Neural circuit logic for modulation and gain control in the auditory cortex
Sensory brain plasticity exhibits a fundamental duality, a yin and yang, in that it is both a source and possible solution for various types of perceptual disorders. When signaling between the ear and the brain is disrupted, the balance of excitation and inhibition tips toward hyperexcitability throughout the central auditory neuroaxis, increasing the 'central gain' on afferent signals so as to partially compensate for a diminished input from the auditory periphery. Our work shows that excess central gain can distort the temporal coding of complex communication sounds and even induce the perception of phantom sounds, contributing to pathophysiological processes such as hypersensitivity and tinnitus. This is the 'yin', the dark side of brain plasticity, wherein the transcriptional, physiological and neurochemical changes that compensate for the loss or degradation of peripheral input can incur debilitating perceptual costs. We are also committed to understand the 'yang' of brain plasticity, how the remarkable malleability of the adult brain can be harnessed and directed towards an adaptive - or even therapeutic - endpoint. Our ongoing research suggests that a cluster of cholinergic cells deep in the basal forebrain may hold the key to adjusting the volume knob in hyperactive cortical circuits.