<p>Abstract: Basal forebrain cholinergic neurons (BFCNs) project throughout the neocortex, hippocampus, and amygdala to regulate arousal, stimulus salience, plasticity, and learning. Our research has shown that cholinergic neurons in the extreme caudal tail of the basal forebrain are functionally distinct from more rostral areas. Whereas the activity of rostral BFCNs are closely related to global brain state, caudal tail BFCNs exhibit rapid, low-threshold phasic responses to a broad class of unconditioned auditory stimuli that rapidly reorganize to enhance the representation of threat-predicting sounds. I will describe how plasticity in caudal tail BFCNs can serve as a teaching signal to guide auditory cortex reorganization during associative learning. Finally, I will discuss the history of “hacking” BFCN activity through direct stimulation protocols to produce targeted forms of plasticity in the auditory cortex. I will describe our ongoing efforts to control the activity of caudal BFCNs and select types of cortical GABAergic interneurons to reduce auditory hypersensitivity, a defining phenotype in aging, sensorineural hearing loss, and several neurodevelopmental and neuropsychiatric disorders. </p>
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