title: Long-term potentiation involves increases in the probability of neurotransmitter release.
abstract: There is great interest in understanding the mechanisms of expression underlying long-term potentiation (LTP). They are agreed to involve an increase in synaptic efficacy, which is described by three multiplicative parameters: p, the probability of neurotransmitter release; n, the number of active release sites; and q, the postsynaptic unit response to transmitter release. We report three new lines of evidence suggesting that increases in p contribute to LTP expression. (i) When the contributions to LTP by p, n, and q are maximized, and p alone is decreased, another high-frequency stimulation elicits additional LTP. The additional potentiation is only associated with decreases in paired-pulse facilitation (PPF) suggesting an increase in p. (ii) There is an inverse relationship between baseline p [corrected] and the magnitude of LTP elicited, consistent with p [corrected] having more or less room to increase when p is smaller or greater. (iii) It has been shown that there is an inverse relationship between the magnitude of LTP induced and the associated changes in PPF. Now I find that decreasing p before inducing LTP moves the set-point for measuring those changes in PPF from before to after p is decreased, which would only occur if p contributes to LTP. Three lines of evidence, then, suggest that increases in p contribute to LTP expression, which is consistent with a presynaptic contribution to LTP. These experiments do not address potential postsynaptic contributions.
authors.affiliation: Department of Neurology and Division of Neuroscience, Baylor College of Medicine, Houston, TX 77030, USA. pschulz@bcm.tmc.edu
authors.forename: P E
authors.initials: PE
authors.lastname: Schulz
mesh_terms: D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000818:Animals; D001418:Baclofen / Q000031:analogs & derivatives / Q000494:pharmacology; D019256:Cadmium Chloride / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D005071:Evoked Potentials / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology*; D066298:In Vitro Techniques; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology*; D018377:Neurotransmitter Agents / Q000378:metabolism*; D010455:Peptides / Q000494:pharmacology; D011336:Probability; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000502:physiology; D018080:Receptors, GABA-B / Q000502:physiology; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology; D013569:Synapses / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects; D013997:Time Factors; D020866:omega-Conotoxin GVIA
chemical_list: D002121:Calcium Channel Blockers; D018377:Neurotransmitter Agents; D010455:Peptides; D018091:Receptors, AMPA; D018080:Receptors, GABA-B; D016194:Receptors, N-Methyl-D-Aspartate; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D015763:2-Amino-5-phosphonovalerate; D020866:omega-Conotoxin GVIA; D001418:Baclofen; D019256:Cadmium Chloride; C057491:2-hydroxysaclofen