C55: Mice Behavior: Altering Purkinje Neurons Within the Cerebellum

Intracellular fibroblast growth factor 12 (Fgf12) is expressed throughout the central nervous system and is known to bind and regulate voltage-gated sodium channels. Sodium channels are critical for the formation and propagation of neuronal action potentials. Fgf12 has also been identified as a locus of mutations underlying epileptic encephalopathy (EIEE) and sudden unexpected death in epilepsy (SUDEP). Previous studies indicate that Fgf12 plays an important role in maintaining the appropriate firing patterns of neurons in the cerebellum. This leads us to hypothesize that the targeted deletion of Fgf12 in mice will cause deficits in behaviors associated with cerebellar function. To examine and test this hypothesis, we utilized two methods for examining two types of cerebellum-related behaviors, that is, motor coordination and social interactions. Our initial set of experiments explored how these behaviors were affected by the targeted deletion of one Fgf12 allele (Fgf12 +/-). Balance and motor coordination were assessed using an elevated balance beam assay and sociability/social novelty was examined using a three-chamber assay. We tested adult (> 6 weeks) wild type and Fgf12 +/- mice and compared their performance on these behavioral tests directly. These experiments indicate there are no significant differences, suggesting a single Fgf12 allele may be sufficient to prevent serious behavioral problems. However, we noted that Fgf12 +/- animals had much more variability in their performance on the elevated balance beam assay than wild type mice. In future studies, we will determine how targeted deletion of both Fgf12 alleles (Fgf12 -/-) affects these behaviors in mice. This work has allowed us to learn about the functioning of the nervous system and its relation to behavioral phenotypes. The three authors of this study hope to pursue careers in medicine, possibly working with individuals suffering from nervous system disorders. Acquiring an in-depth exposure and participating in studies relevant to neurological disease has been a terrific experience.

Authors: Brittany Walterbusch, Biology Major; Ellie Osterholt, Psychology Major, Nick Lipovsek, Biology Major

Advisor: Joey Ransdell, Biology department

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