Motor Performance: Acetylcholine in action

The neurotransmitter acetylcholine influences how male finches perform courtship songs by acting on a region of the premotor cortex called HVC.
  1. Erin M Wall
  2. Sarah C Woolley  Is a corresponding author
  1. Integrated Program in Neuroscience, McGill University, Canada
  2. Center for Research on Brain, Language, and Music, McGill University, Canada
  3. Department of Biology, McGill University, Canada

Acetylcholine is a neurotransmitter that helps organisms filter the vast amounts of information received from the environment. In the sensory cortex, it acts by fine-tuning the activity of neurons to heighten attention, which helps with learning and memory (Sarter and Lustig, 2019; Lee and Dan, 2012; Picciotto et al., 2012).

Heightened attention also boosts the precision and speed of movements (Song, 2019). Previous research in this area has focused on neuromodulation in the basal ganglia, a group of neural structures in the forebrain that help to select, initiate, maintain, and adapt motor actions (Berke, 2018; Mink, 1996; Turner and Desmurget, 2010). For example, dopamine is an important neurotransmitter in this region, and its loss is associated with movement disorders such as Parkinson’s disease. Disrupting acetylcholine signaling also leads to problems with movement, yet the influence of acetylcholine on motor performance is not fully understood (Conner et al., 2010). Now, in eLife, Paul Jaffe and Michael Brainard from the University of California, San Francisco report the results of experiments on songbirds that shed light on the relationship between acetylcholine, arousal, and motor performance (Jaffe and Brainard, 2020).

The team took advantage of the fact that male Bengalese finches naturally alter their song performance depending on their audience. Each male has his own song that he rehearses alone. However, when aroused and courting a female, the male produces a song that is more stereotypical (less variable), longer, and faster (Figure 1A; Sakata et al., 2008). Several specialized neural circuits – some in the cortex, and some in the basal ganglia – are required to learn and produce songs. Researchers can monitor and manipulate these circuits with precision to understand their function (Sakata and Woolley, 2020).

Acetylcholine invigorates motor performance.

(A) During courtship (top), male Bengalese finches sing louder, faster, more stereotyped songs (black notes) to females compared to when they sing alone (grey notes; bottom). (B) Using a combination of local drug infusion and electrophysiological recordings, Jaffe and Brainard demonstrated that changes to song performance may depend on acetylcholine (Ach) acting in the premotor cortical nucleus HVC. When their HVC was stimulated with a drug mimicking acetylcholine (pink infusion; top panel), male finches produced songs similar to courtship songs, despite being alone. On the other hand, blocking acetylcholine naturally released in HVC during courtship singing (bottom panel) made the courtship song performance more similar to non-courtship song even when females were present. (C) HVC is connected to the robust nucleus of the arcopallium (RA) – a region involved in motor vocal output – both directly and through a cortical-basal ganglia circuit (gray box) that involves the basal ganglia nucleus (Area X), the dorsolateral anterior thalamic nucleus (DLM), and the lateral magnocellular nucleus of the anterior nidopallium (LMAN). Creating a lesion in LMAN (blue line) while stimulating HVC with acetylcholine preserved vocal vigor, showing that the neurotransmitter can act independently from the cortical-basal ganglia circuit.

First, Jaffe and Brainard focused on a premotor cortical region called HVC, where they locally infused a drug that mimics the effects of acetylcholine. As a result, males started to sing as if a female were present: songs were faster, louder, and less variable during drug infusion than in control conditions (Figure 1B). Neurons in HVC also started to show the same type of pattern observed during courtship singing towards females – there was, in particular, neural activity increased. Together, these experiments suggest that acetylcholine plays a role in shaping singing behavior in a social context.

Next, they assessed whether differences in behaviour in the presence and absence of a female normally depend on acetylcholine. To this end, Jaffe and Brainard blocked specific acetylcholine receptors, leading to courtship songs in the presence of females becoming lower in pitch, more variable, and altogether more similar to songs performed alone (Figure 1B). Decreasing acetylcholine activity in HVC therefore weakened the vigor of courtship singing, revealing that acetylcholine can drive changes in the brain that energize male performances towards females.

In the brains of songbirds, HVC is connected to the region that controls vocal motor outputs both directly and through a separate circuit that goes through the basal ganglia. Jaffe and Brainard therefore set out to determine which of these pathways acetylcholine acts on to enhance the vigor of the song. They disrupted the circuit that connects the basal ganglia to the vocal output region and showed that, in this context, increased acetylcholine activity in HVC still produced the same enhanced singing behavior (Figure 1C). This demonstrates that acetylcholine can invigorate song performance even without the basal ganglia being involved.

From songbirds to humans, many vertebrates rely on ‘prosodic cues’ such as pitch and tempo to convey motivations and emotions during communication (Pell et al., 2009; Sakata and Vehrencamp, 2012). Knowing how acetylcholine heightens motor performance sheds light on the neural circuits that underlie the production of these cues. Other chemicals, such as dopamine and norepinephrine, also fine-tune the activity of neurons in motor circuits. In the future, understanding how acetylcholine interacts with these neurotransmitters, both in overlapping and independent regions, will be necessary to fully grasp how arousal influences motor behavior.

References

  1. Book
    1. Sakata JT
    2. Woolley SC
    (2020) Scaling the levels of birdsong analysis
    In: Sakata JT, Woolley SC, Fay RR, Popper AN, editors. The Neuroethology of Birdsong, Springer Handbook of Auditory Research. Springer International Publishing. pp. 1–27.
    https://doi.org/10.1007/978-3-030-34683-6

Article and author information

Author details

  1. Erin M Wall

    Erin M Wall is in the Integrated Program in Neuroscience and the Center for Research on Brain, Language and Music, McGill University, Montreal, Canada

    Competing interests
    No competing interests declared
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-7451-319X
  2. Sarah C Woolley

    Sarah C Woolley is in the Center for Research on Brain, Language and Music and the Department of Biology, McGill University, Montreal, Canada

    For correspondence
    sarah.woolley@mcgill.ca
    Competing interests
    No competing interests declared
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-4678-9441

Publication history

  1. Version of Record published: May 19, 2020 (version 1)

Copyright

© 2020, Wall and Woolley

This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.

Metrics

  • 1,282
    Page views
  • 73
    Downloads
  • 1
    Citations

Article citation count generated by polling the highest count across the following sources: Crossref, PubMed Central, Scopus.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  1. Erin M Wall
  2. Sarah C Woolley
(2020)
Motor Performance: Acetylcholine in action
eLife 9:e57515.
https://doi.org/10.7554/eLife.57515

Further reading

    1. Neuroscience
    Ely Contreras, Jacob D Bhoi ... Tiffany M Schmidt
    Research Article Updated

    Melanopsin signaling within intrinsically photosensitive retinal ganglion cell (ipRGC) subtypes impacts a broad range of behaviors from circadian photoentrainment to conscious visual perception. Yet, how melanopsin phototransduction within M1-M6 ipRGC subtypes impacts cellular signaling to drive diverse behaviors is still largely unresolved. The identity of the phototransduction channels in each subtype is key to understanding this central question but has remained controversial. In this study, we resolve two opposing models of M4 phototransduction, demonstrating that hyperpolarization-activated cyclic nucleotide-gated (HCN) channels are dispensable for this process and providing support for a pathway involving melanopsin-dependent potassium channel closure and canonical transient receptor potential (TRPC) channel opening. Surprisingly, we find that HCN channels are likewise dispensable for M2 phototransduction, contradicting the current model. We instead show that M2 phototransduction requires TRPC channels in conjunction with T-type voltage-gated calcium channels, identifying a novel melanopsin phototransduction target. Collectively, this work resolves key discrepancies in our understanding of ipRGC phototransduction pathways in multiple subtypes and adds to mounting evidence that ipRGC subtypes employ diverse phototransduction cascades to fine-tune cellular responses for downstream behaviors.

    1. Neuroscience
    Shai Abramson, Benjamin J Kraus ... Genela Morris
    Short Report Updated

    Analysis of neuronal activity in the hippocampus of behaving animals has revealed cells acting as ‘Time Cells’, which exhibit selective spiking patterns at specific time intervals since a triggering event, and ‘Distance Cells’, which encode the traversal of specific distances. Other neurons exhibit a combination of these features, alongside place selectivity. This study aims to investigate how the task performed by animals during recording sessions influences the formation of these representations. We analyzed data from a treadmill running study conducted by Kraus et al., 2013, in which rats were trained to run at different velocities. The rats were recorded in two trial contexts: a ‘fixed time’ condition, where the animal ran on the treadmill for a predetermined duration before proceeding, and a ‘fixed distance’ condition, where the animal ran a specific distance on the treadmill. Our findings indicate that the type of experimental condition significantly influenced the encoding of hippocampal cells. Specifically, distance-encoding cells dominated in fixed-distance experiments, whereas time-encoding cells dominated in fixed-time experiments. These results underscore the flexible coding capabilities of the hippocampus, which are shaped by over-representation of salient variables associated with reward conditions.