Nicotine modulates GABAergic transmission to dopaminergic neurons in substantia nigra pars compacta.
OBJECTIVE
Dopaminergic neurons in the substantia nigra pars compacta (SNc) play important roles in motor control and drug addiction. As the major afferent, GABAergic innervation controls the activity of SNc dopaminergic neurons. Although it is clear that nicotine modulates SNc dopaminergic neurons by activating subtypes of somatodendritic nicotinic acetylcholine receptors (nAChRs), the detailed mechanisms of this activation remain to be addressed.


METHODS
In the current study, we recorded GABA(A) receptor-mediated spontaneous inhibitory postsynaptic currents (sIPSCs) from dissociated SNc dopaminergic neurons that were obtained using an enzyme-free procedure. These neurons preserved some functional terminals after isolation, including those that release GABA.


RESULTS
We found that both extra- and intra-cellular calcium modulates sIPSCs in these neurons. Furthermore, both nicotine and endogenous acetylcholine enhance the frequency of sIPSCs. Moreover, endogenous acetylcholine tonically facilitates sIPSC frequency, primarily by activating the alpha4beta2* nAChRs on the GABAergic terminals.


CONCLUSIONS
Nicotine facilitates GABA release onto SNc dopaminergic neurons mainly via the activation of presynaptic alpha4beta2* nAChRs.
Xiao
Cheng
C
Department of Anesthesiology, Pharmacology and Physiology, New Jersey Medical School/UMDNJ, Newark, NJ 07103, USA.
Yang
Ke-chun
KC
Zhou
Chun-yi
CY
Jin
Guo-zhang
GZ
Wu
Jie
J
Ye
Jiang-hong
JH
D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D018698:Glutamic Acid / Q000378:metabolism; D066298:In Vitro Techniques; D053444:Inhibitory Postsynaptic Potentials / Q000187:drug effects; D009474:Neurons / Q000378:metabolism; D009538:Nicotine / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000494:pharmacology*; D051381:Rats; D011963:Receptors, GABA-A / Q000378:metabolism*; D011978:Receptors, Nicotinic / Q000187:drug effects / Q000378:metabolism; D017661:Receptors, Presynaptic / Q000187:drug effects / Q000378:metabolism; D013378:Substantia Nigra / Q000187:drug effects / Q000378:metabolism
D018722:Nicotinic Agonists; D011963:Receptors, GABA-A; D011978:Receptors, Nicotinic; D017661:Receptors, Presynaptic; C403531:nicotinic receptor alpha4beta2; D018698:Glutamic Acid; D009538:Nicotine; D000109:Acetylcholine; D002118:Calcium; D004298:Dopamine