Enlargement of PSD Area in Axospinous Synapses After Learning

4.1.1. Effect of Trace Eyeblink Conditioning

We did not detect any change in the total number of axospinous synapses or their morphological subtypes in the rabbit CA1 stratum radiatum 24 h after trace eyeblink conditioning25. Then we examined if an enlargement of PSD area in existing axospinous synapses is characteristic of this type of learning25. Synapses were sampled with disectors from the entire extent of the synaptic layer in a systematic random fashion, and the area of their PSDs was estimated. Comparison of conditioned and pesudoconditioned animals showed that the PSD area was significantly increased following conditioning in nonperforated, but not in perforated, axospinous synapses. To determine whether a PSD enlargement in the conditioned rabbits or PSD shrinkage in the pseudoconditioned controls caused the observed difference in size of nonperforated PSDs between the two groups of animals, unstimulated control rabbits were additionally investigated. It was found that conditioned animals had a significantly larger nonperforated PSD area than unstimulated controls, which were not different in this regard from pseudo-conditioned controls. Thus, the enlargement of nonperforated PSD area in conditioned animals relative to the pseudoconditioned controls represents a conditioning-induced increase in the PSD size. This change involves a decrease in the proportion of nonperforated synapses with PSDs that fell into the smallest size category (PSD area < 20 x 103 nm2) and a concomitant increase in the proportions of those nonperforated synaptic junctions that have larger PSD areas.

The discovery of postsynaptically silent synapses led to the suggestion that the learning-related enlargement of nonperforated PSDs might be associated with an addition of AMPARs25. Electrophysiological experiments have revealed that some synapses in the rat CA1 stratum radiatum exhibit functional NMDARs, but not functional AMPARs41, 42. This makes such synapses postsynaptically silent: they do not generate a postsynaptic response to a release of glutamate at normal resting membrane potentials because NMDAR channels are blocked by extracellular magnesium. Correspondingly, immunohistochemical studies have provided evidence for the existence of hippocampal axospinous synapses exhibiting only NMDAR, but not AMPAR, immunoreactivity associated with relatively small nonperforated PSDs (reviewed in 12). Silent synapses acquire the capability of evoking AMPA-type responses after LTP induction in the rat CA1 stratum radiatum41,42, indicating that they may be transformed into functional synaptic junctions due to the insertion of AMPARs into their PSDs. These findings suggest the hypothesis that the same mechanism may underlie the conditioning-induced PSD enlargement, which would explain why the latter structural synaptic modification is selective for nonperforated axospinous synapses.

4.1.2. Effect of Spatial Memory Acquisition

The hippocampus-dependent version of the Morris water maze task was used in a study aimed at determining whether PSD dimensions are changed in hippocampal axospinous synapses as a consequence of spatial learning40. During the acquisition training session (eight massed trials), adult rats had to find a hidden platform placed in the same pool quadrant. Progressive learning was detected in animals, as indicated by a decrease in the distance to reach the platform through these trails. The reversal training session (four trials) was administered on the next day, with the platform located in the quadrant opposite to the one used previously. Control rats were handled daily. The brain was fixed for electron microscopy 15 min after completing reversal training or handling. Digital reconstructive analyses of micrographs of serial sections through the CA3 stratum lucidum were performed to compute the PSD surface area in synapses formed by mossy fiber terminals and spine protrusions called thorny excrescences. A significant enlargement of PSD surface area was observed in water maze trained animals relative to controls. This change might reflect a pronounced (240%) increase in the proportion of perforated PSDs that also occurred following water maze training because perforated PSDs are known to be typically larger than nonperforated ones.

An earlier study from the same group23 used a different protocol of water maze training (see Section 3.1.4.) and analyzed nonperforated axospinous synapses in the dentate middle molecular layer. The synaptic numerical density per unit volume was estimated. The total length of PSD profiles was measured in single sections, expressed per unit area, and converted into a PSD density estimate per unit volume. The PSD area per synapse was calculated as the ratio of synaptic density to PSD density. The results showed that the mean PSD area was significantly decreased in the water maze trained group as compared with untrained control group, but not the swim-only group. These results are difficult to interpret because they were derived from PSD measurements performed in single sections and might be therefore biased by synapse size, shape, and orientation.

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