Structural and Functional Plasticity Surrounding Implanted Neuroprostheses

This study investigates the structural, functional and genetic consequences of chronically implanted electrode arrays in the brain to inform improved neurotechnology design. Using a combination of novel ex vivo preparations, electrophysiology, two-photon imaging, and spatial transcriptomics, the research characterizes how device implantation and electrical stimulation remodel neural tissue at the cellular and molecular levels. A new "device-in-slice" technique preserves chronically implanted electrodes within thick slices of live rat brain, enabling single-cell electrophysiology and two-photon imaging of neurons located at varying distances from implanted arrays. These experiments revealed pronounced remodeling of neuronal structure near implants: dendritic arbors are disrupted, with asymmetric losses concentrated on the device-facing side, and dendritic spine densities are reduced with a shift toward more immature, likely nonfunctional, spine morphologies.

Functionally, neurons near implants exhibit reduced excitatory neurotransmission, evidenced by decreased frequency of excitatory postsynaptic currents (EPSCs), and alterations in the electrophysiological basis of spiking regularity. In parallel, spatial transcriptomics applied around both recording and stimulating arrays uncovered substantial changes in gene expression associated with device presence and with electrical stimulation. Device implantation induces the expression of hundreds of genes linked to neuroinflammation, reactive glial states, oligodendrocyte function, and cellular metabolism. Electrical stimulation further modulates gene expression in an intensity-dependent manner, with higher-intensity stimulation inducing gene programs associated with damage or plasticity. To translate these large, complex datasets into actionable biomarkers, the team is developing computational analysis tools to distill signatures of device–tissue interactions from spatial transcriptomic profiles.

Together, the structural, functional, and molecular findings provide a multi-scale picture of how implanted neuroprosthetic devices interact with surrounding brain tissue over time. The work emphasizes that both passive implantation and active electrical stimulation can drive distinct but overlapping biological responses, and that device surface chemistry, materials, and architecture likely influence these outcomes. By identifying specific structural alterations (reduced dendritic complexity, spine loss, immature spine morphologies), functional impairments (reduced EPSC frequency, altered spiking regularity), and molecular signatures (induction of neuroinflammatory and glial reactivity genes), the study produces candidate biomarkers for benchmarking next-generation electrode designs. These biomarkers and analytical tools can support iterative testing of new materials, coatings, and stimulation paradigms aimed at minimizing deleterious tissue responses and preserving neuronal function.

The research provides foundational mechanistic insights and practical evaluation strategies that will aid the development of more biocompatible, durable, and effective implantable neurotechnologies for clinical use.