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The Journal of Neuroscience, September 2, 2009, 29(35):10974-10978; doi:10.1523/JNEUROSCI.2123-09.2009

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Brief Communications
Presynaptically Expressed Long-Term Potentiation Increases Multivesicular Release at Parallel Fiber Synapses

Vanessa A. Bender, Jason R. Pugh, and Craig E. Jahr

Vollum Institute, Oregon Health & Science University, Portland, Oregon 97239

Correspondence should be addressed to Craig E. Jahr, Vollum Institute L474, Oregon Health & Science University, 3181 Southwest Sam Jackson Park Road, Portland, OR 97239. Email: jahr{at}ohsu.edu

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 (P_R) 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 P_R is elevated by both short- and long-term plasticity mechanisms.

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Received May 4, 2009; revised July 29, 2009; accepted Aug. 2, 2009.

Correspondence should be addressed to Craig E. Jahr, Vollum Institute L474, Oregon Health & Science University, 3181 Southwest Sam Jackson Park Road, Portland, OR 97239. Email: jahr{at}ohsu.edu

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