Authors: 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
Published: 2020-03-11
DOI: 10.1038/s41380-020-0686-8
Source: Full article
AbstractStress 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.