Mechanisms of Rapid Modulation of Auditory Responsiveness

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Summary How do rapid variations of the waking state influence central auditory responses and what is the role of noradrenergic and cholinergic systems? The central hypothesis that we wish to examine is “Rapid modulation of the waking state result from variations in activity of the noradrenergic and cholinergic pathways and occur along a continuum from: 1) reduced responses owing to cortical/subcortical spontaneous slow rhythms/low frequency cell and network burst firing during low arousal, 2) quiescent but accurately responsive networks during intermediate alertness, and 3) reduced responsiveness during high arousal or walking owing to high levels of both excitatory and inhibitory spontaneous activity. This is a timely topic, given that modulation of auditory responses and processing is important not only to normal hearing, but also in the recovery of function following damage or disease. Here we will test our central hypothesis (stated above) by performing extracellular unit and whole cell (synaptic) recordings from auditory cortical neurons and related subcortical structures (medial geniculate, inferior colliculus) during precisely measured variations in the waking state along with monitoring and manipulating the the activity of ascending cholinergic and noradrenergic pathways. Together, these results will yield a significant increase in our understanding of the cellular and network mechanisms of both normal, and recovery, of auditory cortical and subcortical function.