HCN2 in cholinergic interneurons of the nucleus accumbens mediates reward response
Lee, J.; Weinberger, M.; Kawahara, Y.; Cheng, J.; Umscweif, G.; Medrihan, L.; Flajolet, M.; Nishi, A.; Sagi, Y.
Show abstract
Cholinergic interneurons (ChIs) of the nucleus accumbens (NAc) are important for mediating the behavioral response to rewarding stimuli. A major role for these cells is to regulate dopamine (DA) transmission by activating cholinergic receptors at local DAergic nerve terminals. However, the mechanisms that enable cholinergic neurons to enhance DA release in response to reward remain unknown. Here we report that the hyperpolarization-activated cyclic nucleotide-gated channel 2 (HCN2) in NAc ChIs mediates an enhancement in DA signaling in response to rewarding stimuli. The HCN current in NAc ChIs and its modulation by DA, as well as the increase in cholinergic efflux by local cocaine infusion were impaired in mice with deletion of HCN2 in cholinergic cells. Enhancement in the DA efflux and signaling in the NAc in response to rewarding stimuli, as well as cocaine conditioning were also dependent on HCN2 in ChIs. These results provide a mechanistic link between the activity of NAc ChIs and reward encoding.
Matching journals
The top 3 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Regulation of dopamine-dependent transcription and cocaine action by Gadd45b 97%
- Conditional, inducible gene silencing in dopamine neurons reveals a sex-specific role for Rit2 GTPase in acute cocaine response and striatal function 96%
- Release of endogenous dynorphin opioids in the prefrontal cortex disrupts cognition 96%
Similar papers in this journal
- Glutamatergic dysfunction leads to a hyper-dopaminergic phenotype through deficits in short-term habituation: a mechanism for aberrant salience. 96%
- Retinoic acid-mediated homeostatic plasticity drives cell type-specific CP-AMPAR accumulation in nucleus accumbens core and incubation of cocaine craving 95%
- Ethanol's interaction with BK channel α subunit residue K361 does not mediate behavioral responses to alcohol in mice 95%
Similar papers in this journal
- Epac2 in midbrain dopamine neurons contributes to cocaine reinforcement via facilitation of dopamine release 97%
- The cation channel mechanisms of subthreshold inward depolarizing currents in the VTA dopaminergic neurons and their roles in the chronic-stress-induced depression-like behavior 96%
- Neurexins Regulate GABA Co-release by Dopamine Neurons 96%
Similar papers in this journal
- Suppression of cortico-striatal circuit activity improves cognitive flexibility and prevents body weight loss in activity-based anorexia in rats 96%
- CRF release from a unique subpopulation of accumbal neurons constrains action-outcome acquisition in reward learning 95%
- Histone deacetylase 5 in prelimbic prefrontal cortex limits context-associated cocaine seeking 95%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.