A tonically active master neuron modulates mutually exclusive motor states at two timescales.

Continuity of behaviors requires animals to make smooth transitions between mutually exclusive behavioral states. Neural principles that govern these transitions are not well understood. Caenorhabditis elegans spontaneously switch between two opposite motor states, forward and backward movement, a phenomenon thought to reflect the reciprocal inhibition between interneurons AVB and AVA. Here, we report that spontaneous locomotion and their corresponding motor circuits are not separately controlled. AVA and AVB are neither functionally equivalent nor strictly reciprocally inhibitory. AVA, but not AVB, maintains a depolarized membrane potential. While AVA phasically inhibits the forward promoting interneuron AVB at a fast timescale, it maintains a tonic, extrasynaptic excitation on AVB over the longer timescale. We propose that AVA, with tonic and phasic activity of opposite polarities on different timescales, acts as a master neuron to break the symmetry between the underlying forward and backward motor circuits. This master neuron model offers a parsimonious solution for sustained locomotion consisted of mutually exclusive motor states.

Maximally predictive states: From partial observations to long timescales.

Isolating slower dynamics from fast fluctuations has proven remarkably powerful, but how do we proceed from partial observations of dynamical systems for which we lack underlying equations? Here, we construct maximally predictive states by concatenating measurements in time, partitioning the resulting sequences using maximum entropy, and choosing the sequence length to maximize short-time predictive information. Transitions between these states yield a simple approximation of the transfer operator, which we use to reveal timescale separation and long-lived collective modes through the operator spectrum. Applicable to both deterministic and stochastic processes, we illustrate our approach through partial observations of the Lorenz system and the stochastic dynamics of a particle in a double-well potential. We use our transfer operator approach to provide a new estimator of the Kolmogorov-Sinai entropy, which we demonstrate in discrete and continuous-time systems, as well as the movement behavior of the nematode worm C. elegans.

Post-embryonic remodeling of the C. elegans motor circuit.

During development, animals can maintain behavioral output even as underlying circuitry structurally remodels. After hatching, C. elegans undergoes substantial motor neuron expansion and synapse rewiring while the animal continuously moves with an undulatory pattern. To understand how the circuit transitions from its juvenile to mature configuration without interrupting functional output, we reconstructed the C. elegans motor circuit by electron microscopy across larval development. We observed the following: First, embryonic motor neurons transiently interact with the developing post-embryonic motor neurons prior to remodeling of their juvenile wiring. Second, post-embryonic neurons initiate synapse development with their future partners as their neurites navigate through the juvenile nerve cords. Third, embryonic and post-embryonic neurons sequentially build structural machinery needed for the adult circuit before the embryonic neurons relinquish their roles to post-embryonic neurons. Fourth, this transition is repeated region by region along the body in an anterior-to-posterior sequence, following the birth order of neurons. Through this orchestrated and programmed rewiring, the motor circuit gradually transforms from asymmetric to symmetric wiring. These maturation strategies support the continuous maintenance of motor patterns as the juvenile circuit develops into the adult configuration.

Extrasynaptic signaling enables an asymmetric juvenile motor circuit to produce symmetric undulation.

In many animals, there is a direct correspondence between the motor patterns that drive locomotion and the motor neuron innervation. For example, the adult C. elegans moves with symmetric and alternating dorsal-ventral bending waves arising from symmetric motor neuron input onto the dorsal and ventral muscles. In contrast to the adult, the C. elegans motor circuit at the juvenile larval stage has asymmetric wiring between motor neurons and muscles but still generates adult-like bending waves with dorsal-ventral symmetry. We show that in the juvenile circuit, wiring between excitatory and inhibitory motor neurons coordinates the contraction of dorsal muscles with relaxation of ventral muscles, producing dorsal bends. However, ventral bending is not driven by analogous wiring. Instead, ventral muscles are excited uniformly by premotor interneurons through extrasynaptic signaling. Ventral bends occur in anti-phasic entrainment to activity of the same motor neurons that drive dorsal bends. During maturation, the juvenile motor circuit is replaced by two motor subcircuits that separately drive dorsal and ventral bending. Modeling reveals that the juvenile's immature motor circuit is an adequate solution to generate adult-like dorsal-ventral bending before the animal matures. Developmental rewiring between functionally degenerate circuit solutions, which both generate symmetric bending patterns, minimizes behavioral disruption across maturation.

WormPose: Image synthesis and convolutional networks for pose estimation in C. elegans.

An important model system for understanding genes, neurons and behavior, the nematode worm C. elegans naturally moves through a variety of complex postures, for which estimation from video data is challenging. We introduce an open-source Python package, WormPose, for 2D pose estimation in C. elegans, including self-occluded, coiled shapes. We leverage advances in machine vision afforded from convolutional neural networks and introduce a synthetic yet realistic generative model for images of worm posture, thus avoiding the need for human-labeled training. WormPose is effective and adaptable for imaging conditions across worm tracking efforts. We quantify pose estimation using synthetic data as well as N2 and mutant worms in on-food conditions. We further demonstrate WormPose by analyzing long (∼ 8 hour), fast-sampled (∼ 30 Hz) recordings of on-food N2 worms to provide a posture-scale analysis of roaming/dwelling behaviors.

Adaptive, locally linear models of complex dynamics.

The dynamics of complex systems generally include high-dimensional, nonstationary, and nonlinear behavior, all of which pose fundamental challenges to quantitative understanding. To address these difficulties, we detail an approach based on local linear models within windows determined adaptively from data. While the dynamics within each window are simple, consisting of exponential decay, growth, and oscillations, the collection of local parameters across all windows provides a principled characterization of the full time series. To explore the resulting model space, we develop a likelihood-based hierarchical clustering, and we examine the eigenvalues of the linear dynamics. We demonstrate our analysis with the Lorenz system undergoing stable spiral dynamics and in the standard chaotic regime. Applied to the posture dynamics of the nematode Caenorhabditis elegans, our approach identifies fine-grained behavioral states and model dynamics which fluctuate about an instability boundary, and we detail a bifurcation in a transition from forward to backward crawling. We analyze whole-brain imaging in C. elegans and show that global brain dynamics is damped away from the instability boundary by a decrease in oxygen concentration. We provide additional evidence for such near-critical dynamics from the analysis of electrocorticography in monkey and the imaging of a neural population from mouse visual cortex at single-cell resolution.

Structural Differences in Gray Matter between Glider Pilots and Non-Pilots. A Voxel-Based Morphometry Study.

Glider flying is a unique skill that requires pilots to control an aircraft at high speeds in three dimensions and amidst frequent full-body rotations. In the present study, we investigated the neural correlates of flying a glider using voxel-based morphometry. The comparison between gray matter densities of 15 glider pilots and a control group of 15 non-pilots exhibited significant gray matter density increases in left ventral premotor cortex, anterior cingulate cortex, and the supplementary eye field. We posit that the identified regions might be associated with cognitive and motor processes related to flying, such as joystick control, visuo-vestibular interaction, and oculomotor control.