Control of Brain State Transitions with a Photoswitchable Muscarinic Agonist
Abstract 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/d...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2021-07-01
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| Series: | Advanced Science |
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| Online Access: | https://doi.org/10.1002/advs.202005027 |
| _version_ | 1818907561451061248 |
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| author | Almudena Barbero‐Castillo Fabio Riefolo Carlo Matera Sara Caldas‐Martínez Pedro Mateos‐Aparicio Julia F. Weinert Aida Garrido‐Charles Enrique Claro Maria V. Sanchez‐Vives Pau Gorostiza |
| author_facet | Almudena Barbero‐Castillo Fabio Riefolo Carlo Matera Sara Caldas‐Martínez Pedro Mateos‐Aparicio Julia F. Weinert Aida Garrido‐Charles Enrique Claro Maria V. Sanchez‐Vives Pau Gorostiza |
| author_sort | Almudena Barbero‐Castillo |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-12-19T21:57:05Z |
| format | Article |
| id | doaj.art-ceb0194ddfd34b49832898394cc8f2a8 |
| institution | Directory Open Access Journal |
| issn | 2198-3844 |
| language | English |
| last_indexed | 2024-12-19T21:57:05Z |
| publishDate | 2021-07-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj.art-ceb0194ddfd34b49832898394cc8f2a82022-12-21T20:04:15ZengWileyAdvanced Science2198-38442021-07-01814n/an/a10.1002/advs.202005027Control of Brain State Transitions with a Photoswitchable Muscarinic AgonistAlmudena Barbero‐Castillo0Fabio Riefolo1Carlo Matera2Sara Caldas‐Martínez3Pedro Mateos‐Aparicio4Julia F. Weinert5Aida Garrido‐Charles6Enrique Claro7Maria V. Sanchez‐Vives8Pau Gorostiza9Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS) Barcelona 08036 SpainInstitute for Bioengineering of Catalonia (IBEC) The Barcelona Institute for Science and Technology Barcelona 08028 SpainInstitute for Bioengineering of Catalonia (IBEC) The Barcelona Institute for Science and Technology Barcelona 08028 SpainInstitut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS) Barcelona 08036 SpainInstitut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS) Barcelona 08036 SpainInstitut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS) Barcelona 08036 SpainInstitute for Bioengineering of Catalonia (IBEC) The Barcelona Institute for Science and Technology Barcelona 08028 SpainInstitut de Neurociències and Departament de Bioquímica i Biologia Molecular Unitat de Bioquímica de Medicina Universitat Autònoma de Barcelona (UAB) Barcelona 08193 SpainInstitut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS) Barcelona 08036 SpainInstitute for Bioengineering of Catalonia (IBEC) The Barcelona Institute for Science and Technology Barcelona 08028 SpainAbstract 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.https://doi.org/10.1002/advs.202005027brain stateslight‐mediated controlmuscarinic acetylcholine receptorsneuromodulationphotopharmacology |
| spellingShingle | Almudena Barbero‐Castillo Fabio Riefolo Carlo Matera Sara Caldas‐Martínez Pedro Mateos‐Aparicio Julia F. Weinert Aida Garrido‐Charles Enrique Claro Maria V. Sanchez‐Vives Pau Gorostiza Control of Brain State Transitions with a Photoswitchable Muscarinic Agonist Advanced Science brain states light‐mediated control muscarinic acetylcholine receptors neuromodulation photopharmacology |
| title | Control of Brain State Transitions with a Photoswitchable Muscarinic Agonist |
| title_full | Control of Brain State Transitions with a Photoswitchable Muscarinic Agonist |
| title_fullStr | Control of Brain State Transitions with a Photoswitchable Muscarinic Agonist |
| title_full_unstemmed | Control of Brain State Transitions with a Photoswitchable Muscarinic Agonist |
| title_short | Control of Brain State Transitions with a Photoswitchable Muscarinic Agonist |
| title_sort | control of brain state transitions with a photoswitchable muscarinic agonist |
| topic | brain states light‐mediated control muscarinic acetylcholine receptors neuromodulation photopharmacology |
| url | https://doi.org/10.1002/advs.202005027 |
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