Basal forebrain control of sensorimotor activity

Neural processing changes according to behavioral state. Brainstem and forebrain neuromodulatory systems have been widely implicated in this phenomenon, mediating states of sleep, arousal, and attention. The forebrain song system of oscine songbirds exhibits numerous state-dependent properties potentially related to the manifold behavioral functions of song. One example is the state-dependent ‘gating’ of auditory responses in the zebra finch song motor system that are exquisitely tuned to playback of autogenous song. Responses are strong during sleep or anesthesia and suppressed or diminished during wakefulness. We investigated the neuromodulatory basis of this phenomenon, focusing on the basal forebrain (BF) cholinergic system.; A complex pattern of suppression of auditory activity was observed in the song motor nuclei HVc and RA following injections of cholinergic agonists into HVc of anesthetized zebra finches. Nicotine and muscarine appear to act on distinct but overlapping pathways within HVc; muscarine appears to inhibit HVc neurons that project to RA (HVc-RAn) as well as interneurons (HVc-In), but nicotine appears to affect HVc-In only. Stimulation of the endogenous BF cholinergic fibers in conjunction with local pharmacological manipulations of HVc establishes that, in anesthetized birds, BF can gate song system auditory responses through cholinergic release in HVc. In vitro experiments in HVc reveal pathway-specific effects. Cholinergic agonists directly suppress activity in HVc-In and some HVc-RAn, but increase activity in neurons projecting to basal ganglia Area X. Preliminary behavioral data support functional, ongoing modulation of cholinergic tone in the song system during singing.; The auditory suppression we report differs from the widely reported enhancement of sensory activity by acetylcholine (ACh). Here sensorimotor activity in the song motor pathway is suppressed by ACh, while a pathway that may in part contribute to song perception is excited. Thus, we hypothesize that the cholinergic BF can differentially affect attentional processing of external sensory perceptual and internal sensorimotor activity. We propose that dynamically fluctuating levels of ACh have direct consequences for neural processing and sensorimotor behavior related to song.