Information processing by the cerebellar cortex

Abstract

The cerebellum coordinates movement by generating the signals needed for the precise performance of motor tasks. To compose these signals, the cerebellum samples information from brain regions and sensory modalities related to the programming and execution of movement. One of two major afferent systems responsible for bringing this information into the cerebellum, mossy fibers, relays it to granule cells via excitatory synaptic connections within the cerebellar cortex. Purkinje cells integrate information relayed by granule cells, as well as inhibitory synaptic inputs from interneurons, and generate the signals necessary for motor coordination. This thesis analyzes synaptic communication between granule cells and Purkinje cells within the context of the computational circuitry of the cerebellar cortex. The first study found that Purkinje cells linearly encode the strength of granule cell synaptic input in their maximum firing rate in the presence and absence of inhibitory synaptic transmission and independently of the location or temporal pattern of granule cell input. Given that Purkinje cells are the main integrators and sole output of the cerebellar cortex, their linear algorithm has consequences for the nature of the computations performed by the cerebellum to coordinate movement. The second study found that the two types of granule cell synaptic inputs onto Purkinje cells, parallel fiber and ascending inputs, are equally as effective in driving the firing of Purkinje cells. Consistent with this observation, parallel fiber unitary excitatory synaptic current amplitudes are indistinguishable from ascending ones, and their input strengths are comparable. The next study estimated the variability of the maximum firing rate response of Purkinje cells to granule cell synaptic input and used it to show that the maximum firing rate of Purkinje cells could be used to discriminate granule cell input patterns learned via long-term depression under physiological conditions of input asynchrony and intact inhibition. Finally, the last study found that genetic alterations in Purkinje cells that cause episodic ataxia type-2 alter the intrinsic pace-making of Purkinje cells, which disrupts the ability of Purkinje cells to accurately encode the strength of granule cell synaptic input.