A Critical Role of Inhibition in Temporal Processing Maturation in the Primary Auditory Cortex

Abstract

Faithful representation of sound envelopes in primary auditory cortex (A1) is vital for temporal processing and perception of natural sounds. However, the emergence of cortical temporal processing mechanisms during development remains poorly understood. Although cortical inhibition has been proposed to play an important role in this process, direct in-vivo evidence has been lacking. Using loose-patch recordings in rat A1 immediately after hearing onset, we found that stimulus-following ability in fast-spiking neurons was significantly better than in regular-spiking (RS) neurons. In-vivo whole-cell recordings of RS neurons revealed that inhibition in the developing A1 demonstrated much weaker adaptation to repetitive stimuli than in adult A1. Furthermore, inhibitory synaptic inputs were of longer duration than observed in vitro and in adults. Early in development, overlap of the prolonged inhibition evoked by 2 closely following stimuli disrupted the classical temporal sequence between excitation and inhibition, resulting in slower following capacity. During maturation, inhibitory duration gradually shortened accompanied by an improving temporal following ability of RS neurons. Both inhibitory duration and stimulus-following ability demonstrated exposure-based plasticity. These results demonstrate the role of inhibition in setting the pace for experience-dependent maturation of temporal processing in the auditory cortex.

Development of temporal auditory processing in childhood: Changes in efficiency rather than temporal-modulation selectivity

“…This higher variability may be related to the stochastic nature of neural responses, which may reduce with neural maturation. This reduction with age might arise because of progressive increase in neural inhibition and decrease in spontaneous neural activity in auditory brain structures over development (Babola et al, 2018;Cai et al, 2017;Wang & Bergles, 2015). Decrease of internal noise levels with age could also relate to progressive decrease in random fluctuations of selective auditory attention capacities (Jones et al, 2015).…”

The ins and outs of inhibitory synaptic plasticity: Neuron types, molecular mechanisms and functional roles

“…The initial reports that GABAergic synapses are plastic suggested that ISP contributes to cortical circuit refinement (Komatsu & Iwakiri, 1993;Maffei et al, 2004Maffei et al, , 2006 and possibly learning (Buzsaki, 1997;Kano, 1995;Nugent, Penick, & Kauer, 2007). Since these pioneering studies, experimental work demonstrated that changes in inhibitory synaptic efficacy are associated with adaptation of olfactory responses in drosophila (Das et al, 2011), with changes in sensory experience (Cai et al, 2018;D'Amour & Froemke, 2015;House et al, 2011;Maffei et al, 2004Maffei et al, , 2006, fear conditioning (Letzkus et al, 2011;Lucas, Jegarl, Morishita, & Clem, 2016;Xu et al, 2014) and exposure to drugs of abuse (Dacher & Nugent, 2011;Nugent et al, 2007). The specific mechanisms by which ISP contributes to learning and memory are only beginning to being unravelled.…”

Preserving Inhibition during Developmental Hearing Loss Rescues Auditory Learning and Perception

“…GABA A receptor blockade results in cortical neuron responses at lower sound levels, to a broader range of sound levels, to a broader range of modulation rates, and to a broader range of stimulus durations (Chen and Jen, 2000;Wang et al, 2002Wang et al, , 2016Razak and Fuzessery, 2009). Specific manipulations of FS parvalbumin-positive interneurons or low threshold spiking somatostatin-positive interneurons, suggest that FS cells provide temporally precise feedforward inhibition to auditory cortical pyramidal neurons (Hamilton et al, 2013;Li et al, 2014Li et al, , 2015Natan et al, 2017;Cai et al, 2018;Keller et al, 2018;Liu et al, 2019). Together, these observations suggest that the strong FS inhibition contributes to the temporal following ability of pyramidal neurons.…”