Morphological Correlates of Long-term Potentiation and Ageing in the Hippocampus of Rats

Dhanrajan, T. M. (1999). Morphological Correlates of Long-term Potentiation and Ageing in the Hippocampus of Rats. PhD thesis The Open University.



This thesis has examined age-dependent changes in neural plasticity in rat hippocampal dentate gyrus using unbiased morphological techniques at light and electron microscope level. It considers whether there is a morphological basis to explain why some aged animals sustain, whilst others fail to sustain, potentiation in the dentate gyrus of the hippocampus after unilateral induction of LTP, 45 minutes after stimulation of the perforant pathway. Previous data in young adult rats (5 months old) have demonstrated that the morphology of dendritic spines and synapses within the hippocampus is altered at 10-30 minutes, and 24 hrs following LTP induction. The data obtained in the present study suggest that differences in spine and synaptic morphological parameters appear to be correlated with the ability to maintain LTP in the aged rats. Those maintaining LTP had a tendency to longer spine length, and a decrease in spine and synaptic densities, there was a significant increase in the number of complex axospinous perforated synapses.
Here, in young rats, LTP resulted in a significant increase in the density of spine synapses and total synaptic density. The mean spine density was also higher in the stimulated hemisphere, but spine length decreased. However, there was a significant increase in the number of bifurcating spines and axospinous perforated complex synapses in the stimulated compared to the contralateral control hemisphere.
An age-dependent comparison indicated that spine density and synaptic densities are significantly higher in the younger rats, but spine length was significantly greater in the aged rats. LTP does not seem to cause morphological changes per se at the time examined post potentiation. However, an important finding of the present study is that the percentage of axospinous complex perforated synapses is significantly higher in the stimulated hemisphere of aged and young rats that sustained LTP compared to those that did not. The percentage of branched spines and simple axospinous perforated synapses is significantly higher in both the stimulated & unstimulated hemisphere of aged rats that failed to sustain LTP. Therefore a proportion of the branched spines and perforated synapses would appear to be the result of high frequency stimulation, rather than LTP induction per se.

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