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.