Pattern separation and completion of distinct axonal inputs transmitted via micro-tunnels between co-cultured hippocampal dentate, CA3, CA1 and entorhinal cortex networks

Poli, Daniele; Wheeler, Bruce C.; DeMarse, Thomas B.; Brewer, Gregory J.

doi:10.1088/1741-2552/aabc20

Cited by 26 publications

(30 citation statements)

References 64 publications

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“…These densities were chosen to mimic the ratio of neuronal densities in vivo: EC-DG 1:3, DG-CA3 3:1, CA3-CA 11:1.25, and CA1-EC 1.25:1 (Braitenberg and Schuz, 2004). The plating and culture medium was NbActiv4 (BrainBits, Springfield, IL, United States) to promote synaptogenesis closer to in vivo densities (Brewer et al, 2008;Poli et al, 2018b). This medium is the classic Neurobasal/B27 medium (Brewer et al, 1993) supplemented with creatine, cholesterol, and low levels of estrogen.…”

Section: Methodsmentioning

confidence: 99%

The Flow of Axonal Information Among Hippocampal Subregions: 1. Feed-Forward and Feedback Network Spatial Dynamics Underpinning Emergent Information Processing

Vakilna

Tang

Wheeler

et al. 2021

Front. Neural Circuits

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The tri-synaptic pathway in the mammalian hippocampus enables cognitive learning and memory. Despite decades of reports on anatomy and physiology, the functional architecture of the hippocampal network remains poorly understood in terms of the dynamics of axonal information transfer between subregions. Information inputs largely flow from the entorhinal cortex (EC) to the dentate gyrus (DG), and then are processed further in the CA3 and CA1 before returning to the EC. Here, we reconstructed elements of the rat hippocampus in a novel device over an electrode array that allowed for monitoring the directionality of individual axons between the subregions. The direction of spike propagation was determined by the transmission delay of the axons recorded between two electrodes in microfluidic tunnels. The majority of axons from the EC to the DG operated in the feed-forward direction, with other regions developing unexpectedly large proportions of feedback axons to balance excitation. Spike timing in axons between each region followed single exponential log-log distributions over two orders of magnitude from 0.01 to 1 s, indicating that conventional descriptors of mean firing rates are misleading assumptions. Most of the spiking occurred in bursts that required two exponentials to fit the distribution of inter-burst intervals. This suggested the presence of up-states and down-states in every region, with the least up-states in the DG to CA3 feed-forward axons and the CA3 subregion. The peaks of the log-normal distributions of intra-burst spike rates were similar in axons between regions with modes around 95 Hz distributed over an order of magnitude. Burst durations were also log-normally distributed around a peak of 88 ms over two orders of magnitude. Despite the diversity of these spike distributions, spike rates from individual axons were often linearly correlated to subregions. These linear relationships enabled the generation of structural connectivity graphs, not possible previously without the directional flow of axonal information. The rich axonal spike dynamics between subregions of the hippocampus reveal both constraints and broad emergent dynamics of hippocampal architecture. Knowledge of this network architecture may enable more efficient computational artificial intelligence (AI) networks, neuromorphic hardware, and stimulation and decoding from cognitive implants.

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Section: Methodsmentioning

confidence: 99%

The Flow of Axonal Information Among Hippocampal Subregions: 1. Feed-Forward and Feedback Network Spatial Dynamics Underpinning Emergent Information Processing

Vakilna

Tang

Wheeler

et al. 2021

Front. Neural Circuits

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“…Technologies such as MEAs may be used to acquire the electrophysiology from multiple recording sites, as well as to record cell responses evoked by chemical ( Pancrazio et al, 2003 ) or electrical ( Wagenaar et al, 2004 ) perturbations. In particular, MEAs simultaneously monitor long-term spontaneous recordings and responses induced by stimulation protocols using from 60 or 120 ( Poli et al, 2018 ) up to 4,000 or 10,000 electrodes ( Berdondini et al, 2009 ). Therefore, this technology allows high control of the system, supporting a direct reconstruction of the underlying functions and dynamics at the network scale ( Poli et al, 2017 ).…”

Section: Brain Organoid Functions Provided By Integrated Electrophysimentioning

confidence: 99%

“…Studies in cellular neuroscience mainly focus on in vivo animal models ( Marbacher et al, 2018 ), ex vivo brain slices ( Brai et al, 2018 ), and in vitro two-dimensional (2D) cultures ( Poli et al, 2018 ). However, these three different experimental conditions have some limitations.…”

Section: Introductionmentioning

confidence: 99%

Experimental and Computational Methods for the Study of Cerebral Organoids: A Review

2019

Self Cite

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Cerebral (or brain) organoids derived from human cells have enormous potential as physiologically relevant downscaled in vitro models of the human brain. In fact, these stem cell-derived neural aggregates resemble the three-dimensional (3D) cytoarchitectural arrangement of the brain overcoming not only the unrealistic somatic flatness but also the planar neuritic outgrowth of the two-dimensional (2D) in vitro cultures. Despite the growing use of cerebral organoids in scientific research, a more critical evaluation of their reliability and reproducibility in terms of cellular diversity, mature traits, and neuronal dynamics is still required. Specifically, a quantitative framework for generating and investigating these in vitro models of the human brain is lacking. To this end, the aim of this review is to inspire new computational and technology driven ideas for methodological improvements and novel applications of brain organoids. After an overview of the organoid generation protocols described in the literature, we review the computational models employed to assess their formation, organization and resource uptake. The experimental approaches currently provided to structurally and functionally characterize brain organoid networks for studying single neuron morphology and their connections at cellular and sub-cellular resolution are also discussed. Well-established techniques based on current/voltage clamp, optogenetics, calcium imaging, and Micro-Electrode Arrays (MEAs) are proposed for monitoring intra- and extra-cellular responses underlying neuronal dynamics and functional connections. Finally, we consider critical aspects of the established procedures and the physiological limitations of these models, suggesting how a complement of engineering tools could improve the current approaches and their applications.

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“…Multi-modular networks can be electrically stimulated with the possibility to have a better control over the evoked activity, thanks to the structural and functional confinement ensured by the neuronal circuits. Several studies have been conducted within this framework, in particular, for investigating the relationship between structural and functional connectivity [60], and for understanding the role played by each circuit in processing neural information [61] [62].…”

Section: Network Events: Identification and Similaritymentioning

confidence: 99%

The emergence of dynamical instantaneous memory in the spontaneous activity of spatially confined neuronal assemblies in vitro

Piasetzky

Bisio

Kanner

et al. 2018

Preprint

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Understanding the dynamics between communicating cell assemblies is essential for deciphering the neural code and identifying the mechanism underlying memory formation. In this work, in order to unveil possible emergent intrinsic memory phenomena in the communication between cell assemblies, we study the spontaneous dynamics of in vitro spatially confined inter-connected neuronal circuits grown on multi-electrode arrays. The spontaneous dynamics of the global network was characterized by the coupling of the activity independently generated by each circuit.The asymptotic functional connectivity of the network reflected its modular organization. Instantaneous functional connectivity maps on ten seconds epochs, revealed more complex dynamical states with the simultaneous activation of distinct circuits. When looking at the similarity of the generated network events, we observed 2 that spontaneous network events occurring at temporal distances below two dozens of seconds had an average higher similarity compared to randomly played network events. Such a memory phenomenon was not observed in networks where spontaneous events were less frequent and in networks topologically organized as open lines. These results support the hypothesis that dynamical instantaneous memory, characterized by drifting network dynamics with decaying degree of similarity, is an intrinsic property of neuronal networks.

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Pattern separation and completion of distinct axonal inputs transmitted via micro-tunnels between co-cultured hippocampal dentate, CA3, CA1 and entorhinal cortex networks

Abstract: To the best of our knowledge, these are the first direct measures of pattern separation and completion for axonal transmission to the somata target outputs at the rate and digital population levels in each of four stages of the EC-DG-CA3-CA1 circuit.

Cited by 26 publications

References 64 publications

The Flow of Axonal Information Among Hippocampal Subregions: 1. Feed-Forward and Feedback Network Spatial Dynamics Underpinning Emergent Information Processing

The Flow of Axonal Information Among Hippocampal Subregions: 1. Feed-Forward and Feedback Network Spatial Dynamics Underpinning Emergent Information Processing

Experimental and Computational Methods for the Study of Cerebral Organoids: A Review

The emergence of dynamical instantaneous memory in the spontaneous activity of spatially confined neuronal assemblies in vitro

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