Inputs from Sequentially Developed Parallel Fibers Are Required for Cerebellar Organization

Abstract

Summary: Neuronal activity is believed to be important for brain development; however, it remains unclear as to how spatiotemporal distributions of synaptic excitation contribute to neural network formation. Bifurcated axons of cerebellar granule cells, parallel fibers (PFs), are made in an orderly inside-out manner during postnatal development. In this study, we induced a blockade of neurotransmitter release from specific bundles of developing PFs and tested the effects of biased PF inputs on cerebellar development. The blockade of different layers of PFs at different developmental times results in varying degrees of abnormal cerebellar development. Furthermore, cerebellar network abnormalities are not restored when PF inputs are restored in adulthood and, hence, result in motor dysfunction. We thus conclude that spatiotemporally unbiased synaptic transmission from sequentially developed PFs is crucial for cerebellar network formation and motor function, supporting the idea that unbiased excitatory synaptic transmission is crucial for network formation. : Park et al. demonstrate that interrupting synaptic transmission from a part of parallel fibers (PFs) causes abnormal cerebellar development, including Purkinje cell degeneration, reduced climbing fiber innervation, or altered interneuron positioning, which leads to motor dysfunctions. This suggests critical periods and locations of PF inputs required for cerebellar network organization. Keywords: cerebellum, granule cell, parallel fiber, Purkinje cell, motor function, postnatal development, tetanus toxin, projection-dependent labeling, climbing fiber, molecular layer interneuron