Local production of corticotropin-releasing hormone in prefrontal cortex modulates male-specific novelty exploration.
Local production of corticotropin-releasing hormone in prefrontal cortex modulates male-specific novelty exploration.
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DOI：
10.1073/pnas.2211454119
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发表时间：
2022-12-06
影响因子：
11.1
通讯作者：
中科院分区：
文献类型：
--
作者：
CRH is a well-known neuropeptide hormone associated with stress response and anxiety. It is mainly secreted by paraventricular neurons in the hypothalamus. However, CRH is also produced by a sparse population of cortical interneurons that project locally in the medial prefrontal cortex. Using genetic manipulations, we show that CRH released by this interneuron population regulates exploration of novel objects and novel mice in a sex-specific manner. Neuromodulatory substances can be released from distal afferents for communication between brain structures or produced locally to modulate neighboring circuit elements. Corticotropin-releasing hormone (CRH) from long-range neurons in the hypothalamus projecting to the medial prefrontal cortex (mPFC) has been shown to induce anxiety-like behaviors. However, the role of CRH produced in the mPFC has not been investigated. Here we demonstrate that a specific class of mPFC interneurons that express CRH (CrhINs) releases CRH upon high-frequency stimulation to enhance excitability of layer 2/3 pyramidal cells (L2/3 PCs) expressing the CRH receptors. When stimulated at low frequency, CrhINs release GABA resulting in the inhibition of oxytocin receptor-expressing interneurons (OxtrINs) and L2/3 PCs. Conditional deletion of CRH in mPFC CrhINs and chemogenetic activation of CrhINs have opposite effects on novelty exploration in male but not in female mice, and do not affect anxiety-related behaviors in either males or females. Our data reveal that CRH produced by local interneurons in the mPFC is required for sex-specific novelty exploration and suggest that our understanding of complex behaviors may require knowledge of local and remote neuromodulatory action.
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影响因子：
25
作者：
Gouwens NW;Sorensen SA;Berg J;Lee C;Jarsky T;Ting J;Sunkin SM;Feng D;Anastassiou CA;Barkan E;Bickley K;Blesie N;Braun T;Brouner K;Budzillo A;Caldejon S;Casper T;Castelli D;Chong P;Crichton K;Cuhaciyan C;Daigle TL;Dalley R;Dee N;Desta T;Ding SL;Dingman S;Doperalski A;Dotson N;Egdorf T;Fisher M;de Frates RA;Garren E;Garwood M;Gary A;Gaudreault N;Godfrey K;Gorham M;Gu H;Habel C;Hadley K;Harrington J;Harris JA;Henry A;Hill D;Josephsen S;Kebede S;Kim L;Kroll M;Lee B;Lemon T;Link KE;Liu X;Long B;Mann R;McGraw M;Mihalas S;Mukora A;Murphy GJ;Ng L;Ngo K;Nguyen TN;Nicovich PR;Oldre A;Park D;Parry S;Perkins J;Potekhina L;Reid D;Robertson M;Sandman D;Schroedter M;Slaughterbeck C;Soler-Llavina G;Sulc J;Szafer A;Tasic B;Taskin N;Teeter C;Thatra N;Tung H;Wakeman W;Williams G;Young R;Zhou Z;Farrell C;Peng H;Hawrylycz MJ;Lein E;Ng L;Arkhipov A;Bernard A;Phillips JW;Zeng H;Koch C
通讯作者：
Koch C
影响因子：
5.3
作者：
Kratzer S;Mattusch C;Metzger MW;Dedic N;Noll-Hussong M;Kafitz KW;Eder M;Deussing JM;Holsboer F;Kochs E;Rammes G
通讯作者：
Rammes G
影响因子：
3.4
作者：
Laubach M;Amarante LM;Swanson K;White SR
通讯作者：
White SR
影响因子：
4.3
作者：
Dedic, Nina;Kuhne, Claudia;Deussing, Jan M.
通讯作者：
Deussing, Jan M.
影响因子：
4.3
作者：
Ghaderi, Parviz;Marateb, Hamid Reza;Safari, Mir-Shahram
通讯作者：
Safari, Mir-Shahram