Nicotine enhancement of fast excitatory synaptic transmission in CNS by presynaptic receptors.
The behavioral and cognitive effects of nicotine suggest that nicotinic acetylcholine receptors (nAChRs) participate in central nervous system (CNS) function. Although nAChR subunit messenger RNA (mRNA) and nicotine binding sites are common in the brain, there is little evidence for synapses mediated by nAChRs in the CNS. To test whether, CNS nAChRs might modify rather than mediate transmission, the regulation of excitatory synaptic transmission by these receptors was examined. Nanomolar concentrations of nicotine enhanced both glutamatergic and cholinergic synaptic transmission by activation of presynaptic nAChRs that increased presynaptic [Ca2]i. Pharmacological and subunit deletion experiments reveal that these presynaptic nAChRs include the alpha 7 subunit. These findings reveal that CNS nAChRs enhance fast excitatory transmission, providing a likely mechanism for the complex behavioral effects of nicotine.
McGehee
D S
DS
Department of Cell Biology and Anatomy, Columbia University, College of Physicians and Surgeons, New York, NY 10032, USA.
Heath
M J
MJ
Gelber
S
S
Devay
P
P
Role
L W
LW
D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D001921:Brain / Q000187:drug effects / Q000502:physiology*; D002038:Bungarotoxins / Q000378:metabolism / Q000494:pharmacology; D002118:Calcium / Q000502:physiology; D002642:Chick Embryo; D046508:Culture Techniques; D005728:Ganglia, Sympathetic / Q000187:drug effects / Q000502:physiology; D018698:Glutamic Acid / Q000378:metabolism; D008969:Molecular Sequence Data; D009538:Nicotine / Q000378:metabolism / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000378:metabolism / Q000494:pharmacology*; D017729:Presynaptic Terminals / Q000737:chemistry / Q000187:drug effects / Q000502:physiology*; D011978:Receptors, Nicotinic / Q000032:analysis / Q000502:physiology*; D013569:Synapses / Q000187:drug effects / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects*; D013787:Thalamic Nuclei / Q000187:drug effects / Q000502:physiology
D002038:Bungarotoxins; D018722:Nicotinic Agonists; D011978:Receptors, Nicotinic; D018698:Glutamic Acid; D009538:Nicotine; D002118:Calcium