Functional neuronal circuits emerge in the absence of developmental activity.

The complex neuronal circuitry of the brain develops from limited information contained in the genome. After the genetic code instructs the birth of neurons, the emergence of brain regions, and the formation of axon tracts, it is believed that temporally structured spiking activity shapes circuits for behavior. Here, we challenge the learning-dominated assumption that spiking activity is required for circuit formation by quantifying its contribution to the development of visually-guided swimming in the larval zebrafish. We found that visual experience had no effect on the emergence of the optomotor response (OMR) in dark-reared zebrafish. We then raised animals while pharmacologically silencing action potentials with the sodium channel blocker tricaine. After washout of the anesthetic, fish could swim and performed with 75-90% accuracy in the OMR paradigm. Brain-wide imaging confirmed that neuronal circuits came 'online' fully tuned, without requiring activity-dependent plasticity. Thus, complex sensory-guided behaviors can emerge through activity-independent developmental mechanisms.

Neuroscience Needs Network Science.

The brain is a complex system comprising a myriad of interacting neurons, posing significant challenges in understanding its structure, function, and dynamics. Network science has emerged as a powerful tool for studying such interconnected systems, offering a framework for integrating multiscale data and complexity. To date, network methods have significantly advanced functional imaging studies of the human brain and have facilitated the development of control theory-based applications for directing brain activity. Here, we discuss emerging frontiers for network neuroscience in the brain atlas era, addressing the challenges and opportunities in integrating multiple data streams for understanding the neural transitions from development to healthy function to disease. We underscore the importance of fostering interdisciplinary opportunities through workshops, conferences, and funding initiatives, such as supporting students and postdoctoral fellows with interests in both disciplines. By bringing together the network science and neuroscience communities, we can develop novel network-based methods tailored to neural circuits, paving the way toward a deeper understanding of the brain and its functions, as well as offering new challenges for network science.

Neuroscience needs Network Science.

The brain is a complex system comprising a myriad of interacting elements, posing significant challenges in understanding its structure, function, and dynamics. Network science has emerged as a powerful tool for studying such intricate systems, offering a framework for integrating multiscale data and complexity. Here, we discuss the application of network science in the study of the brain, addressing topics such as network models and metrics, the connectome, and the role of dynamics in neural networks. We explore the challenges and opportunities in integrating multiple data streams for understanding the neural transitions from development to healthy function to disease, and discuss the potential for collaboration between network science and neuroscience communities. We underscore the importance of fostering interdisciplinary opportunities through funding initiatives, workshops, and conferences, as well as supporting students and postdoctoral fellows with interests in both disciplines. By uniting the network science and neuroscience communities, we can develop novel network-based methods tailored to neural circuits, paving the way towards a deeper understanding of the brain and its functions.

Complex computation from developmental priors.

Machine learning (ML) models have long overlooked innateness: how strong pressures for survival lead to the encoding of complex behaviors in the nascent wiring of a brain. Here, we derive a neurodevelopmental encoding of artificial neural networks that considers the weight matrix of a neural network to be emergent from well-studied rules of neuronal compatibility. Rather than updating the network's weights directly, we improve task fitness by updating the neurons' wiring rules, thereby mirroring evolutionary selection on brain development. We find that our model (1) provides sufficient representational power for high accuracy on ML benchmarks while also compressing parameter count, and (2) can act as a regularizer, selecting simple circuits that provide stable and adaptive performance on metalearning tasks. In summary, by introducing neurodevelopmental considerations into ML frameworks, we not only model the emergence of innate behaviors, but also define a discovery process for structures that promote complex computations.

SITH: An R package for visualizing and analyzing a spatial model of intratumor heterogeneity.

Cancer progression, including the development of intratumor heterogeneity, is inherently a spatial process. Mathematical models of tumor evolution may be a useful starting point for understanding the patterns of heterogeneity that can emerge in the presence of spatial growth. A commonly studied spatial growth model assumes that tumor cells occupy sites on a lattice and replicate into neighboring sites. Our R package SITH provides a convenient interface for exploring this model. Our efficient simulation algorithm allows for users to generate 3D tumors with millions of cells in under a minute. For visualizing the distribution of mutations throughout the tumor, SITH provides interactive graphics and summary plots. Additionally, SITH can produce synthetic bulk and single-cell DNA-seq datasets by sampling from the simulated tumor. A streamlined API makes SITH a useful tool for investigating the relationship between spatial growth and intratumor heterogeneity. SITH is a part of CRAN and can be installed by running install.packages("SITH") from the R console. See https://CRAN.R-project.org/package=SITH for the user manual and package vignette.

Constructing graphs from genetic encodings.

Our understanding of real-world connected systems has benefited from studying their evolution, from random wirings and rewirings to growth-dependent topologies. Long overlooked in this search has been the role of the innate: networks that connect based on identity-dependent compatibility rules. Inspired by the genetic principles that guide brain connectivity, we derive a network encoding process that can utilize wiring rules to reproducibly generate specific topologies. To illustrate the representational power of this approach, we propose stochastic and deterministic processes for generating a wide range of network topologies. Specifically, we detail network heuristics that generate structured graphs, such as feed-forward and hierarchical networks. In addition, we characterize a Random Genetic (RG) family of networks, which, like Erdos-Rényi graphs, display critical phase transitions, however their modular underpinnings lead to markedly different behaviors under targeted attacks. The proposed framework provides a relevant null-model for social and biological systems, where diverse metrics of identity underpin a node's preferred connectivity.

Uncovering the genetic blueprint of the C. elegans nervous system.

Despite rapid advances in connectome mapping and neuronal genetics, we lack theoretical and computational tools to unveil, in an experimentally testable fashion, the genetic mechanisms that govern neuronal wiring. Here we introduce a computational framework to link the adjacency matrix of a connectome to the expression patterns of its neurons, helping us uncover a set of genetic rules that govern the interactions between neurons in contact. The method incorporates the biological realities of the system, accounting for noise from data collection limitations, as well as spatial restrictions. The resulting methodology allows us to infer a network of 19 innexin interactions that govern the formation of gap junctions in Caenorhabditis elegans, five of which are already supported by experimental data. As advances in single-cell gene expression profiling increase the accuracy and the coverage of the data, the developed framework will allow researchers to systematically infer experimentally testable connection rules, offering mechanistic predictions for synapse and gap junction formation.

A Genetic Model of the Connectome.

The connectomes of organisms of the same species show remarkable architectural and often local wiring similarity, raising the question: where and how is neuronal connectivity encoded? Here, we start from the hypothesis that the genetic identity of neurons guides synapse and gap-junction formation and show that such genetically driven wiring predicts the existence of specific biclique motifs in the connectome. We identify a family of large, statistically significant biclique subgraphs in the connectomes of three species and show that within many of the observed bicliques the neurons share statistically significant expression patterns and morphological characteristics, supporting our expectation of common genetic factors that drive the synapse formation within these subgraphs. The proposed connectome model offers a self-consistent framework to link the genetics of an organism to the reproducible architecture of its connectome, offering experimentally falsifiable predictions on the genetic factors that drive the formation of individual neuronal circuits.