Cause and Consequence of Purkinje Cell Signals in the Cerebellar Flocculus

Abstract

How environmental stimuli are processed by neural circuits and how neural circuits control behavior are fundamental questions in systems neuroscience, describing both ends of its research spectrum. At one end, neural structures can be identified that are dedicated to the processing of information from our sensory organs. At the other end, specific parts of our brain are directly involved in the control of our musculoskeletal system, generating the movements of our body. The cerebellum is a neural structure that is functionally situated right in the middle between sensory input and motor output. It receives sensory as well as motor-related input from various afferent sources and its output can influence motor execution, but also sensory perception. Hence, to describe cerebellar activity, the label “sensory” or “motor” is often too narrow or dependent on the interpretation of the experimental data. Furthermore, sensory and motor signals are sometimes difficult to tell apart. For instance, looking out of the window of a moving car creates a powerful visual sensation of movement. The moving image of the world, or optic flow, is detected by motion sensitive cells in the retina and used by the brain to generate eye movements in the direction of the detected movement. These compensatory eye movements restore a stable image on the retina. To find out whether the neural activity of a certain part of the cerebellum has anything to do with this tracking eye movement, we could examine if eye movements with different velocities and directions coincide with comparable changes in neural activity. Using optic flow of various velocities and directions as a visual stimulus will produces a nice set of eye movement responses, but it also raises the problem of correlation between the visual stimulus and the eye movement. Each change of visual stimulus induces retinal slip (sensory), which consequently results in a compensatory eye movement response (motor) proportional in magnitude and direction to the visual stimulus. In turn, the eye movement response has an immediate effect on the magnitude of the retinal slip itself. Neural signals that show a correlation with retinal slip will therefore also show tight correlation with the measured eye movement. The challenge is then to find out which of the two signals is cause or consequence of the recorded neural activity. Central to this thesis are the signals present in the train of action potentials generated by Purkinje cells in the cerebellar flocculus. Experiments are described that make use of electrophysiological recordings of the two distinct types of action potentials generated by Purkinje cells: complex spikes and simple spikes. The flocculus is part of the neural circuit involved in the generation of gaze stabilization reflexes; eye movements that are made to stabilize the image of the environment on the retina (Baarsma and Collewijn, 1974). Purkinje cell activity is related to eye movement behavior, visual input and vestibular input. The experiments described in this thesis are designed to disentangle the signals encoded by the complex and simple spikes of the floccular Purkinje cells.