Deep behavioural phenotyping of the Q175 Huntington disease mouse model: effects of age, sex, and weight.

BACKGROUND: Huntington disease (HD) is a neurodegenerative disorder with complex motor and behavioural manifestations. The Q175 knock-in mouse model of HD has gained recent popularity as a genetically accurate model of the human disease. However, behavioural phenotypes are often subtle and progress slowly in this model. Here, we have implemented machine-learning algorithms to investigate behaviour in the Q175 model and compare differences between sexes and disease stages. We explore distinct behavioural patterns and motor functions in open field, rotarod, water T-maze, and home cage lever-pulling tasks. RESULTS: In the open field, we observed habituation deficits in two versions of the Q175 model (zQ175dn and Q175FDN, on two different background strains), and using B-SOiD, an advanced machine learning approach, we found altered performance of rearing in male manifest zQ175dn mice. Notably, we found that weight had a considerable effect on performance of accelerating rotarod and water T-maze tasks and controlled for this by normalizing for weight. Manifest zQ175dn mice displayed a deficit in accelerating rotarod (after weight normalization), as well as changes to paw kinematics specific to males. Our water T-maze experiments revealed response learning deficits in manifest zQ175dn mice and reversal learning deficits in premanifest male zQ175dn mice; further analysis using PyMouseTracks software allowed us to characterize new behavioural features in this task, including time at decision point and number of accelerations. In a home cage-based lever-pulling assessment, we found significant learning deficits in male manifest zQ175dn mice. A subset of mice also underwent electrophysiology slice experiments, revealing a reduced spontaneous excitatory event frequency in male manifest zQ175dn mice. CONCLUSIONS: Our study uncovered several behavioural changes in Q175 mice that differed by sex, age, and strain. Our results highlight the impact of weight and experimental protocol on behavioural results, and the utility of machine learning tools to examine behaviour in more detailed ways than was previously possible. Specifically, this work provides the field with an updated overview of behavioural impairments in this model of HD, as well as novel techniques for dissecting behaviour in the open field, accelerating rotarod, and T-maze tasks.

Standardized 3D test object for multi-camera calibration during animal pose capture.

Accurate capture of animal behavior and posture requires the use of multiple cameras to reconstruct three-dimensional (3D) representations. Typically, a paper ChArUco (or checker) board works well for correcting distortion and calibrating for 3D reconstruction in stereo vision. However, measuring the error in two-dimensional (2D) is also prone to bias related to the placement of the 2D board in 3D. We proposed a procedure as a visual way of validating camera placement, and it also can provide some guidance about the positioning of cameras and potential advantages of using multiple cameras. We propose the use of a 3D printable test object for validating multi-camera surround-view calibration in small animal video capture arenas. The proposed 3D printed object has no bias to a particular dimension and is designed to minimize occlusions. The use of the calibrated test object provided an estimate of 3D reconstruction accuracy. The approach reveals that for complex specimens such as mice, some view angles will be more important for accurate capture of keypoints. Our method ensures accurate 3D camera calibration for surround image capture of laboratory mice and other specimens.

PyMouseTracks: Flexible Computer Vision and RFID-Based System for Multiple Mouse Tracking and Behavioral Assessment.

PyMouseTracks (PMT) is a scalable and customizable computer vision and radio frequency identification (RFID)-based system for multiple rodent tracking and behavior assessment that can be set up within minutes in any user-defined arena at minimal cost. PMT is composed of the online Raspberry Pi (RPi)-based video and RFID acquisition with subsequent offline analysis tools. The system is capable of tracking up to six mice in experiments ranging from minutes to days. PMT maintained a minimum of 88% detections tracked with an overall accuracy >85% when compared with manual validation of videos containing one to four mice in a modified home-cage. As expected, chronic recording in home-cage revealed diurnal activity patterns. In open-field, it was observed that novel noncagemate mouse pairs exhibit more similarity in travel trajectory patterns than cagemate pairs over a 10-min period. Therefore, shared features within travel trajectories between animals may be a measure of sociability that has not been previously reported. Moreover, PMT can interface with open-source packages such as DeepLabCut and Traja for pose estimation and travel trajectory analysis, respectively. In combination with Traja, PMT resolved motor deficits exhibited in stroke animals. Overall, we present an affordable, open-sourced, and customizable/scalable mouse behavior recording and analysis system.

Automated task training and longitudinal monitoring of mouse mesoscale cortical circuits using home cages.

We report improved automated open-source methodology for head-fixed mesoscale cortical imaging and/or behavioral training of home cage mice using Raspberry Pi-based hardware. Staged partial and probabilistic restraint allows mice to adjust to self-initiated headfixation over 3 weeks' time with ~50% participation rate. We support a cue-based behavioral licking task monitored by a capacitive touch-sensor water spout. While automatically head-fixed, we acquire spontaneous, movement-triggered, or licking task-evoked GCaMP6 cortical signals. An analysis pipeline marked both behavioral events, as well as analyzed brain fluorescence signals as they relate to spontaneous and/or task-evoked behavioral activity. Mice were trained to suppress licking and wait for cues that marked the delivery of water. Correct rewarded go-trials were associated with widespread activation of midline and lateral barrel cortex areas following a vibration cue and delayed frontal and lateral motor cortex activation. Cortical GCaMP signals predicted trial success and correlated strongly with trial-outcome dependent body movements.

How to shed $11 billion. Questions linger, but some think Medicaid Commission's plan to cut $11 billion from Medicaid will mirror Congress' proposal.

HHS' Medicaid Commission presented its first proposal for cutting $10 billion from the Medicaid program while still keeping it viable. Questions remain about how well the recommendations will work and some, like John Goodman, left, of the Washington-based National Center for Policy Analysis, said the proposal is a short-term solution for a program that needs a "complete overhaul."

Assessing four decades of Medicare, Medicaid.

Medicare and Medicaid were born 40 years ago, offering the first federally funded safety net for senior citizens, the uninsured and the disabled. While President Theodore Roosevelt, left, first proposed a national health insurance program in 1912, it took decades of political infighting before a program could be created. A look at the past, present and possible future of these important programs begins on Page 6.