Cooperative synaptic and intrinsic plasticity in a disynaptic limbic circuit drive stress-induced anhedonia and passive coping in mice.
Marco PignatelliHugo A TejedaDavid J BarkerLeonardo BontempiJocelyn WuAlejandra LopezSissi Palma RibeiroFederica LucantonioEric M PariseAngélica Torres-BerrioYocasta Alvarez-BagnarolRosa A M MarinoZhao-Lin CaiMingshan XueMarisela MoralesCarol A TammingaEric J NestlerAntonello BonciPublished in: Molecular psychiatry (2020)
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.
Keyphrases
- stress induced
- prefrontal cortex
- depressive symptoms
- social support
- mouse model
- spinal cord
- bipolar disorder
- minimally invasive
- white matter
- type diabetes
- machine learning
- multiple sclerosis
- early stage
- electronic health record
- sentinel lymph node
- deep brain stimulation
- lymph node
- adipose tissue
- brain injury
- blood brain barrier
- data analysis
- high fat diet induced