2024_Mondragon-Gonzalez_NatureNeuroscience

Data for the paper "Closed-loop recruitment of striatal interneurons prevents compulsive-like grooming behaviours" by Mondragón-González et al.,2024, Nature Neuroscienc

Bio-inspired benchmark generator for extracellular multi-unit recordings

International audienceThe analysis of multi-unit extracellular recordings of brain activity has led to the development of numerous tools, ranging from signal processing algorithms to electronic devices and applications. Currently, the evaluation and optimisation of these tools are hampered by the lack of ground-truth databases of neural signals. These databases must be parameterisable, easy to generate and bio-inspired, i.e. containing features encountered in real electrophysiological recording sessions. Towards that end, this article introduces an original computational approach to create fully annotated and parameterised benchmark datasets, generated from the summation of three components: neural signals from compartmental models and recorded extracellular spikes, non-stationary slow oscillations, and a variety of different types of artefacts. We present three application examples. (1) We reproduced in-vivo extracellular hippocampal multi-unit recordings from either tetrode or polytrode designs. (2) We simulated recordings in two different experimental conditions: anaesthetised and awake subjects. (3) Last, we also conducted a series of simulations to study the impact of different level of artefacts on extracellular recordings and their influence in the frequency domain. Beyond the results presented here, such a benchmark dataset generator has many applications such as calibration, evaluation and development of both hardware and software architectures

Closed-loop recruitment of striatal interneurons prevents compulsive-like grooming behaviors

International audienceCompulsive behaviors have been associated with striatal hyperactivity. Parvalbumin-positive striatal interneurons (PVIs) in the striatum play a crucial role in regulating striatal activity and suppressing prepotent inappropriate actions. To investigate the potential role of striatal PVIs in regulating compulsive behaviors, we assessed excessive self-grooming—a behavioral metric of compulsive-like behavior—in male Sapap3 knockout mice (Sapap3-KO). Continuous optogenetic activation of PVIs in striatal areas receiving input from the lateral orbitofrontal cortex reduced self-grooming events in Sapap3-KO mice to wild-type levels. Aiming to shorten the critical time window for PVI recruitment, we then provided real-time closed-loop optogenetic stimulation of striatal PVIs, using a transient power increase in the 1–4 Hz frequency band in the orbitofrontal cortex as a predictive biomarker of grooming onsets. Targeted closed-loop stimulation at grooming onsets was as effective as continuous stimulation in reducing grooming events but required 87% less stimulation time, paving the way for adaptive stimulation therapeutic protocols

Closed-loop recruitment of striatal parvalbumin interneurons prevents the onset of compulsive behaviours

ABSTRACT A prominent electrophysiological feature of compulsive behaviours is striatal hyperactivity, yet, its underlying regulatory processes still need to be characterised. Within the striatum, parvalbumin-positive interneurons (PVI) exert a powerful feed-forward inhibition essential for the regulation of striatal activity and are implied in the suppression of prepotent inappropriate actions. To investigate the potential role of striatal PVI in regulating striatal activity and compulsive behaviours, we used the Sapap3 knockout mice (Sapap3-KO), which exhibit compulsive-like self-grooming. We first showed that the number of compulsive-like events in Sapap3-KO mice was reduced to normal levels by continuous optogenetic activation of striatal PVI in the centromedial striatum. To narrow down the critical time window of striatal PVI recruitment for regulating compulsive-like grooming, we then developed a novel closed-loop optogenetic stimulation pipeline. Upon a predictive biomarker of grooming onsets, characterised by a transient power increase of 1-4 Hz frequency band in the orbitofrontal cortex, we provided real-time closed-loop stimulation of striatal PVI. This targeted closed-loop optogenetics approach reduced grooming events as efficiently as continuous recruitment of striatal PVI with a reduction of stimulation time of 87%. Together, these results demonstrated that recruitment of striatal PVI at the initiation of the compulsive events is sufficient to drastically reduce compulsive-like behaviours and pave the way for targeted closed-loop therapeutic protocols