Distinct hypothalamus-habenula circuits govern risk preference

Appropriate risk evaluation is essential for survival in complex, uncertain environments. Confronted with choosing between certain (safe) and uncertain (risky) options, animals show strong preference for either option consistently across extended time periods. How such risk preference is encoded in the brain remains elusive. A candidate region is the lateral habenula (LHb), which is prominently involved in various value-guided behaviors. Here, using a balanced two-alternative choice task and longitudinal two-photon calcium imaging, we find LHb neurons with risk-preference-selective activity reflecting individual risk preference prior to action selection. By employing whole-brain anatomical tracing, multi-fiber photometry, and projection- and cell-type-specific optogenetics, we identify glutamatergic LHb projections from lateral and medial hypothalamus (LH/MH) that provide functionally distinct synaptic inputs before action selection. Optogenetic stimulation of MH->LHb axons evoked excitatory and inhibitory postsynaptic responses, whereas LH->LHb projections were excitatory. We thus reveal functionally distinct hypothalamus-habenula circuits that govern risk preference in habitual economic decision-making.