Guillaume Viejo

The generation of the head-direction (HD) signal, a cornerstone of the brain’s navigation system, is classically attributed to the lateral mammillary nucleus (LMN) and associated brainstem structures, where attractor-like dynamics are thought to maintain population coherence. Here, using multi-site recordings and optogenetic perturbations along the mammillary–thalamic–cortical pathway, we demonstrate that HD neurons in the anterodorsal nucleus of the thalamus (ADN) maintain coherent population dynamics even when their LMN inputs become decorrelated during non-REM sleep. These findings reveal that thalamic coherence does not strictly depend on structured input from the LMN; instead, it can emerge from local thalamic processes involving shared inhibition and non-linear responses. Together, our findings reveal a previously unrecognized, state-dependent shift in the circuit organizing the HD signal, establishing the thalamus as an active substrate capable of independently sustaining internal representations across brain states.

Spatial orientation is a universal ability that allows animals to navigate their environment. In mammals, the head-direction (HD) system is an essential component of the brain’s navigation system, yet the stability of its underlying neuronal code remains unclear. Here, by longitudinally tracking the activity of the same HD cells in freely moving mice, we show that the internal organization of population activity in the HD system was preserved for several months. Furthermore, the HD system developed a unique mapping between its internal organization and spatial orientation in each environment. This was not affected by visits to other environments and was stabilized with experience. These findings demonstrate that stable neuronal code supports the sense of direction and forms long-lasting orientation memories.

Datasets collected in neuroscientific studies are of ever-growing complexity, often combining high-dimensional time series data from multiple data acquisition modalities. Handling and manipulating these various data streams in an adequate programming environment is crucial to ensure reliable analysis, and to facilitate sharing of reproducible analysis pipelines. Here, we present Pynapple, the PYthon Neural Analysis Package, a lightweight python package designed to process a broad range of time-resolved data in systems neuroscience. The core feature of this package is a small number of versatile objects that support the manipulation of any data streams and task parameters. The package includes a set of methods to read common data formats and allows users to easily write their own. The resulting code is easy to read and write, avoids low-level data processing and other error-prone steps, and is open source. Libraries for higher-level analyses are developed within the Pynapple framework but are contained within a collaborative repository of specialized and continuously updated analysis routines. This provides flexibility while ensuring long-term stability of the core package. In conclusion, Pynapple provides a common framework for data analysis in neuroscience.

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. 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.