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Brain Structure and Function

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30.05.2022 | Original Article

GABAergic interneurons’ feedback inhibition of dorsal raphe-projecting pyramidal neurons of the medial prefrontal cortex suppresses feeding of adolescent female mice undergoing activity-based anorexia

verfasst von: Muzi Du, Adrienne Santiago, Cenk Akiz, Chiye Aoki

Erschienen in: Brain Structure and Function | Ausgabe 6/2022

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Abstract

Anorexia Nervosa (AN) is characterized by voluntary food restriction, excessive exercise and extreme body weight loss. AN is particularly prevalent among adolescent females experiencing stress-induced anxiety. We used the animal model, activity-based anorexia (ABA), which captures these characteristics of AN, to reveal the neurobiology underlying individual differences in AN vulnerability. Dorsal raphe (DR) regulates feeding and is recruited when coping inescapable stress. Through chemogenetic activation, we investigated the role of mPFC pyramidal neurons projecting to DR (mPFC→DR) in adolescent female mice’s decision to eat or exercise following ABA induction. Although the DREADD ligand C21 could activate 44% of the mPFC→DR neurons, this did not generate significant group mean difference in the amount of food intake, compared to control ABA mice without chemogenetic activation. However, analysis of individuals’ responses to C21 revealed a significant, positive correlation between food intake and mPFC→DR neurons that co-express cFos, a marker for neuronal activity. cFos expression by GABAergic interneurons (GABA-IN) in mPFC was significantly greater than that for the control ABA mice, indicating recruitment of GABA-IN by mPFC→DR neurons. Electron microscopic immunohistochemistry revealed that GABAergic innervation is 60% greater for the PFC→DR neurons than adjacent Layer 5 pyramidal neurons without projections to DR. Moreover, individual differences in this innervation correlated negatively with food intake specifically on the day of C21 administration. We propose that C21 activates two antagonistic pathways: (1) PFC→DR pyramidal neurons that promote food intake; and (2) GABA-IN in the mPFC that dampen food intake through feedback inhibition of mPFC→DR neurons.

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Titel: GABAergic interneurons’ feedback inhibition of dorsal raphe-projecting pyramidal neurons of the medial prefrontal cortex suppresses feeding of adolescent female mice undergoing activity-based anorexia
verfasst von: Muzi Du
Adrienne Santiago
Cenk Akiz
Chiye Aoki
Publikationsdatum: 30.05.2022
Verlag: Springer Berlin Heidelberg
Erschienen in: Brain Structure and Function / Ausgabe 6/2022
Print ISSN: 1863-2653
Elektronische ISSN: 1863-2661
DOI: https://doi.org/10.1007/s00429-022-02507-9

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GABAergic interneurons’ feedback inhibition of dorsal raphe-projecting pyramidal neurons of the medial prefrontal cortex suppresses feeding of adolescent female mice undergoing activity-based anorexia

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