Biology subjects

Greer, R.

Publications and source records attributed to Greer, R..

2 recordsLinked to original sources

bioRxiv2025

Chronically implantable μLED arrays for optogenetic cortical surface stimulation in mice

Cortical implants are a proven clinical neurotechnology with the potential to transform our understanding of cognitive processes. These processes rely on complex neuronal networks that are difficult to selectively probe or stimulate. Optogenetics offers cell-type specificity, but achieving the density and coverage required for chronic, high-resolution modulation remains a challenge. Here we present a 100-element {micro}LED array (200 {micro}m pixel pitch, 2 x 2 mm2 footprint) coupled into a miniaturised, flexible system suitable for chronic implantation and optogenetic stimulation of the surface of the mouse cortex. The {micro}LEDs can remain stable for over 300 hours continuous operation time in-vivo, allowing for months-long chronic experiments. Simultaneous electrophysiology recordings confirmed robust neuronal responses corresponding to low {micro}LED drive currents (<5 mA), minimising thermal effects and supporting future wireless operation. The spatial resolution of neuronal responses was consistent with a simulated model of light scattering in the cortical layers, enabling device optimisation. Behavioural experiments with chronically implanted mice demonstrated robust learning during discrimination tasks using spatially distinct optogenetic stimulation patterns.

neuroscience↗

bioRxiv2024

Biophysical mapping of TREM2-ligand interactions reveals shared surfaces for engagement of multiple AD ligands

TREM2 is a signaling receptor expressed on microglia that has emerged as an important potential drug target for Alzheimers disease and other neurodegenerative diseases. While a number of TREM2 signaling ligands have been identified, little is known regarding the structural details of how it engages them. To better understand this, we created a protein library of 28 different TREM2 variants and 11 different sTREM2 variants that could be used to map interactions with various ligands using biolayer interferometry (BLI). The variants are located in previously identified putative binding surfaces on TREM2 called the hydrophobic site, basic site, and site 2. We found that mutations to the hydrophobic site ablated binding to apoE4, oAb42, and TDP-43. Competition binding experiments further supported that apoE4 and oAb42 share overlapping binding sites on TREM2. In contrast, binding to IL-34 was mediated by the basic site at a surface centering on R76. Competition binding experiments validated a unique site for IL-34, showing little to no competition with either oAb42 or apoE4. Altogether, our results suggest that TREM2 utilizes the hydrophobic site (consisting of CDR1, CDR2, and CDR3) as a common site to engage multiple ligands, and further implies that pharmaceutical strategies targeting this surface might be effective to modulate TREM2 functions.

biophysics↗