Nicotine reverses GABAergic inhibition of long-term potentiation induction in the hippocampal CA1 region.
Nicotine is known to enhance cognitive function but the mechanism is unknown. The present study examined the modulatory effect of nicotine on the induction of long-term potentiation (LTP), a synaptic model of learning and memory. A weak tetanic stimulation consisting of 20 pulses at 100 Hz induced stable LTP in the hippocampal CA1. The induction of LTP was completely blocked if the tetanus was delivered in the presence of muscimol (2.5 microM), a gamma-aminobutyric acid (GABA) receptor agonist. This inhibition was sensitive to, and reversed by, not only nicotinic acetylcholine receptor (nAChR) agonists (nicotine and epibatidine), but also the alpha7 nAChR-selective antagonist methyllycaconitine (MLA). Furthermore, ACh-puff activation of alpha7 nAChRs on feedforward interneurons induced inhibitory postsynaptic currents in pyramidal cells that were blocked by nicotine or MLA. In addition, nicotine reduced field monosynaptic inhibitory postsynaptic potentials in the presence of MLA. These results suggest not only two pathways of nicotine-induced disinhibition of pyramidal cells, one involving desensitization of alpha7 nAChRs and the other involving non-alpha7 nAChRs, but also two potential mechanisms underlying the modulatory effect of nicotine on LTP induction, both reducing GABAergic inhibition, thereby indirectly increasing the excitability of pyramidal cells.
Fujii
S
S
Department of Neurobiology and Behavior, University of California, Irvine, CA, USA.
Jia
Y
Y
Yang
A
A
Sumikawa
K
K
D000157:Aconitine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology; D004558:Electric Stimulation; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D018755:GABA Agonists / Q000494:pharmacology; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D007306:Insecticides / Q000494:pharmacology; D007395:Interneurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D017774:Long-Term Potentiation / Q000187:drug effects* / Q000502:physiology*; D009118:Muscimol / Q000494:pharmacology; D009434:Neural Pathways / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D009538:Nicotine / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000494:pharmacology*; D017966:Pyramidal Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D011963:Receptors, GABA-A / Q000187:drug effects* / Q000378:metabolism*; D011978:Receptors, Nicotinic / Q000187:drug effects* / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D019086:Bridged Bicyclo Compounds, Heterocyclic; D018755:GABA Agonists; D007306:Insecticides; D018722:Nicotinic Agonists; D011725:Pyridines; D011963:Receptors, GABA-A; D011978:Receptors, Nicotinic; C054634:methyllycaconitine; D009118:Muscimol; D005680:gamma-Aminobutyric Acid; D009538:Nicotine; C082748:epibatidine; D000157:Aconitine