Expression of long-term potentiation in aged rats involves perforated synapses but dendritic spine branching results from high-frequency stimulation alone.

Evidence for morphological substrates of long-term changes in synaptic efficacy is controversial, partly because it is difficult to employ an unambiguous control. We have used a high-frequency stimulation protocol in vivo to induce long-term potentiation (LTP) in the hippocampal dentate gyrus of aged (22-month-old) rats and have found a clear distinction between animals that sustain LTP and those that fail to sustain it. The "failure group" was used as a specific/"like-with-like" control for morphological changes associated with the expression of LTP per se. Quantitative optical and electron microscopy was used to analyze large populations of dendritic spines and excitatory perforant path synapses; LTP was found to be associated with an increase in numbers of segmented (perforated) postsynaptic densities in spine synapses. In contrast, an increase in the number of branched spines appears to result from high-frequency stimulation alone. These data shed light on the current controversy about the expression mechanism of LTP.