In Vivo Ca2+ Imaging Reveals that Decreased Dendritic Excitability Drives Startle Habituation

Exposure to repetitive startling stimuli induces habitation, a simple form of learning. Despite its simplicity, the precise cellular mechanisms by which repeated stimulation converts a robust behavioral response to behavioral indifference are unclear. Here, we use head-restrained zebrafish larvae to monitor subcellular Ca2+ dynamics in Mauthner neurons, the startle command neurons, during startle habituation in vivo. Using the Ca2+ reporter GCaMP6s, we find that the amplitude of Ca2+ signals in the lateral dendrite of the Mauthner neuron determines startle probability and that depression of this dendritic activity rather than downstream inhibition mediates glycine and N-methyl-D-aspartate (NMDA)-receptor-dependent short-term habituation. Combined, our results suggest a model for habituation learning in which increased inhibitory drive from feedforward inhibitory neurons combined with decreased excitatory input from auditory afferents decreases dendritic and Mauthner neuron excitability. [Display omitted] •GCaMP6s enables analysis of subcellular neuronal activity during startle behavior•Startle regulation occurs both up- and downstream of the Mauthner cell•Downstream inhibition does not play a role in short-term habituation•Short-term habituation is due to depression of Mauthner cell dendritic excitability The neuronal mechanisms that govern short-term habituation of the startle response are unclear. Using GCaMP6s to visualize subcellular activity in the zebrafish startle command neuron, the Mauthner cell, Marsden and Granato show that depression of dendritic excitability rather than downstream inhibition underlies short-term habituation.