arXiv subjects

Anuj K Sharma

Publications and source records attributed to Anuj K Sharma.

3 recordsLinked to original sources

arXiv2023

Inhibitory feedback from the motor circuit gates mechanosensory processing in C. elegans

Animals must integrate sensory cues with their current behavioral context to generate a suitable response. How this integration occurs is poorly understood. Previously we developed high throughput methods to probe neural activity in populations of Caenorhabditis elegans and discovered that the animal's mechanosensory processing is rapidly modulated by the animal's locomotion. Specifically we found that when the worm turns it suppresses its mechanosensory-evoked reversal response. Here we report that C. elegans use inhibitory feedback from turning-associated neurons to provide this rapid modulation of mechanosensory processing. By performing high-throughput optogenetic perturbations triggered on behavior, we show that turning associated neurons SAA, RIV and/or SMB suppress mechanosensory-evoked reversals during turns. We find that activation of the gentle-touch mechanosensory neurons or of any of the interneurons AIZ, RIM, AIB and AVE during a turn is less likely to evoke a reversal than activation during forward movement. Inhibiting neurons SAA, RIV and SMB during a turn restores the likelihood with which mechanosensory activation evokes reversals. Separately, activation of premotor interneuron AVA evokes reversals regardless of whether the animal is turning or moving forward. We therefore propose that inhibitory signals from SAA, RIV and/or SMB gate mechanosensory signals upstream of neuron AVA. We conclude that C. elegans rely on inhibitory feedback from the motor circuit to modulate its response to sensory stimuli on fast timescales. This need for motor signals in sensory processing may explain the ubiquity in many organisms of motor-related neural activity patterns seen across the brain, including in sensory processing areas.

q-bio.NC↗

arXiv2021

Closed-loop targeted optogenetic stimulation of 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 soft touch receptor neurons. Responses to more than $10^4$ 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 posterior 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 $10^3$ 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.

q-bio.NC↗

arXiv2018

Temporal processing and context dependency in C. elegans mechanosensation

A quantitative understanding of how sensory signals are transformed into motor outputs places useful constraints on brain function and helps reveal the brain's underlying computations. We investigate how the nematode C. elegans responds to time-varying mechanosensory signals using a high-throughput optogenetic assay and automated behavior quantification. In the prevailing picture of the touch circuit, the animal's behavior is determined by which neurons are stimulated and by the stimulus amplitude. In contrast, we find that the behavioral response is tuned to temporal properties of mechanosensory signals, like its integral and derivative, that extend over many seconds. Mechanosensory signals, even in the same neurons, can be tailored to elicit different behavioral responses. Moreover, we find that the animal's response also depends on its behavioral context. Most dramatically, the animal ignores all tested mechanosensory stimuli during turns. Finally, we present a linear-nonlinear model that predicts the animal's behavioral response to stimulus.

q-bio.NC↗