A conserved code for anatomy: Neurons throughout the brain embed robust signatures of their anatomical location into spike trains

Abstract

Neurons in the brain are known to encode diverse information through their spiking activity, primarily reflecting external stimuli and internal states. However, whether individual neurons also embed information about their own anatomical location within their spike patterns remains largely unexplored. Here, we show that machine learning models can predict a neuron’s anatomical location across multiple brain regions and structures based solely on its spiking activity. Analyzing high-density recordings from thousands of neurons in awake, behaving mice, we demonstrate that anatomical location can be reliably decoded from neuronal activity across various stimulus conditions, including drifting gratings, naturalistic movies, and spontaneous activity. Crucially, anatomical signatures generalize across animals and even across different research laboratories, suggesting a fundamental principle of neural organization. Examination of trained classifiers reveals that anatomical information is enriched in specific interspike intervals as well as responses to stimuli. Within the visual isocortex, anatomical embedding is robust at the level of layers and primary versus secondary but does not robustly separate individual secondary structures. In contrast, structures within the hippocampus and thalamus are robustly separable based on their spike patterns. Our findings reveal a generalizable dimension of the neural code, where anatomical information is multiplexed with the encoding of external stimuli and internal states. This discovery provides new insights into the relationship between brain structure and function, with broad implications for neurodevelopment, multimodal integration, and the interpretation of large-scale neuronal recordings. Immediately, it has potential as a strategy for in-vivo electrode localization.