Anatomical and functional dissection of cerebellar vermis - fastigial nucleus module in delay eyeblink conditioning

Samenvatting

B.1.2 Abstract
Understanding how brain receives sensory inputs and produces proper motor outputs is a crowning question in neuroscience. Cerebellum is essential for various associative sensorimotor learning tasks, especially when it is concerning timing1-4. To this end, cracking the detailed cerebellar circuits and their computation is an unique entry for achieving the mechanistic understanding of sensorimotor learning. Delay eyeblink conditioning (DEC) is an ideal model for studying this issue in cerebellum5-10. Cerebellar simplex lobule and its connected downstream Anterior Interposed Nucleus (InP) play a critical role in the acquisition and expression of conditioned eyeblink resposes11-16. It is unclear however, whether other parts of the cerebellar circuits are also involved in this task. My recent study and pilot data showed that the conditioned eyeblink response was suppressed when the fastigial nucleus (FN) or its connected cerebellar cortex were inhibited17,18. Based on this new finding, I hypothesize that the acquisition and expression of DEC also critically rely on a previously undescribed vermis-FN module. For this project, I will test this hypothesis by examining the organization and functional involvements of vermis-FN module in DEC. Using anatomical, electrophysiological and behavioral approaches, I plan to first identify the detailed cerebellar vermis-FN circuits and their relevant inputs in DEC (Key objective 1). Next I will study the electrophysiological responses of cerebellar neurons in vermis-FN circuits and the effects of targeted manipulation of these neurons on the acquisition and expression of conditioned eyeblink response (Key objective 2). And last I will explore the interaction between FN and its projections in other brain areas and demonstrate the functional impacts of targeted manipulation of these areas on DEC (Key objective 3). These results will reveal a novel cerebellar pathway that mediates a classic associative learning task, thus greatly advance the current conceptual framework of sensorimotor learning in the cerebellum.

B.1.3 Summary
Understanding how brains receive sensory inputs and produce proper motor outputs is a crowning question in neuroscience. Cerebellum, the small brain, has been considered essential for various associative sensorimotor learning tasks1-4. The detailed neuronal circuits and computational mechanisms cerebellum uses for acquiring and maintaining learned behavior are not fully understood. In this proposal we will use Pavlovian eyeblink conditioning, an ideal model behavioral paradigm to study the cerebellar mechanism in sensorimotor learning in mice. Previous studies have unequivocally illustrated the importance of one part of the cerebellum in eyeblink conditioning; it is currently unclear whether other parts are also involved in this task. Based on our pilot data, we hypothesize that eyeblink conditioning is critically rely on a previously overlooked cerebellar module. For this project I aim to test this hypothesis by examining the organization and functional involvements of this module in eyeblink conditioning. Using anatomical, electrophysiological and behavioral approaches, I plan to localize the detailed anatomical organization and the input regions of this module (Key objective 1). Next I will study the activity pattern of this module and the effects of targeted manipulation of this module in eyeblink conditioning (Key objective 2). Last I will examine the interaction of this module with the downstream brain areas during eyeblink conditioning (Key objective 3). Once accomplished, these results shall reveal a novel cerebellar pathway that mediate the learning and expression of a well described cerebellar learning task, thus potentially update the conceptual framework of the sensorimotor learning in the cerebellum.

Kenmerken

Projectnummer

OCENW.KLEIN.007

Hoofdaanvrager

Dr. Z. Gao

Verbonden aan

Erasmus Universiteit Rotterdam, Erasmus MC, Neurowetenschappen

Looptijd

01/05/2019 tot 30/04/2023