English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Tools annual

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools monthly

Global: Zendy Plus monthly

Presents the access of premium content as premium feature

Premium Content

Global: Zendy Plus annual

Global: Zendy Free Plan

The axon initial segment (AIS) is a specialized neuronal compartment in which synaptic input is converted into action potential (AP) output. This process is supported by a diverse complement of sodium, potassium, and calcium channels (Ca V ). Different classes of sodium and potassium channels are scaffolded at specific sites within the AIS, conferring unique functions, but how calcium channels are functionally distributed within the AIS is unclear. Here, we use conventional two-photon laser scanning and diffraction-limited, high-speed spot two-photon imaging to resolve AP-evoked calcium dynamics in the AIS with high spatiotemporal resolution. In mouse layer 5 prefrontal pyramidal neurons, calcium influx was mediated by a mix of Ca V 2 and Ca V 3 channels that differentially localized to discrete regions. Ca V 3 functionally localized to produce nanodomain hotspots of calcium influx that coupled to ryanodine-sensitive stores, whereas Ca V 2 localized to non-hotspot regions. Thus, different pools of Ca V s appear to play distinct roles in AIS function. SIGNIFICANCE STATEMENT The axon initial segment (AIS) is the site where synaptic input is transformed into action potential (AP) output. It achieves this function through a diverse complement of sodium, potassium, and calcium channels (Ca V ). While the localization and function of sodium channels and potassium channels at the AIS is well described, less is known about the functional distribution of Ca V s. We used high-speed two-photon imaging to understand activity-dependent calcium dynamics in the AIS of mouse neocortical pyramidal neurons. Surprisingly, we found that calcium influx occurred in two distinct domains: Ca V 3 generates hotspot regions of calcium influx coupled to calcium stores, whereas Ca V 2 channels underlie diffuse calcium influx between hotspots. Therefore, different Ca V classes localize to distinct AIS subdomains, possibly regulating distinct cellular processes.

Functional Microstructure of CaV-Mediated Calcium Signaling in the Axon Initial Segment

Functional Microstructure of Ca_V-Mediated Calcium Signaling in the Axon Initial Segment