ArticleBrain stimulation
Photoswitching endogenous glutamate receptors in neural ensembles and single synapses in vivo.
Article in Brain stimulation. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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Who cites it
2 citing papers in PubMed.
- Targeted Covalent Photoswitch for Two-Photon Control of Endogenous Receptors.Journal of the American Chemical Society · 2026Article
- Assessing circuit function in the developingFrontiers in behavioral neuroscience · 2026Review
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Authors and funding
16 authors.
Funding
Abstract
purposeTo interrogate animal physiology in vivo, there is a lack of non-genetic methods to control the activity of endogenous proteins with pharmacological and spatiotemporal precision. To address this need, we recently developed targeted covalent photoswitchable (TCP) compounds that enable the remote control of endogenous glutamate receptors (GluRs) using light.
methodsWe combine the photopharmacological effector TCP9 with neuronal activity sensors to demonstrate all-optical reversible control of endogenous GluRs across multiple spatiotemporal scales in rat brain tissue ex vivo and in Xenopus tadpole brains in vivo.
findingsTCP9 allows photoactivation of neuronal ensembles, individual neurons, and single synapses in ex vivo tissue and in intact brain in vivo, which is challenging using optogenetics and neurotransmitter uncaging. TCP9 covalently targets AMPA and kainate receptors, maintaining their functionality and photoswitchability for extended periods (>8 h) after a single compound application. This allows tracking endogenous receptor physiology during synaptic plasticity events such as the reduction of functional AMPA receptors during long-term depression in hippocampal neurons.
conclusionTCP9 is a unique non-invasive tool for durable labeling, reversible photoswitching, and functional tracking of native receptors in brain tissue without genetic manipulation.
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