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The yin yang pathway in the aversive brain
The habenulo-interpeduncular (Hb-IPN) pathway is an evolutionarily conserved neural pathway mediating diverse pathophysiological behaviors including locomotion, fear, anxiety and nicotine addiction. The left and right habenular nuclei consists of hundreds of neurons that send long axons to project to its target, the interpeduncular nucleus (IPN). In larval zebrafish, the Hb-IPN pathway exhibit striking left-right asymmetry in their morphology, molecular properties and connectivity. While most habenular neurons are glutamatergic, distinct populations of neurons co-express transcripts for various neuromodulators and peptides including acetylcholine and somatostatin. Calcium imaging of spontaneous and evoked activity suggest that neurons with distinct neurotransmitter phenotypes function together. Analysis of calcium activity of the habenular terminals at their target nucleus, the IPN, indicate negative correlation between cholinergic and non-cholinergic neurons. These results suggest an innate negatively correlated relationship between different neuronal populations of the Hb-IPN pathway that may underlie how different aversive emotions manifest in animals.