Fig. 5.
Habenula-interpeduncular mechanisms of nicotine aversion. Neurons in dorsal and ventral mHb express genes implicated in nicotine aversion and other aversion-related behavioral states. These genes include the orphan G-protein coupled receptor (GPCR) GPR151, the transcription factor TCF7L2, the phosphatase PP2A, neurokinins and their receptors, GABAB receptors, and NMDA receptors that contain NR3A subunits. The IPn receives inputs from the nTS that release the neuropeptide GLP-1, which facilitates excitatory transmission in the IPn and thereby enhances nicotine aversion. The IPn also receives inputs from VTA neurons that release dopamine and CRF, both of which increase IPn neural activity. Excitatory transmission in the IPn derived from excitatory inputs is regulated by locally released glycine, nitric oxide, and endocannabinoids. The IPn sends an inhibitory projection to the LDTg that inhibits cholinergic projections from the LDTg to the VTA, which results in decreased activity of VTA dopamine neurons. See main text for further details.