Retrograde inhibition by a specific subset of interpeduncular α5 nicotinic neurons regulates nicotine preference

This is the authors' abstract. We don't add key points for this paper.

Significance The CHRNA5-A3-B4 gene cluster, which encodes the α5, α3, and β4 nicotinic acetylcholine receptor subunits, has been genetically associated with high risk of developing nicotine dependence. Here we show that a specific α5 nicotinic receptor population in the midbrain interpeduncular nucleus (IPN) responds to chronic nicotine by increasing the expression of genes that regulate feedback inhibition of the medial habenula, the major source of input to the IPN. Inhibiting neurotransmitter release from this population of α5 + neurons or reducing expression of one of these genes, Nos1 , blocks the rewarding effects of nicotine. Our data identify molecular mechanisms that may explain the genetic link between CHRNA5 and smoking predisposition in humans.