As the capacity to isolate distinct neuronal cell types has advanced over the past several decades, new two- and three-dimensional in vitro models of the interactions between different brain regions have expanded our understanding of human neurobiology and the origins of disease. These cultures develop distinctive patterns of activity, but the extent that these patterns are determined by the molecular identity of individual cell types versus the specific pattern of network connectivity is unclear. To address the question of how individual cell types interact in vitro, we developed a simplified culture using two excitatory neuronal subtypes known to participate in the in vivo reticulospinal circuit: HB9+ spinal motor neurons and Chx10+ hindbrain V2a neurons. Here, we report the emergence of cell type-specific patterns of activity in culture; on their own, Chx10+ neurons developed regular, synchronized bursts of activity that recruited neurons across the entire culture, whereas HB9+ neuron activity consisted of an irregular pattern. When these two subtypes were cocultured, HB9+ neurons developed synchronized network bursts that were precisely correlated with Chx10+ neuron activity, thereby recreating an aspect of Chx10+ neurons’ role in driving motor activity. These bursts were dependent on AMPA receptors. Our results demonstrate that the molecular classification of the neurons comprising in vitro networks is a crucial determinant of their activity. It is therefore possible to improve both the reproducibility and the applicability of in vitro neurobiological and disease models by carefully controlling the constituent mixtures of neuronal subtypes.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.