The mouse cerebellum from 1 to 34 months: parallel fibers.

Synaptic losses are critical events in the aging brain. In the cerebellum, synapses between the parallel fibers and Purkinje cells are strategic elements of its neuronal circuitry. We have examined the number of synaptic varicosities per parallel fiber in the anterior lobe of the cerebellum in young (1, 2.5 and 5 months), mature (10 and 18 months), and old (26 and 34 months) C57BL/6 mice. This number peaks at 2.5 months and starts to decrease immediately. This decrease is due to a reduction of the linear density of synaptic varicosities along the parallel fibers and a shortening of the parallel fibers. The fastest and most dramatic decline occurs during young adulthood between 2.5 and 5 months when 59% of the synaptic varicosities are lost. Accelerated loss also occurs in old age between 26 and 34 months. Changes between 5 and 26 months are the slowest. Between 2.5 and 34 months, mice lose 87% of their parallel fiber synaptic varicosities. Unlike many post-reproductive processes of aging, the early-onset decline beginning at 2.5 months may be under strong natural selection pressure.