Automated task training and longitudinal monitoring of mouse mesoscale cortical circuits using home cages
Abstract
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.
Data availability
The name of each brain imaging file which contains both the mouse ID and the time stamp can be found in the SQL database (RFIDtag_xxxx_timestamp.raw; see Methods for URL and hosted as a full text file archive on Zenodo (https://doi.org/10.5281/zenodo.3268838) for the 5 cages of male mice that compose figures 1-7 and cage 6 female mice https://doi.org/10.5683/SP2/9RFXRP.All text file behavioral data is included online as well as image data for figures 8 and supplemental figure 2 are found on https://doi.org/10.5281/zenodo.3243572, all data files and code for figures 9 and 10 are found in https://doi.org/10.5683/SP2/ZTOPUM and female mouse behavioral data https://doi.org/10.5683/SP2/9RFXRP. All Python data acquisition code can be found on https://github.com/jamieboyd/AutoHeadFix/ and https://github.com/ubcbraincircuits/AutoHeadFix.
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Code and .mat files for automated homecage paper (Figs 9 and 10)https://doi.org/10.5683/SP2/ZTOPUM.
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Home cage data female mice cage 6 all text file and database informationhttps://doi.org/10.5683/SP2/9RFXRP.
Article and author information
Author details
Funding
Canadian Institutes of Health Research (FDN-143209)
- Timothy H Murphy
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: All procedures were conducted with approval from the University of British Columbia Animal Care Committee and in accordance with guidelines set forth by the Canadian Council for Animal Care.
Copyright
© 2020, Murphy et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Further reading
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Gamma oscillations in brain activity (30–150 Hz) have been studied for over 80 years. Although in the past three decades significant progress has been made to try to understand their functional role, a definitive answer regarding their causal implication in perception, cognition, and behavior still lies ahead of us. Here, we first review the basic neural mechanisms that give rise to gamma oscillations and then focus on two main pillars of exploration. The first pillar examines the major theories regarding their functional role in information processing in the brain, also highlighting critical viewpoints. The second pillar reviews a novel research direction that proposes a therapeutic role for gamma oscillations, namely the gamma entrainment using sensory stimulation (GENUS). We extensively discuss both the positive findings and the issues regarding reproducibility of GENUS. Going beyond the functional and therapeutic role of gamma, we propose a third pillar of exploration, where gamma, generated endogenously by cortical circuits, is essential for maintenance of healthy circuit function. We propose that four classes of interneurons, namely those expressing parvalbumin (PV), vasointestinal peptide (VIP), somatostatin (SST), and nitric oxide synthase (NOS) take advantage of endogenous gamma to perform active vasomotor control that maintains homeostasis in the neuronal tissue. According to this hypothesis, which we call GAMER (GAmma MEdiated ciRcuit maintenance), gamma oscillations act as a ‘servicing’ rhythm that enables efficient translation of neural activity into vascular responses that are essential for optimal neurometabolic processes. GAMER is an extension of GENUS, where endogenous rather than entrained gamma plays a fundamental role. Finally, we propose several critical experiments to test the GAMER hypothesis.
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