Citations

Abstract The dorsomedial striatum (DMS) is primarily recognized for regulating goal-directed reward-seeking behaviors, while the dorsolateral striatum (DLS) is predominantly associated with movement and habitual behaviors. In this study, we sought to investigate two pathways, direct medium spiny neuron (dMSN) and indirect medium spiny neuron (iMSN) in the two dorsal striatal subregions (DMS and DLS) in ethanol-seeking and drinking behaviors. Here, we selectively ablated iMSN DMS→GPe and iMSN DLS→GPe and trained mice to exhibit goal-directed and habitual reward-seeking behaviors using random ratio (RR) and random interval (RI) operant conditioning, respectively. We found that partial ablation of iMSN DLS→GPe exhibited increased resilience to bitter-tasting ethanol solution when subjected to quinine adulterated reward in operant conditioning paradigms, suggesting compulsive-like seeking behavior. Consistently, in a separate cohort of mice, we found that the iMSN DLS→GPe ablated mice show higher preference and consumption of quinine adulterated ethanol solution than control mice in two-bottle choice continuous access drinking, with increasing quinine concentration and exhibit more compulsive-like behavior. On the other hand, ablation of iMSN DMS→GPe resulted in insensitivity to satiety-based reward devaluation in RR-trained mice, consistent with a shift toward habitual behavior but no change in compulsive ethanol-seeking and drinking behavior. Together, our findings demonstrate that DLS iMSN function is essential in inhibiting compulsive-like behavior.

Abstract Deep brain stimulation (DBS) is a targeted manipulation of brain circuitry to treat neurological and neuropsychiatric conditions. Optimal DBS lead placement is essential for treatment efficacy. Current targeting practice is based on preoperative and intraoperative brain imaging, intraoperative electrophysiology, and stimulation mapping. Electrophysiological mapping using extracellular microelectrode recordings aids in identifying functional subdomains, anatomical boundaries, and disease-correlated physiology. The shape of single-unit action potentials may differ due to different biophysical properties between cell-types and brain regions. Here, we describe a technique to parameterize the structure and duration of sorted spike units using a novel algorithmic approach based on canonical response parameterization, and illustrate how it may be used on DBS microelectrode recordings. Isolated spike shapes are parameterized then compared using a spike similarity metric and grouped by hierarchical clustering. When spike morphology is associated with anatomy, we find regional clustering in the human globus pallidus. This method is widely applicable for spike removal and single-unit characterization and could be integrated into intraoperative array-based technologies to enhance targeting and clinical outcomes in DBS lead placement. Author summary We developed a new algorithmic approach to capture the structure of single neuron electrophysiology from microelectrode recordings during deep brain stimulation surgery. This method has broad applications for spike characterization, clustering, removal from the background field potential, and comparison across recording sites. Using this technique, we illustrate regional clustering of spike morphologies in the human globus pallidus.

We studied movement-associated spectral changes in human motor thalamus and observed focal increases in broadband power with movement. This biomarker may be used as a tool for intraoperative functional mapping, DBS targeting, and closed-loop device control.

Abstract Studying mammalian brain function aids our understanding of human brain evolution. We implanted a beagle with a prototype human neuromodulation platform that measures activity from the brain surface. One year later, a set of simple sensory tasks was performed, finding visual and somatosensory representation in the canine homologs of the expected areas in humans. Surprisingly, the canine anterior ectosylvian gyrus, which is anatomically homologous to human receptive speech areas, was selectively active during independent social reinforcement tasks. This suggests that human speech understanding may have evolved from more general mammalian brain structures that are specialized for social reinforcement.