Entropy estimation within 
<i>in vitro</i>
 neural-astrocyte networks as a measure of development instability

Teneggi, Jacopo; Chen, Xin; Balu, Alan; Barrett, Connor; Grisolia, Giulia; Lucia, Umberto; Dzakpasu, Rhonda

doi:10.1103/physreve.103.042412

Cited by 1 publication

(1 citation statement)

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“…Astrocytes have been shown to modulate synchronization, bursting parameters, and morphological maturation in hippocampal co-cultures (Feldt et al, 2010). The use of astrocyte conditioned media, rich in beneficial growth factors, is generally sufficient for enhancing morphological and functional maturation of neuronal cultures (Feldt et al, 2010;Pozzi et al, 2017;Teneggi et al, 2021). However, attempts to recapitulate the arborized morphology of astrocytes in vitro have had limited success, because they are often cultured in media supplemented with fetal bovine serum (FBS) in order to promote survival and proliferation.…”

Section: Introductionmentioning

confidence: 99%

Emergent structural and functional properties of hippocampal multi-cellular aggregates

Acero,

Das,

Rivellini

et al. 2023

Front. Neurosci.

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Hippocampal neural networks are distinctly capable of integrating multi-modal sensory inputs to drive memory formation. Neuroscientific investigations using simplified in vitro models have greatly relied on planar (2D) neuronal cultures made from dissociated tissue. While these models have served as simple, cost-effective, and high-throughput tools for examining various morphological and electrophysiological characteristics of hippocampal networks, 2D cultures fail to reconstitute critical elements of the brain microenvironment that may be necessary for the emergence of sophisticated integrative network properties. To address this, we utilized a forced aggregation technique to generate high-density (>100,000 cells/mm3) multi-cellular three-dimensional aggregates using rodent embryonic hippocampal tissue. We contrasted the emergent structural and functional properties of aggregated (3D) and dissociated (2D) cultures over 28 days in vitro (DIV). Hippocampal aggregates displayed robust axonal fasciculation across large distances and significant neuronal polarization, i.e., spatial segregation of dendrites and axons, at earlier time points compared to dissociated cultures. Moreover, we found that astrocytes in aggregate cultures self-organized into non-overlapping quasi-domains and developed highly stellate morphologies resembling astrocyte structures in vivo. We maintained cultures on multi-electrode arrays (MEAs) to assess spontaneous electrophysiological activity for up to 28 DIV. We found that 3D networks of aggregated cultures developed highly synchronized networks and with high burstiness by 28 DIV. We also demonstrated that dual-aggregate networks became active by 7 DIV, in contrast to single-aggregate networks which became active and developed synchronous bursting activity with repeating motifs by 14 DIV. Taken together, our findings demonstrate that the high-density, multi-cellular, 3D microenvironment of hippocampal aggregates supports the recapitulation of emergent biofidelic morphological and functional properties. Our findings suggest that neural aggregates may be used as segregated, modular building blocks for the development of complex, multi-nodal neural network topologies.

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