An animal’s current behavior influences its response to sensory stimuli, but the molecular and circuitlevel mechanisms of this context-dependent decision-making are not well understood. Caenorhabditis elegans are less likely to respond to a mechanosensory stimulus by reversing if the stimuli is received while the animal turns. Inhibitory feedback from turning associated neurons are needed for this gating. But until now, it has remained unknown precisely where in the circuit gating occurs and which specific neurons and receptors receive inhibition from the turning circuitry. Here, we use genetic manipulations, single-cell rescue experiments, and high-throughput closed-loop optogenetic perturbations during behavior to reveal the specific neuron and receptor responsible for receiving inhibition and altering sensorimotor processing. Our measurements show that an inhibitory acetylcholine-gated chloride channel comprising LGC-47 and ACC-1 expressed in neuron type RIM disrupts mechanosensory evoked reversals during turns, presumably in response to inhibitory signals from turning-associated neuron SAA.
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A high-throughput method to deliver targeted optogenetic stimulation to moving C. elegans populations
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 animal’s body such as its head or tail; it automatically delivers stimuli triggered upon the animal’s behavior; and it achieves high throughput by targeting many animals simultaneously. The instrument was used to optogenetically probe the animal’s behavioral response to competing mechanosensory stimuli in the the anterior and posterior gentle touch receptor neurons. Responses to more than 43,418 stimulus events from a range of anterior–posterior intensity combinations were measured. The animal’s 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 anterior stimulation intensity. We also probed the animal’s 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 9,700 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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- PAR ID:
- 10317770
- Editor(s):
- Sengupta, Piali
- Date Published:
- Journal Name:
- PLOS Biology
- Volume:
- 20
- Issue:
- 1
- ISSN:
- 1545-7885
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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