A distinct hypothalamus-habenula circuit governs risk preference

Abstract

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 value-guided behavior. Here, using a balanced two-alternative choice task and longitudinal two-photon calcium imaging in mice, we identify risk-preference-selective activity in LHb neurons reflecting individual risk preference before action selection. By using whole-brain anatomical tracing, multi-fiber photometry and projection-specific and cell-type-specific optogenetics, we find glutamatergic LHb projections from the medial (MH) but not lateral (LH) hypothalamus providing behavior-relevant synaptic input 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 for risk preference in habitual economic decision-making.