Acetylcholine acts on songbird premotor circuitry to invigorate vocal output

Abstract

Acetylcholine is well-understood to enhance cortical sensory responses and perceptual sensitivity in aroused or attentive states. Yet little is known about cholinergic influences on motor cortical regions. Here we use the quantifiable nature of birdsong to investigate how acetylcholine modulates the cortical (pallial) premotor nucleus HVC and shapes vocal output. We found that dialyzing the cholinergic agonist carbachol into HVC increased the pitch, amplitude, tempo and stereotypy of song, similar to the natural invigoration of song that occurs when males direct their songs to females. These carbachol-induced effects were associated with increased neural activity in HVC and occurred independently of basal ganglia circuitry. Moreover, we discovered that the normal invigoration of female-directed song was also accompanied by increased HVC activity and was attenuated by blocking muscarinic acetylcholine receptors. These results indicate that, analogous to its influence on sensory systems, acetylcholine can act directly on cortical premotor circuitry to adaptively shape behavior.

Arousal elevation drives the development of oscillatory vocal output

“…Arousal-modulated sensory processing has been suggested to be regulated via cholinergic input from the ascending arousal system [53,55]. In the song system of birds, cholinergic modulation of premotor nucleus HVC increases firing rate prior to syllable onsets and enhances song stereotypy, resembling the effect of females' presence [56]. These changes are consistent with our model's increases in baseline arousal level.…”

Complementary roles of serotonergic and cholinergic systems in decisions about when to act

“… 7 , 27 ACh is also linked to cognitive processes, including attention and memory, 28 , 29 signaling transition in movement state, and invigorating volitional movements. 30 , 31 , 32 , 33 Despite the diverse functions of the cholinergic system, a common theme is potentiating action in response to environmental stimuli. 29 , 34 This is supported by emerging evidence that ACh can rapidly and selectively modulate activity in specific brain areas.…”

Cellular transcriptomics reveals evolutionary identities of songbird vocal circuits

“…VIP-like neurons (here GABA-5) play a prominent disinhibitory role in regulating neocortical activity (57), raising the possibility that there is an analogous disinhibitory motif present in avian microcircuits. Cholinergic interneurons (here GABA-8) provide a local source of acetylcholine, a neuromodulator known to influence song properties (58). LGE-class interneurons (here GABA-1) establish sparsely active ensembles of odorant-driven neural activity in the olfactory bulb through feedforward and lateral inhibition (59,60) and could potentially contribute similarly to sparsely patterned activity that is a hallmark of HVC projection neurons (61,62).…”