Cooperative synaptic and intrinsic plasticity in a disynaptic limbic circuit drive stress-induced anhedonia and passive coping in mice

Marco Pignatelli; Hugo A Tejeda; David J Barker; Leonardo Bontempi; Jocelyn Wu; Alejandra Lopez; Sissi Palma Ribeiro; Federica Lucantonio; Eric M Parise; Angélica Torres-Berrio; Yocasta Alvarez-Bagnarol; Rosa A M Marino; Zhao-Lin Cai; Mingshan Xue; Marisela Morales; Carol A Tamminga; Eric J Nestler; Antonello Bonci

doi:10.1038/s41380-020-0686-8

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Cooperative synaptic and intrinsic plasticity in a disynaptic limbic circuit drive stress-induced anhedonia and passive coping in mice

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Cooperative synaptic and intrinsic plasticity in a disynaptic limbic circuit drive stress-induced anhedonia and passive coping in mice

Marco Pignatelli, Hugo A Tejeda, David J Barker, Leonardo Bontempi, Jocelyn Wu, Alejandra Lopez, Sissi Palma Ribeiro, Federica Lucantonio, Eric M Parise, Angélica Torres-Berrio, …

Molecular psychiatry

03/11/2020

DOI: https://doi.org/10.1038/s41380-020-0686-8

PMID: 32161361

Abstract

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.

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Title: Cooperative synaptic and intrinsic plasticity in a disynaptic limbic circuit drive stress-induced anhedonia and passive coping in mice
Creators: Marco Pignatelli - Department of Psychiatry and Taylor Family Institute for Innovative Psychiatric Research, Washington University School of Medicine, St Louis, MO, 63110, USA. marco.pignatelli@wustl.edu
Hugo A Tejeda - Neuromodulation and Synaptic Integration Unit, National Institute of Mental Health Intramural Research Program, Bethesda, MD, USA. hugo.tejeda@nih.gov
David J Barker - Neuronal Networks Section, National Institute on Drug Abuse Intramural Research Program, Baltimore, MD, USA
Leonardo Bontempi - Synaptic Plasticity Section, National Institute on Drug Abuse Intramural Research Program, Baltimore, MD, USA
Jocelyn Wu - Synaptic Plasticity Section, National Institute on Drug Abuse Intramural Research Program, Baltimore, MD, USA
Alejandra Lopez - Synaptic Plasticity Section, National Institute on Drug Abuse Intramural Research Program, Baltimore, MD, USA
Sissi Palma Ribeiro - Synaptic Plasticity Section, National Institute on Drug Abuse Intramural Research Program, Baltimore, MD, USA
Federica Lucantonio - Solomon Snyder Department of Neuroscience, Johns Hopkins School of Medicine, Baltimore, MD, USA
Eric M Parise - Nash Family Department of Neuroscience, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, 10029, NY, USA
Angélica Torres-Berrio - Nash Family Department of Neuroscience, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, 10029, NY, USA
Yocasta Alvarez-Bagnarol - Synaptic Plasticity Section, National Institute on Drug Abuse Intramural Research Program, Baltimore, MD, USA
Rosa A M Marino - Synaptic Plasticity Section, National Institute on Drug Abuse Intramural Research Program, Baltimore, MD, USA
Zhao-Lin Cai - The Cain Foundation Laboratories, Jan and Dan Duncan Neurological Research Institute at Texas Children's Hospital, Houston, TX, 77030, USA
Mingshan Xue - The Cain Foundation Laboratories, Jan and Dan Duncan Neurological Research Institute at Texas Children's Hospital, Houston, TX, 77030, USA
Marisela Morales - Neuronal Networks Section, National Institute on Drug Abuse Intramural Research Program, Baltimore, MD, USA
Carol A Tamminga - Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA
Eric J Nestler - Nash Family Department of Neuroscience, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, 10029, NY, USA
Antonello Bonci - Global Institutes on Addictions, Miami, FL, USA
Publication Details: Molecular psychiatry
Date published: 03/11/2020
Grant note: R00 DA043572 / NIDA NIH HHS P50 MH066172 / NIMH NIH HHS R01 MH051399 / NIMH NIH HHS R01 MH117089 / NIMH NIH HHS
Academic Unit: Psychology (SAS)
Language: English
Resource Type: Journal article
Identifiers: 991031664405504646