A hypothalamus-habenula circuit controls aversion.

Area of Science:

• Neuroscience
• Molecular Biology
• Computational Neuroscience

Background:

• The lateral habenula (LHb) is crucial for aversion processing and mood regulation, influencing dopamine and serotonin systems.
• Maladaptive changes in emotional valence processing circuits are implicated in affective disorders.

Purpose of the Study:

• To identify and characterize the specific glutamatergic (Vglut2) inputs controlling the LHb.
• To compare the roles of inputs from the globus pallidus internal segment (GPi) and lateral hypothalamic area (LHA) to the LHb in encoding negative value.

Main Methods:

• Monosynaptic rabies tracing to map presynaptic inputs to LHA Vglut2 and GPi neurons.
• In vivo calcium imaging to record LHA Vglut2 neuron activity during appetitive and aversive conditioning paradigms.

Main Results:

• LHb-projecting LHA Vglut2 neurons, but not GPi neurons, encode negative valence.
• LHA Vglut2 neurons receive predominantly limbic inputs, while GPi neurons receive sensorimotor inputs.
• LHA Vglut2 neurons exhibit distinct activity patterns for reward and aversion, including prediction of aversive events like mild foot shocks.

Conclusions:

• The glutamatergic LHA-LHb circuit is a critical node for encoding negative value and predicting aversive outcomes.
• This circuit plays a significant role in survival functions and emotional well-being.
• Findings provide new insights into the neural basis of affective disorders.