Language
English
Publication Date
10-3-2025
Journal
Nature Communications
DOI
10.1038/s41467-025-63867-4
PMID
41044179
PMCID
PMC12494759
PubMedCentral® Posted Date
10-3-2025
PubMedCentral® Full Text Version
Post-print
Abstract
Measuring synaptic efficacy and defining the rules for induction of synaptic plasticity at identified connections in the mammalian brain is essential for understanding how synapses contribute to learning and memory. This requires new approaches to selectively evoke presynaptic activity and measure postsynaptic responses with high spatiotemporal resolution and high sensitivity over long periods in vivo. Here we develop an all-optical approach to probe synaptic plasticity at identified cerebellar synapses in awake, behaving mice. We developed and applied JEDI-2Psub, a genetically encoded voltage indicator with increased sensitivity around resting membrane potentials, to record subthreshold and suprathreshold activity in Purkinje cell (PC) dendrites while selectively activating their granule cell (GrC) inputs using optogenetics and their climbing fiber (CF) inputs using sensory stimulation. We measured synaptic potentials and complex spike signals across the dendrites of multiple neighboring PCs, enabling us to examine correlations in voltage signals within and between neurons. We show how pairing GrC activity with sensory-evoked CF inputs can trigger long-term plasticity of inhibitory responses in PCs. These results provide a blueprint for defining the rules for plasticity induction at identified synapses in awake animals during behavior.
Keywords
Animals, Neuronal Plasticity, Purkinje Cells, Optogenetics, Mice, Synapses, Dendrites, Male, Cerebellum, Mice, Inbred C57BL, Female
Published Open-Access
yes
Recommended Citation
Carolan, Jacques; Land, Michelle A; Lu, Xiaoyu; et al., "All-Optical Voltage Interrogation for Probing Synaptic Plasticity In Vivo" (2025). Faculty and Staff Publications. 3874.
https://digitalcommons.library.tmc.edu/baylor_docs/3874