Neuronal nicotinic acetylcholine receptors (nAChRs) belong to the superfamily of ligand-gated ion channels and are widely expressed throughout the central and peripheral nervous systems. nAChRs play crucial roles in modulating a wide range of higher cognitive functions by mediating presynaptic, postsynaptic, and extrasynaptic signaling1.
Nicotinic acetylcholine receptors containing α6 subunits (nAChRα6) exhibit a unique expression pattern in the mammalian brain. nAChRs α6 are abundantly expressed in the midbrain dopaminergic (DAergic) system, including mesocorticolimbic and nigrostriatal pathways, and particularly present in presynaptic nerve terminals2. nAChRα6 expressed on DAergic neurons can be activated by endogenous acetylcholine (Ach) or exogenous nicotine and analogs, which suggests that the activation of nAChRα6 may play a vital role in central cholinergic circuits, including modulation of locomotor behaviour and drug addiction3. In addition, nAChRα6 is particularly susceptible to nigrostriatal damage, which may lead to Parkinson’s disease (PD)4. nAChRα6 are also expressed by sensory neurons; therefore, they may also play a role in disorders related to sensory perception5.
