REMY: HEAD-FIXED BEHAVIOR AND ELECTROPHYSIOLOGY IN RATS

Head fixation methods for mice freely running on a wheel/treadmill have proven revolutionary in systems neuroscience (e.g. Dombeck et al 2010, Saleem et al. 2013 Poort et al. 2022). They provide the necessary stability to utilize cutting-edge technologies for recording neuronal activity while animals perform behavioral tasks, including in virtual reality environments. Head fixation also enables more accurate ways to monitor eye movements and facial expressions (for experimental and welfare purposes), and better control over the animal's sensory input, when compared to freely moving experiments.

Rats are capable of more complex behaviors while enabling higher–density neuronal recordings than mice. Yet due to their size and the strength that comes with it, head fixation has so far required highly restrictive fixation methods that prevent the animal from moving, let alone running naturally in a virtual reality environment.

In collaboration with the Totah lab at the University of Helsinki, we are developing tools to enable complex behavioral experiments with head-fixed, behaving rats on a treadmill/VR setup. First validated for chronic electrophysiology recordings, we are now working on expanding the range of capabilities to acute electrophysiology recordings, calcium imaging and potentially, MRI compatibility for the head fixation.

Performance

Rat head fixation is successfully achieved by combining an innovative headplate design (patent pending) with a carefully adapted surgery protocol. Together, these advances allow an implant so stable that skull screws become unnecessary.

Developed over a period of several years, the method was thoroughly tested:

  • 125 animals implanted

  • 93% success rate

  • 3-8 months of recordings from behaving animals

  • Validated for chronic electrophysiology, including ECoG arrays and silicon probes

    Related publications

    Data collected on behaving head-fixed rats has so far led to one publication:

    In addition, a preprint was published in 2022 and 2 posters presented at SfN 2022:

    A methods paper describing all procedures is in preparation.

    Elements of the rat head-fixed behavior setup

    In addition to the head fixation itself, the setup comprises several other components:

    • A cylindrical treadmill with a roughened fiberglass surface. This provides appropriate traction for the animal’s paws. Running speed is measured by a rotary encoder.
    • A liquid reward delivery system.
    • A metal frame, based on an optical rail system, that can flexibly accommodate various sensors (cameras to monitor the animal and measure eye movements), actuators (sensory stimulation with sound, etc) and accessories (e.g. infrared lighting).
    • A microcontroller that interfaces the various sensors, actuators and accessories using analog and digital input/output.
    • Grounding.

    A simplified, MRI-compatible, version is also under development for awake fMRI experiments.

    Current status

    A prototype version of head-fixed behavior + chronic/acute electrophysiology is currently being tested by our first adopter, a systems neuroscience lab in the US.

    Two MRI-compatible versions are being developed in collaboration with 2 functional imaging labs. A head-fixation only version is currently being tested by a lab in the UK, while a version for a larger scanner bore that includes a treadmill is under development for a lab in Finland.

    We’ll update this page regularly as we finalize the setup.

    Questions or comments? Get in touch by email: contact at 3dneuro dot com; on Twitter @3Dneuro, or with our contact form, link below.