title: Presynaptically expressed long-term potentiation increases multivesicular release at parallel fiber synapses.
abstract: At a number of synapses, long-term potentiation (LTP) can be expressed by an increase in presynaptic strength, but it is unknown whether presynaptic LTP is expressed solely through an increase in the probability that a single vesicle is released or whether it can increase multivesicular release (MVR). Here, we show that presynaptic LTP decreases inhibition of AMPA receptor EPSCs by a low-affinity antagonist at parallel fiber-molecular layer interneuron (PF-MLI) synapses. This indicates that LTP induction results in larger glutamate concentration transients in the synaptic cleft, a result indicative of MVR, and suggests that MVR can be modified by long-term plasticity. A similar decrease in inhibition was observed when release probability (PR) was increased by forskolin, elevated extracellular Ca2+, and paired-pulse facilitation. Furthermore, we show that MVR may occur under baseline physiological conditions, as inhibition increased when P(R) was lowered by reducing extracellular Ca2+ or by activating presynaptic adenosine receptors. These results suggest that at PF-MLI synapses, MVR occurs under control conditions and is increased when PR is elevated by both short- and long-term plasticity mechanisms.
authors.affiliation: Vollum Institute, Oregon Health & Science University, Portland, Oregon 97239, USA.
authors.forename: Vanessa A
authors.initials: VA
authors.lastname: Bender
authors.forename: Jason R
authors.initials: JR
authors.lastname: Pugh
authors.forename: Craig E
authors.initials: CE
authors.lastname: Jahr
mesh_terms: D000818:Animals; D002531:Cerebellum / Q000378:metabolism; D017774:Long-Term Potentiation / Q000502:physiology*; D009412:Nerve Fibers / Q000378:metabolism*; D017729:Presynaptic Terminals / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013569:Synapses / Q000378:metabolism; D013572:Synaptic Vesicles / Q000378:metabolism*