title: Nicotine modulates GABAergic transmission to dopaminergic neurons in substantia nigra pars compacta.
abstract: 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.
authors.affiliation: Department of Anesthesiology, Pharmacology and Physiology, New Jersey Medical School/UMDNJ, Newark, NJ 07103, USA.
authors.forename: Cheng
authors.initials: C
authors.lastname: Xiao
authors.forename: Ke-chun
authors.initials: KC
authors.lastname: Yang
authors.forename: Chun-yi
authors.initials: CY
authors.lastname: Zhou
authors.forename: Guo-zhang
authors.initials: GZ
authors.lastname: Jin
authors.forename: Jie
authors.initials: J
authors.lastname: Wu
authors.forename: Jiang-hong
authors.initials: JH
authors.lastname: Ye
mesh_terms: 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
chemical_list: 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