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2.
Cell Chem Biol ; 31(7): 1324-1335.e20, 2024 Jul 18.
Artículo en Inglés | MEDLINE | ID: mdl-38729162

RESUMEN

The ability to optically stimulate and inhibit neurons has revolutionized neuroscience research. Here, we present a direct, potent, user-friendly chemical approach for optically silencing neurons. We have rendered saxitoxin (STX), a naturally occurring paralytic agent, transiently inert through chemical protection with a previously undisclosed nitrobenzyl-derived photocleavable group. Exposing the caged toxin, STX-bpc, to a brief (5 ms) pulse of light effects rapid release of a potent STX derivative and transient, spatially precise blockade of voltage-gated sodium channels (NaVs). We demonstrate the efficacy of STX-bpc for parametrically manipulating action potentials in mammalian neurons and brain slice. Additionally, we show the effectiveness of this reagent for silencing neural activity by dissecting sensory-evoked swimming in larval zebrafish. Photo-uncaging of STX-bpc is a straightforward method for non-invasive, reversible, spatiotemporally precise neural silencing without the need for genetic access, thus removing barriers for comparative research.


Asunto(s)
Neuronas , Pez Cebra , Animales , Neuronas/metabolismo , Neuronas/efectos de los fármacos , Saxitoxina/farmacología , Saxitoxina/metabolismo , Saxitoxina/química , Potenciales de Acción/efectos de los fármacos , Humanos , Conducta Animal/efectos de los fármacos , Larva/efectos de los fármacos , Larva/metabolismo , Luz , Ratones
3.
bioRxiv ; 2024 Feb 12.
Artículo en Inglés | MEDLINE | ID: mdl-38405778

RESUMEN

Fast electrical signaling in dendrites is central to neural computations that support adaptive behaviors. Conventional techniques lack temporal and spatial resolution and the ability to track underlying membrane potential dynamics present across the complex three-dimensional dendritic arbor in vivo. Here, we perform fast two-photon imaging of dendritic and somatic membrane potential dynamics in single pyramidal cells in the CA1 region of the mouse hippocampus during awake behavior. We study the dynamics of subthreshold membrane potential and suprathreshold dendritic events throughout the dendritic arbor in vivo by combining voltage imaging with simultaneous local field potential recording, post hoc morphological reconstruction, and a spatial navigation task. We systematically quantify the modulation of local event rates by locomotion in distinct dendritic regions and report an advancing gradient of dendritic theta phase along the basal-tuft axis, then describe a predominant hyperpolarization of the dendritic arbor during sharp-wave ripples. Finally, we find spatial tuning of dendritic representations dynamically reorganizes following place field formation. Our data reveal how the organization of electrical signaling in dendrites maps onto the anatomy of the dendritic tree across behavior, oscillatory network, and functional cell states.

4.
Nat Commun ; 15(1): 6295, 2024 Jul 26.
Artículo en Inglés | MEDLINE | ID: mdl-39060234

RESUMEN

Fast electrical signaling in dendrites is central to neural computations that support adaptive behaviors. Conventional techniques lack temporal and spatial resolution and the ability to track underlying membrane potential dynamics present across the complex three-dimensional dendritic arbor in vivo. Here, we perform fast two-photon imaging of dendritic and somatic membrane potential dynamics in single pyramidal cells in the CA1 region of the mouse hippocampus during awake behavior. We study the dynamics of subthreshold membrane potential and suprathreshold dendritic events throughout the dendritic arbor in vivo by combining voltage imaging with simultaneous local field potential recording, post hoc morphological reconstruction, and a spatial navigation task. We systematically quantify the modulation of local event rates by locomotion in distinct dendritic regions, report an advancing gradient of dendritic theta phase along the basal-tuft axis, and describe a predominant hyperpolarization of the dendritic arbor during sharp-wave ripples. Finally, we find that spatial tuning of dendritic representations dynamically reorganizes following place field formation. Our data reveal how the organization of electrical signaling in dendrites maps onto the anatomy of the dendritic tree across behavior, oscillatory network, and functional cell states.


Asunto(s)
Región CA1 Hipocampal , Dendritas , Células Piramidales , Animales , Dendritas/fisiología , Dendritas/metabolismo , Células Piramidales/fisiología , Células Piramidales/metabolismo , Ratones , Región CA1 Hipocampal/fisiología , Región CA1 Hipocampal/citología , Potenciales de la Membrana/fisiología , Masculino , Ratones Endogámicos C57BL , Hipocampo/fisiología , Hipocampo/citología , Navegación Espacial/fisiología , Locomoción/fisiología
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