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.

Highlights

  • The neuromodulator acetylcholine has a well-established role in enhancing sensory perception in states of heightened arousal, but whether acetylcholine acts centrally to exert an analogous influence on behavioral outputs is largely unknown

  • For each feature, the sum of changes elicited by carbachol and LMAN inactivations individually was not significantly different from the combined carbachol + LMAN inactivation condition (p > 0.05 in each case, sign-rank test). These results indicate that increased cholinergic tone in HVC modulates song via primary motor circuitry independently of input from the songbird basal-ganglia

  • The finding that cholinergic signaling within HVC contributes to social modulation of song led us to wonder if directed song and microdialysis of carbachol elicit similar changes to HVC activity

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Summary

Chapter 1: Introduction

Diseases of the cholinergic system, such as Alzheimer’s disease, are often associated with movement and speech abnormalities that can include reduced movement vigor, such as diminished grip strength, slower reaching movements, slower gait, and loss of verbal fluency (Buchman et al, 2007; Ferris and Farlow, 2013; Goldman et al, 1999) While these observations motivate the idea that acetylcholine could modulate motor cortical regions to enhance movement vigor in states of arousal, there have been no direct tests of this possibility. The forebrain premotor nucleus HVC and motor nucleus RA are essential for song adult song production, and are analogous to mammalian vocal premotor and motor cortex, respectively (Figure 2.1A) Because these structures are dedicated to song production, it is possible to manipulate and record activity at loci that are linked to quantifiable behavioral output. As in mammalian systems, the extent to which cholinergic action on motor forebrain regions contributes to these arousal-related changes to behavior has not been examined

Acetylcholine invigorates song and increases song stereotypy
Acetylcholine invigorates movement via the motor pathway
Acetylcholine increases neural activity in HVC
Acetylcholine enhances low-frequency rhythmic activity in HVC
Acetylcholine contributes to the social modulation of song
HVC activity is modulated by social context
Methods
A Pre tropine
HVC activity is correlated with acoustic output
Greater HVC activity predicts lower behavioral variability
Chapter 4: Discussion
Neuromodulatory control of motor vigor
Neuromodulatory contributions to social modulation of song
Neural mechanisms underlying cholinergic invigoration of song
Contributions of HVC to acoustic variability
Findings
Parallels between cholinergic modulation of motor and other brain regions
Full Text
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