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

Compulsive 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.

Bio-inspired benchmark generator for extracellular multi-unit recordings.

The 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.