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Control of Brain State Transitions with a Photoswitchable Muscarinic Agonist
Barbero-Castillo, Almudena (Institut d'Investigacions Biomèdiques August Pi i Sunyer)
Riefolo, Fabio (Centro de Investigación Biomédica en Red de Bioingeniería, Biomateriales y Nanomedicina)
Matera, Carlo (University of Milan)
Caldas-Martínez, Sara (Institut d'Investigacions Biomèdiques August Pi i Sunyer)
Mateos-Aparicio, Pedro (Institut d'Investigacions Biomèdiques August Pi i Sunyer)
Weinert, Julia F. (Institut d'Investigacions Biomèdiques August Pi i Sunyer)
Garrido-Charles, Aida (Centro de Investigación Biomédica en Red de Bioingeniería, Biomateriales y Nanomedicina)
Claro Izaguirre, Enrique (Universitat Autònoma de Barcelona)
Sánchez-Vives, María V (Institució Catalana de Recerca i Estudis Avançats)
Gorostiza, Pau (Institució Catalana de Recerca i Estudis Avançats)

Data: 2021
Resum: The ability to control neural activity is essential for research not only in basic neuroscience, as spatiotemporal control of activity is a fundamental experimental tool, but also in clinical neurology for therapeutic brain interventions. Transcranial-magnetic, ultrasound, and alternating/direct current (AC/DC) stimulation are some available means of spatiotemporal controlled neuromodulation. There is also light-mediated control, such as optogenetics, which has revolutionized neuroscience research, yet its clinical translation is hampered by the need for gene manipulation. As a drug-based light-mediated control, the effect of a photoswitchable muscarinic agonist (Phthalimide-Azo-Iper (PAI)) on a brain network is evaluated in this study. First, the conditions to manipulate M2 muscarinic receptors with light in the experimental setup are determined. Next, physiological synchronous emergent cortical activity consisting of slow oscillations-as in slow wave sleep-is transformed into a higher frequency pattern in the cerebral cortex, both in vitro and in vivo, as a consequence of PAI activation with light. These results open the way to study cholinergic neuromodulation and to control spatiotemporal patterns of activity in different brain states, their transitions, and their links to cognition and behavior. The approach can be applied to different organisms and does not require genetic manipulation, which would make it translational to humans. Brain pathologies often require drug treatments, however drugs act all over the central nervous system. Wouldn't it be good to determine where/when a drug should be active? Drugs can be made sensitive to light, to be activated at specific times and locations. This study demonstrates that a light-activated cholinergic drug can effectively modulate activity in the cerebral cortex network.
Ajuts: European Commission. Horizon 2020 785907
European Commission. Horizon 2020 945539
European Commission. Horizon 2020 101016787
Generalitat de Catalunya 2017-SGR-1442
Ministerio de Economía y Competitividad CTQ2016-80066-R
Agencia Estatal de Investigación BFU2017-85048-R
Agència de Gestió d'Ajuts Universitaris i de Recerca IU16-011508
Drets: Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original. Creative Commons
Llengua: Anglès
Document: Article ; recerca ; Versió publicada
Matèria: Brain states ; Light-mediated control ; Muscarinic acetylcholine receptors ; Neuromodulation ; Photopharmacology
Publicat a: Advanced science, Vol. 8 (may 2021) , ISSN 2198-3844

DOI: 10.1002/advs.202005027
PMID: 34018704

11 p, 1.9 MB

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