Description:

The department of Physiology welcomes Mark J. Wagner, Ph.D., with Stanford University.

Abstract

In striking contrast to the rest of the brain, evolutionary expansion of the cerebellum has kept pace with that of neocortex, and these two structures contain ~99% of all neurons in humans. The entire neocortex and the cerebellum are also reciprocally connected by some of the densest long-range projections in the brain that are universal across mammals. While highly diverse neocortical areas contribute to this circuit, the downstream cerebellar circuitry is highly stereotyped. This strongly hints at a general and conserved algorithm at the heart of cortico-cerebellar circuitry. My work aims to understand these basic computations by observing and manipulating cortico-cerebellar circuit interactions while animals acquire novel skills, via multi-site two-photon calcium imaging, optogenetics, and viral-genetic anatomical tools. By developing two-photon calcium imaging in cerebellar granule cells, I unexpectedly found reward-related neural activity demonstrating prominent cognitive input to these cells likely from neocortex. More recently, I devised a preparation for simultaneous two photon calcium imaging of neocortical output neurons and downstream cerebellar granule cells during weeks-long learning processes, revealing their learned codependent activity patterns. My ongoing studies of cortex-cerebellum transmission employ several interconnected approaches: characterizing broader neural circuit interactions; probing plasticity rules during learning; and generating synaptic connectivity maps to integrate into circuit physiology models.