Continuous, modulated cerebellar output is required for ongoing movements, and the suppression of cerebellar output, either via lesions or inactivation, impedes even well practiced movements. However, whether changes in cerebellar output can directly drive the transition into a unique motor state has not been explored. Freezing, as occurs during both innate and conditioned defense behaviors, is a motor state involving the suppression of voluntary movement while maintaining and elevated arousal state and muscle tone. Such freezing responses require activation of the ventro-lateral periaqueductal gray, which, receives input from the fastigial cerebellar nucleus. In fact, previous work indicates that lesion of the cerebellar vermis impairs innate freezing behaviors, suggesting that cerebellar output might modulate freezing behaviors mediated by the periaqueductal gray. Despite these findings, the role of the fastigial nucleus in modulating the firing rate of neurons in the ventro- lateral periaqueductal gray has not been explicitly tested. Here, I will test the hypothesis that (1) activity in the fastigial cerebellar nucleus modulates firing in the PAG and regulates innate freezing and (2) that sex differences in the synaptic and intrinsic properties within the fastigial cerebellar nucleus contribute to differences in innate freezing. To do this, I propose to use a combination of in vitro and in vivo electrophysiology in both the fastigial cerebellar nucleus and the ventro-lateral periaqueductal gray to explicitly examine how the spontaneous and synaptically evoked activity in the fastigial cerebellar nucleus modulates spiking patterns in the ventro-lateral periaqueductal gray. Then, using in vivo recordings and directly manipulating fastigial neuron activity using optogenetics, I will examine whether activation or suppression of cerebellar activity is sufficient to drive freezing behaviors. Together, these experiments will directly test whether synaptically evoked changes in cerebellar output can drive freezing, and provide experimental insight into how cerebellar output is integrated in downstream nuclei to drive behavior.

Public Health Relevance

The cerebellum is a brain region necessary for the coordination of movement. Animals, including humans can fully stop moving or ?freeze? to protect themselves. We will test whether it also controls freezing: a complete lack of voluntary movement.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32NS106720-02
Application #
9673620
Study Section
Special Emphasis Panel (ZNS1)
Program Officer
Chen, Daofen
Project Start
2018-04-01
Project End
2021-03-31
Budget Start
2019-04-01
Budget End
2020-03-31
Support Year
2
Fiscal Year
2019
Total Cost
Indirect Cost
Name
Northwestern University at Chicago
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
160079455
City
Chicago
State
IL
Country
United States
Zip Code
60611