Search bioRxiv⌕ Search

Biology subjects

Legare, A.

Publications and source records attributed to Legare, A..

2 recordsLinked to original sources

Function aligns with geometry in locally connected neuronal networks

The geometry of the brain imposes fundamental constraints on neuronal network organization and dynamics, yet how these constraints give rise to observed patterns of brain activity remains unclear. Here, we investigate how geometric eigenmodes relate to functional connectivity gradients in three-dimensional neural systems using a combination of generative network simulations and cellular-resolution calcium imaging in larval zebrafish. We show that functional connectivity gradients emerging from network activity naturally align with the geometric eigenmodes of the underlying spatial embedding when connectivity is predominantly local. By systematically increasing the prevalence of long-range connections, we reveal a robust geometry-function correspondence that progressively deteriorates as local connectivity is disrupted. We then show that spatial filtering can artificially imprint geometric patterns on functional gradients, highlighting an important methodological confound. To validate our computational results, we conduct volumetric calcium imaging experiments at cellular resolution in the optic tectum of zebrafish larvae, uncovering functional gradients that closely align with geometric eigenmodes. As predicted from simulations, the eigenmode-gradient mapping exhibits a cutoff point that quantitatively reflects the spatial extent of the regions connectivity kernel, inferred from single-neuron morphologies. This geometry-functional alignment disappears at brain-wide scale, where long-range connections are more prevalent. Our findings demonstrate how short-range anatomical connectivity anchors functional connectivity gradients to the brains geometry.

neuroscience↗

Structural and genetic determinants of zebrafish functional brain networks

Network science has significantly advanced our understanding of brain networks across species, revealing universal connectivity principles. While human studies based on magnetic resonance imaging (MRI) have established several network principles at macroscopic scales, recent breakthroughs, including high-amplitude regional co-activation patterns and spatially contiguous functional gradients, remain unexplored at cellular resolution in animal models. Here, we employ whole-brain functional imaging at cellular resolution in larval zebrafish, combined with anatomical and spatial genetic expression profile databases, to investigate the structural and genetic basis of functional brain networks. We show that mesoscopic functional connectivity (FC) is a robust measure of brain activity that captures the individuality of larvae. Using a public dataset of thousands of single-neuron reconstructions, we reveal a strong coupling between FC and structural connectivity (SC). Numerous properties of the connectome that account for indirect pathways and diffusion mechanisms individually and collectively predict interregional correlations. The hierarchical modular structure of SC and FC significantly overlaps in space, and modules identified within the connectome constrain the shape of both spontaneous and stimulus-driven activity patterns. Using visual stimuli and tail monitoring, we identify a functional network gradient that maps onto the sensorimotor function of brain regions. Finally, we identify a set of genes whose co-expression in brain regions significantly predicts regional FC. Our findings reproduce several key features of mammalian brain networks in zebrafish, demonstrating the potential for studying large-scale network phenomena in smaller, optically accessible vertebrate brains.

neuroscience↗