Search for: All records

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 ofCaenorhabditis elegansand 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 thatC.elegansuse 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 thatC.elegansrely 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. 

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. 

A worm called Caenorhabditis elegans has a nervous system made up of only 302 neurons, far fewer than the billions of cells that comprise our own brains. And yet these few hundred neurons are enough for these worms to detect and respond to their surroundings. C. elegans is thus a popular choice for studying how nervous systems process sensory information and use it to control behavior. Yet, most experiments to date have used only simple stimuli, such as taps or pokes, and studied a handful of behaviors, such as whether or not a worm stops moving or backs up. This limits the conclusions it has been possible to draw. Liu et al. therefore set out to determine how the worm’s nervous system responds to more complex stimuli. These included physical stimuli, such as taps on the side of the dish containing the worms, as well as simulated stimuli. To generate the latter, Liu et al. used a technique called optogenetics to directly activate the neurons in the worm’s body that would normally detect information from the senses, by simply shining a light on the worms. Doing so gives the worm the sensation of a physical stimulus, even though none was present. Liu et al. then used mathematics to examine the relationships between the stimuli and the worms’ responses. The results confirmed that worms usually respond to simple stimuli, such as taps on the side of their dish, by backing up. But they also revealed more advanced forms of stimulus processing. The worms responded differently to stimuli that increased over time versus decreased, for example. A worm's response to a stimulus also varied depending on what the worm was doing at the time. Worms that were in the middle of turns, for instance, ignored stimuli to which they would normally respond. This suggests that an animal’s current behavior influences how its nervous system interprets sensory information. The discovery of relatively sophisticated responses to sensory stimuli in C. elegans indicates that even simple nervous systems are capable of flexible sensory processing. This lays a foundation for understanding how neural circuits interpret sensory signals. Building on this work will ultimately help us understand how more complicated nervous systems interpret and respond to the world.