Biology subjects

Gates, S. J.

Publications and source records attributed to Gates, S. J..

3 recordsLinked to original sources

bioRxiv2025

Collective Learning in Living Neural Networks Facilitated by Contextual Background Photostimulation

This study explores collective learning in living neural networks, focusing on group-to-group Hebbian learning, i.e., strengthening and weakening of links dependent on the precise timing of their activities. While neuronal plasticity is now well understood for single pairs of neurons, recent research has demonstrated that groups of tens of neurons are required to encode information in mammalian brains. Thus, it is critical to understand how mechanisms of plasticity, in particular spike-timing-dependent plasticity (STDP) operate at the group scale. We find that neuronal groups can reach significant plasticity after only 45 stimuli when a proper tradeoff between pulse duration and photostimulation effectiveness is chosen. Background stimulation, which enhances the reliability of response for the targeted neuronal groups, is necessary for rapid network-level Hebbian learning. By demonstrating enhanced learning in the presence of background activity, this study underscores the highly cooperative character of neurons and the importance of investigating learning, information flow, and memory formation at the network scale.

neuroscience↗

bioRxiv2023

Development of an Accelerated Cellular Model for Alzheimer's Disease

Alzheimers Disease (AD) is a leading cause of dementia characterized by amyloid plaques and neurofibrillary tangles, and its pathogenesis remains unclear. Current cellular models for AD often require several months to exhibit phenotypic features due to the lack of an aging environment in vitro. Lamin A is a key component of the nuclear lamina. And progerin, a truncated protein resulting from specific lamin A mutations, causes Hutchinson-Gilford Progeria Syndrome (HGPS), a disease that prematurely ages individuals. Studies have reported that lamin A expression is induced in the brains of AD patients, and overlapping cellular phenotypes have been observed between HGPS and AD cells. In this study, we investigated the effects of exogenous progerin expression on neural progenitor cells carrying familial AD mutations (FAD). Within three to four weeks of differentiation, these cells exhibited robust AD phenotypes, including increased tau phosphorylation, amyloid plaque accumulation, and an elevated A{beta}42 to A{beta}40 ratio. Additionally, progerin expression significantly increased AD cellular phenotypes such as cell death and cell cycle re-entry. Our results suggest that progerin expression could be used to create an accelerated model for AD development and drug screening. Significance StatementAlzheimers Disease (AD) contributes to most dementia, while its mechanism is still under investigation. One of the challenges for studying AD is the model issue, including the genetic divergence of animals and human, and the rejuvenation of induced pluripotent stem cells (iPSCs). Progerin is a mutant lamin A found in the accelerated aging disease progeria. There are a lot of molecular similarities between Alzheimers Disease (AD) and progeria. Here, we developed an accelerated 2D/3D cell model system for AD by ectopically expressing progerin in a previously characterized AD cell model carrying familial AD (FAD) mutations. Our study showed that progerin addition could accelerate AD phenotypical progression, including tau phosphorylation and formation of {beta}-amyloid plaques.

cell biology↗

bioRxiv2023

Coupled Biomechanical and Ionic Excitability in Developing Neural Cell Networks

Waves and oscillations play a key role in the flow and processing of information in the brain. Recent work has demonstrated that in addition to electrical activity, biomechanical signaling can also be excitable and thus capable of self-sustaining oscillations and waves. Here we measured the biomechanical dynamics of actin polymerization in neural precursor cells throughout their differentiation into populations of neurons and astrocytes. Fluorescence-based live-cell imaging allowed us to analyze the dynamics of actin in conjunction with the dynamics of calcium signals. Actin dynamics throughout differentiation showed a rhythmic character, localized mostly in processes, with changes in scale associated with differentiation. Furthermore, actin dynamics impact ionic dynamics, with an increase in the frequency of calcium bursts accompanied by a decrease in cell-cell correlations when actin dynamics is inhibited. This impact of cytoskeletal dynamics on cell-cell coupling and ionic neural cell signaling suggests that information flow in the brain may be able to harness both biomechanical and electrical/ionic excitability.

cell biology↗