Astrocytes Accumulate Evidence that Actions are Futile and Trigger Behavioral State Switches in Zebrafish

Seminar | March 8 | 2-3:30 p.m. | 560 Evans Hall

 Misha Ahrens, HHMI Janelia Research Campus

 Neuroscience Institute, Helen Wills

When a behavior repeatedly fails to achieve its goal, animals often give up and become passive, which can be strategic for preserving energy or regrouping between attempts. It is unknown how the brain identifies behavioral failures and mediates this behavioral state switch. In larval zebrafish swimming in virtual reality, visual feedback can be withheld so that swim attempts fail to trigger expected visual flow. After tens of seconds of such motor futility, animals become passive for similar durations. Whole-brain calcium imaging revealed noradrenergic neurons that responded specifically after failed swim attempts, and radial astrocytes whose calcium levels accumulated with increasing numbers of failed attempts. Using cell ablation and optogenetic and chemogenetic activation, we found that noradrenergic neurons progressively activate radial astrocytes, which then suppress swimming. Thus, radial astrocytes perform a computation critical for behavior: they accumulate evidence that current actions are ineffective and consequently drive changes in behavioral states.