1. Cooperative synaptic and intrinsic plasticity in a disynaptic limbic circuit drive stress-induced anhedonia and passive coping in mice
- Author
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Carol A. Tamminga, Antonello Bonci, David J. Barker, Jocelyn Wu, Eric M. Parise, Leonardo Bontempi, Sissi Palma Ribeiro, Angélica Torres-Berrío, Alejandra Lopez, Marisela Morales, Marco Pignatelli, Hugo A. Tejeda, Mingshan Xue, Zhao-Lin Cai, Yocasta Alvarez-Bagnarol, Eric J. Nestler, Federica Lucantonio, and Rosa Anna Maria Marino
- Subjects
0301 basic medicine ,Anhedonia ,Lateral hypothalamus ,Physiology ,Hippocampus ,Nucleus accumbens ,Biology ,Medium spiny neuron ,Nucleus Accumbens ,Article ,Mice ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,0302 clinical medicine ,Adaptation, Psychological ,medicine ,Animals ,Molecular Biology ,Receptors, Dopamine D1 ,Mice, Inbred C57BL ,Psychiatry and Mental health ,030104 developmental biology ,Excitatory postsynaptic potential ,Brain stimulation reward ,medicine.symptom ,Depotentiation ,Neuroscience ,030217 neurology & neurosurgery - 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.
- Published
- 2020
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