Fig. 5

SF Neurons Are Hyperexcited by Weak Acoustic Stimuli in cyfip2 Mutants and Reversal of the Hypersensitivity Phenotype

(A) Representative SF neuron Ca²⁺ responses in cyfip2 siblings and mutants 1 s before (F₀) and 150 ms after (peak) medium-intensity (−12 dB) acoustic stimulation. Dashed circles indicate SF cell bodies, arrowheads mark cells that fired according to our criteria (see text). Scale bar, 10 μm.

(B) Distribution of SF neuron firing probability (n = 48 cells from 8 siblings, 36 cells from 6 mutants; ^∗∗∗∗p < 0.0001, Mann-Whitney test).

(C) Startle sensitivity index of cyfip2^p400 siblings and mutants expressing Tg(hsp70:cyfip2-GFP) 4 dpf before 8 heat shock cycles at 37°C separated by 120 min (d4 pre; ^∗p = 0.025, unpaired t test). The same larvae were tested for startle sensitivity after heat shock at 6 dpf (d6 post; ^∗∗p = 0.0018, paired t test). cyfip2^p400 mutants without the hsp70:cyfip2-GFP transgene remained hypersensitive (p = 0.46, paired t test).

(D) Model of Cyfip2’s role in the startle circuit. In cyfip2 mutants, activity is enhanced in the VIII-SF-M-cell pathway, either through a direct VIII-SF connection or through an indirect connection via an unknown cell population (question mark), leading to enhanced M-cell firing and startle behavior. In wild-type fish, Cyfip2 potentially acts at pre- and/or postsynaptic sites, indicated by asterisks, to dampen neural activity.