Stimulation modulates cell assemblies linked with gene networks in the human temporal cortex ex vivo

Area of Science:

• Neuroscience
• Genetics
• Neuromodulation

Background:

• Deep brain stimulation (DBS) of the temporal cortex shows promise for enhancing learning and memory in cognitive impairment.
• The precise neural and genetic mechanisms of how DBS affects human brain circuits remain largely unknown.

Purpose of the Study:

• To investigate the direct neural and genetic mechanisms of brain stimulation in the human temporal cortex.
• To elucidate how temporal cortex stimulation modulates neural activity and gene expression.

Main Methods:

• Developed an ex vivo approach using microelectrode array stimulation and recording on resected human temporal cortex.
• Employed single-cell multiomics to correlate physiological changes with gene expression patterns.

Main Results:

• Temporal cortex stimulation preferentially increased firing rates in pyramidal cells over interneurons.
• Observed strengthening of neuronal cell assemblies and identified specific gene regulatory networks involved.
• Linked physiological changes to cell type-specific gene expression, highlighting immediate early, synaptic, and ion channel genes.

Conclusions:

• Deep brain stimulation (DBS) of the temporal cortex activates specific excitatory neurons and enhances cell assembly activity.
• Identified gene networks supporting these effects, providing a foundation for targeted neuromodulation strategies.
• Findings suggest potential for harnessing cell type-specific genetic signatures for therapeutic benefit.