Evidence for loss of synaptic AMPA receptors in anterior piriform cortex of aged mice.

It has been suggested that age-related impairments in learning and memory may be due to age-related deficits in long-term potentiation of glutamatergic synaptic transmission. For example, olfactory discrimination learning is significantly affected by aging in mice and this may be due, in part, to diminished synaptic plasticity in piriform cortex. In the present study, we tested for alterations in electrophysiological properties and synaptic transmission in this simple cortical network. Whole-cell recordings were made from principal neurons in slices of anterior piriform cortex from young (3-6 months old) and old (24-28 months) C57Bl/6 mice. Miniature excitatory postsynaptic currents (mEPSCs) mediated by AMPA receptors were collected from cells in presence of tetrodotoxin (TTX) and held at -80 mV in voltage-clamp. Amplitudes of mEPSCs were significantly reduced in aged mice, suggesting that synaptic AMPA receptor expression is decreased during aging. In a second set of experiments, spontaneous excitatory postsynaptic currents (s/mEPSCs) were recorded in slices from different cohorts of young and old mice, in the absence of TTX. These currents resembled mEPSCs and were similarly reduced in amplitude in old mice. The results represent the first electrophysiological evidence for age-related declines in glutamatergic synaptic function in the mammalian olfactory system.