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Uncovering the roles of CAST/ELKS protein family in the regulation of synaptic transmission and plasticity

Uncovering the roles of CAST/ELKS protein family in the regu...

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中国神经科学学会第十二届全国学术会议

作者： Wei Dong Monica Montesinos Matthias Lübbert R.Oliver Goral Travis Putzke Kevin Goff Debbie Guerrero-Given Akari Hagiwara Maya Yamazaki Manabu Abe Kenji Sakimura Naomi Kamasawa Toshihisa Ohtsuka Samuel M.Young,Jr Key Laboratory of Medical Electrophysiology Ministry of Education Collaborative Innovation Center for Prevention and Treatment of Cardiovascular Disease/Institute of Cardiovascular Research Southwest Medical University

Synapses utilize a network of proteins, the cytomatrix at the active zone(CAZ) to tightly regulate synaptic strength and SV release kinetics to match the changing needs of the neuronal circuit. The CAST/ELKS family, central components of the CAZ, have been implicated as key proteins that regulate synaptic function. However, their functional roles in the regulation of neuronal circuits remain unresolved. Using a newly created CAST KO/ELKS conditional KO mouse line which overcomes the embryonic lethality associated with constitutive KO of ELKS proteins, we analyzed the role of the CAST/ELKS protein family in regulation of presynaptic function to match the needs of the neuronal circuit. To do so, we utilized the calyx of held, a large excitatory presynaptic terminal located in the auditory brainstem and the dominant input for driving postsynaptic spiking in the Medial Nucleus of the trapezoid body(MNTB) to help encode sound information. We carried out electrophysiological and ultrastructural analysis in both the immature(prehearing postnatal day,(P9-11) and functionally mature(hearing, P16-P21) calyx to elucidate the roles of the CAST/ELKS proteins. Here we identify for the first time, that the CAST/ELKS protein family regulates voltage gated Ca channel abundance in the presynaptic terminal. In addition, loss of CAST/ELKS proteins did not affect basal synaptic transmission. However, loss of CAST/ELKS resulted in increased release probability while decreasing the size of the RRP available for action potential mediated release in the functionally mature calyx. Therefore, we conclude that the CAST/ELKS proteins are critical molecules that differentially control key parameters of synaptic function in response to the changing neuronal circuit demand.

关键词： calyx of held synaptic transmission plasticity pre-synaptic terminal CAST/ELKS

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