Structural, Functional, and Genetic Changes Surrounding Electrodes Implanted in the Brain

• DOI: 10.1021/acs.accounts.4c00057
• Publication Date: 2024-04-17T15:19:46Z
• Authors: Bhavna Gupta; Akash Saxena; Mason L. Perillo; Lauren C. Wade-Kleyn; Cort H. Thompson; Erin K. Purcell
• Keywords: Neuropil; Stimulus (psychology); Brain implant; Brain tissue

ConspectusImplantable neurotechnology enables monitoring and stimulating of the brain signals responsible for performing cognitive, motor, sensory tasks. Electrode arrays implanted in are increasingly used clinic to treat a variety sources neurological diseases injuries. However, implantation foreign body typically initiates tissue response characterized by physical disruption vasculature neuropil as well initiation inflammation induction reactive glial states. Likewise, electrical stimulation can induce damage surrounding depending on intensity waveform parameters applied stimulus. These phenomena, turn, likely influenced surface chemistry characteristics materials employed, but further information is needed effectively link biological responses observed specific aspects device design. In order inform improved design implantable neurotechnology, we investigating basic science principles governing device–tissue integration. We employing multiple techniques characterize structural, functional, genetic changes that occur cells electrodes. First, have developed new "device-in-slice" technique capture chronically electrodes within thick slices live rat interrogation with single-cell electrophysiology two-photon imaging techniques. Our data revealed several observations remodeling devices: (a) there was significant dendritic arbors neurons near implants, where losses were driven asymmetrically implant-facing side. (b) There loss spine densities shift toward more immature (nonfunctional) morphologies. (c) reduction excitatory neurotransmission evidenced frequency postsynaptic currents (EPSCs). Lastly, (d) electrophysiological underpinnings neuronal spiking regularity. parallel, initiated studies explore gene expression devices through spatial transcriptomics, which both recording arrays. found associated hundreds genes neuroinflammation, reactivity, oligodendrocyte function, cellular metabolism induces or plasticity manner dependent upon currently developing computational analysis tools distill biomarkers interactions from large transcriptomics sets. results improve current understanding while producing benchmarking effects novel electrode designs responses. As next generation developed, it will be important understand influence materials, chemistries, implant architectures performance relationship signaling pathways.