Processing of mossy fiber activity in the cerebellar cortex: A combination of computer modeling and electrophysiological experiments.

摘要

A combination of computer modeling and experimental approaches were taken to study tactile sensory processing in the cerebellar cortex. First, a detailed computer simulation of the cerebellar cortex was built. This model included the physiological properties of the different cells involved and their synaptic distributions. The model was used to study how a single tactile stimulus, arriving in the granule cell layer, is translated into Purkinje cell activity, the output of the cerebellar cortex. The model was also used to study the lack of beam-like Purkinje cell activation after a focal stimulation of the granule cell layer in opposition to the most accepted theory of cerebellar cortical function: The beam hypothesis. The model predicts that the fast coupling between the axons of granule cells with a small number of inhibitory cells generates a compensatory driving force on the Purkinje cell's dendritic tree that cancels the beam activation. The main prediction of the model is that when suppressing the inhibitory influence on Purkinje cells a beam would be observed.; Second, simultaneous recordings of Purkinje cells sharing the same granule cell input were collected while the receptive field of one of them was stimulated. The cortex was bathed with bicuculline to block inhibitory input to Purkinje cells and the stimulation repeated. In the control case, only one of the Purkinje cells responded to the stimulus; the others showed inhibition or did not respond at all. After bicuculline application, beams of Purkinje cell activity were observed, thus confirming our simulation predictions.; Third, using a detailed Purkinje cell model the effects of different levels of granule cell and molecular interneuron input on the output of this cell were explored. The results suggest that the granule cell input is divided in two functional synaptic systems. The first one drives the Purkinje cell to fire and comes from the ascending segment part of the granule cell axon. The second one, combined with molecular interneuron activity, modulates the response of the Purkinje cell to ascending segment input.; Based on the computational and experimental results of this work, we propose that parallel fibers and molecular interneurons have a modulatory effect on the response of the Purkinje cell to the more direct and strong ascending segment input.