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

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 excitatory LDT g input to the VTA , channelrhodopsin‐2 (ChR2) was expressed in LDT g cholinergic neurons of ChAT::Cre mice (ChAT‐ChR2 mice) or in LDT g glutamatergic neurons of VG luT2::Cre mice ( VG luT2‐ChR2 mice). Mice were tested in a 3‐chamber place preference apparatus where entry into a light‐paired chamber resulted in VTA light stimulation of LDT g‐cholinergic or LDT g‐glutamatergic axons for the duration of a chamber stay. Ch AT ‐ChR2 mice spent more time in the light‐paired chamber and subsequently showed conditioned place preference for the light‐paired chamber in the absence of light. VG luT2‐ChR2 mice, entered the light‐paired chamber significantly more times than a light‐unpaired chamber, but remained in the light‐paired chamber for short time periods and did not show a conditioned place preference. When each entry into the light‐paired chamber resulted in a single train of VTA light stimulation, VG luT2‐ChR2 mice entered the light‐paired chamber significantly more times than the light‐unpaired chamber, but spent approximately equal amounts of time in the two chambers. VTA excitation of LDT g‐glutamatergic inputs may be more important for reinforcement of initial chamber entry while VTA excitation of LDT g‐cholinergic inputs may be more important for the rewarding effects of chamber stays. We suggest that LDT g‐cholinergic and LDT g‐glutamatergic inputs to the VTA each contribute to the net rewarding effects of exciting LDT g axons in the VTA .