Cognitive experience alters cortical involvement in goal-directed navigation
- Harvard Medical School, United States
Abstract
Neural activity in the mammalian cortex has been studied extensively during decision tasks, and recent work aims to identify under what conditions cortex is actually necessary for these tasks. We discovered that mice with distinct cognitive experiences, beyond sensory and motor learning, use different cortical areas and neural activity patterns to solve the same navigation decision task, revealing past learning as a critical determinant of whether cortex is necessary for goal-directed navigation. We used optogenetics and calcium imaging to study the necessity and neural activity of multiple cortical areas in mice with different training histories. Posterior parietal cortex and retrosplenial cortex were mostly dispensable for accurate performance of a simple navigation task. In contrast, these areas were essential for the same simple task when mice were previously trained on complex tasks with delay periods or association switches. Multi-area calcium imaging showed that, in mice with complex-task experience, single-neuron activity had higher selectivity and neuron-neuron correlations were weaker, leading to codes with higher task information. Therefore, past experience is a key factor in determining whether cortical areas have a causal role in goal-directed navigation.
Data availability
Data have been deposited in Dryad with the DOI: https://doi.org/10.5061/dryad.34tmpg4nr.
-
Cognitive experience alters cortical involvement in goal-directed navigationDryad Digital Repository, doi:10.5061/dryad.34tmpg4nr.
Article and author information
Author details
Christopher D Harvey
Funding
National Institutes of Health (R01 MH107620)
- Christopher D Harvey
JSPS Overseas Research Fellowship
- Shinichiro Kira
EMBO Postdoctoral Fellowship
- Sofia Soares
Stuart H.Q. & Victoria Quan Fellowship
- Noah L Pettit
National Institutes of Health (R01 NS089521)
- Christopher D Harvey
National Institutes of Health (R01 NS108410)
- Christopher D Harvey
National Institutes of Health (DP1 MH125776)
- Christopher D Harvey
Louis Perry Jones Postdoctoral Fellowship
- Charlotte Arlt
Alice and Joseph Brooks Postdoctoral Fellowship
- Charlotte Arlt
Uehara Foundation Research Fellowship
- Shinichiro Kira
Leonard and Isabelle Goldenson Postdoctoral Fellowship
- Shinichiro Kira
NARSAD Young Investigator Grant
- Shinichiro Kira
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Mathieu Wolff, CNRS, University of Bordeaux, France
Ethics
Animal experimentation: All experimental procedures were approved by the Harvard Medical School Institutional Animal Care and Use Committee (protocol # 00000073-6) and were performed in compliance with the Guide for the Care and Use of Laboratory Animals.
Version history
- Received: December 2, 2021
- Preprint posted: December 10, 2021 (view preprint)
- Accepted: June 22, 2022
- Accepted Manuscript published: June 23, 2022 (version 1)
- Version of Record published: July 6, 2022 (version 2)
Copyright
© 2022, Arlt 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
-
- 2,419
- views
-
- 542
- 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)
Cognitive experience alters cortical involvement in goal-directed navigation
eLife 11:e76051.
https://doi.org/10.7554/eLife.76051
Further reading
-
- Neuroscience
Abnormal activity in the cerebellar nuclei can be used to predict motor symptoms and induce them experimentally, pointing to potential therapeutic strategies.
-
- Cell Biology
- Neuroscience
One of the most extensively studied members of the Ras superfamily of small GTPases, Rac1 is an intracellular signal transducer that remodels actin and phosphorylation signaling networks. Previous studies have shown that Rac1-mediated signaling is associated with hippocampal-dependent working memory and longer-term forms of learning and memory and that Rac1 can modulate forms of both pre- and postsynaptic plasticity. How these different cognitive functions and forms of plasticity mediated by Rac1 are linked, however, is unclear. Here, we show that spatial working memory in mice is selectively impaired following the expression of a genetically encoded Rac1 inhibitor at presynaptic terminals, while longer-term cognitive processes are affected by Rac1 inhibition at postsynaptic sites. To investigate the regulatory mechanisms of this presynaptic process, we leveraged new advances in mass spectrometry to identify the proteomic and post-translational landscape of presynaptic Rac1 signaling. We identified serine/threonine kinases and phosphorylated cytoskeletal signaling and synaptic vesicle proteins enriched with active Rac1. The phosphorylated sites in these proteins are at positions likely to have regulatory effects on synaptic vesicles. Consistent with this, we also report changes in the distribution and morphology of synaptic vesicles and in postsynaptic ultrastructure following presynaptic Rac1 inhibition. Overall, this study reveals a previously unrecognized presynaptic role of Rac1 signaling in cognitive processes and provides insights into its potential regulatory mechanisms.
