Closed-loop all-optical interrogation of neural circuits in vivo

Understanding the causal relationship between neural activity and behavior requires the ability to perform rapid and targeted interventions in ongoing activity. Here we describe a closed-loop all-optical strategy for dynamically controlling neuronal activity patterns in awake mice. We rapidly tailored and delivered two-photon optogenetic stimulation based on online readout of activity using simultaneous two-photon imaging, thus enabling the manipulation of neural circuit activity ‘on the fly’ during behavior.A closed-loop all-optical strategy allows manipulation of neurons on the basis of their ongoing activity and can be used to clamp neuronal activity to a preset level, boost sensory-evoked activity or yoke together the activity of trigger and target neurons.

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