Seminar "Cerebellum - beyond the motor efference copy" by Dr. Aleksandra Budra

Date: Thursday, February 28th

Time: 10:00 – 11:00

Venue: D015, Lab1

Speaker: Dr. Aleksandra Budra

Title: Cerebellum - beyond the motor efference copy

Abstract: The cerebellum is often viewed as serving motor functions, but clinical and anatomical evidence support a broader role in cognition. Here we present a map of the posterior cerebellum's adult and developmental influence over flexible and social behavior. Using chemogenetic perturbation in mice, we found that reversal learning required lobule VI in adulthood, and multiple lobules during development. Moreover, social preference in adulthood required normal activity from crus I during development. Principal component analysis identified eigenbehaviors relating to movement and nonmotor behavioral traits, and differential roles for lobules in regulating them. Contributions to behavioral phenotypes increased with the amount of each lobule inactivated. Using an anterograde transsynaptic viral tracer, HSV-H129, we found paths from posterior cerebellum to prelimbic, orbitofrontal, and anterior cingulate cortex, providing a route for the cerebellum to influence higher function. Our results are consistent with the hypothesis that the cerebellum actively contributes to executive functions. Furthermore, these experiments provide direct evidence for the idea that the cerebellum acts during sensitive periods to shape the developing brain.

Bio:Throughout my Ph.D. studies and Postdoctoral Fellowships my work had focused on unraveling the function of the cerebellum in health and disease, encompassing two research lines: Line-1 integrated experimental techniques with modeling to investigate the mechanisms of cerebellar learning. I have established that the modulation of cerebellar activity is essential for motor learning and helped to develop a computer model that reproduces experimental data and can predict motor impairments based on neural activity. Using intravital two-photon imaging, we discovered that granule cells acquire signals predictive of motor performance . This marked a paradigm shift in the understanding of cerebellar coding. We are working on incorporating those findings into our model. Furthermore, I have developed tools for monitoring neuronal activity that advance two-photon imaging. In Line-2, I investigated the role of the cerebellum in autism spectrum disorder (ASD). We showed that cerebellar deficits are common in ASD. Recently, by disrupting cerebellar activity during different stages of development, we established a critical period during which specific cerebellar regions are crucial for non-motor behaviors. This work has been made possible by the VENI-ZonMw grant. In June 2018 I was awarded a VIDI-ZonMw grant to work on understanding the cerebello-cerebral networks underlying shared autistic traits.