Robust and Intensity-Dependent Synaptic Inhibition Underlies the Generation of Non-monotonic Neurons in the Mouse Inferior Colliculus

Abstract

Intensity and frequency are the two main properties of sound. The non-monotonic neurons in the auditory system are thought to represent sound intensity. The central nucleus of the inferior colliculus (ICC), as an important information integration nucleus of the auditory system, is also involved in the processing of intensity encoding. Although previous researchers have hinted at the importance of inhibitory effects on the formation of non-monotonic neurons, the specific underlying synaptic mechanisms in the ICC are still unclear. Therefore, we applied the in vivo whole-cell voltage-clamp technique to record the excitatory and inhibitory postsynaptic currents (EPSCs and IPSCs) in the ICC neurons, and compared the effects of excitation and inhibition on the membrane potential outputs. We found that non-monotonic neuron responses could not only be inherited from the lower nucleus but also be created in the ICC. By integrating with a relatively weak IPSC, approximately 35% of the monotonic excitatory inputs remained in the ICC. In the remaining cases, monotonic excitatory inputs were reshaped into non-monotonic outputs by the dominating inhibition at high intensity, which also enhanced the non-monotonic nature of the non-monotonic excitatory inputs.

Synaptic excitation underlies processing of paired stimulation in the mouse inferior colliculus

“…Short latencies suggested ascending pathways of excitation and inhibition from the lower auditory nuclei (Ono & Oliver, 2014) because longer latencies were attributed to the increased number of synapses in a pathway (Phillips & Hall, 1990; Walmsley et al., 1998). Consistent with our previous work (Liu et al., 2019), no obvious difference was demonstrated between the latencies of EPSCs and IPSCs. In addition, the range of latencies among those IC neurons suggested that both monosynaptic and polysynaptic pathways were activated (Mauger et al., 2010).…”

“…In addition, the range of latencies among those IC neurons suggested that both monosynaptic and polysynaptic pathways were activated (Mauger et al., 2010). It is important to note that the CF of a neuron was typically obtained according to the TRF of the contralateral EPSCs because the TRFs of contralateral and ipsilateral stimulation displayed the same CF (Xiong et al., 2013) and similar phenomena were also noted for excitatory and inhibitory TRFs (Liu et al., 2019; Wei et al., 2018). In this study, recordings were performed in anesthetized mice due to technical demands of whole‐cell recordings and blockage of the AN.…”

“…A reference electrode was placed in the prefrontal cortex. Then, a small bone window craniotomy was performed to expose both inferior colliculi under a surgical microscope (WPI, Sarasota, FL, United States) according to the atlas for the mouse brain: −5.2 mm from Bregma and 1 mm lateral to the midline without the removal of the dura (Liu et al., 2019). Vaseline was adopted to prevent the exposed brain areas from desiccation before the mouse was returned to a cage for recovery with food and water ad libitum.…”

Bilateral Interactions in the Mouse Dorsal Inferior Colliculus Enhance the Ipsilateral Neuronal Responses and Binaural Hearing

“…The surgical procedures used for mouse electrophysiological recordings were similar to those methods that we previously reported ( Wei et al, 2018 ; Liu et al, 2019 ; Wang et al, 2019 ; Wu et al, 2021 ). Mice were anaesthetized with pentobarbital (60–80 mg/kg, i. p., Sigma, United States) and atropine (0.25 mg/kg, s. c., Nandao, China).…”

“…A 700B amplifier (Axon, United States) was used to take our electrophysiological recordings. To perform in vivo loose-patch recordings, the micropipette containing artificial cerebrospinal fluid (ACSF; in mM: 124 NaCl, 2.5 KCl, 25 NaHCO 3 , two CaCl 2 , one MgCl 2 , 1.23 NaH 2 PO 4 , 20 glucose, pH = 7.28) and 0.5% biocytin was attached to the neuron with a loose seal (0.2–1 MΩ) ( Liu et al, 2019 ; Wu et al, 2021 ). The spike shapes (action potentials) were monitored and stored by Brain Ware (TDT 3, Tucker-Davis Technologies, United States) during recording.…”