Reversible photocontrol of dopaminergic transmission in wild-type animals

Understanding the dopaminergic system is a priority in neurobiology and neuropharmacology. Dopamine receptors are involved in the modulation of fundamental physiological functions and dysregulation of dopaminergic transmission is associated with major neurological disorders. However, the available t...

Descripción completa

Detalles Bibliográficos
Autores: Matera, Carlo, Calvé, Pablo, Casadó Anguera, Verònica, Sortino, Rosalba, Gomila, Alexandre M. J., Moreno Guillén, Estefanía, Gener, Thomas, Delgado-Sallent, Cristina, Nebot, Pau, Costazza, Davide, Conde-Berriozábal, Sara, Masana Nadal, Mercè, Hernando, Jordi, Casadó, Vicent, Puig, M. Victoria, Gorostiza Langa, Pablo Ignacio
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2022
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:2445/189693
Acceso en línea:https://hdl.handle.net/2445/189693
Access Level:acceso abierto
Palabra clave:Dopamina
Electrofisiologia
Dopamine
Electrophysiology
Descripción
Sumario:Understanding the dopaminergic system is a priority in neurobiology and neuropharmacology. Dopamine receptors are involved in the modulation of fundamental physiological functions and dysregulation of dopaminergic transmission is associated with major neurological disorders. However, the available tools to dissect the endogenous dopaminergic circuits have limited specificity, reversibility, resolution, or require genetic manipulation. Here we introduce azodopa, a novel photoswitchable ligand that enables reversible spatiotemporal control of dopaminergic transmission. We demonstrate that azodopa activates D1-like receptors in vitro in a light-dependent manner. Moreover, it enables reversibly photocontrolling zebrafish motility on a time scale of seconds and allows separating the retinal component of dopaminergic neurotransmission. Azodopa increases the overall neural activity in the cortex of anesthetized mice and displays illuminationdependent activity in individual cells. Azodopa is the first photoswitchable dopamine agonist with demonstrated efficacy in wildtype animals and opens the way to remotely controlling dopaminergic neurotransmission for fundamental and therapeutic purposes.