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Neuronal tuning to threat exposure remains stable in the mouse prefrontal cortex over multiple days.

ABSTRACT: Intense threat elicits action in the form of active and passive coping. The medial prefrontal cortex (mPFC) executes top-level control over the selection of threat coping strategies, but the dynamics of mPFC activity upon continuing threat encounters remain unexplored. Here, we used 1-photon calcium imaging in mice to probe the activity of prefrontal pyramidal cells during repeated exposure to intense threat in a tail suspension (TS) paradigm. A subset of prefrontal neurons displayed selective activation during TS, which was stably maintained over days. During threat, neurons showed specific tuning to active or passive coping. These responses were unrelated to general motion tuning and persisted over days. Moreover, the neural manifold traversed by low-dimensional population activity remained stable over subsequent days of TS exposure and was preserved across individuals. These data thus reveal a specific, temporally, and interindividually conserved repertoire of prefrontal tuning to behavioral responses under threat.

SUBMITTER: Sylte OC

PROVIDER: S-EPMC10783789 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature

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Neuronal tuning to threat exposure remains stable in the mouse prefrontal cortex over multiple days.

Sylte Ole Christian OC Muysers Hannah H Chen Hung-Ling HL Bartos Marlene M Sauer Jonas-Frederic JF

PLoS biology 20240111 1

Intense threat elicits action in the form of active and passive coping. The medial prefrontal cortex (mPFC) executes top-level control over the selection of threat coping strategies, but the dynamics of mPFC activity upon continuing threat encounters remain unexplored. Here, we used 1-photon calcium imaging in mice to probe the activity of prefrontal pyramidal cells during repeated exposure to intense threat in a tail suspension (TS) paradigm. A subset of prefrontal neurons displayed selective a ...[more]

PMID: 38206890

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Project description:Conditioned changes in the emotional response to threat (e.g. aversive unconditioned stimulus; UCS) are mediated in part by the prefrontal cortex (PFC). Unpredictable threats elicit large emotional responses, while the response is diminished when the threat is predictable. A better understanding of how PFC connectivity to other brain regions varies with threat predictability would provide important insights into the neural processes that mediate conditioned diminution of the emotional response to threat. The present study examined brain connectivity during predictable and unpredictable threat exposure using a fear conditioning paradigm (previously published in Wood et al., 2012) in which unconditioned functional magnetic resonance imaging data were reanalyzed to assess effective connectivity. Granger causality analysis was performed using the time series data from 15 activated regions of interest after hemodynamic deconvolution, to determine regional effective connectivity. In addition, connectivity path weights were correlated with trait anxiety measures to assess the relationship between negative affect and brain connectivity. Results indicate the dorsomedial PFC (dmPFC) serves as a neural hub that influences activity in other brain regions when threats are unpredictable. In contrast, the dorsolateral PFC (dlPFC) serves as a neural hub that influences the activity of other brain regions when threats are predictable. These findings are consistent with the view that the dmPFC coordinates brain activity to take action, perhaps in a reactive manner, when an unpredicted threat is encountered, while the dlPFC coordinates brain regions to take action, in what may be a more proactive manner, to respond to predictable threats. Further, dlPFC connectivity to other brain regions (e.g. ventromedial PFC, amygdala, and insula) varied with negative affect (i.e. trait anxiety) when the UCS was predictable, suggesting that stronger connectivity may be required for emotion regulation in individuals with higher levels of negative affect.

Dataset Information

Neuronal tuning to threat exposure remains stable in the mouse prefrontal cortex over multiple days.

Publications

Neuronal tuning to threat exposure remains stable in the mouse prefrontal cortex over multiple days.

Similar Datasets

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