Intrinsically Active and Pacemaker Neurons in Pluripotent Stem Cell-Derived Neuronal Populations

Stem Cell Reports, 2014 · DOI: http://dx.doi.org/10.1016/j.stemcr.2014.01.006 · Published: March 11, 2014

Physiology Neurology Regenerative Medicine & Stem Cells

Simple Explanation

Neurons derived from pluripotent stem cells can form functional networks in vitro. These networks exhibit spontaneous activity, suggesting the presence of intrinsically active neurons (IANs). This study provides evidence for IANs in PSC-neuronal networks using mouse embryonic stem cells. IANs remain active even when fast synaptic communication is blocked. They possess intrinsic mechanisms for autonomous neuronal activity and contribute to synchronous network bursting. The pacemaker properties of IANs may be relevant for transplantation of neural tissues, potentially influencing the functional activity of both grafted and existing host neuronal networks.

Study Duration

4 Months

Participants

Mouse embryonic stem cells

Evidence Level

Not specified

Key Findings

1
Pluripotent stem cell-derived neuronal networks contain intrinsically active neurons (IANs) that remain active after blocking fast synaptic communication.
2
The autonomous activity of IANs depends on persistent sodium currents but not on L-type calcium channels.
3
IANs exhibit diverse intrinsic firing behaviors, including regular spiking, irregular spiking, stuttering, bursting, and mixed firing.

Research Summary

The study demonstrates the existence of intrinsically active neurons (IANs) in pluripotent stem cell-derived neuronal networks, using mouse embryonic stem cells. These IANs are functionally integrated into the PSC-neuronal assemblies, contribute to network activities, and exhibit pacemaker-like properties. The intrinsic activity of PSC IANs relies on persistent sodium currents, but not on LTCC activity.

Practical Implications

Transplantation Strategies

The intrinsic activity and pacemaker properties of IANs may be particularly relevant for interventions involving transplantation of neural tissues, as they may influence the functional activity of grafted and existing host neuronal networks.

Understanding Brain Development

Understanding the mechanisms of spontaneous activity and synchronicity in PSC-derived neuronal networks is crucial for understanding brain development and function.

Drug Discovery

The identification of ion channels involved in the autonomous activity of IANs (e.g., persistent sodium channels) may provide potential targets for drug development.

Study Limitations

1
The study primarily used mouse embryonic stem cells; further research is needed to confirm these findings in human PSC-derived neurons.
2
The specific inhibitory or excitatory identity of type IV IANs (pacemaker neurons) remains to be determined.
3
The possibility that other ion channels or neurosteroids contribute to or influence autonomous activity in IANs cannot be excluded.

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