Simultaneous mesoscopic measurement and manipulation of mouse cortical activity
Pascha Matveev1, Anna J Li1, Zhiwen Ye1
1Department of Neurobiology and Biophysics, University of Washington, Seattle, WA, USA.
Biorxiv : the Preprint Server for Biology
|November 18, 2024
Summary
Researchers developed a new system for simultaneous brain-wide recording and manipulation of neural activity in mice. This tool enables studying how mesoscopic cortical dynamics influence behavior and brain function.
Area of Science:
- Neuroscience
- Systems Neuroscience
- Computational Neuroscience
Background:
- Mesoscopic brain activity, characterized by coordinated neural population fluctuations, is crucial for perception, cognition, and sensorimotor integration.
- Direct causal links between mesoscopic dynamics and behavior necessitate methods for simultaneous manipulation and observation of activity across brain regions.
Purpose of the Study:
- To develop a novel system for simultaneous recording and manipulation of dorsal cortical activity in awake mice.
- To enable large-scale electrophysiology and observe effects across multiple brain regions concurrently.
- To facilitate the study of cortex-wide activity, subcortical spiking, and behavior following cortical perturbations.
Main Methods:
- Developed a system for simultaneous widefield single-photon calcium imaging and galvo-targeted laser stimulation of the dorsal cortex in awake mice.
- Utilized transgenic mice expressing GCaMP (calcium sensor) and systemically administered adeno-associated virus for ChrimsonR (excitatory opsin) expression.
- Achieved non-interfering light channels for imaging and opsin activation, with characterized spatial and temporal resolution suitable for targeted interventions.
Main Results:
- Demonstrated a novel technique for simultaneous recording and manipulation of mesoscopic cortical activity across the entire dorsal surface.
- Established the system's stability over months, making it suitable for long-term behavioral experiments.
- Confirmed non-interference between imaging and opsin activation light channels.
Conclusions:
- The developed system allows for unprecedented investigation of causal relationships between cortical dynamics and behavior.
- This technique supports closed-loop control of cortical activity and opens new avenues for understanding brain computation.
- The method is adaptable for large-scale electrophysiology and long-term studies in awake, behaving animals.


