Specialized coding patterns among dorsomedial prefrontal neuronal ensembles predict conditioned reward seeking
- Medical University of South Carolina, United States
Abstract
Non-overlapping cell populations within dorsomedial prefrontal cortex (dmPFC), defined by gene expression or projection target, control dissociable aspects of reward seeking through unique activity patterns. However, even within these defined cell populations considerable cell-to-cell variability is found, suggesting that greater resolution is needed to understand information processing in dmPFC. Here we use two-photon calcium imaging in awake, behaving mice to monitor the activity of dmPFC excitatory neurons throughout Pavlovian reward conditioning. We characterize five unique neuronal ensembles that each encode specialized information related to a sucrose reward, reward-predictive cues, and behavioral responses to those cues. The ensembles differentially emerge across daily training sessions - and stabilize after learning - in a manner that improves the predictive validity of dmPFC activity dynamics for deciphering variables related to behavioral conditioning. Our results characterize the complex dmPFC neuronal ensemble dynamics that stably predict reward availability and initiation of conditioned reward seeking following cue-reward learning.
Data availability
All data generated for this study are available on Dryad Digital Repository, accessible here: https://doi.org/10.5061/dryad.xksn02vg8. We are in the process of uploading raw videos for these data to the Image Data Resource (https://idr.openmicroscopy.org/), as there is a 3 week lead time to get the data uploaded and special considerations are required for datasets of >1TB. Code will be uploaded to GitHub upon publication. All data, code, and raw imaging files will be uploaded to these open-source repositories prior to publication.
-
Behavioral and Imaging data for: Grant et al. (2021). Specialized coding patterns among dorsomedial prefrontal neuronal ensembles predict conditioned reward seekingDryad Digital Repository, doi:10.5061/dryad.xksn02vg8.
Article and author information
Author details
Funding
National Institute of Drug Abuse (R01-DA051650)
- James M Otis
MUSC Cocaine and Opioid Center on Addiction Pilot Award (P50-DA046374)
- Roger I Grant
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: Experiments were performed in the dark phase and in accordance with the NIH Guide for the Care and Use of Laboratory Animals with approval from the Institutional Animal Care and Use Committee at the Medical University of South Carolina (Approval ID: IACUC-2018-00363; Renewed November 30, 2020).
Copyright
© 2021, Grant 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
-
- 2,510
- views
-
- 340
- downloads
-
- 24
- 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)
Specialized coding patterns among dorsomedial prefrontal neuronal ensembles predict conditioned reward seeking
eLife 10:e65764.
https://doi.org/10.7554/eLife.65764
Further reading
-
- Neuroscience
Motivation depends on dopamine, but might be modulated by acetylcholine which influences dopamine release in the striatum, and amplifies motivation in animal studies. A corresponding effect in humans would be important clinically, since anticholinergic drugs are frequently used in Parkinson’s disease, a condition that can also disrupt motivation. Reward and dopamine make us more ready to respond, as indexed by reaction times (RT), and move faster, sometimes termed vigour. These effects may be controlled by preparatory processes that can be tracked using electroencephalography (EEG). We measured vigour in a placebo-controlled, double-blinded study of trihexyphenidyl (THP), a muscarinic antagonist, with an incentivised eye movement task and EEG. Participants responded faster and with greater vigour when incentives were high, but THP blunted these motivational effects, suggesting that muscarinic receptors facilitate invigoration by reward. Preparatory EEG build-up (contingent negative variation [CNV]) was strengthened by high incentives and by muscarinic blockade, although THP reduced the incentive effect. The amplitude of preparatory activity predicted both vigour and RT, although over distinct scalp regions; frontal activity predicted vigour, whereas a larger, earlier, central component predicted RT. The incentivisation of RT was partly mediated by the CNV, though vigour was not. Moreover, the CNV mediated the drug’s effect on dampening incentives, suggesting that muscarinic receptors underlie the motivational influence on this preparatory activity. Taken together, these findings show that a muscarinic blocker impairs motivated action in healthy people, and that medial frontal preparatory neural activity mediates this for RT.
-
- Neuroscience
Gamma oscillations in brain activity (30–150 Hz) have been studied for over 80 years. Although in the past three decades significant progress has been made to try to understand their functional role, a definitive answer regarding their causal implication in perception, cognition, and behavior still lies ahead of us. Here, we first review the basic neural mechanisms that give rise to gamma oscillations and then focus on two main pillars of exploration. The first pillar examines the major theories regarding their functional role in information processing in the brain, also highlighting critical viewpoints. The second pillar reviews a novel research direction that proposes a therapeutic role for gamma oscillations, namely the gamma entrainment using sensory stimulation (GENUS). We extensively discuss both the positive findings and the issues regarding reproducibility of GENUS. Going beyond the functional and therapeutic role of gamma, we propose a third pillar of exploration, where gamma, generated endogenously by cortical circuits, is essential for maintenance of healthy circuit function. We propose that four classes of interneurons, namely those expressing parvalbumin (PV), vasointestinal peptide (VIP), somatostatin (SST), and nitric oxide synthase (NOS) take advantage of endogenous gamma to perform active vasomotor control that maintains homeostasis in the neuronal tissue. According to this hypothesis, which we call GAMER (GAmma MEdiated ciRcuit maintenance), gamma oscillations act as a ‘servicing’ rhythm that enables efficient translation of neural activity into vascular responses that are essential for optimal neurometabolic processes. GAMER is an extension of GENUS, where endogenous rather than entrained gamma plays a fundamental role. Finally, we propose several critical experiments to test the GAMER hypothesis.
