Gray matter NG2 cells display multiple Ca2+-signaling pathways and highly motile processes

Area of Science:

• Neuroscience
• Cell Biology
• Glial Cell Research

Background:

• NG2 cells, a distinct glial type in the mammalian central nervous system (CNS), receive direct synaptic input from neurons.
• The functional significance of this neuronal innervation and its impact on NG2 cell intracellular calcium concentration ([Ca(2+)](i)) remain largely unexplored.

Purpose of the Study:

• To investigate the consequences of neuronal synaptic input on NG2 cells, specifically focusing on intracellular calcium dynamics.
• To elucidate the signaling pathways involved in calcium elevation within NG2 cells and their structural basis for communication.

Main Methods:

• Utilized transgenic mice with fluorescently labeled NG2 cells for live imaging.
• Combined patch-clamp recordings, Ca(2+)-imaging, mRNA analysis, and focal pressure application in acute hippocampal slices.
• Employed electron microscopy, immunostaining, and time-lapse imaging to analyze NG2 cell structure and motility.

Main Results:

• NG2 cells exhibit [Ca(2+)](i) elevations upon activation of voltage-gated Ca(2+)-channels, Ca(2+)-permeable AMPA-receptors, and group I metabotropic glutamate receptors.
• Calcium influx is amplified by Ca(2+)-induced Ca(2+)-release; neuronal stimulation causes postsynaptic currents but not somatic [Ca(2+)](i) increases.
• NG2 cells form both symmetric and asymmetric synapses with neurons, express vesicular glutamate transporter 1, possess motile actin-based processes, and lack glial filaments, microtubules, and ER.

Conclusions:

• NG2 cell calcium signaling appears localized to their processes, potentially mediating transmitter release or influencing cell motility.
• NG2 cells possess the structural and molecular machinery necessary for active, two-way communication with neighboring neurons in the gray matter.