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This Article Full Text Full Text (PDF) Supplemental data All Versions of this Article: 581/2/581    most recent jphysiol.2007.129833v1 Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Fedchyshyn, M. J. Articles by Wang, L.-Y. Search for Related Content PubMed PubMed Citation Articles by Fedchyshyn, M. J. Articles by Wang, L.-Y. Related Collections Neuroscience

¹ The Program for Neuroscience and Mental Health, and Division of Neurology, The Hospital for Sick Children and Department of Physiology, University of Toronto, 555 University Avenue, Toronto, Ontario, Canada M5G 1X8

The temporal fidelity of synaptic transmission is constrained by the reproducibility of time delays such as axonal conduction delay and synaptic delay, but very little is known about the modulation of these distinct components. In particular, synaptic delay is not generally considered to be modifiable under physiological conditions. Using simultaneous paired patch-clamp recordings from pre- and postsynaptic elements of the calyx of Held synapse, in juvenile mouse auditory brainstem slices, we show here that synaptic activity (20–200 Hz) leads to activity-dependent increases in synaptic delay and its variance as well as desynchronization of evoked responses. Such changes were most robust at 200 Hz in 2 mM extracellular Ca²⁺ ([Ca²⁺]_o), and could be attenuated by lowering [Ca²⁺]_o to 1 mM, increasing temperature to 35°C, or application of the GABA_BR agonist baclofen, which inhibits presynaptic Ca²⁺ currents (I_Ca). Conduction delay also exhibited slight activity-dependent prolongation, but this prolongation was only sensitive to temperature, and not to [Ca²⁺]_o or baclofen. Direct voltage-clamp recordings of I_Ca evoked by repeated action potential train template (200 Hz) revealed little jitter in the timing and kinetics of I_Ca under various conditions, suggesting that increases in synaptic delay and its variance occur downstream of Ca²⁺ entry. Loading the Ca²⁺ chelator EGTA-AM into terminals reduced the progression rate, the extent of activity-dependent increases in various delay components, and their variance, implying that residual Ca²⁺ accumulation in the presynaptic nerve terminal induces these changes. Finally, by applying a test pulse at different intervals following a 200 Hz train (150 ms), we demonstrated that prolongation in the various delay components reverses in parallel with recovery in synaptic strength. These observations suggest that a depletion of the readily releasable pool of SVs during high-frequency activity may downregulate not only synaptic strength but also decrease the temporal fidelity of neurotransmission at this and other central synapses.

(Received 3 February 2007; accepted after revision 5 March 2007; first published online 8 March 2007)
Corresponding author L-Y. Wang: Division of Neurology, The Hospital for Sick Children, 555 University Avenue, Toronto, Ontario, Canada M5G 1X8. Email: luyang.wang{at}utoronto.ca