# Structural and Functional Plasticity Surrounding Implanted Neuroprostheses

> **NIH NIH R01** · MICHIGAN STATE UNIVERSITY · 2022 · $347,024

## Abstract

PROJECT SUMMARY
The development of implantable devices capable of recording or stimulating electrical activity in the brain has
created unprecedented opportunities to treat and study neurological diseases and injuries. However, a reactive
tissue response typically occurs following implantation which is widely believed to interfere with long-term device
performance. Inflammatory microglia and astrocytes encapsulate and isolate devices from neurons, while
neuronal signal sources are lost within the recordable radius of the electrode surface. While these observations
may contribute to signal instability and recording loss over time, the mechanistic link between specific
inflammatory events and changes in signal quality remains unclear. Our group is expanding upon the current
basic science understanding of device-tissue integration and recently published a study which showed shifts in
subtype-specific markers of synaptic transmission surrounding implanted electrode arrays. Our data indicated
an early elevation of markers of excitatory transmission (vesicular glutamate transporter-1, VGLUT1) three days
post-implantation that was followed by a subsequent shift to increased expression of labeling for inhibitory
neurotransmission (vesicular GABA transporter, VGAT). We hypothesize that structural and functional plasticity
of synaptic inputs surrounding devices could contribute to loss of recorded signals. We further hypothesize that
the timed elevation of glutamate and GABA release may act as “go” and “stop” cues which mediate the reactive
tissue response. In this proposal, we will build upon our initial observations, further investigating the underlying
mechanisms and functional consequences of synaptic plasticity on device performance. In Specific Aim 1, we
will define the functional impacts of glutamatergic synaptic remodeling at the electrode interface on recorded
signal quality and reactive gliosis. We will correlate transporter expression with signal quality and assess the
effects of VGLUT1 knockdown on signal quality and tissue response. In Specific Aim 2, we similarly will define
the functional impacts of GABAergic synaptic remodeling at the electrode interface on recorded signal quality
and reactive gliosis. We hypothesize that while early glutamate release may incite neurotoxicity and reactive
gliosis, subsequent GABA release acts in an anti-inflammatory capacity to preserve neuronal viability and
mitigate further glial reactivity. In Specific Aim 3, we will reveal structural plasticity in the dendritic arbors of
neurons at the electrode interface. For this aim, we will use two photon imaging to assess changes in dendritic
spine density and morphology surrounding devices captured in ex vivo brain tissue slices. For all aims, we will
test both silicon and polyimide-based arrays to compare results between device designs commonly used in the
field. We will inspect impedance measurements and post-mortem scanning electron microscopy images for signs
...

## Key facts

- **NIH application ID:** 10335797
- **Project number:** 5R01NS107451-04
- **Recipient organization:** MICHIGAN STATE UNIVERSITY
- **Principal Investigator:** Erin K Purcell
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $347,024
- **Award type:** 5
- **Project period:** 2019-01-15 → 2023-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10335797

## Citation

> US National Institutes of Health, RePORTER application 10335797, Structural and Functional Plasticity Surrounding Implanted Neuroprostheses (5R01NS107451-04). Retrieved via AI Analytics 2026-06-11 from https://api.ai-analytics.org/grant/nih/10335797. Licensed CC0.

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