Current Methods for Determining the Role of Climbing Fibers in Cerebellar Function

TOPICAL COLLECTIONS

Guest Editors

Jessica Verpeut

Princeton University

As a Postdoctoral Research Assistant at the Princeton Neuroscience Institute, Dr. Jessica Verpeut studies the influence of cerebellar activity on neocortical structure and behavior in the laboratory of Professor Samuel S.-H. Wang. The cerebellum has classically been known to fine-tune movement and action, but its role in cognitive and flexible behaviors is poorly understood. In integrating neural circuit dissection with unsupervised behavior classification, Jessica aims to understand how cerebellar disruption modulates distal neocortical structure and behavior. She has developed a novel pipeline to manipulate neural signaling, quantify behavioral tracking using machine learning, and analyze neural activation by whole-brain light-sheet microscopy and tissue-clearing techniques. Describing how the cerebellum guides the maturation of the neocortex will help to further understand intricate details of animal behavior in neurodevelopmental disorders. Jessica completed her PhD at Rutgers University in Endocrinology and Animal Biosciences in 2015. In her dissertation, she described how a ketogenic diet fed during development could protect the noradrenergic system and resolve behavioral deficits in a mouse model with cerebellar dysfunction, the Engrailed-2 null mouse. In 2010, Jessica earned a Bachelor of Science in Animal Science and a Bachelor of Science in Psychology from Pennsylvania State University.

Alyssa Wilson

Princeton University

Alyssa Wilson is a Postdoctoral Fellow in Neuroscience at the Princeton Neuroscience Institute, in the lab of Sebastian Seung. Her work is focused on describing how neurons rewire during normal postnatal development and during memory consolidation in adulthood, using functional and structural correlates of synaptic plasticity. Functional information is measured through in vivo imaging of fluorescent markers of calcium transients in neurons. To gather structural information about synaptic connectivity, she has helped to develop a state-of-the-art technique known as high-throughput electron microscopy, in which a very high resolution (nanometers per pixel) 3D image volume of brain tissue is generated and membranes are stained. In this technique, every cell, its organelles, and synapses between neurons can be directly visualized. From these images, she applies machine learning to identify cells and their connections, and measures the patterns in synaptic connectivity between neurons. Alyssa earned a PhD in physics from Harvard University (2017), where she did her dissertation research in electron-microscopy-based analysis of neural circuits (published in Cell Reports, 2019). She received an MPhil in Atomic, Mesoscopic and Optical Physics from the University of Cambridge in 2010 as a Gates Cambridge Scholar. In 2009, Alyssa earned a Bachelor of Science with Honors in Physics, with a minor in Mathematics, from Drexel University.

Collection Overview

The cerebellum is growing in recognition as a brain region with unexpectedly pervasive involvement in nonmotor function. Aside from coordinating precisely timed sensorimotor activity, evidence suggests that the cerebellum is directly involved in shaping reward prediction and in cognitive function. Furthermore, many neurodevelopmental disorders are known to co-occur with cerebellar abnormalities, but this connection has only recently been explored.

Thus, a cellular-level description of how neural wiring in the cerebellum processes input signals, how this wiring develops, and how it is altered during adult learning, can generate valuable insights and potential therapies for neurodevelopmental disorders. Its stereotyped cytoarchitecture and superficial location also make the cerebellum an excellent system to study in vivo, resulting in observations that reflect actual circuit function.

Climbing fibers, central to cerebellar learning, originate from outside the cerebellum and generate large, complex bursts of activity when a cerebellar response produces an unexpected outcome. Conventional theories postulate that this activity weakens inputs responsible for extraneous responses and helps shape appropriate responses. However, recent evidence suggests that climbing fiber function may differ from this prediction.

This collection will share current approaches to exploring the functional role of cerebellar climbing fibers, with the goals of elucidating 1) behavior that initiates climbing fiber activity, 2) methods that monitor climbing fiber activity in awake, behaving animals, 3) methods that distinguish climbing fiber activity from other cerebellar components or to simultaneously measure activity from other cell types, and 4) methods that incorporate morphological information for a better quantification of the neural circuitry.