Biology subjects

Ramstad, O. H.

Publications and source records attributed to Ramstad, O. H..

3 recordsLinked to original sources

bioRxiv2025

Influence of neural network bursts on functional connectivity

Network bursts or synchronized burst events are a typical activity seen in most in vitro neural networks. Network bursts arise early in development and as networks mature, activity becomes dominated by bursts propagating across the entirety of the network. The reason for this developmental plateau in vitro is unknown, but to bypass it would confer a significant advantage in the use of in vitro networks for computation. As most neurons in a network participate in network bursts, burst onset supersedes any ongoing activity thereby placing a limit on short term computations equal to the recovery period between bursts. By assessing 521 multielectrode array recordings from day 4-39 in vitro we find that network bursts influence the connectivity, but this change is only weakly associated with the origin of the network bursts. The impacts of bursts on functional integration and segregation in neural networks are discussed along with approaches to mitigate the development and propagation of network bursts in vitro. Additionally, we hypothesize that burst initiation zones or pacemakers are viable targets for stimulation for computation in the context of control and reservoir.

neuroscience↗

bioRxiv2020

Criticality as a measure of developing proteinopathy in engineered human neural networks

A patterned spread of proteinopathy represents a common characteristic of many neurodegenerative diseases. In Parkinsons disease (PD), misfolded forms of alpha-synuclein proteins aggregate and accumulate in hallmark pathological inclusions termed Lewy bodies and Lewy neurites, which seems to affect selectively vulnerable neuronal populations and propagate within interconnected neuronal networks. Research findings suggest that these proteinopathic inclusions are present at very early timepoints in disease development, even before strong behavioural symptoms of dysfunction arise, but that these underlying pathologies might be masked by homeostatic processes working to maintain the function of the degenerating neural circuits. This study investigates whether inducing the PD-related alpha-synuclein pathology in engineered human neural networks can be associated with changes in network function, and particularly with network criticality states. Self-organised criticality represents the critical point between resilience against perturbation and adaptational flexibility, which appears to be a functional trait in self-organising neural networks, both in vitro and in vivo. By monitoring the developing neural network activity through the use of multielectrode arrays (MEAs) for a period of three weeks following proteinopathy induction, we show that although this developing pathology is not clearly manifest in standard measurements of network function, it may be discerned by differences in network criticality states.

neuroscience↗

bioRxiv2020

Structural and functional alterations associated with the LRRK2 G2019S mutation revealed in structured human neural networks

Mutations in the LRRK2 gene have been widely linked to Parkinsons disease. The G2019S variant has been shown to contribute uniquely to both familial and sporadic forms of the disease. LRRK2-related mutations have been extensively studied, yet the wide variety of cellular and network events directly or indirectly related to these mutations remain poorly understood. In this study, we structured multi-nodal human neural networks carrying the G2019S mutation using custom-designed microfluidic chips coupled to microelectrode-arrays. By applying live imaging approaches, immunocytochemistry and computational modelling, we have revealed alterations in both the structure and function of the resulting neural networks when compared to controls. We provide first evidence of increased neuritic density associated with the G2019S LRRK2 mutation, while previous studies have found either a strong decrease, or no change, compared to controls. Additionally, we corroborate previous findings regarding increased baseline network activity compared to control neural networks. Furthermore, we can reveal additional network alterations attributable to the specific mutation by selectively inducing transient overexcitation to confined parts of the structured multi-nodal networks. These alterations, which we were able to capture both at the micro- and mesoscale manifested as differences in relative network activity and correlation, as well as in mitochondria activation, neuritic remodelling, and synaptic alterations. Our study thus provides important new insights into early signs of neural network pathology significantly expanding upon the current knowledge relating to the G2019S Parkinsons disease mutation.

neuroscience↗