Evolving alterations of structural organization and functional connectivity in feedforward neural networks after induced P301L tau mutation DOI Creative Commons

Janelle S. Weir,

Katrine Sjaastad Hanssen, Nicolai Winter‐Hjelm

и другие.

European Journal of Neuroscience, Год журнала: 2024, Номер unknown

Опубликована: Дек. 2, 2024

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

Язык: Английский

Engineered Cortical Microcircuits for Investigations of Neuroplasticity DOI
Nicolai Winter‐Hjelm, Pawel Sikorski, Axel Sandvig

и другие.

Lab on a Chip, Год журнала: 2024, Номер unknown

Опубликована: Янв. 1, 2024

An advanced microfluidic platform integrated with a microelectrode array for the study of structural and functional adaptations neural networks in response to localized perturbations.

Язык: Английский

Процитировано

2
Dysregulation of synaptic transcripts underlies network abnormalities in ALS patient-derived motor neurons DOI Creative Commons

Anna M. Kollstrøm,

Nicholas Christiansen, Axel Sandvig

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Май 31, 2024

Amyotrophic lateral sclerosis (ALS) is characterized by dysfunction and loss of upper lower motor neurons. Several studies have identified structural functional alterations in the neurons before manifestation symptoms, yet underlying cause such how they contribute to progressive degeneration affected neuron networks remain unclear. Importantly, short long-term spatiotemporal dynamics neuronal network activity make it challenging discern ALS-related reconfigurations emerge evolve. To address this, we systematically monitored with a confirmed endogenous C9orf72 mutation. We show that ALS patient-derived display time-dependent neural dysfunction, specifically reduced firing rate spike amplitude, impaired bursting, but higher overall synchrony activity. These changes coincided altered neurite outgrowth branching within networks. Moreover, transcriptional analyses revealed dysregulation molecular pathways involved synaptic development maintenance, cell adhesion, suggesting stabilization. This study identifies early as contributing mechanism resulting network-wide compensation, which may over time render vulnerable neurodegeneration.

Язык: Английский

Процитировано

1
Dysregulation of synaptic transcripts underlies network abnormalities in ALS patient-derived motor neurons DOI

Anna M. Kollstrøm,

Nicholas Christiansen, Axel Sandvig

и другие.

AJP Cell Physiology, Год журнала: 2024, Номер 328(3), С. C1029 - C1044

Опубликована: Дек. 27, 2024

Amyotrophic lateral sclerosis (ALS) is characterized by dysfunction and loss of upper lower motor neurons. Several studies have identified structural functional alterations in the neurons before manifestation symptoms, yet underlying cause such how they contribute to progressive degeneration affected neuron networks remain unclear. Importantly, short- long-term spatiotemporal dynamics neuronal network activity make it challenging discern ALS-related reconfigurations emerge evolve. To address this, we systematically monitored with a confirmed endogenous C9orf72 mutation. We show that ALS patient-derived display time-dependent neural dysfunction, specifically reduced firing rate spike amplitude, impaired bursting, but higher overall synchrony activity. These changes coincided altered neurite outgrowth branching within networks. Moreover, transcriptional analyses revealed dysregulation molecular pathways involved synaptic development maintenance, outgrowth, cell adhesion, suggesting stabilization. This study identifies early as contributing mechanism resulting network-wide compensation, which may over time render vulnerable neurodegeneration.NEW & NOTEWORTHY RNA-sequencing expression genes plasticity. were accompanied impairments disrupted activity, compensations vulnerability ALS.

Язык: Английский

Процитировано

1
Altered structural organization and functional connectivity in feedforward neural networks after induced perturbation DOI Open Access

Janelle S. Weir,

Katrine Sjaastad Hanssen, Nicolai Winter‐Hjelm

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2023, Номер unknown

Опубликована: Сен. 13, 2023

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

Язык: Английский

Процитировано

2
Engineered Cortical Microcircuits for Investigations of Neuroplasticity DOI Creative Commons
Nicolai Winter‐Hjelm, Pawel Sikorski, Axel Sandvig

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Июнь 8, 2024

Abstract Recent advances in neural engineering have opened new ways to investigate the impact of topology on network function. Leveraging microfluidic technologies, it is possible establish modular circuit motifs that promote both segregation and integration information processing engineered networks, similar those observed vivo . However, underlying topologies dynamics response pathological perturbation remains largely unresolved. In this work, we demonstrate utilization platforms with 12 interconnected nodes structure modular, cortical networks. By implementing geometrical constraints inspired by a Tesla valve within connecting microtunnels, additionally exert control over direction axonal outgrowth between nodes. Interfacing these nanoporous microelectrode arrays reveals resulting laminar networks exhibit pronounced segregated integrated functional across layers, mirroring key elements feedforward, hierarchical neocortex. The multi-nodal configuration also facilitates selective individual To illustrate this, induced hypoxia, factor pathogenesis various neurological disorders, well-connected Our findings such perturbations induce ablation flow hypoxic node, while enabling study plasticity adaptations neighboring communication pathways. summary, our presented model system recapitulates fundamental attributes microcircuit organization neocortical rendering highly pertinent for preclinical neuroscience research. This holds promise yielding insights into development, topological organization, neuroplasticity mechanisms neocortex micro- mesoscale level, healthy conditions.

Язык: Английский

Процитировано

0
Reduced spatial spread of nodes in geometric network models improves topology associated with increased computational capabilities DOI Creative Commons
Nicholas Christiansen, Ioanna Sandvig, Axel Sandvig

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Окт. 12, 2024

Biological neural networks are characterized by short average path lengths, high clustering, and modular hierarchical architectures. These complex network topologies strike a balance between local specialization global synchronization via long-range connections, resulting in highly efficient communication. Here, we use geometric model with either an intermediate or connection probability to investigate the effects of wiring cost principles on complexity for different spatial conformations. We find that both probabilities only conform small-world architectures neurons dense clusters due decrease within clusters. Furthermore, small-worldness modularity were reduced systems connections caused reduction allowing novel insight into mechanisms underlying adaptive maladaptive alterations. Our findings corroborate previous work showing distributions play key role development.

Язык: Английский

Процитировано

0
Evolving alterations of structural organization and functional connectivity in feedforward neural networks after induced P301L tau mutation DOI Creative Commons

Janelle S. Weir,

Katrine Sjaastad Hanssen, Nicolai Winter‐Hjelm

и другие.

European Journal of Neuroscience, Год журнала: 2024, Номер unknown

Опубликована: Дек. 2, 2024

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

Язык: Английский

Процитировано

0