Age-related changes in theta frequency stimulation-induced long-term potentiation

Several signaling mechanisms that are crucial for the induction of long-term potentiation (LTP) by theta frequency (5 Hz) trains of synaptic stimulation are altered in aged animals. To determine whether theta frequency stimulation-induced LTP is particularly sensitive to changes in synaptic function that occur in aged animals, we examined whether activating synapses in the hippocampal CA1 region with three different trains of theta pulse stimulation (TPS) has different effects on synaptic strength in hippocampal slices from aged and young mice. Our results indicate that TPS-induced LTP is not diminished in the aged hippocampus but does show a dependence on L-type voltage-sensitive calcium channels that is not seen in young animals. Moreover, we found that the facilitation of TPS-induced LTP by co-activation of β-adrenergic and cholinergic receptors is strongly reduced in slices from aged animals. Together, these results suggest that memory impairments in aged animals might arise, at least in part, from deficits in the ability of modulatory transmitters to regulate activity-dependent forms of synaptic plasticity.