Optimizing intact skull intrinsic signal imaging for subsequent targeted electrophysiology across mouse visual cortex

Area of Science:

• Neuroscience
• Systems Neuroscience

Background:

• Repeatable neural activity measurements are vital for understanding brain function.
• Traditional intrinsic signal imaging (ISI) in mice often requires skull thinning or removal, impacting long-term stability for electrophysiology.
• This instability poses challenges for longitudinal studies, such as those involving behavioral training.

Purpose of the Study:

• To optimize and validate an intact skull intrinsic signal imaging (ISI) system in mice.
• To assess the reliability of retinotopic maps generated by ISI in the primary visual cortex (V1) and higher visual areas (HVAs).
• To verify the accuracy of ISI-derived retinotopy using electrophysiology weeks after imaging.

Main Methods:

• Developed and optimized an intact skull ISI system for mice.
• Assessed imaging quality and duration's impact on retinotopic map reliability in V1 and HVAs.
• Validated ISI map retinotopy against targeted, multi-site electrophysiology (local field potentials).

Main Results:

• Reliable retinotopic maps of V1 and HVAs were obtained with approximately 60 trials of imaging (65 ± 6 min).
• ISI maps demonstrated strong correlation with local field potential (LFP) retinotopy in superficial cortical layers (r² = 0.74–0.82).
• The intact skull ISI system proved suitable for long-term, multi-area electrophysiology.

Conclusions:

• An optimized intact skull ISI system provides reliable, repeatable neural activity mapping in mice.
• This non-invasive imaging approach supports long-term electrophysiological recordings weeks to months post-imaging.
• The system facilitates targeted, multi-area electrophysiology for advanced neuroscience research.