Utilizing slice preparations of GAD67-GFP knock-in mouse, in which GABAergic neurons are specifically labeled with GFP fluorescence, we studied electrophysiological characteristics of GABAergic neurons of IC by whole-cell patch clamp-recording combined with biocytin-intracellular-staining techniques. GABAergic neurons of IC fell into two distinct firing types; (1) tonic type neurons and (2) transient (phasic) type neurons. Tonic type neurons showed regularly repetitive discharge pattern in response to a long depolarizing current pulse (200 ms), and transient type neurons showed spike discharges just at the onset of current pulse. Most of neurons of both types showed depolarizing sag in response to hyperpolarizing current pulse, which were blocked by 0.1 mM ZD7288 (Ih blocker). All two types of tonic neurons showed an AHP, which was blocked by Cd2+ (0.1 mM) and high concentration of apamin (2 microM). One of tonic type neurons (BP) revealed a long delay in spike onset or a longer first spike interval when they were stimulated from hyperpolarized potentials. The remaining tonic neurons (RS) did not show this property. Tonic type neurons were distributed in all region of IC. Morphologically, they were not identical; heterogeneous in somatic diameter, dendritic field size and its orientation. One of transient type neurons (Th-) revealed an AHP after the spike. The other transient type neurons (Th+) showed a depolarization hump after the spike, which were blocked by 0.1-0.2 mM Ni2+. Th+ type neurons were found only in the dorsolateral region of IC, having small dendritic field. Th+ type neurons are likely to be a distinct, homogenous group of GABAergic neuron in IC.

Offset neurons, which fire at the termination of sound, likely encode sound duration and serve to process temporal information. Offset neurons are found in most ascending auditory nuclei; however, the neural mechanisms that evoke offset responses are not well understood. In this study, we examined offset neural responses to tonal stimuli in the inferior colliculus (IC) in vivo with extracellular and intracellular recording techniques in mice. Based on peristimulus time histogram (PSTH) patterns, we classified extracellular offset responses into four types: Offset, Onset-Offset, Onset-Sustained-Offset and Inhibition-Offset types. Moreover, using in vivo whole-cell recording techniques, we found that offset responses were generated in most cells through the excitatory and inhibitory synaptic inputs. However, in a small number of cells, the offset responses were generated as a rebound to hyperpolarization during tonal stimulation. Many offset neurons fired robustly at a preferred duration of tonal stimulus, which corresponded with the timing of rich excitatory synaptic inputs. We concluded that most IC offset neurons encode the termination of the tone stimulus by responding to inherited ascending synaptic information, which is tuned to sound duration. The remainder generates offset spikes de novo through a post-inhibitory rebound mechanism.

GABAergic neurons in the inferior colliculus (IC) play a critical role in auditory information processing, yet their responses to sound are unknown. Here, we used optogenetic methods to characterize the response properties of GABAergic and presumed glutamatergic neurons to sound in the IC. We found that responses to pure tones of both inhibitory and excitatory classes of neurons were similar in their thresholds, response latencies, rate-level functions, and frequency tuning, but GABAergic neurons may have higher spontaneous firing rates. In contrast to their responses to pure tones, the inhibitory and excitatory neurons differed in their ability to follow amplitude modulations. The responses of both cell classes were affected by their location regardless of the cell type, especially in terms of their frequency tuning. These results show that the synaptic domain, a unique organization of local neural circuits in the IC, may interact with all types of neurons to produce their ultimate response to sound. Although the inferior colliculus (IC) in the auditory midbrain is composed of different types of neurons, little is known about how these specific types of neurons respond to sound. Here, for the first time, we characterized the response properties of GABAergic and glutamatergic neurons in the IC. Both classes of neurons had diverse response properties to tones but were overall similar, except for the spontaneous activity and their ability to follow amplitude-modulated sound. Both classes of neurons may compose a basic local circuit that is replicated throughout the IC. Within each local circuit, the inputs to the local circuit may have a greater influence in determining the response properties to sound than the specific neuron types.

The localization of high-frequency sounds in the horizontal plane uses an interaural-level difference (ILD) cue, yet little is known about the synaptic mechanisms that underlie processing this cue in the inferior colliculus (IC) of mouse. Here, we study the synaptic currents that process ILD in vivo and use stimuli in which ILD varies around a constant average binaural level (ABL) to approximate sounds on the horizontal plane. Monaural stimulation in either ear produced EPSCs and IPSCs in most neurons. The temporal properties of monaural responses were well matched, suggesting connected functional zones with matched inputs. The EPSCs had three patterns in response to ABL stimuli, preference for the sound field with the highest level stimulus: (1) contralateral; (2) bilateral highly lateralized; or (3) at the center near 0 ILD. EPSCs and IPSCs were well correlated except in center-preferred neurons. Summation of the monaural EPSCs predicted the binaural excitatory response but less well than the summation of monaural IPSCs. Binaural EPSCs often showed a nonlinearity that strengthened the response to specific ILDs. Extracellular spike and intracellular current recordings from the same neuron showed that the ILD tuning of the spikes was sharper than that of the EPSCs. Thus, in the IC, balanced excitatory and inhibitory inputs may be a general feature of synaptic coding for many types of sound processing.