Experience-dependent modulation of brain-wide visuomotor processing and behavior

To survive, animals must respond appropriately to changing external conditions. To do so quickly, animals use their past experiences to inform future actions. However, how past experience modulate information processing which ultimately influence behavior is still not well understood. Here we addressed this question by investigating how larval zebrafish use past action-outcome relationships to influence future responses to stimuli at the perceptual and behavioral levels.

Fish were first made to adapt to changing locomotor efficacy, the difficulty of translating oneself through space. Fish increase their swim vigor as translation difficulty increases (Kawashima et al, 2016), and might stop trying after a period of vigorous but futile attempts (Mu et al, 2019). Whole-brain calcium imaging revealed that brainwide neural dynamics were modulated after futile swimming, a change that includes but is not limited to neurosensory, neuromotor, neuromodulatory and glial systems. For example, when we subsequently provided optomotor response-driving stimuli, brain regions involved in all stages of this sensory-to-motor transformation -- which included the tectal neuropil, pretectum, nucleus of the medial longitudinal fasciculus (nMLF), cerebellum, parts of the anterior hindbrain and inferior olive -- were altered.

Moreover, we found widespread swim-evoked release of norepinephrine, dopamine and acetylcholine during futile swimming, which were followed by a complex sequence of lateral-to-medial astroglia activation that starts off in the lateral medulla oblongata (L-MO). Optogenetic activation of astroglia in the L-MO was found to be sufficient to suppress the visual response. Overall, this study shows how animals switch between adaptive brain states — how detection of environmental changes quickly leads to persistent and widespread activation of neuromodulatory and glia systems, which in turn, by orchestrating multiple downstream circuits, select for an appropriate behavioral response.