Fast signaling stars of the brain

Astrocyte calcium signals are fast enough to play a role in neuronal information processing and changes in local blood flow, research from Jill Stobart and Prof. Bruno Weber suggests. In their Neuron paper, they show that astrocyte signaling occurs within 100 ms of neuron signaling and finally settle the debate about the importance of these glial cells in fast brain processes.

Astrocytes are in contact with thousands of synapses and are also wrapped around blood vessels. This suggests they may modulate synaptic activity and mediate changes in local blood flow through calcium-dependent mechanisms. However, several studies have reported that astrocytes are too slow to do this. The calcium signals measured in these studies appeared seconds after neuronal activity and after local vasodilation. Therefore, the consensus in the field was that astrocytes are merely listening to neighboring neurons and are not playing an active modulatory role.

Use of different calcium indicators for neurons and astrocytes
Jill Stobart and Bruno Weber at the Institute of Pharmacology and Toxicology – Experimental Imaging and Neuroenergetics, and colleagues have addressed this problem by examining the temporal dynamics of astrocyte calcium micro domains in fine astrocytic processes during sensory stimulation and compared them with nearby neurons. They used 2-photon imaging to visualize a red calcium indicator used to label neurons and green calcium indicators for astrocytes. During imaging, Stobart and colleagues vibrated single whiskers to evoke neuronal activity in the corresponding cortical area of a mouse and analyzed the images using the Toolbox for Matlab CHIPS that allows the automated selection of active microdomains.

Fast astrocyte microdomains
Their results show that there were clearly astrocyte microdomains that had a shorter onset latency than previously reported. These microdomains follow neurons by about a 100 milliseconds and form about 8% of the total astrocyte microdomain population. The fast astrocyte microdomains were detected in astrocyte processes and their endfeet, with which they contact neurons and blood vessels. This suggests that astrocytes are fast enough to play a role in synaptic modulation and neurovascular coupling. While the mechanism underlying these fast microdomains has not been resolved, Stobart and Weber performed experiments to exclude the involvement of known routes. Blocking neuromodulatory pathways such as the acetylcholine, serotonin, and norepinephrine pathways did not affect fast astrocyte signaling. Likewise, in mice lacking the slow calcium receptor IP3 receptor 2, fast calcium signaling by astrocytes was unaltered. These results suggest that the fast astrocytic signaling is truly evoked by local synaptic activity.

Cortical Circuit Activity Evokes Rapid Astrocyte Calcium Signals on a Similar Timescale to Neurons. Stobart JL, Ferrari KD, Barrett MJP, Glück C, Stobart MJ, Zuend M, Weber B. Neuron. 2018 98(4):726-735.e4. PubMed Abstract

See also video abstract


Image: Astrocytes in the brain, Courtesy Prof. Weber