Spatial transcriptomics at the brain-electrode interface in rat motor cortex and the relationship to recording...

Area of Science:

• Neuroscience and Bioengineering
• Molecular Biology
• Biomaterials Science

Background:

• Implanted electrodes in the brain trigger a foreign body response, altering the local tissue environment.
• This response involves microglial activation, astrogliosis, and neuronal cell death, potentially affecting device performance.
• Understanding these changes is crucial for developing advanced neuroprostheses and improving electrophysiological recordings.

Purpose of the Study:

• To investigate physiological changes around implanted brain electrodes using spatial transcriptomics (ST).
• To identify gene expression alterations caused by electrode implantation.
• To correlate differential gene expression with glial reactivity, neuronal loss, and recording quality.

Main Methods:

• Chronic implantation of Michigan-style microelectrode arrays in rats.
• Acquisition of electrophysiological recordings (multi-unit activity, local field potential) over six weeks.
• Spatial transcriptomics on brain tissue cryosections, alongside immunolabeling for neurons and astrocytes.

Main Results:

• Identified up to 553 significantly differentially expressed genes within 300 µm of electrodes at various time points.
• Regression analysis revealed 6-7 key genes strongly correlated with histological and electrophysiological metrics.
• These genes represent potential biomarkers for recording quality and tissue response to implants.

Conclusions:

• Spatial transcriptomics provides novel insights into the mechanisms of tissue response to implanted electrodes.
• Identified candidate biomarkers that may predict or reflect signal quality.
• Developed a new transcriptomics-based approach to analyze brain tissue response to implants and relate it to functional outcomes.