Nicotine Enhancement of Fast Excitatory Synaptic Transmission in CNS by Presynaptic Receptors

• Published in: Science (American Association for the Advancement of Science) 1995-09, Vol.269 (5231), p.1692-1696
• Main Authors: McGehee, Daniel S., Mark J. S. Heath, Gelber, Shari, Devay, Piroska, Role, Lorna W.
• Format: Article
• Language: English
• Subjects: Animals; Base Sequence; Binding Sites; Biological and medical sciences; Brain; Brain - drug effects; Brain - physiology; Bungarotoxins - metabolism; Bungarotoxins - pharmacology; Calcium - physiology; Central nervous system; Central neurotransmission. Neuromudulation. Pathways and receptors; Chick Embryo; Cholinergics; Culture Techniques; Fundamental and applied biological sciences. Psychology; Ganglia, Sympathetic - drug effects; Ganglia, Sympathetic - physiology; Glutamic Acid - metabolism; Messenger RNA; Molecular Sequence Data; Nervous system; Neural transmission; Neurites; Neurons; Nicotine; Nicotine - metabolism; Nicotine - pharmacology; Nicotinic Agonists - metabolism; Nicotinic Agonists - pharmacology; Nicotinic receptors; Oligonucleotides; Pharmacology; Presynaptic Terminals - chemistry; Presynaptic Terminals - drug effects; Presynaptic Terminals - physiology; Receptors; Receptors, Nicotinic - analysis; Receptors, Nicotinic - physiology; Research Article; Short Term Memory; Synapses; Synapses - drug effects; Synapses - physiology; Synaptic transmission; Synaptic Transmission - drug effects; Thalamic Nuclei - drug effects; Thalamic Nuclei - physiology; Vertebrates: nervous system and sense organs
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.7569895

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 [Ca$^{2+}$]$_i$. Pharmacological and subunit deletion experiments reveal that these presynaptic nAChRs include the α7 subunit. These findings reveal that CNS nAChRs enhance fast excitatory transmission, providing a likely mechanism for the complex behavioral effects of nicotine.