arXiv subjects

Manuel Zimmer

Publications and source records attributed to Manuel Zimmer.

7 recordsLinked to original sources

arXiv2024

The time is ripe to reverse engineer an entire nervous system: simulating behavior from neural interactions

Just like electrical engineers understand how microprocessors execute programs in terms of how transistor currents are affected by their inputs, neuroscientists want to understand behavior production in terms of how neuronal outputs are affected by their inputs and internal states. This dependency of neuronal outputs on inputs can be described by a state-dependent input-output (IO)-function. However, to reliably identify these IO-functions, we need to perturb each input and combinations of inputs while observing all the outputs. Here, we argue that such completeness is possible in C. elegans; a complete description that goes all the way from the activity of every neuron to predict behavior. The established and growing toolkit of optophysiology can non-invasively capture and control every neuron's activity and scale to countless experiments. The information from many such experiments can be pooled while capturing the inter-individual variability because neuronal identity and function are largely conserved across individuals. Just like electrical engineers use transistor IO-functions to simulate program execution, we argue that neuronal IO-functions could be used to simulate the impressive breadth of brain states and behaviors of C. elegans.

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arXiv2024

Fibration symmetry-breaking supports functional transitions in a brain network engaged in language

In his book 'A Beautiful Question', physicist Frank Wilczek argues that symmetry is 'nature's deep design,' governing the behavior of the universe, from the smallest particles to the largest structures. While symmetry is a cornerstone of physics, it has not yet been found widespread applicability to describe biological systems, particularly the human brain. In this context, we study the human brain network engaged in language and explore the relationship between the structural connectivity (connectome or structural network) and the emergent synchronization of the mesoscopic regions of interest (functional network). We explain this relationship through a different kind of symmetry than physical symmetry, derived from the categorical notion of Grothendieck fibrations. This introduces a new understanding of the human brain by proposing a local symmetry theory of the connectome, which accounts for how the structure of the brain's network determines its coherent activity. Among the allowed patterns of structural connectivity, synchronization elicits different symmetry subsets according to the functional engagement of the brain. We show that the resting state is a particular realization of the cerebral synchronization pattern characterized by a fibration symmetry that is broken in the transition from rest to language. Our findings suggest that the brain's network symmetry at the local level determines its coherent function, and we can understand this relationship from theoretical principles.

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arXiv2024

Symmetries and synchronization from whole-neural activity in {\it C. elegans} connectome: Integration of functional and structural networks

Understanding the dynamical behavior of complex systems from their underlying network architectures is a long-standing question in complexity theory. Therefore, many metrics have been devised to extract network features like motifs, centrality, and modularity measures. It has previously been proposed that network symmetries are of particular importance since they are expected to underly the synchronization of a system's units, which is ubiquitously observed in nervous system activity patterns. However, perfectly symmetrical structures are difficult to assess in noisy measurements of biological systems, like neuronal connectomes. Here, we devise a principled method to infer network symmetries from combined connectome and neuronal activity data. Using nervous system-wide population activity recordings of the \textit{C.elegans} backward locomotor system, we infer structures in the connectome called fibration symmetries, which can explain which group of neurons synchronize their activity. Our analysis suggests functional building blocks in the animal's motor periphery, providing new testable hypotheses on how descending interneuron circuits communicate with the motor periphery to control behavior. Our approach opens a new door to exploring the structure-function relations in other complex systems, like the nervous systems of larger animals.

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arXiv2024

Fibration symmetries and cluster synchronization in the Caenorhabditis elegans connectome

Capturing how the Caenorhabditis elegans connectome structure gives rise to its neuron functionality remains unclear. It is through fiber symmetries found in its neuronal connectivity that synchronization of a group of neurons can be determined. To understand these we investigate graph symmetries and search for such in the symmetrized versions of the forward and backward locomotive sub-networks of the Caenorhabditi elegans worm neuron network. The use of ordinarily differential equations simulations admissible to these graphs are used to validate the predictions of these fiber symmetries and are compared to the more restrictive orbit symmetries. Additionally fibration symmetries are used to decompose these graphs into their fundamental building blocks which reveal units formed by nested loops or multilayered fibers. It is found that fiber symmetries of the connectome can accurately predict neuronal synchronization even under not idealized connectivity as long as the dynamics are within stable regimes of simulations.

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arXiv2020

Unsupervised learning of control signals and their encodings in $\textit{C. elegans}$ whole-brain recordings

Recent whole brain imaging experiments on $\textit{C. elegans}$ has revealed that the neural population dynamics encode motor commands and stereotyped transitions between behaviors on low dimensional manifolds. Efforts to characterize the dynamics on this manifold have used piecewise linear models to describe the entire state space, but it is unknown how a single, global dynamical model can generate the observed dynamics. Here, we propose a control framework to achieve such a global model of the dynamics, whereby underlying linear dynamics is actuated by sparse control signals. This method learns the control signals in an unsupervised way from data, then uses $\textit{ Dynamic Mode Decomposition with control}$ (DMDc) to create the first global, linear dynamical system that can reconstruct whole-brain imaging data. These control signals are shown to be implicated in transitions between behaviors. In addition, we analyze the time-delay encoding of these control signals, showing that these transitions can be predicted from neurons previously implicated in behavioral transitions, but also additional neurons previously unidentified. Moreover, our decomposition method allows one to understand the observed nonlinear global dynamics instead as linear dynamics with control. 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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arXiv2017

Searching for Biophysically Realistic Parameters for Dynamic Neuron Models by Genetic Algorithms from Calcium Imaging Recording

Individual Neurons in the nervous systems exploit various dynamics. To capture these dynamics for single neurons, we tune the parameters of an electrophysiological model of nerve cells, to fit experimental data obtained by calcium imaging. A search for the biophysical parameters of this model is performed by means of a genetic algorithm, where the model neuron is exposed to a predefined input current representing overall inputs from other parts of the nervous system. The algorithm is then constrained for keeping the ion-channel currents within reasonable ranges, while producing the best fit to a calcium imaging time series of the AVA interneuron, from the brain of the soil-worm, C. elegans. Our settings enable us to project a set of biophysical parameters to the the neuron kinetics observed in neuronal imaging.

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arXiv2014

Brain-wide 3D imaging of neuronal activity in Caenorhabditis elegans with sculpted light

Recent efforts in neuroscience research seek to obtain detailed anatomical neuronal wiring maps as well as information on how neurons in these networks engage in dynamic activities. Although the entire connectivity map of the nervous system of C. elegans has been known for more than 25 years, this knowledge has not been sufficient to predict all functional connections underlying behavior. To approach this goal, we developed a two-photon technique for brain-wide calcium imaging in C. elegans using wide-field temporal focusing (WF-TEFO). Pivotal to our results was the use of a nuclear-localized, genetically encoded calcium indicator (NLS-GCaMP5K) that permits unambiguous discrimination of individual neurons within the densely-packed head ganglia of C. elegans. We demonstrate near-simultaneous recording of activity of up to 70% of all head neurons. In combination with a lab-on-a-chip device for stimulus delivery, this method provides an enabling platform for establishing functional maps of neuronal networks.

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