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Closed-loop targeted optogenetic stimulation of C. elegans populations

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 نشر من قبل Andrew Leifer
 تاريخ النشر 2021
  مجال البحث علم الأحياء فيزياء
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We present a high-throughput optogenetic illumination system capable of simultaneous closed-loop light delivery to specified targets in populations of moving Caenorhabditis elegans. The instrument addresses three technical challenges: it delivers targeted illumination to specified regions of the animals body such as its head or tail; it automatically delivers stimuli triggered upon the animals behavior; and it achieves high throughput by targeting many animals simultaneously. The instrument was used to optogenetically probe the animals behavioral response to competing mechanosensory stimuli in the the anterior and posterior soft touch receptor neurons. Responses to more than $10^4$ stimulus events from a range of anterior-posterior intensity combinations were measured. The animals probability of sprinting forward in response to a mechanosensory stimulus depended on both the anterior and posterior stimulation intensity, while the probability of reversing depended primarily on the posterior stimulation intensity. We also probed the animals response to mechanosensory stimulation during the onset of turning, a relatively rare behavioral event, by delivering stimuli automatically when the animal began to turn. Using this closed-loop approach, over $10^3$ stimulus events were delivered during turning onset at a rate of 9.2 events per worm-hour, a greater than 25-fold increase in throughput compared to previous investigations. These measurements validate with greater statistical power previous findings that turning acts to gate mechanosensory evoked reversals. Compared to previous approaches, the current system offers targeted optogenetic stimulation to specific body regions or behaviors with many-fold increases in throughput to better constrain quantitative models of sensorimotor processing.

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