Astrocytes Speed Action Potential Propagation

Glia affect neural circuits in numerous ways. Microglia strip synapses and clear debris after injury; oligodendrocytes form myelin, which regulates axon conduction velocity and limits sprouting; and astrocytes direct blood flow to active circuits, provide nutrients and growth factors, regulate extracellular ion concentrations, guide neurite growth, promote synaptogenesis, stabilize dendritic spines, and encapsulate synapses to limit the spread of neurotransmitters. Accumulating evidence suggests that astrocytes also influence axonal conduction, for example, by releasing glutamate and ATP along the axon and by regulating extracellular potassium levels at nodes of Ranvier (reviewed in Fields et al. 2015 Neuron 86: 374). Sobieski et al. add to this evidence by showing that action potential shape and propagation speed differ in isolated hippocampal neurons grown in contact with ( ) or without (no-) astrocytes. The first clue that astrocytes affected axonal propagation was the unusual shape of autaptic EPSCs evoked by current injection into no-astrocyte neurons. Not only were the time to peak greater and the peak amplitude lower in no-astrocyte neurons than in astrocyte neurons, but a large-scale asynchrony involving multiple peaks was apparent in EPSCs of no-astrocyte neurons. Importantly, the timing of local peaks within EPSPs was largely invariant across trials, their amplitudes were much larger than quantal amplitudes, and they were insensitive to calcium chelators, suggesting they did not result from delayed release of single vesicles triggered by persistent calcium elevation in axonal terminals. Instead, the multiple peaks seemed to result from asynchronous arrival of action potentials at different terminals. Indeed, action potential propagation speed was significantly reduced in no-astrocyte neurons, which would likely cause release at distal terminals to be delayed relative to release more proximal to the soma. In addition, the spike width was greater in distal axons of no-astrocyte neurons than in astrocyte neurons. These data suggest that astrocytes regulate the rate of action potential propagation and thus the synchrony of release across synaptic terminals. Thus, astrocytes may have a profound impact on neuronal processes that rely on precise spike timing, such as dendritic integration and coincidence detection, spike-timingdependent synaptic plasticity, and the binding of features represented in different brain regions through synchronous activity.