Synaptic noise is fundamental to information processing and transmission in the central nervous system, as it amplifies and optimizes sub-threshold signals, thereby improving action potential initiation and reliable firing maintenance (Ermentrout et al., 2009; Faisal et al., 2008; Wiesenfeld & Moss, 1995). This is particularly important at auditory synapses where acoustic information is encoded by rapid and temporally precise firing rate. In the auditory system, an excess of synaptic noise has been shown to be detrimental to acoustic information, as it contributes to the generation and maintenance of tinnitus and hyperacusis (Kaltenbach, 2006; Wu et al., 2016). Although numerous studies have examined the role of synaptic noise on single cell excitability, little is known about the contribution of presynaptic boutons to synaptic noise within a local circuit, owing in part to the problems of combining noise modulation with monitoring synaptic release. Here we show that positive Kv3 K+ current modulation using 30 µM AUT1 (provided by Autifony Therapeutics) in the dorsal cochlear nucleus of mice reduces the level of synaptic bombardment onto its principal fusiform cells. Using a transgenic mouse line (SyG37) expressing SyGCaMP2-mCherry, a calcium sensor that targets presynaptic terminals, we show that positive Kv3 K+ current modulation decreases calcium fluorescence in a third of individual presynaptic boutons. Furthermore, while maintaining rapid and precise spike timing, positive Kv3 K+ current modulation increased local cross-unit synchrony, a result arising from a reduction in spontaneous activity. In conclusion, our study identifies a unique presynaptic mechanism which contributes to noise reduction, and consequently the coherent activation of neurons in a local circuit.
Future Physiology 2020 (Virutal) (2020) Proc Physiol Soc 46, PC0141
Poster Communications: Sparse presynaptic distribution of Kv3.3 K+ channels fine-tunes synaptic noise and improves coherent neuronal activation
Timothy Olsen1, 2, Alberto Capurro1, 3, Masa Svent1, Nadia Pilati4, Charles Large5, Nick Hartell1, Martine Hamann1
1 University of Leicester, Leicester, United Kingdom 2 University of California, San Francisco, San Francisco, The United States of America 3 University of Newcastle, Newcastle, United Kingdom 4 Autifony Therapeutics, Stevange, United Kingdom 5 Autifony Therapeutics, Stevenage, United Kingdom
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