Optogenetic excitation in the ventral tegmental area of glutamatergic or cholinergic inputs from the laterodorsal tegmental area drives reward

摘要

Abstract Converging evidence shows that ventral tegmental area (VTA ) dopamine neurons receive laterodorsal tegmental nucleus (LDT g) cholinergic and glutamatergic inputs. To test the behavioral consequences of selectively driving the two sources of excitatoryLDT g input to theVTA , channelrhodopsin2 (ChR2) was expressed inLDT g cholinergic neurons of ChAT::Cre mice (ChATChR2 mice) or inLDT g glutamatergic neurons ofVG luT2::Cre mice (VG luT2ChR2 mice). Mice were tested in a 3chamber place preference apparatus where entry into a lightpaired chamber resulted inVTA light stimulation ofLDT gcholinergic orLDT gglutamatergic axons for the duration of a chamber stay. ChAT ChR2 mice spent more time in the lightpaired chamber and subsequently showed conditioned place preference for the lightpaired chamber in the absence of light.VG luT2ChR2 mice, entered the lightpaired chamber significantly more times than a lightunpaired chamber, but remained in the lightpaired chamber for short time periods and did not show a conditioned place preference. When each entry into the lightpaired chamber resulted in a single train ofVTA light stimulation,VG luT2ChR2 mice entered the lightpaired chamber significantly more times than the lightunpaired chamber, but spent approximately equal amounts of time in the two chambers.VTA excitation ofLDT gglutamatergic inputs may be more important for reinforcement of initial chamber entry whileVTA excitation ofLDT gcholinergic inputs may be more important for the rewarding effects of chamber stays. We suggest thatLDT gcholinergic andLDT gglutamatergic inputs to theVTA each contribute to the net rewarding effects of excitingLDT g axons in theVTA .