The role of the cerebello-parietal pathway in state estimation

• Applicant: Professor Dr. Cornelius Schwarz
• Subject Area: Cognitive, Systems and Behavioural Neurobiology
• Term: since 2021
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 464398405

In the ongoing funding period we have delineated the effect of two different predictive systems in the mouse primary somatosensory cortex (S1, whisker representation) - state estimation and sensory gating (SE and SG). To do this we have established a novel experimental paradigm, anatomically opening the sensorimotor loop in a whisker-reach task. We consider this a major advance in the understanding of predictive systems, as both systems similarly attenuate the tactile sensory signal flow, but likely originate from quite different yet overlapping neuronal circuits in the mammalian brain. SE and SG had been notoriously confounded in the literature, and more often than not, the effects of one was discussed in the framework of the other. Our ongoing work applying optogenetic causal interference point to the cerebellum (CB) playing a causal role in generating SE. It likely implements the internal model providing predictive signals. In an attempt to localize the neuronal structures where these predictive signals are compared to sensory feedback, the renewal project will systematically study the presence or emergence of SE along diverse cerebello-parietal pathways. In the ongoing period we have conducted essential prerequisite experiments, mapping out the complexities of these pathways with the help of combined sensory stimulation and optogenetic tagging, in order to find the most promising sites to record and locate SE-like attenuation. Currently we devise the following five candidate regions: the deep cerebellar nuclei (DCN), trigeminal principal nucleus, VPM thalamus (two stations on the lemniscal tactile pathway), trigeminal spinal interposed nucleus and POm thalamus (two stations on the paralemniscal tactile pathway). We found that the thalamic nuclei VPM and POm are large and complex structures, which only show the sought convergence in restricted sub-spaces. VL thalamus, the main recipient of cerebellothalamic fibers, was tested as well, but has not been found to receive whisker tactile signals. We will employ the experimental paradigm established in the first period and apply it to study the five mentioned candidate sites. We are confident that the planned work will lead to the first comprehensive description of the distributed pathways and neuronal mechanisms of SE, on the single neuron level in a mammalian brain.

• DFG Programme: Research Grants