Local control of the action potential in axons

描述（由申请人提供）：在轴突中，动作电位（AP）波形决定神经传递的时间和强度。虽然AP通常被认为是一种刻板的“全有或无”信号，但最近的研究表明，轴突AP波形比以前认为的更具可塑性。一种解释是电压敏感的钾离子通道分布不均匀，存在于不同的轴突室中。轴突在电生理学上的相对不可接近性阻碍了这一主题的探索。这

DESCRIPTION (provided by applicant): In axons, the action potential (AP) waveform determines the timing and strength of neurotransmission. Although the AP is classically thought of as a stereotyped "all or none" signal, recent studies have shown that the axonal AP waveform is more malleable then once thought. One explanation is that a non-uniform distribution of voltage-sensitive potassium (Kv) channels exists within different axonal compartments. The relative inaccessibility of axons to electrophysiology has hampered exploration of this topic. This is especially true with respect to the small axons of interneurons, in which the axonal AP waveform has not been directly observed. To study the AP in interneuron axons, I developed a 2-photon (2P) voltage imaging technique to accurately report fast voltage changes with high spatial and temporal resolution. The compact cerebellar stellate cell was chosen, as these interneurons provide the sole source of inhibition within the cerebellum and play a vital role in the temporal integration of cerebellar output. Preliminary results show APs are shaped at individual boutons by locally expressed Kv channels, allowing AP waveform changes to occur at one bouton without perturbing the AP at nearby boutons. In addition, activity-dependent broadening of the AP occurred at boutons but not in connecting axon shafts, suggesting that inactivating Kv channels expressed at boutons were responsible for this effect. This proposal will explore local AP control in more detail. The 1st aim will determine which Kv subtypes are locally expressed at boutons as well as how local control influences synaptic strength within axons, utilizing patch-clamp recordings and 2P voltage and Ca2+ imaging/uncaging Kv inhibitor. The 2nd aim will uncover which Kv subtypes allow for rapid activity-dependent broadening and the impact of this phenomenon on synaptic transmission. Results from these aims will present new data on how interneuron axons perform complex computations in a site-specific manner, leading to a more complete understanding of neuronal processing.