A novel cholinergic induction of long-term potentiation in rat hippocampus.
1. We studied long-term cholinergic effects on synaptic transmission in submerged hippocampal slices using intra- and extracellular recording techniques. 2. Bath application of submicromolar concentrations of carbachol (CCh) produced a gradually developing, long-lasting increase in the CA1 excitatory postsynaptic potential and population spike. This potentiation was blocked by atropine and, hence, named muscarinic long-term potentiation (LTPm). Application of DL-2-amino-5-phosphonovaleric acid had no effect on LTPm, indicating that this phenomenon is N-methyl-D-aspartate receptor independent. 3. These effects of CCh were not likely to be due to the blockade of one of several K+ conductances by the drug; the time and concentration dependence of LTPm were different from those associated with cholinergic blockade of K+ conductances. 4. Removal of extracellular calcium (Cao2+) from the bath blocked synaptic transmission. CCh added in calcium-free medium induced LTPm, which was revealed upon removal of the drug by washing with normal calcium-containing medium. Neither cutting CA1-CA3 connections nor cessation of synaptic stimulation interfered with LTPm induction. 5. Application of thapsigargin or H-7 together with CCh blocked LTPm, suggesting the involvement of intracellular calcium (Cai2+) stores and protein kinases, respectively, in the LTPm mechanism. 6. Subthreshold cholinergic stimulation coupled with subthreshold tetanic stimulation caused LTP. CCh had no effect when administered after the LTP mechanism had been saturated by repeated suprathreshold tetani. Tetanic stimulation failed to cause LTP when applied after LTPm had been induced by CCh. These experiments indicate that tetanus-induced potentiation and LTPm share a common mechanism and provide a direct link between ACh and mechanisms of synaptic plasticity.
Auerbach
J M
JM
Department of Neurobiology, Weizmann Institute, Rehovot, Israel.
Segal
M
M
D000109:Acetylcholine / Q000502:physiology; D000818:Animals; D002799:Cholinergic Fibers / Q000502:physiology*; D046508:Culture Techniques; D006624:Hippocampus / Q000502:physiology*; D017774:Long-Term Potentiation / Q000502:physiology*; D008297:Male; D009473:Neuronal Plasticity / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D011950:Receptors, Cholinergic / Q000502:physiology*; D013569:Synapses / Q000502:physiology; D009435:Synaptic Transmission / Q000502:physiology*
D011950:Receptors, Cholinergic; D000109:Acetylcholine