Loss of Piccolo Function in Rats Induces Cerebellar Network Dysfunction and Pontocerebellar Hypoplasia Type 3-like Phenotypes

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Figure 9.
Figure 9.

Behavioral outcome of Piccolo LOF resembles PCH3 symptoms. A, Rotarod performance for Pclowt/wt, Pclowt/gt, and Pclogt/gt rats for 16 trials over 4 d. Pclogt/gt rats fell significantly faster than Pclow/w on Trials 6 and 8 and faster than both Pclowt/wt and Pclowt/gt on Trials 9–16. B, Grip strength task for Pclowt/wt, Pclowt/gt, and Pclogt/gt rats for 9 trials over 2 d. No differences were found for forelimb grip strength between the groups. C, Ladder walk task for Pclowt/wt, 859 Pclowt/gt, and Pclogt/gt rats for 3 trials over 1 d. Pclogt/gt rats had a higher rate of stepping errors (ladder rung foot slips/misses) than Pclowt/wt and Pclowt/gt rats. D, Open field task for Pclowt/wt, Pclowt/gt, and Pclogt/gt rats for 1 trial each over 1 d. Pclogt/gt rats performed fewer rearing behaviors than Pclowt/wt and significantly less than Pclowt/gt rats in the perimeter sectors of the arena. Other behaviors, such as crossing the open field and grooming, were not different between the three groups. Animals used in the above experiments are as follows: wt21-wt24; he1-he4; ko20-ko23. E, Locomotor activity of Pclowt/wt, Pclowt/gt, and Pclogt/gt rats during the 12 h dark phase. Pclogt/gt rats covered a >50% longer distance than Pclowt/wt and Pclowt/gt rats. Data points are individual means over 15 nights. F, Performance of Pclowt/wt, Pclowt/gt, and Pclogt/gt rats during the isometric pull-task (handle position 11 mm inside the cage). Only 4 of 11 Pclogt/gt rats succeeded at the 60 g force threshold, and Pclogt/gt rats pulled with a significantly lower success rate at all force thresholds compared with Pclowt/wt and Pclowt/gt. Error bars indicate SEM. Data points represent individual rats. For statistical analysis, see Table 1. Animals used in the above experiments are as follows: wt25-wt34; he5-he8; ko24-ko35. *, **, ***, **** describe significance between Pclowt/wt and Pclogt/gt and #, ##, ### describe significance between Pclowt/wt and Pclogt/gt.

  1. The Journal of Neuroscience vol. 40 no. 14 2943-2959
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