Figure 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 (F_o) 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). Scalebar, 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.