Misha Ahrens’ team at Janelia Research Campus placed zebra fish in virtual reality where swimming produced no progress. Normally, fish give up after ~20 seconds. The researchers found astrocytes were “counting” swim attempts via accumulating calcium. When calcium reached a threshold, astrocytes released adenosine to suppress swimming circuits. When researchers disabled astrocytes with a laser, the fish never stopped swimming; when they artificially activated astrocytes, the fish stopped immediately. This showed astrocytes actively mediate the transition from hope to hopelessness.
Marc Freeman’s lab showed norepinephrine doesn’t just activate astrocytes—it changes their “hearing.” At low norepinephrine (low arousal), astrocytes ignore synaptic activity. At high norepinephrine (high arousal), astrocytes suddenly “listen” to every synapse and modulate neuronal response accordingly. This creates a dynamic gain control system layered atop neuronal networks.
“We did expect that, in large part, the effect of norepinephrine on synapses would be mediated by astrocytes,” Papouin said. “But we did not expect all of it to be!”
The finding of parallel molecular pathways in such distinct species as fruit flies, zebra fish, and mice points to “an evolutionarily conserved way in which astrocytes can profoundly affect neural circuits,” Freeman said.
The results suggest a gaping hole in previous theories of neuromodulation. “In the past, neuroscientists studied neuromodulators and knew they were important in regulating neural circuit function, but none of their thinking, none of their diagrams, none of their models had anything in them other than neurons,” Fields said. “Now we see that they missed a big part of the story.”
