TY - JOUR
T1 - Cooperative synaptic and intrinsic plasticity in a disynaptic limbic circuit drive stress-induced anhedonia and passive coping in mice
AU - Pignatelli, Marco
AU - Tejeda, Hugo A.
AU - Barker, David J.
AU - Bontempi, Leonardo
AU - Wu, Jocelyn
AU - Lopez, Alejandra
AU - Palma Ribeiro, Sissi
AU - Lucantonio, Federica
AU - Parise, Eric M.
AU - Torres-Berrio, Angélica
AU - Alvarez-Bagnarol, Yocasta
AU - Marino, Rosa A.M.
AU - Cai, Zhao Lin
AU - Xue, Mingshan
AU - Morales, Marisela
AU - Tamminga, Carol A.
AU - Nestler, Eric J.
AU - Bonci, Antonello
N1 - Funding Information:
Acknowledgements This research was supported by the Intramural Research Program of the National Institute on Drug Abuse (NIDA) at NIH, NARSAD Young Investigator Award “P&S Fund” (MP), a K99/ R00 Pathway to Independence Award (HAT and DJB), NIH grant R01MH051399 (EJN), NIH grant R01MH117089 and McKnight Foundation (MX). We also acknowledge Baylor College of Medicine Gene Vector Core for producing AAV vectors. We are grateful to Dr Francois Vautier and Joni McKenzie for assistance with transgenic mouse colonies. We thank C. Richie for assistance with viruses and the visual media department at NIDA for assistance in the preparation of figures.
Publisher Copyright:
© 2020, The Author(s).
PY - 2021/6
Y1 - 2021/6
N2 - Stress promotes negative affective states, which include anhedonia and passive coping. While these features are in part mediated by neuroadaptations in brain reward circuitry, a comprehensive framework of how stress-induced negative affect may be encoded within key nodes of this circuit is lacking. Here, we show in a mouse model for stress-induced anhedonia and passive coping that these phenomena are associated with increased synaptic strength of ventral hippocampus (VH) excitatory synapses onto D1 medium spiny neurons (D1-MSNs) in the nucleus accumbens medial shell (NAcmSh), and with lateral hypothalamus (LH)-projecting D1-MSN hyperexcitability mediated by decreased inwardly rectifying potassium channel (IRK) function. Stress-induced negative affective states are prevented by depotentiation of VH to NAcmSh synapses, restoring Kir2.1 function in D1R-MSNs, or disrupting co-participation of these synaptic and intrinsic adaptations in D1-MSNs. In conclusion, our data provide strong evidence for a disynaptic pathway controlling maladaptive emotional behavior.
AB - Stress promotes negative affective states, which include anhedonia and passive coping. While these features are in part mediated by neuroadaptations in brain reward circuitry, a comprehensive framework of how stress-induced negative affect may be encoded within key nodes of this circuit is lacking. Here, we show in a mouse model for stress-induced anhedonia and passive coping that these phenomena are associated with increased synaptic strength of ventral hippocampus (VH) excitatory synapses onto D1 medium spiny neurons (D1-MSNs) in the nucleus accumbens medial shell (NAcmSh), and with lateral hypothalamus (LH)-projecting D1-MSN hyperexcitability mediated by decreased inwardly rectifying potassium channel (IRK) function. Stress-induced negative affective states are prevented by depotentiation of VH to NAcmSh synapses, restoring Kir2.1 function in D1R-MSNs, or disrupting co-participation of these synaptic and intrinsic adaptations in D1-MSNs. In conclusion, our data provide strong evidence for a disynaptic pathway controlling maladaptive emotional behavior.
UR - http://www.scopus.com/inward/record.url?scp=85081937201&partnerID=8YFLogxK
U2 - 10.1038/s41380-020-0686-8
DO - 10.1038/s41380-020-0686-8
M3 - Article
C2 - 32161361
AN - SCOPUS:85081937201
SN - 1359-4184
VL - 26
SP - 1860
EP - 1879
JO - Molecular Psychiatry
JF - Molecular Psychiatry
IS - 6
ER -