Social defeat stress-specific increase in c-Fos expression in the extended amygdala in mice: Involvement of dopamine D1 receptor in the medial prefrontal cortex

Chisato Numa,Tomoyuki Furuyashiki,Hirotaka Nagai,Midori Nagai,Masayuki Taniguchi,Ryota Shinohara

doi:10.1038/s41598-019-52997-7

Abstract

We recently reported that dopamine D1 receptor in the medial prefrontal cortex (mPFC) is activated by subthreshold social defeat stress and suppresses the induction of depressive-like behavior in mice. However, which mPFC projection(s) mediates this antidepressant-like effect remains poorly understood. Here we show that social defeat stress specifically increased c-Fos expression, a marker for neuronal activity, in distinct brain regions involved in emotional regulation, relative to novelty-induced exploration. Among these brain areas, D1 knockdown in the mPFC decreased social defeat stress-induced c-Fos expression in the interstitial nucleus of the posterior limb of the anterior commissure (IPAC), a subregion of the extended amygdala. Using retrograde adeno-associated virus vectors and transgenic mice expressing Cre recombinase under the D1 promoter, we also found that D1-expressing deep-layer pyramidal neurons in the mPFC send direct projections to the IPAC. These findings indicate that social defeat stress specifically activates neurons in distinct brain areas, among which the IPAC is regulated by dopamine D1 receptor in the mPFC perhaps through direct projections. Thus, this study provides hints toward identifying neural circuits that underlie antidepressant-like effects of stress-induced dopamine D1 receptor signaling in the mPFC.

Highlights

We recently reported that dopamine D1 receptor in the medial prefrontal cortex is activated by subthreshold social defeat stress and suppresses the induction of depressive-like behavior in mice
These findings indicate that neurons in distinct brain regions including the extended amygdala, an anatomical continuity of GABAergic neurons in bed nucleus of the stria terminalis (BNST), IPAC and central amygdala (CeA) involved in emotional regulation[14], were selectively activated by social defeat stress, whereas neurons in other brain regions including prelimbic cortex (PL), infralimbic cortex (IL), anterior cingulate cortex (ACC), substantia innominata (SI), ventral tegmental area (VTA) and supramammillary nucleus (SUM) were activated by both the exploration and the stress
We found that single exposure to social defeat stress induced c-Fos expression in multiple brain areas

Summary

Introduction

We recently reported that dopamine D1 receptor in the medial prefrontal cortex (mPFC) is activated by subthreshold social defeat stress and suppresses the induction of depressive-like behavior in mice. We show that social defeat stress increased c-Fos expression, a marker for neuronal activity, in distinct brain regions involved in emotional regulation, relative to novelty-induced exploration Among these brain areas, D1 knockdown in the mPFC decreased social defeat stressinduced c-Fos expression in the interstitial nucleus of the posterior limb of the anterior commissure (IPAC), a subregion of the extended amygdala. In the present study, using c-Fos expression, a marker for neuronal activity, we found that single exposure to social defeat stress activates distinct brain areas including the extended amygdala, relative to novelty-induced exploration Among these brain areas, knockdown of dopamine D1 receptor in the mPFC decreased social defeat stress-induced c-Fos expression in the interstitial nucleus of the posterior limb of the anterior commissure (IPAC), a subregion of the extended amygdala

Methods

Results

Conclusion