Stimulus-dependent relationships between behavioral choice and sensory neural responses
Abstract
Understanding perceptual decision-making requires linking sensory neural responses to behavioral choices. In two-choice tasks, activity-choice covariations are commonly quantified with a single measure of choice probability (CP), without characterizing their changes across stimulus levels. We provide theoretical conditions for stimulus dependencies of activity-choice covariations. Assuming a general decision-threshold model, which comprises both feedforward and feedback processing and allows for a stimulus-modulated neural population covariance, we analytically predict a very general and previously unreported stimulus dependence of CPs. We develop new tools, including refined analyses of CPs and generalized linear models with stimulus-choice interactions, which accurately assess the stimulus- or choice-driven signals of each neuron, characterizing stimulus-dependent patterns of choice-related signals. With these tools, we analyze CPs of macaque MT neurons during a motion discrimination task. Our analysis provides preliminary empirical evidence for the promise of studying stimulus dependencies of choice-related signals, encouraging further assessment in wider data sets.
Data availability
No data was collected as part of this study.
-
A relationship between behavioral choice and the visual responses of neurons in macaque MTData from the Vis Neurosci 1996 paper by these authors and with this title.
Article and author information
Author details
Funding
National Institute of Neurological Disorders and Stroke (R01 NS108410)
- Stefano Panzeri
National Institute of Neurological Disorders and Stroke (U19 NS107464)
- Stefano Panzeri
National Eye Institute (R01 EY028811)
- Ralf M Haefner
Fondation Bertarelli
- Daniel Chicharro
National Institute of Neurological Disorders and Stroke (U19 NS118246)
- Ralf M Haefner
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2021, Chicharro 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
-
- 1,884
- views
-
- 266
- downloads
-
- 6
- 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
-
- Cell Biology
- Neuroscience
Reactive astrocytes play critical roles in the occurrence of various neurological diseases such as multiple sclerosis. Activation of astrocytes is often accompanied by a glycolysis-dominant metabolic switch. However, the role and molecular mechanism of metabolic reprogramming in activation of astrocytes have not been clarified. Here, we found that PKM2, a rate-limiting enzyme of glycolysis, displayed nuclear translocation in astrocytes of EAE (experimental autoimmune encephalomyelitis) mice, an animal model of multiple sclerosis. Prevention of PKM2 nuclear import by DASA-58 significantly reduced the activation of mice primary astrocytes, which was observed by decreased proliferation, glycolysis and secretion of inflammatory cytokines. Most importantly, we identified the ubiquitination-mediated regulation of PKM2 nuclear import by ubiquitin ligase TRIM21. TRIM21 interacted with PKM2, promoted its nuclear translocation and stimulated its nuclear activity to phosphorylate STAT3, NF-κB and interact with c-myc. Further single-cell RNA sequencing and immunofluorescence staining demonstrated that TRIM21 expression was upregulated in astrocytes of EAE. TRIM21 overexpressing in mice primary astrocytes enhanced PKM2-dependent glycolysis and proliferation, which could be reversed by DASA-58. Moreover, intracerebroventricular injection of a lentiviral vector to knockdown TRIM21 in astrocytes or intraperitoneal injection of TEPP-46, which inhibit the nuclear translocation of PKM2, effectively decreased disease severity, CNS inflammation and demyelination in EAE. Collectively, our study provides novel insights into the pathological function of nuclear glycolytic enzyme PKM2 and ubiquitination-mediated regulatory mechanism that are involved in astrocyte activation. Targeting this axis may be a potential therapeutic strategy for the treatment of astrocyte-involved neurological disease.
-
- Neuroscience
Alzheimer’s disease (AD) leads to progressive memory decline, and alterations in hippocampal function are among the earliest pathological features observed in human and animal studies. GABAergic interneurons (INs) within the hippocampus coordinate network activity, among which type 3 interneuron-specific (I-S3) cells expressing vasoactive intestinal polypeptide and calretinin play a crucial role. These cells provide primarily disinhibition to principal excitatory cells (PCs) in the hippocampal CA1 region, regulating incoming inputs and memory formation. However, it remains unclear whether AD pathology induces changes in the activity of I-S3 cells, impacting the hippocampal network motifs. Here, using young adult 3xTg-AD mice, we found that while the density and morphology of I-S3 cells remain unaffected, there were significant changes in their firing output. Specifically, I-S3 cells displayed elongated action potentials and decreased firing rates, which was associated with a reduced inhibition of CA1 INs and their higher recruitment during spatial decision-making and object exploration tasks. Furthermore, the activation of CA1 PCs was also impacted, signifying early disruptions in CA1 network functionality. These findings suggest that altered firing patterns of I-S3 cells might initiate early-stage dysfunction in hippocampal CA1 circuits, potentially influencing the progression of AD pathology.