Mesoscale cortex-wide neural dynamics predict goal-directed, but not random actions in mice several seconds prior to movement
- University of British Columbia, Canada
- University of Florida, United States
- University of Ottawa, Canada
Abstract
Volition - the sense of control or agency over one's voluntary actions - is widely recognized as the basis of both human subjective experience and natural behavior in non-human animals. Several human studies have found peaks in neural activity preceding voluntary actions, e.g. the readiness potential (RP), and some have shown upcoming actions could be decoded even before awareness. Others propose that random processes underlie and explain pre-movement neural activity. Here we seek to address these issues by evaluating whether pre-movement neural activity in mice contains structure beyond that present in random neural activity. Implementing a self-initiated water-rewarded lever pull paradigm in mice while recording widefield [Ca++] neural activity we find that cortical activity changes in variance seconds prior to movement and that upcoming lever pulls could be predicted between 3 to 5 seconds (or more in some cases) prior to movement. We found inhibition of motor cortex starting at approximately 5sec prior to lever pulls and activation of motor cortex starting at approximately 2sec prior to a random unrewarded left limb movement. We show that mice, like humans, are biased towards commencing self-initiated actions during specific phases of neural activity but that the pre-movement neural code changes over time in some mice and is widely distributed as behavior prediction improved when using all vs single cortical areas. These findings support the presence of structured multi-second neural dynamics preceding self-initiated action beyond that expected from random processes. Our results also suggest that neural mechanisms underlying self-initiated action could be preserved between mice and humans.
Data availability
Code for generating all figures is provided here:https://github.com/catubc/elife_self_init_paperDatasets are provided on Dryad under the information below:Mitelut, Catalin (2022), Mesoscale cortex-wide neural dynamics predict self-initiated actions in mice several seconds prior to movement, Dryad,Dataset, https://doi.org/10.5061/dryad.ttdz08m0z
-
Mesoscale cortex-wide neural dynamics predict self-initiated actions in mice several seconds prior to movementDryad Digital Repository, doi:10.5061/dryad.ttdz08m0z.
Article and author information
Author details
Nicholas V Swindale
Funding
Canadian Institutes of Health Research (MOP-15360)
- Catalin Mitelut
- Yongxu Zhang
- Yuki Sekino
- Jamie D Boyd
- Federico Bollanos
- Nicholas V Swindale
- Greg Silasi
- Timothy H Murphy
Canadian Institutes of Health Research (MOP-12675)
- Catalin Mitelut
- Yongxu Zhang
- Yuki Sekino
- Jamie D Boyd
- Federico Bollanos
- Nicholas V Swindale
- Greg Silasi
- Shreya Saxena
- Timothy H Murphy
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Gordon J Berman, Emory University, United States
Ethics
Animal experimentation: Mouse protocols were approved by the University of British Columbia Animal Care Committee and followed the Canadian Council on Animal Care and Use guidelines (protocols A13-0336 and A14-0266).
Version history
- Received: December 18, 2021
- Preprint posted: December 20, 2021 (view preprint)
- Accepted: November 2, 2022
- Accepted Manuscript published: November 3, 2022 (version 1)
- Version of Record published: November 17, 2022 (version 2)
Copyright
© 2022, Mitelut et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
Metrics
-
- 1,368
- views
-
- 205
- downloads
-
- 9
- citations
Views, downloads and citations are aggregated across all versions of this paper published by eLife.
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)
Mesoscale cortex-wide neural dynamics predict goal-directed, but not random actions in mice several seconds prior to movement
eLife 11:e76506.
https://doi.org/10.7554/eLife.76506
Further reading
-
- Cell Biology
- Computational and Systems Biology
Bats have unique characteristics compared to other mammals, including increased longevity and higher resistance to cancer and infectious disease. While previous studies have analyzed the metabolic requirements for flight, it is still unclear how bat metabolism supports these unique features, and no study has integrated metabolomics, transcriptomics, and proteomics to characterize bat metabolism. In this work, we performed a multi-omics data analysis using a computational model of metabolic fluxes to identify fundamental differences in central metabolism between primary lung fibroblast cell lines from the black flying fox fruit bat (Pteropus alecto) and human. Bat cells showed higher expression levels of Complex I components of electron transport chain (ETC), but, remarkably, a lower rate of oxygen consumption. Computational modeling interpreted these results as indicating that Complex II activity may be low or reversed, similar to an ischemic state. An ischemic-like state of bats was also supported by decreased levels of central metabolites and increased ratios of succinate to fumarate in bat cells. Ischemic states tend to produce reactive oxygen species (ROS), which would be incompatible with the longevity of bats. However, bat cells had higher antioxidant reservoirs (higher total glutathione and higher ratio of NADPH to NADP) despite higher mitochondrial ROS levels. In addition, bat cells were more resistant to glucose deprivation and had increased resistance to ferroptosis, one of the characteristics of which is oxidative stress. Thus, our studies revealed distinct differences in the ETC regulation and metabolic stress responses between human and bat cells.
-
- Computational and Systems Biology
- Neuroscience
Normal aging leads to myelin alterations in the rhesus monkey dorsolateral prefrontal cortex (dlPFC), which are positively correlated with degree of cognitive impairment. It is hypothesized that remyelination with shorter and thinner myelin sheaths partially compensates for myelin degradation, but computational modeling has not yet explored these two phenomena together systematically. Here, we used a two-pronged modeling approach to determine how age-related myelin changes affect a core cognitive function: spatial working memory. First, we built a multicompartment pyramidal neuron model fit to monkey dlPFC empirical data, with an axon including myelinated segments having paranodes, juxtaparanodes, internodes, and tight junctions. This model was used to quantify conduction velocity (CV) changes and action potential (AP) failures after demyelination and subsequent remyelination. Next, we incorporated the single neuron results into a spiking neural network model of working memory. While complete remyelination nearly recovered axonal transmission and network function to unperturbed levels, our models predict that biologically plausible levels of myelin dystrophy, if uncompensated by other factors, can account for substantial working memory impairment with aging. The present computational study unites empirical data from ultrastructure up to behavior during normal aging, and has broader implications for many demyelinating conditions, such as multiple sclerosis or schizophrenia.
