Synaptic strength and postsynaptically silent synapses through advanced aging in rat hippocampal CA1 pyramidal neurons

Abstract 

Synaptic dysfunction is thought to contribute to age-related learning impairments. Detailed information regarding the presence of silent synapses and the strength of functional ones through advanced aging, however, is lacking. Here we used paired-pulse minimal stimulation techniques in CA1 stratum radiatum to determine whether the amplitude of spontaneous and evoked miniature excitatory postsynaptic currents (sEPSCs and eEPSCs, respectively) changes over the lifespan of rats in hippocampal CA1 pyramidal neurons, and whether silent synapses are present in adult and aged rats. The amplitudes of both sEPSCs and eEPSCs at resting membrane potential (i.e., clamped at −65mV) initially increased between 2 weeks and 3 months, but then remained constant through 36 months of age. The potency of the eEPSCs at depolarized membrane potentials (i.e., clamped at +40mV), however, was highest among 36-month old rats. Additionally, presynaptically silent synapses in CA1 stratum radiatum disappeared between 2 weeks and 3 months, but postsynaptically silent synapses were present through advanced aging. The similarity of silent and functional synapses in CA1 hippocampus at resting membrane potentials throughout adulthood in rats may indicate that impairments in the mechanisms of synaptic plasticity and its subsequent stabilization, rather than deficient synaptic transmission, underlie age-related cognitive decline. Such a notion is consistent with the increased amplitude of synaptic currents at depolarized potentials, perhaps suggesting an upregulation in the expression of synaptic NMDA receptors once rats reach advanced age.

Keywords: Synapse, Hippocampus, CA1, Aging, EPSC, Silent synapse, Minimal stimulation, Whole-cell