Abstract
Technical complexities associated with studies of defined synapses in the mammalian CNS have made it difficult to determine whether CNS synaptic vesicles respond to repetitive monosynaptic activation in the same ways as do PNS vesicles. Moreover, even in the PNS, the specific ultrastructural correlates of short-term synaptic potentiation are not well characterized. In the present studies, therefore, the Schaffer collateral-commissural fiber projection to field CA1 of the hippocampus was used as a model brain system in which to assess quantitative relations between dynamic vesicle patterns and frequency potentiation and depression. Anesthetized rats were perfused with aldehyde fixative during stimulation trains and concomitant microelectrode recording in order to study temporal correlations between physiology and synaptic structure. In addition, young and aged animals were compared to determine whether there are ultrastructural correlates of a previously described age-related impairment of hippocampal frequency potentiation. After 1 min of 10 Hz synaptic stimulation (stim), frequency potentiation of the population spike was correlated with increases in local vesicles (LV; within 150 nm of the active zone) and in vesicles directly apposed (AV) to the active zone membrane of CA 1 synapses. In addition, the ratio LVD: DVD of local-to-distant vesicle (DV; beyond 150 nm) densities was increased under all stimulation conditions. After 10 min of 10 Hz stim, or 1 min of 40 Hz stim, some vesicle depletion (approximately 25%) was present, as was some spike depression or decline from peak potentiation. However, LV depletion was not well correlated with degree of spike depression. Mean dendritic spine area was also increased in association with potentiation (at 1 min of 10 Hz stim) in young rats. Membrane infoldings similar to the cisternae described in other systems were seen with repetitive stimulation, providing evidence of vesicle recycling in these CNS terminals. In comparison to young control animals, terminals in non-stimulated aged group control rats exhibited a higher LVD:DVD ratio and a reduced DVD. In addition, the stimulation-induced increase in AV at 1 min of 10 Hz stim was not present in aged rat synapses. However, no age-related differences in vesicle-density measures were found at any stimulation point.