Postsynaptic alpha 4 beta 2 and alpha 7 type nicotinic acetylcholine receptors contribute to the local and endogenous acetylcholine-mediated synaptic transmissions in nigral dopaminergic neurons.
The local and endogenous nicotinic neuronal transmissions of dopaminergic neurons in the substantia nigra were confirmed electrophysiologically using a slice-patch technique. After identifying dopaminergic neurons based on their electrophysiological characteristics, miniature postsynaptic inward currents were recorded in the presence of atropine (a muscarinic acetylcholine receptor antagonist), bicuculline (a GABA receptor antagonist) and L-glutamic acid diethyl ester (GDEE) (a non-selective glutamate receptor antagonist). Under conditions that eliminated muscarinic, GABAergic and glutamatergic synaptic transmissions, we found miniature currents that were inhibited by the specific neuronal nicotinic receptor antagonists, dihydro-beta-erythroidine (DHbetaE) and/or methyllycaconitine (MLA) (selective alpha4beta2 and/or alpha7 nicotinic acetylcholine receptor antagonists, respectively). Under the same extracellular conditions, local stimulations in the vicinity of a target neuron evoked excitatory postsynaptic inward currents (EPSCs). These EPSCs were elicited in an extracellular Ca(2+) dependent manner and were also blocked by DHbetaE and/or MLA. These results suggest that dopaminergic neurons in the substantia nigra receive excitatory cholinergic inputs that are mediated via at least two types of postsynaptic nicotinic receptors, namely alpha7 and alpha4beta2 subtypes.
Matsubayashi
Hiroaki
H
Department of Molecular and Pharmacological Neuroscience, Graduate School of Biomedical Sciences, Hiroshima University, 1-2-3 Kasumi, Minami, Hiroshima 734-8551, Japan.
Amano
Taku
T
Seki
Takahiro
T
Sasa
Masashi
M
Sakai
Norio
N
D000109:Acetylcholine / Q000502:physiology; D000818:Animals; D004298:Dopamine / Q000502:physiology*; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D066298:In Vitro Techniques; D009474:Neurons / Q000187:drug effects; D018733:Nicotinic Antagonists / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011978:Receptors, Nicotinic / Q000502:physiology*; D013378:Substantia Nigra / Q000187:drug effects / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D064569:alpha7 Nicotinic Acetylcholine Receptor
C579165:Chrna7 protein, rat; D018733:Nicotinic Antagonists; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor; C403531:nicotinic receptor alpha4beta2; D000109:Acetylcholine; D004298:Dopamine