Journal article
Molecular mechanisms regulating presynaptic neurotransmitter release and their impact on neuronal circuit function
The FASEB journal, Vol.33(S1), pp.201.3-201.3
04/2019
DOI: 10.1096/fasebj.2019.33.1_supplement.201.3
Abstract
Deciphering the molecular mechanisms that govern neurotransmitter release at the presynaptic terminal is essential for understanding synaptic strength, plasticity, modulation and pathology. Voltage‐gated Ca2+ channels (VGCCs) regulate the magnitude and location of Ca2+ entry into presynaptic terminals of the central nervous system (CNS) and this determines the probability and kinetics of release of neurotransmitter‐filled synaptic vesicles (SVs) which ultimately impact neuronal circuit output and behavior. Located within the presynaptic terminal is the active zone, a dense network of proteins, which are implicated to regulate SV release by controlling VGCC function. However, the molecular mechanisms by which active zone proteins control VGCC density and organization within the presynaptic terminal are unclear. The calyx of Held, a glutamatergic presynaptic terminal in the auditory brainstem utilizes rapid and temporally precise action potential signaling for encoding information. Since it is the sole input to drive post‐synaptic action potential spiking and due to the ability to directly measure presynaptic Ca2+ currents and correlate them to SV release rates, the calyx is an exceptional model for gaining mechanistic insights into the presynaptic regulation of SV release and neuronal circuit output. We are using transgenic mouse models and novel viral vectors to manipulate presynaptic active zone proteins and CaV2 subtypes at the calyx during different developmental stages. In combination with these molecular manipulations, we utilized morphological analysis of VGGC organization in the presynaptic active zone and presynaptic ultrastructure and electrophysiology to determine their impact on synaptic biophysics, transmission and plasticity. Our results have identified key molecules and uncovered molecular mechanisms regulating CaV2 subtype levels, organization and proximity to SVs thereby controlling synaptic transmission and neuronal circuit output.
Support or Funding Information
Current Research Support: National Institute of Deafness and Communication Disorders (R01 DC014093), the University of Iowa.
This is from the Experimental Biology 2019 Meeting. There is no full text article associated with this published in The FASEB Journal.
Details
- Title: Subtitle
- Molecular mechanisms regulating presynaptic neurotransmitter release and their impact on neuronal circuit function
- Creators
- Samuel M Young - University of Iowa
- Resource Type
- Journal article
- Publication Details
- The FASEB journal, Vol.33(S1), pp.201.3-201.3
- Publisher
- The Federation of American Societies for Experimental Biology
- DOI
- 10.1096/fasebj.2019.33.1_supplement.201.3
- ISSN
- 0892-6638
- eISSN
- 1530-6860
- Number of pages
- 1
- Grant note
- University of Iowa National Institute of Deafness and Communication Disorders (R01 DC014093)
- Language
- English
- Date published
- 04/2019
- Academic Unit
- Anatomy and Cell Biology; Iowa Neuroscience Institute; Otolaryngology
- Record Identifier
- 9984071931602771
Metrics
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