Serge Faumont et al. (2006) Neuronal Development, Synaptic Function, and Behavior Meeting "Simultaneous Recording of Command Neuron Activity and Behavior in C. elegans"

Tod Thiele, Thad Lindsay, Serge Faumont, Shawn Lockery

[Neuronal Development, Synaptic Function, and Behavior Meeting, 2006]

Modulation of the frequency or duration of reverse locomotion is the final common path for many complex behaviors in C. elegans including chemotaxis, thermotaxis, and aerotaxis. Reversals are thought to be regulated by a network of command neurons consisting of the ventral cord interneurons AVA, AVB, AVD, and PVC, but physiological experiments to directly correlate command neuron activity with behavior are lacking. Thus, it remains unclear how the command neurons regulate locomotion. To address this issue, we recorded the activity of AVA neurons during locomotion using the cameleon calcium probe in a submerged, semi-restrained swimming preparation in which the animal was glued by the neck to the substrate, leaving the tail free to move. Under these conditions, the animal exhibited clearly recognizable episodes of forward and reverse swimming. To record neuronal activity and behavior simultaneously, we used an inverted microscope with two objectives focused on the preparation: a high-power objective (63x) for imaging the neuron , and a low-power objective (10x) for imaging the behavior. We observed a tight correlation between calcium transients in AVA interneurons and spontaneous reversal behavior. Specifically, calcium concentration was high during reverse locomotion and low during forward locomotion. Moreover, the duration of each spontaneous reversal precisely matched the duration of the corresponding calcium transient. In addition, reversals evoked by sensory stimulation, such as changes in NaCl concentration, were also associated with calcium transients in AVA. These findings support a model in which sensory activity modifies AVA activity, which in turn modifies reversal behavior. Additionally, we have begun to investigate the activity of neurons synaptically connected to AVA. In simultaneous recordings of AVA and the interneuron RIM-which has gap junctions with AVA and has been implicated in the regulation of reversal frequency-AVA and RIM were coactive during reversals. This result suggests that the neural correlate of behavioral reversals may involve activation of more than one neuron class.

Shawn Lockery et al. (2007) International Worm Meeting "Sensory regulation of command neuron state transitions: Theory and experiment."

Thad Lindsay, Shawn Lockery, Tod Thiele, Nathan Dunn, Serge Faumont

[International Worm Meeting, 2007]

Locomotory state in C. elegans (forward vs. reverse) is thought to be controlled by a network of forward and reverse command neurons in two reciprocally connected pools, but how this network is regulated by sensory input is poorly understood. According to one hypothesis, known as the Stochastic Switch Model, each pool acts as a probabilistic binary unit (OFF = 0, ON = 1). The model assumes that the rate constant for transitions to the ON state (a₀₁) at any point in time t is a sigmoidal function S(x) of net synaptic input I such that a₀₁(t) = a_max S(I(t)) where a_max is a scale factor. According to the Stochastic Switch Model, sensory input to each unit acts to bias the probability of the ON state. In one configuration of the model, modulation of bias is reciprocal. For example, a sensory stimulus that promotes forward locomotion would excite the forward unit and inhibit the reverse unit; a stimulus that promotes reverse locomotion would produce the opposite pattern of synaptic effects. Alternatively, the modulation may be non-reciprocal such that sensory input affects the bias of one unit but not the other. To distinguish between these two configurations in the context of chemotaxis, we presented worms with stepwise changes in the concentration of the chemoattractant NaCl and measured the rate constants for forward-to-reverse and reverse-to-forward transitions. Rate constants were analyzed in terms of a reduced version of the Stochastic Switch Model that enabled us to compute I(t) for each unit using the above equation. We found that in response to upward steps in NaCl, a forward-promoting stimulus, the forward unit was excited whereas the reverse unit was inhibited. This result indicates that upsteps promote forward locomotion by a reciprocal control mechanism. In contrast, we found that in response to downward steps in NaCl, a reverse-promoting stimulus, the forward unit was unaffected whereas the reverse unit was excited. This result indicates that downsteps promote reverse locomotion by a non-reciprocal mechanism. Taken together, these results suggest the hypothesis that locomotory bias in response to chemosensory inputs is established by different control mechanisms depending on stimulus polarity. We plan to test this hypothesis by recording synaptic potentials from command neurons in response to direct activation of chemosensory neurons. Support: NIH MH051383 and NSF IOB-0543643.

Scholz, Monika et al. (2019) International Worm Meeting "Predicting locomotion from whole-brain neural dynamics in freely moving animals."

Randi, Francesco, Leifer, Andrew, Yu, Xinwei, Shaevitz, Joshua, Linder, Ashley, Scholz, Monika, Sharma, Anuj

[International Worm Meeting, 2019]

How do patterns of neural activity across the brain represent an animal's behavior? Recent techniques for recording from large populations of neurons are providing new insights into how locomotion is encoded in population-level neural activity. Studies from mammalian systems suggest that behavioral information may be more prevalent throughout the brain and may account for a larger fraction of neural dynamics than previously thought. In C. elegans, pioneering studies revealed that the worm's neural dynamics during immobilization exhibit striking stereotyped low-dimensional patterns of neural activity that dominate brain-wide dynamics (Kato et al., 2015). These dynamics are hypothesized to map onto a motor sequence consisting of forward, backward and turning locomotion. One interpretation is that the majority of the worm brain's activity may be involved in encoding these locomotory behaviors. Here we seek to directly measure how patterns of neural activity represent locomotion by recording brain-wide calcium activity in freely-moving animals. We record calcium activity simultaneously from the majority of head neurons in C. elegans during unrestrained spontaneous locomotory behavior (Scholz et al., 2018). We find that a subset of neurons distributed throughout the head encode locomotion. By taking a linear combination of these neurons' activity, we predict the animal's velocity and body curvature and further infer the animal's posture from neural activity alone. The collective activity of these neurons outperforms single neurons at predicting velocity or body curvature. We further attempt to estimate the identity of neurons involved in the prediction. Among neurons important for the prediction are well-known locomotory neurons, as well as neurons not traditionally associated with locomotion. We compare the neural activity of the same animal during unrestrained movement and during immobilization and observe large differences in their neural dynamics. Intriguingly, during unrestrained movement we estimate that only a small fraction of the brain's overall neural dynamics are encoding velocity and body curvature. We speculate that the rest of the brain's neural dynamics may be involved in encoding other behaviors, processing sensory information or maintaining internal brain states. Kato, S., Kaplan, H.S., Schrodel, T., Skora, S., Lindsay, T.H., Yemini, E., Lockery, S., and Zimmer, M. (2015). Global brain dynamics embed the motor command sequence of Caenorhabditis elegans. Cell 163, 656-669. Scholz, M., Linder, A.N., Randi, F., Sharma, A.K., Yu, X., Shaevitz, J.W., and Leifer, A. (2018). Predicting natural behavior from whole-brain neural dynamics. BioRxiv 445643.