Tools for interfacing, extracting, and analyzing neural signals using wide-field fluorescence imaging and optogenetics in awake behaving mice

Imaging of multiple cells has rapidly multiplied the rate of data acquisition as well as our knowledge of the complex dynamics within the mammalian brain. The process of data acquisition has been dramatically enhanced with highly affordable, sensitive image sensors enable high-throughput detection of neural activity in intact animals. Genetically encoded calcium sensors deliver a substantial boost in signal strength and in combination with equally critical advances in the size, speed, and sensitivity of image sensors available in scientific cameras enables high-throughput detection of neural activity in behaving animals using traditional wide-field fluorescence microscopy. However, the tremendous increase in data flow presents challenges to processing, analysis, and storage of captured video, and prompts a reexamination of traditional routines used to process data in neuroscience and now demand improvements in both our hardware and software applications for processing, analyzing, and storing captured video. This project demonstrates the ease with which a dependable and affordable wide-field fluorescence imaging system can be assembled and integrated with behavior control and monitoring system such as found in a typical neuroscience laboratory. An Open-source MATLAB toolbox is employed to efficiently analyze and visualize large imaging data sets in a manner that is both interactive and fully automated. This software package provides a library of image pre-processing routines optimized for batch-processing of continuous functional fluorescence video, and additionally automates a fast unsupervised ROI detection and signal extraction routine. Further, an extension of this toolbox that uses GPU programming to process streaming video, enabling the identification, segmentation and extraction of neural activity signals on-line is described in which specific algorithms improve signal specificity and image quality at the single cell level in a behaving animal. This project describes the strategic ingredients for transforming a large bulk flow of raw continuous video into proportionally informative images and knowledge

Unique contributions of parvalbumin and cholinergic interneurons in organizing striatal networks during movement

Published in final edited form as: Nat Neurosci. 2019 April ; 22(4): 586–597. doi:10.1038/s41593-019-0341-3.Striatal pavalbumin (PV) and cholinergic (CHI) interneurons are poised to play major roles in behavior by coordinating the networks of medium spiny cells that relay motor output. However, the small numbers and scattered distribution of these cells has made it difficult to directly assess their contribution to activity in networks of MSNs during behavior. Here, we build upon recent improvements in single cell calcium imaging combined with optogenetics to test the capacity of PVs and CHIs to affect MSN activity and behavior in mice engaged in voluntarily locomotion. We find that PVs and CHIs have unique effects on MSN activity and dissociable roles in supporting movement. PV cells facilitate movement by refining the activation of MSN networks responsible for movement execution. CHIs, in contrast, synchronize activity within MSN networks to signal the end of a movement bout. These results provide new insights into the striatal network activity that supports movement.Accepted manuscrip

Self-maintaining or continuously refreshed? The genetic structure of Euphausia lucens populations in the Benguela upwelling ecosystem

Populations of Euphausia lucens over the shelf of the southern Benguela upwelling region could be self-maintaining. Alternatively, they could be continually refreshed by expatriates from the SW Atlantic that enter the system via South Atlantic Central Water in the south, before developing and then being lost through advection off Namibia. These two hypotheses are investigated here by examining geographic heterogeneity and molecular variation (cox1 and ND1) of the species across its distributional range in the Southern Hemisphere. Comparisons are made with E. vallentini, which is assumed to show panmixia associated with its circumglobal distribution between 50 and 60°S. Phylogenetic analysis with mitochondrial 16S ribosomal RNA and cytochrome oxidase 1 (cox1) confirmed that E. lucens and E. vallentinirepresent sister taxa. Strong geographic structuring of cox1 and ND1 mtDNA genetic variation by ocean basin was recorded in E. lucens, indicating that neritic populations off South Africa are likely self-maintaining. This contrasts with the results for E. vallentini, which appears to occur as a single panmictic population across its distributional range. These differences are likely related to the habitats (neritic, E. lucens; oceanic, E. vallentini) occupied by each species. The results of the neutrality tests are consistent with demographic processes and suggest growth in E. lucens and equilibrium or shrinkage in E. vallentini. Although purifying selection cannot be ruled out in the former, the very few haplotypes recovered from E. vallentini could indicate that any population expansion following a crash is not yet reflected in the relatively slowly evolving mtDNA markers used here. Further work using other methods is recommended.Web of Scienc

The Reinforcing Therapist Performance (RTP) experiment: Study protocol for a cluster randomized trial

<p>Abstract</p> <p>Background</p> <p>Rewarding provider performance has been recommended by the Institute of Medicine as an approach to improve the quality of treatment, yet little empirical research currently exists that has examined the effectiveness and cost-effectiveness of such approaches. The aim of this study is to test the effectiveness and cost-effectiveness of providing monetary incentives directly to therapists as a method to improve substance abuse treatment service delivery and subsequent client treatment outcomes.</p> <p>Design</p> <p>Using a cluster randomized design, substance abuse treatment therapists from across 29 sites were assigned by site to either an implementation as usual (IAU) or pay-for-performance (P4P) condition.</p> <p>Participants</p> <p>Substance abuse treatment therapists participating in a large dissemination and implementation initiative funded by the Center for Substance Abuse Treatment.</p> <p>Intervention</p> <p>Therapists in both conditions received comprehensive training and ongoing monitoring, coaching, and feedback. However, those in the P4P condition also were given the opportunity to earn monetary incentives for achieving two sets of measurable behaviors related to quality implementation of the treatment.</p> <p>Outcomes</p> <p>Effectiveness outcomes will focus on the impact of the monetary incentives to increase the proportion of adolescents who receive a targeted threshold level of treatment, months that therapists demonstrate monthly competency, and adolescents who are in recovery following treatment. Similarly, cost-effectiveness outcomes will focus on cost per adolescent receiving targeted threshold level of treatment, cost per month of demonstrated competence, and cost per adolescent in recovery.</p> <p>Trial Registration</p> <p>Trial Registration Number: NCT01016704</p