Roles of endogenous cholinergic neurons in the induction of long-term potentiation at hippocampal mossy fiber synapses. 1994

T Maeda, and S Kaneko, and M Satoh
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Kyoto University, Japan.

To evaluate the functional role of endogenous acetylcholine (ACh) in the induction of long-term potentiation (LTP) at mossy fiber-CA3 synapses, the influence of cholinergic hypofunction on it was investigated. Administration of a cholinergic neurotoxin, ethylcholine mustard aziridinium ion (AF64A; 5 nmol, i.c.v.), to guinea pigs one week prior to preparing slices resulted in a significant decrease in the magnitude of LTP, associated with a significant decrease in cholineacetyltransferase (ChAT) activity and the number of ChAT immunoreactive cells in the hippocampal slices. Bath-application of a cholinesterase inhibitor, physostigmine at 0.1 microM and 10 microM, attenuated and augmented, respectively, the magnitude of LTP in slices prepared from vehicle-treated animals (naive slices), whereas that in slices prepared from AF64A-treated animals (lesioned slices) was not significantly affected by physostigmine at any concentration tested. The induction of LTP in naive slices was inhibited or facilitated by a muscarinic M1 antagonist pirenzepine (1 microM) and by an M2 antagonist AF-DX 116 (1 microM) alone, respectively, whereas that in lesioned slices was not significantly changed by either of them. Furthermore, bath-applied carbachol (CCh) at 0.01-10 microM augmented the magnitude of LTP in lesioned slices, whereas the induction of LTP in naive slices was inhibited and facilitated by CCh at 0.01-0.1 microM and 1-10 microM, respectively, as reported previously. Such an augmentation of LTP by CCh was reversed by pirenzepine, but not by AF-DX 116. These observations suggest that AF64A induces the defect in ACh release and the hypofunction of M2 receptors, but not of M1, at least during the induction of LTP at mossy fiber-CA3 synapses.(ABSTRACT TRUNCATED AT 250 WORDS)

UI MeSH Term Description Entries
D008297 Male Males
D009412 Nerve Fibers Slender processes of NEURONS, including the AXONS and their glial envelopes (MYELIN SHEATH). Nerve fibers conduct nerve impulses to and from the CENTRAL NERVOUS SYSTEM. Cerebellar Mossy Fibers,Mossy Fibers, Cerebellar,Cerebellar Mossy Fiber,Mossy Fiber, Cerebellar,Nerve Fiber
D009466 Neuromuscular Blocking Agents Drugs that interrupt transmission of nerve impulses at the skeletal neuromuscular junction. They can be of two types, competitive, stabilizing blockers (NEUROMUSCULAR NONDEPOLARIZING AGENTS) or noncompetitive, depolarizing agents (NEUROMUSCULAR DEPOLARIZING AGENTS). Both prevent acetylcholine from triggering the muscle contraction and they are used as anesthesia adjuvants, as relaxants during electroshock, in convulsive states, etc. Neuromuscular Blocker,Neuromuscular Blocking Agent,Neuromuscular Blockers,Agent, Neuromuscular Blocking,Agents, Neuromuscular Blocking,Blocker, Neuromuscular,Blockers, Neuromuscular,Blocking Agent, Neuromuscular,Blocking Agents, Neuromuscular
D009474 Neurons The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM. Nerve Cells,Cell, Nerve,Cells, Nerve,Nerve Cell,Neuron
D010275 Parasympathetic Nervous System The craniosacral division of the autonomic nervous system. The cell bodies of the parasympathetic preganglionic fibers are in brain stem nuclei and in the sacral spinal cord. They synapse in cranial autonomic ganglia or in terminal ganglia near target organs. The parasympathetic nervous system generally acts to conserve resources and restore homeostasis, often with effects reciprocal to the sympathetic nervous system. Nervous System, Parasympathetic,Nervous Systems, Parasympathetic,Parasympathetic Nervous Systems,System, Parasympathetic Nervous,Systems, Parasympathetic Nervous
D010890 Pirenzepine An antimuscarinic agent that inhibits gastric secretion at lower doses than are required to affect gastrointestinal motility, salivary, central nervous system, cardiovascular, ocular, and urinary function. It promotes the healing of duodenal ulcers and due to its cytoprotective action is beneficial in the prevention of duodenal ulcer recurrence. It also potentiates the effect of other antiulcer agents such as CIMETIDINE and RANITIDINE. It is generally well tolerated by patients. Gastrotsepin,Gastrozepin,L-S 519,LS-519,Piren-Basan,Pirenzepin,Pirenzepin Von Ct,Pirenzepin-Ratiopharm,Pirenzepine Dihydrochloride,Pyrenzepine,Ulcoprotect,Ulgescum,Dihydrochloride, Pirenzepine,LS 519,LS519,Piren Basan,Pirenzepin Ratiopharm,Von Ct, Pirenzepin
D002217 Carbachol A slowly hydrolyzed CHOLINERGIC AGONIST that acts at both MUSCARINIC RECEPTORS and NICOTINIC RECEPTORS. Carbamylcholine,Carbacholine,Carbamann,Carbamoylcholine,Carbastat,Carbocholine,Carboptic,Doryl,Isopto Carbachol,Jestryl,Miostat,Carbachol, Isopto
D002794 Choline A basic constituent of lecithin that is found in many plants and animal organs. It is important as a precursor of acetylcholine, as a methyl donor in various metabolic processes, and in lipid metabolism. Bursine,Fagine,Vidine,2-Hydroxy-N,N,N-trimethylethanaminium,Choline Bitartrate,Choline Chloride,Choline Citrate,Choline Hydroxide,Choline O-Sulfate,Bitartrate, Choline,Chloride, Choline,Choline O Sulfate,Citrate, Choline,Hydroxide, Choline,O-Sulfate, Choline
D002795 Choline O-Acetyltransferase An enzyme that catalyzes the formation of acetylcholine from acetyl-CoA and choline. EC 2.3.1.6. Choline Acetylase,Choline Acetyltransferase,Acetylase, Choline,Acetyltransferase, Choline,Choline O Acetyltransferase,O-Acetyltransferase, Choline
D006168 Guinea Pigs A common name used for the genus Cavia. The most common species is Cavia porcellus which is the domesticated guinea pig used for pets and biomedical research. Cavia,Cavia porcellus,Guinea Pig,Pig, Guinea,Pigs, Guinea

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