Journal article
Presynaptic Rac1 controls synaptic strength through the regulation of synaptic vesicle priming
eLife, Vol.11, e81505
10/10/2022
DOI: 10.7554/eLife.81505
PMCID: PMC9584605
PMID: 36214784
Abstract
Synapses contain a limited number of synaptic vesicles (SVs) that are released in response to action potentials (APs). Therefore, sustaining synaptic transmission over a wide range of AP firing rates and timescales depends on SV release and replenishment. Although actin dynamics impact synaptic transmission, how presynaptic regulators of actin signaling cascades control SV release and replenishment remains unresolved. Rac1, a Rho GTPase, regulates actin signaling cascades that control synaptogenesis, neuronal development, and postsynaptic function. However, the presynaptic role of Rac1 in regulating synaptic transmission is unclear. To unravel Rac1’s roles in controlling transmitter release, we performed selective presynaptic ablation of Rac1 at the mature mouse calyx of Held synapse. Loss of Rac1 increased synaptic strength, accelerated EPSC recovery after conditioning stimulus trains, and augmented spontaneous SV release with no change in presynaptic morphology or AZ ultrastructure. Analyses with constrained short-term plasticity models revealed faster SV priming kinetics and, depending on model assumptions, elevated SV release probability or higher abundance of tightly docked fusion-competent SVs in Rac1-deficient synapses. We conclude that presynaptic Rac1 is a key regulator of synaptic transmission and plasticity mainly by regulating the dynamics of SV priming and potentially SV release probability.
Details
- Title: Subtitle
- Presynaptic Rac1 controls synaptic strength through the regulation of synaptic vesicle priming
- Creators
- Christian Keine - Carl von Ossietzky Universität OldenburgMohammed Al-Yaari - University of IowaTamara Radulovic - Carl von Ossietzky Universität OldenburgConnon I Thomas - Max Planck Florida Institute for NeurosciencePaula Valiño RamosDebbie Guerrero-Given - Max Planck Florida Institute for NeuroscienceMrinalini Ranjan - Göttingen Graduate School for Neurosciences, Biophysics, and Molecular Biosciences, Göttingen, Germany.Holger Taschenberger - Department of Molecular Neurobiology, Max Planck Institute for Multidisciplinary Sciences, Göttingen, Germany.Naomi Kamasawa - Max Planck Florida Institute for NeuroscienceSamuel M Young Jr - University of Iowa
- Resource Type
- Journal article
- Publication Details
- eLife, Vol.11, e81505
- DOI
- 10.7554/eLife.81505
- PMID
- 36214784
- PMCID
- PMC9584605
- NLM abbreviation
- Elife
- eISSN
- 2050-084X
- Grant note
- DOI: 10.13039/100000055, name: National Institute on Deafness and Other Communication Disorders, award: R01 DC014093; DOI: 10.13039/100000065, name: National Institute of Neurological Disorders and Stroke, award: R01 NS110742; DOI: 10.13039/501100001659, name: Deutsche Forschungsgemeinschaft, award: 420075000; name: Max Planck Institute for Multidisciplinary Sciences, award: open access funding; name: Max Planck Florida Institute for Neuroscience, award: open access funding; DOI: 10.13039/100008893, name: University of Iowa, award: University Funds and University of Iowa Healthcare CCOM Distinguished Scholar Award
- Language
- English
- Date published
- 10/10/2022
- Academic Unit
- Anatomy and Cell Biology; Iowa Neuroscience Institute; Otolaryngology
- Record Identifier
- 9984305894202771
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