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Closed-loop optogenetic intervention in mice.

ABSTRACT: Optogenetic interventions offer novel ways of probing, in a temporally specific manner, the roles of specific cell types in neuronal network functions of awake, behaving animals. Despite the unique potential for temporally specific optogenetic intervention in disease states, a major hurdle in its broad application to unpredictable brain states in a laboratory setting is constructing a real-time responsive system. We recently created a closed-loop system for stopping spontaneous seizures in chronically epileptic mice by using optogenetic intervention. This system performs with a very high sensitivity and specificity, and the strategy is not only relevant to epilepsy but also can also be used to react to diverse brain states in real time, with optogenetic or other interventions. The protocol presented here is highly modular and requires variable amounts of time to perform. We describe the basic construction of a complete system, and we include our downloadable custom closed-loop detection software, which can be used for this purpose.

SUBMITTER: Armstrong C

PROVIDER: S-EPMC3988315 | biostudies-literature | 2013 Aug

REPOSITORIES: biostudies-literature

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Closed-loop optogenetic intervention in mice.

Armstrong Caren C Krook-Magnuson Esther E Oijala Mikko M Soltesz Ivan I

Nature protocols 20130711 8

Optogenetic interventions offer novel ways of probing, in a temporally specific manner, the roles of specific cell types in neuronal network functions of awake, behaving animals. Despite the unique potential for temporally specific optogenetic intervention in disease states, a major hurdle in its broad application to unpredictable brain states in a laboratory setting is constructing a real-time responsive system. We recently created a closed-loop system for stopping spontaneous seizures in chron ...[more]

PMID: 23845961

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Project description:OBJECTIVE:Optogenetics provides a means to probe functional connections between brain areas. By activating a set of presynaptic neurons and recording the activity from a downstream brain area, one can establish the sign and strength of a feedforward connection. One challenge is that there are virtually limitless patterns that can be used to stimulate a presynaptic brain area. Functional influences on downstream brain areas can depend not just on whether presynaptic neurons were activated, but how they were activated. Corticofugal axons from the auditory cortex (ACtx) heavily innervate the auditory tectum, the inferior colliculus (IC). Here, we sought to determine whether different modes of corticocollicular activation could titrate the strength of feedforward modulation of sound processing in IC neurons. APPROACH:We used multi-channel electrophysiology and optogenetics to record from multiple regions of the IC in awake head-fixed mice while optogenetically stimulating ACtx neurons expressing Chronos, an ultra-fast channelrhodopsin. To identify cortical activation patterns associated with the strongest effects on IC firing rates, we employed a closed-loop evolutionary optimization procedure that tailored the voltage command signal sent to the laser based on spike feedback from single IC neurons. MAIN RESULTS:Within minutes, our evolutionary search procedure converged on ACtx stimulation configurations that produced more effective and widespread enhancement of IC unit activity than generic activation parameters. Cortical modulation of midbrain spiking was bi-directional, as the evolutionary search procedure could be programmed to converge on activation patterns that either suppressed or enhanced sound-evoked IC firing rate. SIGNIFICANCE:This study introduces a closed-loop optimization procedure to probe functional connections between brain areas. Our findings demonstrate that the influence of descending feedback projections on subcortical sensory processing can vary both in sign and degree depending on how cortical neurons are activated in time.

Dataset Information

Closed-loop optogenetic intervention in mice.

Publications

Closed-loop optogenetic intervention in mice.

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