Roles of Molecular Layer Interneurons in Shaping Purkinje Cell Output

Abstract

The cerebellum is an ideal structure to understand how nervous systems process information. Sensory and cortical information to the cerebellum come through mossy fibers and are relayed through granule cells. Granule cells form direct excitatory inputs onto Purkinje cells and also activate molecular layer interneurons, which provide inhibitory inputs onto Purkinje cells. In this thesis, the roles of molecular layer interneurons in shaping the output of Purkinje cells are delineated.;Using an in vitro slice preparation, it is demonstrated that decreases from the baseline firing rate of Purkinje cells, as mediated through disynaptic inhibition, are a linear function of the strength of granule cell activation. Furthermore, it is proposed and demonstrated that a common granule cell input can generate reciprocal firing rates in two populations of Purkinje cells. The mathematical relationship by which excitation and inhibition combine in Purkinje cells is also determined. Evoked decreases in firing rate subtract from evoked increases in firing rate demonstrating that Purkinje cells sum the activity of their excitatory and inhibitory inputs. Furthermore, it is proposed and demonstrated that when summation occurs between two inputs whose activity is proportional, the resulting output of Purkinje cells changes in gain with respect to the output when only one input is active. The short-term synaptic plasticity of the interneuron to Purkinje cell synapse is also examined. From experiments and simulations, it is found that short-term plasticity at the interneuron-Purkinje cell synapse supports a linear relationship between interneuron activity and the resulting GABA conductance of Purkinje cells. This linear input-output relationship is due to the depression of the phasic amplitudes of the IPSCs being counterbalanced by the slowing of the decay kinetics of each IPSC.;Combined with previous experimental results, the findings of this thesis can explain how the observed signals of Purkinje cell in vivo are generated. Furthermore, the results of this thesis can be generalized to principle neurons of other nervous systems, which exhibit similar signaling properties of Purkinje cells.