Age-associated synapse elimination in mouse parasympathetic ganglia.

Little is known about the effects of aging on synapses in the mammalian nervous system. We examined the innervation of individual mouse submandibular ganglion (SMG) neurons for evidence of age-related changes in synapse efficacy and number. For approximately 85% of adult life expectancy (30 months) the efficacy of synaptic transmission, as determined by excitatory postsynaptic potential (EPSP) amplitudes, remains constant. Similarly, the number of synapses contacting individual SMG neurons is also unchanged. After 30 months of age, however, some neurons (23%) dramatically lose synaptic input exhibiting both smaller EPSP amplitude and fewer synaptic boutons. Attenuation of both the amplitude and frequency of miniature EPSPs was also observed in neurons from aged animals. Electron micrographs revealed that, although there were many vesicle-laden preganglionic axonal processes in the vicinity of the postsynaptic membrane, the number of synaptic contacts was significantly lower in old animals. These results demonstrate primary, age-associated synapse elimination with functional consequences that cannot be explained by pre- or postsynaptic cell death.