and intensities similarly to a previous study (Egorova et al, 2020).…”

Microprism-based two-photon imaging of the mouse inferior colliculus reveals novel organizational principles of the auditory midbrain

“…Given that ketamine was reported to increase the duration of the tone-evoked response in the auditory cortex (Guo et al, 2012), the same effect could increase the AUC for the tone-evoked response that might result in a positive average of SMI. Additionally, while LC had a higher average of TMIs than that of the DC of anesthetized animals, the LC had a lower mean of TMIs than that of the DC of awake animals indicating that ketamine may specifically modulate the response properties of the LC via its effects on GABAergic cells (Behrens et al, 2007;Deane et al, 2020;Weckmann et al, 2019), given that GABAergic inhibition reportedly contripute to the processing of the temporally modulated signals (Alluri et al, 2021;Burger & Pollak, 1998;Cai et al, 2018;Gourévitch, Mahrt, Bakay, Elde, & Portfors, 2020). In both anesthetized and awake animals, matrix neurons had always a consistent ratio between the cells with suppressed (~ 70%) and enhanced (~30%) auditory responses induced by bimodal stimulation.…”