Aversion Encoding and Behavioral State Modulation of Physiologically Defined Cell Types in the Lateral Habenula

The lateral habenula (LHb) integrates aversive information to regulate motivated behaviors. Despite recent advances in identifying neuronal diversity at the molecular level, in vivo electrophysiological diversity of LHb neurons remains poorly understood. Understanding this diversity is essential for deciphering how information is processed in the LHb. To address this gap, we conducted in vivo juxtacellular recording and labeling of single LHb neurons in mice. Morphological analysis revealed a direct axonal projection of LHb neurons to the mediodorsal thalamus. To analyze in vivo LHb firing patterns, we applied an unsupervised clustering algorithm. This analysis identified four distinct spontaneous firing patterns of LHb neurons, which were consistent across both anesthetized and awake states. To determine whether these firing patterns correlate with function, we recorded neuronal responses to foot shock stimulation in anesthetized mice and monitored spontaneous behavior in awake mice. We found that low-firing, bursting neurons were preferentially modulated by foot shocks in anesthetized mice and also tracked behavioral states in awake mice. Collectively, our findings indicate significant electrophysiological diversity among LHb neurons, which is associated with their modulation by aversive stimuli and behavioral state.