Highlights d High-throughput behavioral analysis of dark-flash habituation in larval zebrafish d Multiple components of the response adapt with different habituation kinetics d Controlled by multiple circuit loci with different molecular requirements d Modular habituation selectively tunes behavioral components based on context

Animals continuously integrate sensory information and select contextually appropriate responses. Here, we show that zebrafish larvae select a behavioral response to acoustic stimuli from a pre-existing choice repertoire in a context-dependent manner. We demonstrate that this sensorimotor choice is modulated by stimulus quality and history, as well as by neuromodulatory systems-all hallmarks of more complex decision making. Moreover, from a genetic screen coupled with whole-genome sequencing, we identified eight mutants with deficits in this sensorimotor choice, including mutants of the vertebrate-specific G-protein-coupled extracellular calcium-sensing receptor (CaSR), whose function in the nervous system is not well understood. We demonstrate that CaSR promotes sensorimotor decision making acutely through Gα and Gα signaling, modulated by clathrin-mediated endocytosis. Combined, our results identify the first set of genes critical for behavioral choice modulation in a vertebrate and reveal an unexpected critical role for CaSR in sensorimotor decision making.

Color losses of central origin (cerebral achromatopsia and dyschromatopsia) can result from cortical damage and are most commonly associated with stroke. Such cases have the potential to provide useful information regarding the loci of the generation of the percept of color. One available tool to examine this issue is the chromatic visual evoked potential (cVEP). The cVEP has been used successfully to objectively quantify losses in color vision capacity in both congenital and acquired deficiencies of retinal origin but has not yet been applied to cases of color losses of cortical origin. In addition, it is not known with certainty which cortical sites are responsible for the generation of the cVEP waveform components. Here we report psychophysical and electrophysiological examination of a patient with color deficits resulting from a bilateral cerebral infarct in the ventral occipitotemporal region. Although this patient demonstrated pronounced color losses of a general nature, the waveform of the cVEP remains unaffected. Contrast response functions of the cVEP are also normal for this patient. The results suggest that the percept of color arises after the origin of the cVEP and that normal activity in those areas that give rise to the characteristic negative wave of the cVEP are not sufficient to provide for the normal sensation of color.

Habituation is a simple form of learning, where animals learn to reduce their responses to repeated innocuous stimuli. While habituation is simple in concept, its exact implementation in the vertebrate brain is not clear. It could occur via a single plasticity event at a singular site in the circuit, or alternatively via more complex strategies that combine multiple mechanisms at various processing stages and sites. Here, we use a visual habituation assay in larval zebrafish, where larvae habituate to sudden reductions in illumination (dark flashes). We find that 8 different components of this response habituate, including the probability of executing a response, its latency, and measures of its magnitude. Through behavioural analyses, we find that habituation of these different behavioural components occurs independently of each other and at different locations in the circuit. Further, we use genetic and pharmacological manipulations to show that habituation of different behavioural components are molecularly distinct. These results are consistent with a model by which visual habituation originates from the combination of multiple independent processes, which each act to adapt specific components of behaviour. This may allow animals to more specifically habituate behaviour based on stimulus context or internal state.

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