Brain-state invariant thalamo-cortical coordination revealed by non-linear encoders

Understanding how neurons cooperate to integrate sensory inputs and guide behavior is a fundamental problem in neuroscience. A large body of methods have been developed to study neuronal firing at the single cell and population levels, generally seeking interpretability as well as predictivity. However, these methods are usually confronted with the lack of ground-truth necessary to validate the approach. Here, using neuronal data from the head-direction (HD) system, we present evidence demonstrating how gradient boosted trees, a non-linear and supervised Machine Learning tool, can learn the relationship between behavioral parameters and neuronal responses with high accuracy by optimizing the information rate. Interestingly, and unlike other classes of Machine Learning methods, the intrinsic structure of the trees can be interpreted in relation to behavior (e.g. to recover the tuning curves) or to study how neurons cooperate with their peers in the network. We show how the method, unlike linear analysis, reveals that the coordination in thalamo-cortical circuits is qualitatively the same during wakefulness and sleep, indicating a brain-state independent feed-forward circuit. Machine Learning tools thus open new avenues for benchmarking model-based characterization of spike trains.Author summary: The thalamus is a brain structure that relays sensory information to the cortex and mediates cortico-cortical interaction. Unraveling the dialogue between the thalamus and the cortex is thus a central question in neuroscience, with direct implications on our understanding of how the brain operates at the macro scale and of the neuronal basis of brain disorders that possibly result from impaired thalamo-cortical networks, such as absent epilepsy and schizophrenia. Methods that are classically used to study the coordination between neuronal populations are usually sensitive to the ongoing global dynamics of the networks, in particular desynchronized (wakefulness and REM sleep) and synchronized (non-REM sleep) states. They thus fail to capture the underlying temporal coordination. By analyzing recordings of thalamic and cortical neuronal populations of the HD system in freely moving mice during exploration and sleep, we show how a general non-linear encoder captures a brain-state independent temporal coordination where the thalamic neurons leading their cortical targets by 20-50ms in all brain states. This study thus demonstrates how methods that do not assume any models of neuronal activity may be used to reveal important aspects of neuronal dynamics and coordination between brain regions.