Neocortex-cerebellum Circuitry Unit

National Institute Of Neurological Disorders And Stroke

Investigators

Linked publications, trials & patents

Abstract

This is the first year of operation of our lab. A substantial fraction of this period was spent on initial lab setup: acquiring equipment; building custom microscopy and behavioral apparatus; recruiting trainees; and rederiving and establishing multi-transgene mouse lines. Despite numerous supply chain issues, we succeeded in building the first dual site two photon microscope, providing four laser paths with independent high speed power control, two independent resonant galvo scan paths, and a photostimulation pathway. We have nearly all components for the labs second custom two photon microscope, except one critical component deeply impacted by supply chain issues. We have also built several robotic manipulanda for behavioral studies. Despite delays caused by errors at the vendor contracted to carry out the rederivation procedures, we recently finished rederiving our triple and quadruple transgenic lines. We also recruited several trainees, including one MRS student that started in October and recently returned to medical school; three postbac IRTAs that began in the late winter; one student IRTA that began late winter; and one visiting fellow postdoctoral researcher that began several months ago. Our research projects in the present year test theories posited based on our prior work. Specifically, we previously developed the first recordings in behaving animals from granule cells cerebellar input cells that make up more than half of all mammalian neuronsusing two photon imaging in awake behaving transgenic mice. By combining this with our forelimb manipulandum task, we demonstrated distributed cerebellar signaling of learned reward expectations. We then developed the first chronic simultaneous cortex-cerebellum dual-site two photon imaging, which revealed that cerebellar representations co-emerged with those in the neocortex through recurrent neural dialogs during learning. Learned predictive signaling of this behavior also shaped cerebellar climbing fiber dynamics in our two photon mesoscope recordings. By demonstrating nonclassical signaling in key pathways for cerebellar learning, this raised fundamental questions about the relationship between activity in these pathways, which is central to theories of cerebellar plasticity that rely on such temporal relationships. This year we have pursued several research projects testing theories inspired by the above findings. We are nearing completion of a study of the interaction dynamics of the two cerebellar input pathways, climbing fibers and granule cells. The project aims to determine how activity relationships between these two pathways correspond to behavioral performance, and how those relationships evolve over days of novel learning. This allows us to test fundamental principles of cerebellar plasticity, learning, and computation. In addition, we have been pursuing research into the relationship of cerebellar reward anticipation signaling to broader brain reward dopaminergic signaling. This work will more definitively link cerebellar reward signals to classical brain reward processing frameworks. Finally, we have initiated optical building and design for multisite two photon imaging and optogenetics to chronically probe causal interactions between cortico-cerebellar networks.