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.

No abstract

Previous work by Cho and Choi describing the development of a cyanoacrylamide-based fluorescence sensor for reversible detection of thiols in homogenous solutions was inadvertently omitted from the reference list of this Article. This work should have been cited in the first paragraph of the discussion, following the rationale behind the development of the Michael acceptor, as follows: 'A fluorescent sensor based on the cyanoacrylamide Michael acceptor has previously been shown to reversibly react with thiols in homogenous solutions but without any cellular applications, possibly due to the low quantum yield and poor aqueous solubility