Structure-function dynamics of engineered, modular neuronal networks with controllable afferent-efferent connectivity

Journal of Neural Engineering, Journal Year: 2023, Volume and Issue: 20(4), P. 046024 - 046024

Published: July 3, 2023

Abstract Objective. Microfluidic devices interfaced with microelectrode arrays have in recent years emerged as powerful platforms for studying and manipulating vitro neuronal networks at the micro- mesoscale. By segregating populations using microchannels only permissible to axons, can be designed mimic highly organized, modular topology of assemblies brain. However, little is known about how underlying topological features such engineered contribute their functional profile. To start addressing this question, a key parameter control afferent or efferent connectivity within network. Approach. In study, we show that microfluidic device featuring axon guiding channels geometrical constraints inspired by Tesla valve effectively promotes unidirectional axonal outgrowth between nodes, thereby enabling us connectivity. Main results. Our results moreover indicate these exhibit more efficient network organization higher modularity compared single nodal controls. We verified applying designer viral tools fluorescently label neurons visualize structure networks, combined extracellular electrophysiological recordings embedded nanoporous microelectrodes study dynamics during maturation. furthermore electrical stimulations induce signals selectively transmitted feedforward fashion populations. Significance. A advantage our microdevice ability longitudinally manipulate both function high accuracy. This model system has potential provide novel insights into development, organization, neuroplasticity mechanisms mesoscale healthy perturbed conditions.

Language: Английский

---

Micro-and mesoscale aspects of neurodegeneration in engineered human neural networks carrying the LRRK2 G2019S mutation

Frontiers in Cellular Neuroscience, Journal Year: 2024, Volume and Issue: 18

Published: April 5, 2024

Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene have been widely linked to Parkinson’s disease, where G2019S variant has shown contribute uniquely both familial and sporadic forms of disease. LRRK2-related mutations extensively studied, yet wide variety cellular network events related these remain poorly understood. The advancement availability tools for neural engineering now enable modeling selected pathological aspects neurodegenerative disease human networks vitro . Our study revealed distinct pathology associated dynamics engineered cortical carrying LRRK2 mutation compared healthy isogenic control networks. neurons self-organized into with aberrant morphology mitochondrial dynamics, affecting emerging structure–function relationships at micro-and mesoscale. Taken together, findings our points toward an overall heightened metabolic demand mutation, as well a resilience change response perturbation, controls.

Language: Английский

---

ALS patient-derived motor neuron networks exhibit microscale dysfunction and mesoscale compensation rendering them highly vulnerable to perturbation

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 4, 2024

Summary Amyotrophic lateral sclerosis affects upper and lower motor neurons, causing progressive neuropathology leading to structural functional alterations of affected neural networks long prior development symptoms. Certain genetic mutations, such as expansions in C9orf72 , predispose neuron populations pathological dysfunction. However, it is not known how underlying predisposition dynamics within vulnerable networks. Here, we studied micro-and mesoscale ALS patient derived over time. We show, for the first time, that neurons with endogenous develop classical cytopathology form cytoplasmic TDP-43 inclusions self-organise into computationally efficient networks, albeit hallmarks higher metabolic cost compared healthy controls. These included microscale impairments compensation including increased centralisation function. Moreover, show these are highly susceptible transient perturbation by exhibiting induced hyperactivity.

Language: Английский

---

AAV genome modification for efficient AAV production

Heliyon, Journal Year: 2023, Volume and Issue: 9(4), P. e15071 - e15071

Published: April 1, 2023

The adeno-associated virus (AAV) is one of the most potent vectors in gene therapy. experimental profile this vector shows its efficiency and accepted safety, which explains increased usage by scientists for research treatment a wide range diseases. These studies require using functional, pure, high titers particles. In fact, current knowledge AAV structure genome helps improve scalable production vectors. review, we summarize latest on optimization through modifying or biological processes inside cell.

Language: Английский

---

Information Encoding in Bursting Spiking Neural Network Modulated by Astrocytes

Entropy, Journal Year: 2023, Volume and Issue: 25(5), P. 745 - 745

Published: May 1, 2023

We investigated a mathematical model composed of spiking neural network (SNN) interacting with astrocytes. analysed how information content in the form two-dimensional images can be represented by an SNN spatiotemporal pattern. The includes excitatory and inhibitory neurons some proportion, sustaining excitation–inhibition balance autonomous firing. astrocytes accompanying each synapse provide slow modulation synaptic transmission strength. An image was uploaded to stimulation pulses distributed time reproducing shape image. found that astrocytic prevented stimulation-induced hyperexcitation non-periodic bursting activity. Such homeostatic regulation neuronal activity makes it possible restore supplied during lost raster diagram due At biological point, our shows act as additional adaptive mechanism for regulating activity, which is crucial sensory cortical representations.

Language: Английский

---

Engineered Cortical Microcircuits for Investigations of Neuroplasticity

Lab on a Chip, Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 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.

Language: Английский

---

Reverse engineering of feedforward cortical-Hippocampal microcircuits for modelling neural network function and dysfunction

Scientific Reports, Journal Year: 2024, Volume and Issue: 14(1)

Published: Oct. 29, 2024

Abstract Engineered biological neural networks are indispensable models for investigation of function and dysfunction from the subcellular to network level. Notably, advanced neuroengineering approaches significant interest their potential replicate topological functional organization brain networks. In this study, we reverse engineered feedforward primary cortical hippocampal neurons, using a custom-designed multinodal microfluidic device with Tesla valve inspired microtunnels. By interfacing nanoporous microelectrodes, show that exhibit capacity both segregated integrated activity, mimicking dynamics. To advocate broader applicability our model system, induced localized perturbations amyloid beta study impact pathology on functionality. Additionally, demonstrate long-term culturing subregion- layer specific neurons extracted entorhinal cortex hippocampus adult Alzheimer’s-model mice rats. Our results thus highlight approach engineering anatomically relevant dynamic structure-function relationships in healthy pathological conditions.

Language: Английский

---

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

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: May 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.

Language: Английский

---

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

AJP Cell Physiology, Journal Year: 2024, Volume and Issue: 328(3), P. C1029 - C1044

Published: Dec. 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.

Language: Английский

---

Rheological Characterization of Three-Dimensional Neuronal Cultures Embedded in PEGylated Fibrin Hydrogels

Gels, Journal Year: 2023, Volume and Issue: 9(8), P. 642 - 642

Published: Aug. 9, 2023

Three-dimensional (3D) neuronal cultures are valuable models for studying brain complexity in vitro, and the choice of bulk material which neurons grow is a crucial factor establishing successful cultures. Indeed, development network functionality influenced by mechanical properties selected material; turn, these may change due to neuron-matrix interactions that alter microstructure material. To advance our understanding interplay between their environment, here we utilized PEGylated fibrin hydrogel as scaffold mouse primary carried out rheological characterization over three-week period, both with without cells. We observed hydrogels exhibited an elastic response could be described terms Young's modulus E. The procured stable E≃420 Pa, while neuron-laden showed higher E≃590 Pa during early stages decreased E≃340 at maturer stages. Our results suggest processes dynamically modify structure development, potentially compromising stability functional traits developing network.

Language: Английский

---