Document Type

Article

Version Deposited

Published Version

Publication Date

3-13-2019

Publication Title

The Journal of Neuroscience : The Official Journal of the Society for Neuroscience

DOI

10.1523/JNEUROSCI.2701-18.2019

Abstract

The PFC and extended frontostriatal circuitry support higher cognitive processes that guide goal-directed behavior. PFC-dependent cognitive dysfunction is a core feature of multiple psychiatric disorders. Unfortunately, a major limiting factor in the development of treatments for PFC cognitive dysfunction is our limited understanding of the neural mechanisms underlying PFC-dependent cognition. We recently demonstrated that activation of corticotropin-releasing factor (CRF) receptors in the caudal dorsomedial PFC (dmPFC) impairs higher cognitive function, as measured in a working memory task. Currently, there remains much unknown about CRF-dependent regulation of cognition, including the source of CRF for cognition-modulating receptors and the output pathways modulated by these receptors. To address these issues, the current studies used a viral vector-based approach to chemogenetically activate or inhibit PFC CRF neurons in working memory-tested male rats. Chemogenetic activation of caudal, but not rostral, dmPFC CRF neurons potently impaired working memory, whereas inhibition of these neurons improved working memory. Importantly, the cognition-impairing actions of PFC CRF neurons were dependent on local CRF receptors coupled to protein kinase A. Additional electrophysiological recordings demonstrated that chemogenetic activation of caudal dmPFC CRF neurons elicits a robust degradation of task-related coding properties of dmPFC pyramidal neurons and, to a lesser extent, medium spiny neurons in the dorsomedial striatum. Collectively, these results demonstrate that local CRF release within the caudal dmPFC impairs frontostriatal cognitive and circuit function and suggest that CRF may represent a potential target for treating frontostriatal cognitive dysfunction.

Comments

For articles published after 2014, the Society for Neuroscience (SfN) retains an exclusive license to publish the article for 6 months; after 6 months, the work becomes available to the public to copy, distribute, or display under the terms of the Creative Commons Attribution 4.0 International License (CC-BY).

Creative Commons License

Creative Commons Attribution 4.0 License
This work is licensed under a Creative Commons Attribution 4.0 License.

Published Citation

Hupalo S, Martin AJ, Green RK, Devilbiss DM, Berridge CW. Prefrontal corticotropin-releasing factor (CRF) neurons act locally to modulate frontostriatal cognition and circuit function. Journal of Neuroscience. 2019 Mar 13;39(11):2080-2090. Epub 2019 Jan 16. doi: 10.1523/JNEUROSCI.2701-18.2019. PMID: 30651328.

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