Axonal varicosity distributions along parallel fibers: a new angle on a cerebellar circuit

Presynaptic terminals occur along unmyelinated axons in specialized compartments called axonal varicosities or synaptic boutons. Since the first descriptions of varicose axons by Cajal and others, the spatial organization of varicosities along axons has attracted the attention of neuroscientists. Quantitative light- and electron-microscopic analyses of varicosity spacing in the cerebellum and elsewhere have recently provided a clearer picture of this organization, and theoretical analyses now incorporate varicosity spacing as an essential parameter in structural models of neural connectivity. Here we review the salient features of varicosity spacing, with emphasis on cerebellar parallel fibers as a model system. Measured globally across the entire approximately 5 mm lengths of parallel fibers, the overall mean spacing of varicosities is 5.2 microm. Measured locally, however, mean spacing follows a proximodistal gradient, increasing with distance from the point of bifurcation from the ascending axon. Measured at the level of individual varicosities, parallel fiber varicosity distributions follow a distinct pattern characterized by a fixed relationship between the spacing variability and mean. This pattern equally describes varicosity distributions in a number of other brain regions, and therefore appears to constitute a general scaling relationship for excitatory varicose axons. We further discuss evidence for common principles underlying the placement of both varicosities and synapses along axons.