A major goal of computational neuroscience is to understand the relationship between synapse-level structure and network-level functionality. Caenorhabditis elegans is a model organism to probe this relationship due to the historic availability of the synaptic structure (connectome) and recent advances in whole brain calcium imaging techniques. Recent work has applied the concept of network controllability to neuronal networks, discovering some neurons that are able to drive the network to a certain state. However, previous work uses a linear model of the network dynamics, and it is unclear if the real neuronal network conforms to this assumption. Here, we propose a method to build a global, low-dimensional model of the dynamics, whereby an underlying global linear dynamical system is actuated by temporally sparse control signals. A key novelty of this method is discovering candidate control signals that the network uses to control itself. We analyse these control signals in two ways, showing they are interpretable and biologically plausible. First, these control signals are associated with transitions between behaviours, which were previously annotated via expert-generated features. Second, these signals can be predicted both from neurons previously implicated in behavioural transitions but also additional neurons previously unassociated with these behaviours. The proposed mathematical framework is generic and can be generalized to other neurosensory systems, potentially revealing transitions and their encodings in a completely unsupervised way.

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Recent whole-brain calcium imaging recordings of the nematode C. elegans have demonstrated that the neural activity associated with behavior is dominated by dynamics on a low-dimensional manifold that can be clustered according to behavioral states. Previous models of C. elegans dynamics have either been linear models, which cannot support the existence of multiple fixed points in the system, or Markov-switching models, which do not describe how control signals in C. elegans neural dynamics can produce switches between stable states. It remains unclear how a network of neurons can produce fast and slow timescale dynamics that control transitions between stable states in a single model. We propose a global, nonlinear control model which is minimally parameterized and captures the state transitions described by Markov-switching models with a single dynamical system. The model is fit by reproducing the timeseries of the dominant PCA mode in the calcium imaging data. Long and short time-scale changes in transition statistics can be characterized via changes in a single parameter in the control model. Some of these macro-scale transitions have experimental correlates to single neuro-modulators that seem to act as biological controls, allowing this model to generate testable hypotheses about the effect of these neuro-modulators on the global dynamics. The theory provides an elegant characterization of control in the neuron population dynamics in C. elegans. Moreover, the mathematical structure of the nonlinear control framework provides a paradigm that can be generalized to more complex systems with an arbitrary number of behavioral states.

Recent whole-brain calcium imaging recordings of the nematode C. elegans have demonstrated that neural activity is dominated by dynamics on a low-dimensional manifold that can be clustered according to behavioral states. Despite progress in modeling the dynamics with linear or locally linear models, it remains unclear how a single network of neurons can produce the observed features. In particular, there are multiple clusters, or fixed points, observed in the data which cannot be characterized by a single linear model. We propose a nonlinear control model which is global and parameterized by only four free parameters that match the features displayed by the low-dimensional C. elegans neural activity. In addition to reproducing the average probability distribution of the data, long and short time-scale changes in transition statistics can be characterized via changes in a single parameter. Some of these macro-scale transitions have experimental correlates to single neuro-modulators that seem to act as biological controls, allowing this model to generate testable hypotheses about the effect of these neuro-modulators on the global dynamics. The theory provides an elegant characterization of the neuron population dynamics in C. elegans. Moreover, the mathematical structure of the nonlinear control framework provides a paradigm that can be generalized to more complex systems with an arbitrary number of behavioral states.

No abstract