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.

Public Health Relevance

The fundamental unit of communication in brain cells is the action potential, which is generated and shaped by specialized proteins called ion channels. Ion channel dysfunction has been implicated in many neurological disorders. This proposal will perform a novel and detailed exploration of potassium ion channels that control the action potential, thereby expanding our knowledge of brain function and pathology.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
1F32NS083127-01A1
Application #
8707049
Study Section
Special Emphasis Panel (ZRG1-F03B-G (20))
Program Officer
Silberberg, Shai D
Project Start
2014-03-16
Project End
2017-03-15
Budget Start
2014-03-16
Budget End
2015-03-15
Support Year
1
Fiscal Year
2014
Total Cost
$53,282
Indirect Cost
Name
Max Planck Florida Corporation
Department
Type
DUNS #
022946007
City
Jupiter
State
FL
Country
United States
Zip Code
33458