Commentary Cell Science Reviews Vol 5 No 3 ISSN 1742-8130

α6-containing nicotinic receptors unmasked in vivo:
selective dopaminergic neuronal expression and activation in motor and reward pathways

Neuronal nicotinic acetylcholine receptors (nAChRs) containing the α6 subunit (α6*) are significantly expressed in key motor and reward dopaminergic brain areas including the mesolimbic and mesostriatal pathways. Activated by the endogenous neurotransmitter, acetylcholine (ACh), as well as the addictive component of tobacco, nicotine, α6* nAChRs are hypothesized to play a role in nicotine dependence and motor control yet the function of these receptors in physiology and behavior has remained elusive. In a recent report, Drenan et al. provide a significant step forward in elucidating the importance of α6* nAChRs. By genetically engineering a BAC-transgenic mouse expressing α6* nAChR with a gain of function mutation, Drenan et al. revealed that these receptors are critical for the motor stimulating effects of ACh and nicotine. Importantly, α6* nAChRs are selectively expressed only in DAergic neurons in midbrain and not GABAergic interneurons indicating that they could be paramount for the reinforcing properties of nicotine and may represent a therapeutic target for motor diseases associated with dopamine insufficiency. Together the result from this study provide a new tool to unlock the mysteries of α6* nAChRs in modulating DAergic neurotransmission, as well as uncovering the role of the cholinergic system in motor activity and motivation.

Click to access complete issue ($5.49) and to download full article in or formats