ePoster

TWO-PHOTON CALCIUM IMAGING AND PHOTOCONTROL OF MUSCARINIC ACTIVITY IN LAYER 2/3 OF THE MOUSE SOMATOSENSORY CORTEX

Víctor Cilleros-Mañéand 14 co-authors

Institut de Bioenginyeria de Catalunya (IBEC)

FENS Forum 2026 (2026)
Barcelona, Spain
Board PS03-08AM-647

Presentation

Date TBA

Board: PS03-08AM-647

Poster preview

TWO-PHOTON CALCIUM IMAGING AND PHOTOCONTROL OF MUSCARINIC ACTIVITY IN LAYER 2/3 OF THE MOUSE SOMATOSENSORY CORTEX poster preview

Event Information

Poster Board

PS03-08AM-647

Abstract

Muscarinic acetylcholine receptors (mAChRs) contribute to both the facilitation and inhibition of cortical activity, with a role in attention, wakefulness and sleep states regulation. Ambient acetylcholine is sensed by extrasynaptic mAChRs, and in particular M1 is present in all cortical layers where it enhances the excitability of pyramidal cells. Current pharmacological tools that regulate neural activity lack tissue selectivity and affect the entire nervous system and cannot be used to activate or inhibit selective regions on demand. On the other hand, light-mediated optogenetics, which has revolutionized neuroscience, requires gene manipulation and has difficult clinical translation. Photopharmacology, the development of molecules with light-sensitive moieties, allows focalized switching, reduces adverse effects and enhances efficacy. Here we characterise a photoswitchable muscarinic activator derivative that is inactive in dark and activates M1 receptors when they are illuminated with tissue-penetrating amber light (590nm). We combined the use of this light-responsive effector with two-photon calcium imaging to optically control neuron activity of the somatosensory cortex layer 2/3. We demonstrate that a photoswitchable molecule and the application of patterns of light can be used to control drug activity on demand. Muscarinic activation with 590nm light produced a clear difference in activity, whereas no changes in calcium activity were observed in the control group for the same illumination cycles. All mice recovered without behaviour impairments, which demonstrates that this compound does not produce acute toxicity. Ultimately, the presented photoswitch should perform as a unique tool to optically control muscarinic endogenous receptors in brain tissue without genetic manipulation.

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