Fig. 3. Selective deletion of Tropomyosin Receptor Kinase B (TrkB) in CST-expressing cells results in motor impairments, hyperactivity, seizures and death.

(A) Representative photo of hindlimb clasping in CST^cre/TrkB^flox/flox mice, in which limbs retract inwards towards the midline. (B) CST^cre/TrkB^flox/flox mice develop hindlimb clasping behavior, which is not observed in Ctrl mice (n=6 Ctrl, n=7 CST^cre/TrkB^flox/flox; 2-way RM ANOVA, genotype effect, p<0.0001 and genotype-time interaction, p<0.001. Post-hoc tests revealed genotype-dependent differences from P19 to P23, P19-p<0.05, P20–23- p<0.0001). (C-E) CST^cre/TrkB^flox/flox mice exhibit hyperactivity in the homecage. Data is displayed as total seconds engaging in the behavior in a 24 hr period (n=4/group). (C) CST^cre/TrkB^flox/flox mice spend more time walking than Ctrl mice (t-test, p=0.0038). (D) CST^cre/TrkB^flox/flox mice sleep less than Ctrl mice (t-test, p=0.0008). (E) Increased repetitive jumping activity in CST^cre/TrkB^flox/flox mice (t-test, p=0.0428). (F) Racine scores of seizures observed in CST^cre/TrkB^flox/flox. Seizure onset occurred at P21, and progressed in severity until death. No seizures were observed in Ctrl mice (n=19/group). (G) Survival data for CST^cre/TrkB^flox/flox. 50% of mutants die by P32, and the majority die by 5–6 weeks postnatal (n=15 Ctrl, n=8 CST^cre/TrkB^flox/flox)(Mantel-Cox log-rank test, p=0.0173). Data are represented as mean ± SEM (*p<0.05, **p<0.01, ***p<0.001, **** p<0.0001).