Astrocytes restrict discharge duration and neuronal sodium loads during recurrent network activity

Area of Science:

• Neuroscience
• Cellular Biology
• Biochemistry

Background:

• Neuronal activity, particularly sodium ion influx, is energy-intensive and must be controlled.
• Astrocytes potentially regulate neuronal excitation by clearing glutamate and potassium from the extracellular space.

Purpose of the Study:

• To investigate the role of astrocytes in managing sodium ion concentrations during neuronal network activity.
• To understand the impact of astrocyte function on neuronal sodium homeostasis and network stability.

Main Methods:

• Sodium imaging in mouse hippocampal slices.
• Field potential and whole-cell patch-clamp recordings.
• Measurement of extracellular potassium ([K(+)]o).
• Induction of network activity using Mg(2+)-free, bicuculline-containing saline.

Main Results:

• Neurons showed sodium increases up to 22 mM during epileptiform bursts.
• Astrocyte sodium concentration increased up to 8.5 mM, sometimes followed by an undershoot.
• Inhibition of glutamate uptake led to irreversible sodium increases and neuronal swelling.
• The gliotoxin NaFAc disrupted astrocyte function, elevating sodium and prolonging network activity.

Conclusions:

• Recurrent neuronal bursting causes sodium transients in both neurons and astrocytes.
• Glutamate transporters are essential for maintaining network activity and preventing sodium overload.
• Astrocyte metabolism is critical for neuronal recovery from sodium loads during synchronized activity.