Biology subjects

Weir, J. S.

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

3 recordsLinked to original sources

bioRxiv2023

Altered structural organization and functional connectivity in feedforward neural networks after induced perturbation

Reciprocal structure-function relationships underlie both healthy and pathological behaviors in complex neural networks. Thus, understanding neuropathology and network dysfunction requires a thorough investigation of the complex interactions between structural and functional network reconfigurations in response to perturbation. Such adaptations are often difficult to study in vivo. For example, subtle, evolving changes in synaptic connectivity, transmission, and the electrophysiological shift from healthy to pathological states, as for example alterations that may be associated with evolving neurodegenerative disease, such as Alzheime[r]s, are difficult to study in the brain. Engineered in vitro neural networks are powerful models that enable selective targeting, manipulation, and monitoring of dynamic neural network behavior at the micro- and mesoscale in physiological and pathological conditions. In this study, we engineered feedforward cortical neural networks using two-nodal microfluidic devices with controllable connectivity interfaced with microelectrode arrays (mMEAs). We induced P301L mutated tau protein to the presynaptic node of these networks and monitored network dynamics over three weeks. Induced perturbation resulted in altered structural organization and extensive axonal retraction starting in the perturbed node. Perturbed networks also exhibited functional changes in intranodal activity, which manifested as an overall decline in both firing rate and bursting activity, with a progressive increase in synchrony over time, and decrease in internodal signal propagation between pre- and postsynaptic nodes. These results provide insights into dynamic structural and functional reconfigurations at the micro- and mesoscale as a result of evolving pathology and illustrate the utility of engineered networks as models of network function and dysfunction.

neuroscience↗

bioRxiv2023

Inhibition of excitatory synaptic transmission alters functional organization and efficiency in cortical neural networks

Fundamental neural mechanisms such as activity dependent Hebbian and homeostatic neuroplasticity are driven by balanced excitatory - inhibitory synaptic transmission, and work in tandem to coordinate and regulate complex neural network dynamics in both healthy and perturbed conditions. These neuroplasticity processes shape neural network activity, as well as structural and functional aspects of network organization, information transmission and processing. While crucial for all aspects of network function, understanding how the brain utilizes plasticity mechanisms to retain or regain function during and after perturbation is often challenging. This is because these processes occur at varying spatiotemporal scales simultaneously across diverse circuits and brain regions and are thus highly complicated to distinguish from other underlying mechanisms. However, neuroplasticity and self-organizing properties of the brain are largely conserved in in vitro biological neural networks, and as such, these networks enable us to investigate both structural and functional plasticity responses to perturbation networks at the micro and mesoscale level. In this study, we selectively silenced excitatory synaptic transmission in in vitro neural networks to investigate the impact of the perturbation on structural and functional network organization and resilience. Our results demonstrate that selective inhibition of excitatory transmission leads to transient de-clustering of modular structure, increased path length and degree in perturbed networks. These changes indicate a transient loss of network efficiency; with the network subsequently reorganizing to a state of increased clustering and short path lengths following recovery. These findings highlight the remarkable capacity of neural networks to reconfigure their functional organization following perturbation. The ability to detect and decode such processes as they evolve highlights the robustness of our models to investigate certain dynamic network properties that are often not accessible by in vivo methods.

neuroscience↗

bioRxiv2022

Selective inhibition of excitatory synaptic transmission alters the emergent bursting dynamics of in vitro neural networks

Neurons in vitro connect to each other and form neural networks that display emergent electrophysiological activity. This activity begins as spontaneous uncorrelated firing in the early phase of development, and as functional excitatory and inhibitory synapses mature, the activity typically emerges as spontaneous network bursts. Network bursts are events of coordinated global activation among many neurons interspersed with periods of silencing and are important for synaptic plasticity, neural information processing, and network computation. While bursting is the consequence of balanced excitatory-inhibitory (E/I) interactions, the functional mechanisms underlying their evolution from physiological to potentially pathophysiological states, such as decreasing or increasing in synchrony, are still poorly understood. Synaptic activity, especially that related to maturity of E/I synaptic transmission, is known to strongly influence these processes. In this study, we used selective chemogenetic inhibition to target and disrupt excitatory synaptic transmission in in vitro neural networks to study functional response and recovery of spontaneous network bursts over time. We found that over time, inhibition resulted in increases in both network burstiness and synchrony. Our results indicate that the disruption in excitatory synaptic transmission during early network development likely affected inhibitory synaptic maturity which resulted in an overall decrease in network inhibition at later stages. These findings lend support to the importance of E/I balance in maintaining physiological bursting dynamics and, conceivably, information processing capacity in neural networks.

neuroscience↗