Die Rolle der cerebelloparietalen Projektion für die Bestimmung des kinematischen Zustands des Körpers

01/06/2021 to 31/05/2024

A dominant theory in the field of sensorimotor integration is that the sensory signal flow is
integrated with internal predictions about sensory consequences of ongoing movements and
other contextual parameters. Such predictions are thought to be generated by an internal model
based on an efference copy and other contextual signals. The site of the internal model is
assumed to be the cerebellum. The optimal integration of predictive signals with sensory feedback
to yield the sensory prediction error has been called state estimation. Although state estimation
is a classical concept, its site of computation is not known. One problem has been the anatomical
complexities of cerebellar output pathways. Another one is that state estimation may not be
unique to cerebellar circuits. For instance, mammalian neocortex is almost certain to provide
predicative signals as well. Such non-cerebellar predictive signals may realize different types of
behavioral control, perhaps playing out on different time scales and/or related to different learning
systems. Little is known about the interplay of different types of predictive signals.
In this project, we will focus on cerebellar state estimation, which is most directly related to
movement generation. The outputs of the cerebellum massively reach the sensorimotor cortex
and we will systematically disentangle cerebellar predictive signals from assumed neocortical
ones. We will track prediction signals on the complex cerebello-parietal pathway using multineuron extracellular electrophysiology, identify their cerebellar origin using causal, optogenetic
analysis, and study their interplay with known parietal predictive signals of presumed cortical
provenience. We established a novel behavioral tool to realize such analysis in extensive
preliminary work. It translates a classic approach, the opening of the reafferent loop pioneered by
Curtis Bell working in weakly electric fish in the 1980ies, to the use in behaviorally trained mice
that perform defined whisker movements. This analysis will allow us to disentangle sensory
prediction, and state estimation signals and localize them within the branched output stream of
signals originating in the cerebellum and projecting to the neocortex. Starting from the cerebellar
output we will parse the signals in motor thalamus, sensorimotor higher order thalamus and tactile
thalamus. Finally, we will monitor signals in primary/secondary somatosensory cortex and
neighboring posterior parietal area.