When faced with a safe option and a risky option of similar expected value, individuals often show stable preferences: some consistently avoid risk, whereas others are more willing to accept uncertainty. How such individual risk preference is represented in neural circuits has remained poorly understood. Yaroslav Sych contributed to investigate how the brain encodes risk preference during value-guided decision-making., in a study led by Fritjof Helmchen’s group at the University of Zurich,.
This study focused on the lateral habenula, a small epithalamic structure involved in value-guided behavior, aversion and motivational state. Using a balanced two-alternative choice task in mice, the authors showed that risk preference is reflected in lateral habenula activity before action selection. In other words, habenula dynamics did not simply report the outcome of a previous choice; they carried information about the animal’s upcoming risk-related decision.
A central advance of the study is the identification of functionally distinct hypothalamus–habenula pathways. Combining whole-brain anatomical tracing, multi-fiber photometry, two-photon calcium imaging, optogenetic perturbations and slice physiology, the work revealed that projections from medial and lateral hypothalamic regions to the lateral habenula contribute differently to risk-related decision-making. In particular, medial hypothalamus inputs to the lateral habenula provided behaviorally relevant signals before action selection, whereas lateral hypothalamic inputs played a distinct functional role.
At the cellular level, microendoscopic two-photon imaging revealed lateral habenula neurons whose activity was selective for the animal’s risk preference. This selectivity decreased when medial hypothalamic inputs were silenced, supporting a causal role for this pathway in shaping risk-related habenula activity. Slice experiments further showed that medial hypothalamus projections can evoke both excitatory and inhibitory postsynaptic responses in lateral habenula neurons, consistent with fine-tuned gain control, whereas lateral hypothalamus projections were predominantly excitatory.
A useful way to summarize the result is: risk preference is not encoded by a single “risk neuron” or a generic reward signal. It emerges from specific circuit interactions between hypothalamic inputs and lateral habenula neurons, before the animal commits to a choice.
This work adds a circuit-level mechanism to our understanding of economic decision-making. It shows that stable individual differences in risk preference can be traced to defined hypothalamus–habenula pathways, linking value-guided behavior to specific anatomical and functional motifs. Because the lateral habenula is also implicated in depression, addiction and maladaptive decision-making, these findings may help frame future studies of psychiatric conditions in which risk evaluation and choice policies are altered.
To know more:
- Groos, D., Reuss, A. M., Rupprecht, P., Stachniak, T., Lewis, C., Han, S., Roggenbach, A., Sturman, O., Sych, Y., Wieckhorst, M., et al. (2025). A distinct hypothalamus–habenula circuit governs risk preference. Nature Neuroscience, 28, 361–373. https://doi.org/10.1038/s41593-024-01856-4.