Cross-individual translation of spontaneous zebrafish brain activity through a shared latent representation.

Abstract

Spontaneous activity is a hallmark of brain function, reflecting the underlying circuit organization. Identifying conserved structure across individuals in this self-sustained activity has remained a longstanding challenge, especially in vertebrates where one-to-one neuron correspondence is inaccessible. Here, we introduce latent-aligned Restricted Boltzmann Machines (LaRBMs), an unsupervised generative approach that uncovers a common representational space from cell-resolved whole-brain recordings in larval zebrafish. This latent space consists of spatially localized coactivation motifs, or cell assemblies, that generalize across animals and form interpretable building blocks of population-wide activity. LaRBMs enable bidirectional mapping of instantaneous whole-brain activity patterns between individuals: Activity patterns from one fish can be encoded into the latent space and decoded into another. The translated patterns are assigned high probability by the recipient model and retain the original spatial organization. These results show that spontaneous activity in the vertebrate brain is highly stereotyped at the level of functional cell assemblies and can be reliably captured through a common latent code. Because it provides an interpretable and quantitative framework for functional cross-individual alignment, LaRBM paves the way for comparative phenotyping of brain activity across developmental, genetic, and pathological variation.