Intrinsically active and pacemaker neurons in pluripotent stem cell-derived neuronal populations

Area of Science:

• Neuroscience
• Stem Cell Biology

Background:

• Pluripotent stem cells (PSCs) differentiate into neurons that form self-organizing, functional networks in vitro.
• These PSC-derived neuronal networks exhibit spontaneous, synchronous network activities without external stimulation.
• The spontaneous activity suggests the presence of intrinsically active neurons (IANs) within these networks.

Purpose of the Study:

• To provide evidence for the existence of intrinsically active neurons (IANs) in pluripotent stem cell-derived neuronal networks.
• To characterize the properties and functional integration of these IANs.

Main Methods:

• Utilized mouse embryonic stem cells for neuronal differentiation.
• Employed extracellular multielectrode array recordings.
• Conducted intracellular patch-clamp recordings.
• Applied pharmacological inhibition of fast synaptic communication.

Main Results:

• Demonstrated the existence of intrinsically active neurons (IANs) in PSC-neuronal networks.
• Confirmed that IANs maintain autonomous activity even after synaptic inhibition.
• Showed that IANs possess intrinsic mechanisms for autonomous neuronal firing.
• Found that IANs are functionally integrated into neuronal populations, contributing to network bursting.
• Identified pacemaker properties within the PSC-derived IAN subpopulation.

Conclusions:

• Intrinsically active neurons (IANs) are present and functional in stem cell-derived neuronal networks.
• The identified IANs possess intrinsic activity and pacemaker properties.
• These properties are significant for neural tissue transplantation and regulating host neuronal networks.