Introducing the brain: astrocyte speed control (Introduction)

by David Turell , Friday, October 15, 2021, 14:54 (923 days ago) @ David Turell

Astrocytes influence axon speed controls:

https://www.science.org/doi/10.1126/science.abh2858

"Glia control white matter information flow
The myelinated axons of the white matter mediate rapid information transmission between the brain’s processing nodes. Axonal excitability and conduction speed are key determinants of neural circuit function, but it is largely unknown how they are regulated. Lezmy et al. examined the effects of adenosine on the functional properties of myelinated axons. They observed activity-dependent calcium rise in astrocyte processes, calcium-triggered ATP release from astrocytes, activation of adenosine receptors in the axon initial segment and the nodes of Ranvier, increased cyclic AMP concentration, activation of HCN2 channels, and depolarization of axons by 5 to 10 millivolts. This molecular pathway enabled astrocytes to increase the excitability of pyramidal neurons and to profoundly decrease the axonal conduction velocity. Astrocytes thus control signaling speed in myelinated axons. "

"RESULTS
Astrocytes closely approach the axons of myelinated neurons in layer V of the cerebral cortex that enter the corpus callosum. Uncaging Ca2+ within astrocytes or stimulating spike trains in neurons evoked a rise of astrocyte [Ca2+]i that triggered the release of ATP-containing vesicles from these cells. This evoked an inward current in the AIS and nodes of Ranvier of the pyramidal neurons. Pharmacology showed that this was mediated by the activation of Gs-linked adenosine A2a receptors (A2aRs), implying that the released ATP was converted to adenosine by extracellular enzymes. The A2aRs raise the intracellular concentration of cyclic AMP, which activates hyperpolarization-activated cyclic nucleotide–gated (HCN) channels mediating the inward hyperpolarization-activated current (Ih) and thus depolarizes the cell. In the AIS, the activation of A2aRs alters excitability and hence action potential generation, whereas in the nodes of Ranvier, it decreases the conduction speed of the action potential along the axon.

"CONCLUSION
As in the gray matter, astrocyte [Ca2+]i regulates the release of ATP into the extracellular space in the white matter. After conversion to adenosine, this regulates the excitability and conduction speed of myelinated axons. The changes in excitability at the AIS will lead to changes in the relationship between the synaptic input and action potential output of the cell. The altered conduction speed of the myelinated axon may change neural circuit function by changing the action potential arrival time at the cell’s output synapses, thus altering the integration of signals in postsynaptic neurons. Variations in astrocyte-derived adenosine level can occur between wake and sleep states, and the extracellular adenosine concentration rises during energy deprivation conditions. These changes in adenosine level could thus control white matter information flow and neural circuit function."

Comment: this tells us how astrocytes do their work but not how adenosine lev els are ultimately regulated. Doing this type of research never ends as the designed fine controls are seemingly endless.