Biology subjects

Garrett, J.

Publications and source records attributed to Garrett, J..

3 recordsLinked to original sources

bioRxiv2025

Stimulation with ECoG electrodes modulates cortical activity and sensory processing in the awake mouse brain

Electrical stimulation has been widely used to probe neural network properties and treat dysfunction. Electrocorticography (ECoG) electrodes, long used for activity monitoring, can also stimulate the brain in a minimally invasive and chronic manner. However, how cortical surface electrical stimulation impacts cortical network activity remains poorly understood. Using in vivo calcium imaging in the awake mouse brain with chronically implanted ECoG electrodes, we measured how electrical stimulation modulates the activity of visual cortical neurons, including during concurrent visual stimulation. We found that cortical surface electrical stimulation initially activates L2/3 neurons followed by prolonged inhibition lasting seconds after stimulation. Electrical stimulation suppresses the activity of neurons at their preferred grating orientation but enhances their responses to non-preferred visual stimuli, thereby reducing sensory feature selectivity. By measuring how electrical stimulation modulates the activity of inhibitory neuron subtypes including PV, SST, and NDNF interneurons, we propose a circuit model in which L1 NDNF interneurons are strongly activated by cortical electrical stimulation and, in turn, inhibit L2/3 excitatory neurons and PV interneurons through volume transmission of GABA.

neuroscience↗

bioRxiv2020

Discovery and Development of Novel DNA-PK Inhibitors by Targeting the unique Ku-DNA Interaction

DNA-dependent protein kinase (DNA-PK) plays a critical role in the non-homologous end joining (NHEJ) repair pathway and the DNA damage response (DDR). DNA-PK has therefore been pursued for the development of anti-cancer therapeutics in combination with ionizing radiation (IR). We report the discovery of a new class of DNA-PK inhibitors that act via a novel mechanism of action, inhibition of the Ku-DNA interaction. We have developed a series of highly potent and specific Ku-DNA binding inhibitors (Ku-DBis) that block the Ku-DNA interaction and inhibit DNA-PK kinase activity. Ku-DBis directly interact with the Ku and inhibit in vitro NHEJ, cellular NHEJ, and potentiate the activity of IR and radiomimetics. Analysis of Ku-null cells demonstrates that Ku-DBis cellular activity is a direct result of Ku inhibition, as Ku-null cells are insensitive to Ku-DBis. The utility of Ku-DBis was also demonstrated in a CRISPR gene-editing model where we demonstrate that the efficiency of gene insertion events was increased in cells pre-treated with Ku-DBis, consistent with inhibition of NHEJ and activation of homologous recombination to facilitate gene insertion. These data demonstrate the discovery and application of new series of compounds that modulate DNA repair pathways via a unique mechanism of action.

biochemistry↗

bioRxiv2017

Sonic Kayaks: Environmental monitoring and experimental music by citizens

The Sonic Kayak is a musical instrument with which to investigate nature, developed during open hacklab events. Kayaks rigged with underwater environmental sensors allow paddlers to hear real-time water temperature sonifications and underwater sounds, generating live music from the marine world. Sensor data is also logged every second with GPS, time and date, allowing fine scale mapping of water temperatures and underwater noise that was previously unattainable using standard research equipment. The system provides the paddler with an extra dimension of senses with which to explore the underwater climate, while enabling citizens to gather data for scientific research. The system can be used as a citizen-science data-collection device, research equipment for professional scientists, or a sound-art installation in its own right, and has been implemented in a public setting at the British Science Festival 2016, demonstrating the considerable advantages of adopting transdisciplinary approaches during project development. Here we present instructions for building the open-hardware and open-source software, tests of the sensors used, and preliminary data demonstrating applications for the Sonic Kayak in marine climate and noise-pollution research.

ecology↗