A distinct hypothalamus-habenula circuit governs risk preference

Area of Science:

• Neuroscience
• Decision-making research
• Behavioral economics

Background:

• Risk evaluation is critical for survival in uncertain environments.
• Individual animals exhibit consistent risk preferences when choosing between safe and risky options.
• The neural basis of how the brain encodes risk preference remains largely unknown.

Purpose of the Study:

• To investigate the neural mechanisms underlying risk preference in the brain.
• To identify specific brain regions and neuronal activity associated with consistent risk-taking behavior.
• To elucidate the functional role of hypothalamic inputs to the lateral habenula in economic decision-making.

Main Methods:

• Utilized a balanced two-alternative choice task in mice to assess risk preference.
• Employed longitudinal two-photon calcium imaging to monitor neuronal activity in the lateral habenula (LHb).
• Conducted whole-brain anatomical tracing, multi-fiber photometry, and projection-specific optogenetics to map and manipulate neural circuits.

Main Results:

• Identified risk-preference-selective neuronal activity in the LHb that predicts individual risk preference before action selection.
• Discovered that glutamatergic projections from the medial hypothalamus (MH) to the LHb, but not the lateral hypothalamus (LH), provide behavior-relevant synaptic input.
• Demonstrated that MH→LHb projections elicit both excitatory and inhibitory postsynaptic responses, while LH→LHb projections are exclusively excitatory.

Conclusions:

• The lateral habenula contains neurons that encode individual risk preferences.
• Functionally distinct hypothalamus-habenula circuits, specifically MH→LHb projections, play a crucial role in mediating risk preference during decision-making.
• This study reveals novel neural pathways involved in habitual economic decision-making and risk assessment.