Exploring the Contribution of Thalamic and Hippocampal Input on Cortical Dynamics in a Brain-on-a-Chip Model

Brofiga, Martina; Pisano, Marietta; Callegari, Francesca; Massobrio, Paolo

doi:10.1109/tmrb.2021.3072234

Cited by 10 publications

(8 citation statements)

References 45 publications

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“…S1A Fig shows an example of a network with 50% of inhibitory neurons, which displayed a very low scattered spiking activity with a MFR value of 0.08 sp/s (<0.1 sp/s), and the complete lack of bursts. The activity intensified as the inhibitory/ excitatory ratio decreased, reaching a MFR > 0.1 sp/s (active node) only when the percentage of inhibitory neurons dropped to 40% S1B Fig) . However, the activity started to organize into bursts and network bursts only at 30% inhibitory cells (S1C Fig) and only at 20% (S1E Fig), it showed a MFR comparable to the one found in vitro [19,24], as well as the temporal organization of the network bursts [25]. With lower percentages of inhibitory cells (S1D Fig), the network lost its balance and the firing rate shot at unphysiological values higher than 190 sp/s.…”

Section: Three-dimensionality Slows Down Spiking and Bursting Activit...mentioning

confidence: 57%

Modeling the three-dimensional connectivity of in vitro cortical ensembles coupled to Micro-Electrode Arrays

Callegari

Brofiga²,

Massobrio³

2023

PLoS Comput Biol

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Nowadays, in vitro three-dimensional (3D) neuronal networks are becoming a consolidated experimental model to overcome most of the intrinsic limitations of bi-dimensional (2D) assemblies. In the 3D environment, experimental evidence revealed a wider repertoire of activity patterns, characterized by a modulation of the bursting features, than the one observed in 2D cultures. However, it is not totally clear and understood what pushes the neuronal networks towards different dynamical regimes. One possible explanation could be the underlying connectivity, which could involve a larger number of neurons in a 3D rather than a 2D space and could organize following well-defined topological schemes. Driven by experimental findings, achieved by recording 3D cortical networks organized in multi-layered structures coupled to Micro-Electrode Arrays (MEAs), in the present work we developed a large-scale computational network model made up of leaky integrate-and-fire (LIF) neurons to investigate possible structural configurations able to sustain the emerging patterns of electrophysiological activity. In particular, we investigated the role of the number of layers defining a 3D assembly and the spatial distribution of the connections within and among the layers. These configurations give rise to different patterns of activity that could be compared to the ones emerging from real in vitro 3D neuronal populations. Our results suggest that the introduction of three-dimensionality induced a global reduction in both firing and bursting rates with respect to 2D models. In addition, we found that there is a minimum number of layers necessary to obtain a change in the dynamics of the network. However, the effects produced by a 3D organization of the cells is somewhat mitigated if a scale-free connectivity is implemented in either one or all the layers of the network. Finally, the best matching of the experimental data is achieved supposing a 3D connectivity organized in structured bundles of links located in different areas of the 2D network.

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Section: Three-dimensionality Slows Down Spiking and Bursting Activit...mentioning

confidence: 57%

Modeling the three-dimensional connectivity of in vitro cortical ensembles coupled to Micro-Electrode Arrays

Callegari

Brofiga²,

Massobrio³

2023

PLoS Comput Biol

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“…Although bioprinted and scaffold-based models of the thalamus have not yet been reported, brain-on-a-chip models have been developed that contain cortical and thalamic co-cultures 149 . In such microfluidic devices with integrated MEAs, the activity of cortical ensembles can be monitored, which is differentially modulated by thalamic and hippocampal inputs 150 .…”

Section: Region-specific Cns Modelsmentioning

confidence: 99%

Functional bioengineered models of the central nervous system

2023

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The functional complexity of the central nervous system (CNS) is unparalleled in living organisms. Its nested cells, circuits and networks encode memories, move bodies and generate experiences. Neural tissues can be engineered to assemble model systems that recapitulate essential features of the CNS and to investigate neurodevelopment, delineate pathophysiology, improve regeneration and accelerate drug discovery. In this Review, we discuss essential structure–function relationships of the CNS and examine materials and design considerations, including composition, scale, complexity and maturation, of cell biology-based and engineering-based CNS models. We highlight region-specific CNS models that can emulate functions of the cerebral cortex, hippocampus, spinal cord, neural-X interfaces and other regions, and investigate a range of applications for CNS models, including fundamental and clinical research. We conclude with an outlook to future possibilities of CNS models, highlighting the engineering challenges that remain to be overcome.

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“…The interaction between thalamus and cortex has also been the center of great interest. In vitro studies highlighted how cortical neurons act as the site of initiation of bursting events [ 122 ] and that the thalamic ones promote a redistribution of inhibitory functional connections [ 123 ]. Recently, the cortico-hippocampal circuit has been studied from both a functional and a structural point of view, pointing out the role of inhibitory connections during the development of the network in modulating the cortical dynamic [ 124 ].…”

Section: Neuromorphic Neuroprostheses: State-of-the-art and Perspectivesmentioning

confidence: 99%

“…( b ) Example of spontaneous cortical activity recorded by means of a 60- (top) and 4096-electrodes (bottom) MEA. In addition to the technological part, in vitro experimental models should simultaneously embed three features: ( c ) three-dimensionality connectivity (top, adapted from [ 123 ], bottom, from [ 124 ]); ( d ) modularity topology (top, adapted from [ 123 ]); ( e ) heterogeneity, i.e., the existence of different neuronal types (top, adapted from [ 123 ], bottom, from [ 122 ], where cortical (red) and thalamic (green) neurons are interconnected to realize a complex neuronal networks).…”

Section: Neuromorphic Neuroprostheses: State-of-the-art and Perspectivesmentioning

confidence: 99%

Neuromorphic-Based Neuroprostheses for Brain Rewiring: State-of-the-Art and Perspectives in Neuroengineering

et al. 2022

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Neuroprostheses are neuroengineering devices that have an interface with the nervous system and supplement or substitute functionality in people with disabilities. In the collective imagination, neuroprostheses are mostly used to restore sensory or motor capabilities, but in recent years, new devices directly acting at the brain level have been proposed. In order to design the next-generation of neuroprosthetic devices for brain repair, we foresee the increasing exploitation of closed-loop systems enabled with neuromorphic elements due to their intrinsic energy efficiency, their capability to perform real-time data processing, and of mimicking neurobiological computation for an improved synergy between the technological and biological counterparts. In this manuscript, after providing definitions of key concepts, we reviewed the first exploitation of a real-time hardware neuromorphic prosthesis to restore the bidirectional communication between two neuronal populations in vitro. Starting from that ‘case-study’, we provide perspectives on the technological improvements for real-time interfacing and processing of neural signals and their potential usage for novel in vitro and in vivo experimental designs. The development of innovative neuroprosthetics for translational purposes is also presented and discussed. In our understanding, the pursuit of neuromorphic-based closed-loop neuroprostheses may spur the development of novel powerful technologies, such as ‘brain-prostheses’, capable of rewiring and/or substituting the injured nervous system.

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Exploring the Contribution of Thalamic and Hippocampal Input on Cortical Dynamics in a Brain-on-a-Chip Model

Cited by 10 publications

References 45 publications

Modeling the three-dimensional connectivity of in vitro cortical ensembles coupled to Micro-Electrode Arrays

Modeling the three-dimensional connectivity of in vitro cortical ensembles coupled to Micro-Electrode Arrays

Functional bioengineered models of the central nervous system

Neuromorphic-Based Neuroprostheses for Brain Rewiring: State-of-the-Art and Perspectives in Neuroengineering

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