Response outcome gates the effect of spontaneous corticalstate fluctuations on perceptual decisions
Abstract
Sensory responses of cortical neurons are more discriminable when evoked on a baseline of desynchronized spontaneous activity, but cortical desynchronization has not generally been associated with more accurate perceptual decisions. Here we show that mice perform more accurate auditory judgements when activity in the auditory cortex is elevated and desynchronized before stimulus onset, but only if the previous trial was an error, and that this relationship is occluded if previous outcome is ignored. We confirmed that the outcome-dependent effect of brain state on performance is neither due to idiosyncratic associations between the slow components of either signal, nor to the existence of specific cortical states evident only after errors. Instead, errors appear to gate the effect of cortical state fluctuations on discrimination accuracy. Neither facial movements nor pupil size during the baseline were associated with accuracy, but they were predictive of measures of responsivity, such as the probability of not responding to the stimulus or of responding prematurely. These results suggest that the functional role of cortical state on behavior is dynamic and constantly regulated by performance monitoring systems.
Data availability
All data and code necessary to reproduce the main findings of this manuscript are deposited on Dryad (https://dx.doi.org/10.5061/dryad.w0vt4b8vf).
-
Response outcome gates the effect of spontaneous cortical state fluctuations on perceptual decisionsDryad Digital Repository, doi:10.5061/dryad.w0vt4b8vf.
Article and author information
Author details
Funding
Fundação para a Ciência e a Tecnologia (Postdoctoral fellowship,SFRH/BPD/119737/2016)
- Davide Reato
H2020 Marie Skłodowska-Curie Actions (Postdoctoral fellowship,H2020-MSCA-IF-2016 75381)
- Davide Reato
Fundação para a Ciência e a Tecnologia (Doctoral fellowships)
- Raphael Steinfeld
Fundação Champalimaud
- Alfonso Renart
Marie Curie Career Integration Grant (PCIG11-GA-2012-322339)
- Alfonso Renart
Human Frontier Science Program (Young Investigator Award,RGY0089)
- Alfonso Renart
EU FP7 (ICT-2011-9-600925)
- Alfonso Renart
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Jonas Obleser, University of Lübeck, Germany
Ethics
Animal experimentation: All procedures were reviewed and approved by the Champalimaud Centre for the Unknown animalwelfare committee and approved by the Portuguese Direção Geral de Veterinária (Ref. No.6090421/000/000/2019).
Version history
- Preprint posted: September 3, 2021 (view preprint)
- Received: July 11, 2022
- Accepted: May 16, 2023
- Accepted Manuscript published: May 17, 2023 (version 1)
- Accepted Manuscript updated: May 19, 2023 (version 2)
- Version of Record published: June 5, 2023 (version 3)
Copyright
© 2023, Reato 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
-
- 583
- views
-
- 80
- downloads
-
- 2
- citations
Views, downloads and citations are aggregated across all versions of this paper published by eLife.
Download links
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)
Further reading
-
- Genetics and Genomics
- Neuroscience
Single-cell RNA sequencing reveals the extent to which marmosets carry genetically distinct cells from their siblings.
-
- Cell Biology
- Neuroscience
Mutations in Drosophila Swiss Cheese (SWS) gene or its vertebrate orthologue Neuropathy Target Esterase (NTE) lead to progressive neuronal degeneration in flies and humans. Despite its enzymatic function as a phospholipase is well-established, the molecular mechanism responsible for maintaining nervous system integrity remains unclear. In this study, we found that NTE/SWS is present in surface glia that forms the blood-brain-barrier (BBB) and that NTE/SWS is important to maintain its structure and permeability. Importantly, BBB glia-specific expression of Drosophila NTE/SWS or human NTE in the sws mutant background fully rescues surface glial organization and partially restores BBB integrity, suggesting a conserved function of NTE/SWS. Interestingly, sws mutant glia showed abnormal organization of plasma membrane domains and tight junction rafts accompanied by the accumulation of lipid droplets, lysosomes, and multilamellar bodies. Since the observed cellular phenotypes closely resemble the characteristics described in a group of metabolic disorders known as lysosomal storage diseases (LSDs), our data established a novel connection between NTE/SWS and these conditions. We found that mutants with defective BBB exhibit elevated levels of fatty acids, which are precursors of eicosanoids and are involved in the inflammatory response. Also, as a consequence of a permeable BBB, several innate immunity factors are upregulated in an age-dependent manner, while BBB glia-specific expression of NTE/SWS normalizes inflammatory response. Treatment with anti-inflammatory agents prevents the abnormal architecture of the BBB, suggesting that inflammation contributes to the maintenance of a healthy brain barrier. Considering the link between a malfunctioning BBB and various neurodegenerative diseases, gaining a deeper understanding of the molecular mechanisms causing inflammation due to a defective BBB could help to promote the use of anti-inflammatory therapies for age-related neurodegeneration.