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 , RatonesRESUMEN
Animals influence how they disperse in the environment by sensing local cues and adapting how they move. However, controlling dispersal can present a particular challenge early in life when animals tend to be more limited in their capacities to sense and move. To what extent and by what mechanisms can newly hatched fish control how they disperse? Here, we reveal hatchling sensorimotor mechanisms for controlling dispersal by combining swim tracking and precise sensory manipulations of a model species, zebrafish. In controlled laboratory experiments, if we physically constrained hatchlings or blocked sensations of motion through vision and the lateral line, hatchlings responded by elevating their buoyancy and passively moving with faster surface currents. Complementarily, in stagnant water, hatchlings covered more ground using hyperstable swimming, strongly orienting based on graviception. Using experimentally calibrated hydrodynamic simulations, we show that these hatchling behaviors nearly tripled diffusivity and made dispersal robust to local conditions, suggesting this multisensory strategy may provide important advantages for early life in a variable environment.