The convergence of aversion and reward signals in individual neurons of the mice lateral habenula

Abstract

The lateral habenula (LHb) and ventral tegmental area (VTA) are two structures closely connected, and they serve as aversion and reward junction of the brain, respectively. This study investigated whether single neurons in the LHb/VTA respond to both aversion and reward stimuli and how these neurons regulate aversion and reward processing. Using optogenetic combined with multi-channel recording of LHb / VTA neuronal discharge, we found that most single neurons in the LHb/ VTA respond to both aversion and reward stimuli. Interestingly, majority of neurons in LHb were aversion-activated and reward-inhibited neurons, consisting mainly of glutamatergic neurons, while most neurons in VTA were reward-activated and aversion-inhibited neurons, which inhibited by glutamatergic neurons in the LHb. Furthermore, optogenetic activation or inhibition of glutamatergic neurons in LHb and their terminals in VTA could induce aversive or reward behaviors. These results indicate that identical neurons in the LHb and VTA have different responses to reward and aversion stimuli. The aversion behaviors induced by activating LHb glutamatergic neurons may be due to its inhibition on reward-activated neurons in VTA. This study suggests that interplay between the LHb and VTA neurons may play a key role in regulating reward and aversion behaviors.