Biology subjects

van Beest, E. H.

Publications and source records attributed to van Beest, E. H..

4 recordsLinked to original sources

bioRxiv2023

Tracking neurons across days with high-density probes

Neural activity spans multiple scales from milliseconds to months. Its evolution can be recorded with chronic electrodes, and especially with high-density arrays such as Neuropixels probes, which measure each spike at tens of sites and record hundreds of neurons. These arrays often record units with consistent spike waveforms over time, but produce vast amounts of data that require new approaches for tracking neurons across recordings. To meet this need, we developed UnitMatch, an open-access pipeline that operates after spike sorting, based only on each units average spike waveform. We tested UnitMatch in Neuropixels recordings from the mouse brain, where it tracked neurons across weeks. In visual cortex, a neurons selectivity for visual stimuli and correlation with other neurons remained stable over days. In striatum, neuronal responses changed across days during learning of a task. UnitMatch is thus a promising tool to reveal invariance or plasticity in neural activity across days.

neuroscience↗

bioRxiv2023

Reusable, flexible, and lightweight chronic implants for Neuropixels probes

Electrophysiology has proven invaluable to record neural activity, and the development of Neuropixels probes dramatically increased the number of recorded neurons. These probes are often implanted acutely, but acute recordings cannot be performed in freely moving animals and the recorded neurons cannot be tracked across days. To study key behaviors such as navigation, learning, and memory formation, the probes must be implanted chronically. An ideal chronic implant should (1) allow stable recordings of neurons for weeks; (2) allow reuse of the probes after explantation; (3) be light enough for use in mice. Here, we present the "Apollo Implant", an open-source and editable device that meets these criteria and accommodates up to two Neuropixels 1.0 or 2.0 probes. The implant comprises a "payload" module which is attached to the probe and is recoverable, and a "docking" module which is cemented to the skull. The design is adjustable, making it easy to change the distance between probes, the angle of insertion, and the depth of insertion. We tested the implant across eight labs in head-fixed mice, freely moving mice, and freely moving rats. The number of neurons recorded across days was stable, even after repeated implantations of the same probe. The Apollo implant provides an inexpensive, lightweight, and flexible solution for reusable chronic Neuropixels recordings.

neuroscience↗

bioRxiv2022

Unraveling the therapeutic mechanism of deep-brain stimulation

Deep-brain stimulation (DBS) is an effective treatment for patients suffering from otherwise therapy-resistant psychiatric disorders, including obsessive-compulsive disorder. Modulation of cortico-striatal circuits has been suggested as a mechanism of action. To gain mechanistic insight, we monitored neuronal activity in cortico-striatal regions in a mouse model for compulsive behavior, while systematically varying clinically-relevant parameters of internal-capsule DBS. DBS showed dose-dependent effects on both brain and behavior: An increasing, yet balanced, number of excited and inhibited neurons was recruited, scattered throughout cortico-striatal regions, while compulsive grooming decreased. Such neuronal recruitment did not alter basic brain function such as resting-state activity, and only occurred in awake animals, indicating a dependency on network activity. In addition to these widespread effects, we observed specific involvement of the medial orbitofrontal cortex in therapeutic outcomes, which was corroborated by optogenetic stimulation. Together, our findings provide mechanistic insight into how DBS exerts its therapeutic effects on compulsive behaviors.

neuroscience↗

bioRxiv2022

The direct and indirect pathways of the basal ganglia antagonistically influence cortical activity and perceptual decisions

The striatum, input nucleus of the basal ganglia, receives topographically organized input from the cortex and gives rise to the direct and indirect pathways with antagonistic effects on the output of the basal ganglia. We optogenetically stimulated the direct and indirect pathways in mice and measured their influence on perceptual decisions and neuronal activity in the cortex. In a task in which mice had to detect a visual stimulus, unilateral direct-pathway stimulation increased the probability of lick responses to the non-stimulated side and increased cortical activity globally. In contrast, indirect-pathway stimulation increased the probability of licks to the stimulated side and decreased activity in visual cortical areas. To probe the possible role of the two pathways in working memory, we trained the mice to report the location of a stimulus with licking one of two spouts, after a memory delay. Direct-pathway stimulation prior to and during the memory delay enhanced both the neural representation of a contralateral visual stimulus and the number of contraversive choices, whereas indirect-pathway stimulation had the opposite effects, in accordance with an antagonistic influence of the direct and indirect pathways on licking direction. Our results demonstrate how these two pathways influence perceptual decisions and working memories, and modify activity in the cerebral cortex. One sentence summaryVisuomotor transformations are influenced antagonistically by the direct and indirect pathways of the basal ganglia during visual detection and working memory tasks

neuroscience↗