Conclusions

Quantitative electron microscopic studies of the mammalian brain have provided evidence that the cellular mechanisms of memory formation following behavioral learning include synaptogenesis manifested by an increase in the number of excitatory synapses involving dendritic spines in pertinent brain regions (Figure 23.3B). The structural synaptic modification of this kind has been reported most frequently and appears to be typical of different forms of behavioral learning. As opposed to the earlier electron microscopic work, synapse quantification during the last decade was performed with unbiased stereological methods for obtaining estimates of synapse number per postsynaptic neuron or per entire volume of a synapse-containing layer. In spite of this, some recent studies failed to detect a learning-induced increase in synapse number when a single time point along the learning curve was examined. This underscores the necessity of probing the time course of behavioral acquisition for the establishment of changes in synapse number associated with learning. Because the implementation of this approach at the electron microscopic level is impractical, a promising avenue of future research would be to combine electron microscopic quantification of axospinous synapses with pilot time-lapse imaging of dendritic spines on living neurons in slices or in vivo. Then quantitative electron microscopic analyses can be carried out only when additional new spines are found to be formed following learning. Another form of learning-induced restructuring of synaptic connectivity, which also involves synaptogenesis, is the addition of MSBs (Figure 23.3C). Although the existence of this structural synaptic alteration is well documented, its relationship to the de novo formation of single-synapse boutons at various phases of the learning process needs to be investigated.

Quantitative electron microscopic analyses have also revealed that behavioral learning promotes a structural remodeling of existing synapses. The most demonstrative example of this is an enlargement of the PSD (Figure 23.3D). Such a change was shown to selectively involve nonperforated axospinous synapses that had the smallest PSDs. The latter usually lack the AMPAR immunoreactivity, which probably makes them postsynaptically silent. The increase in nonperforated PSD area was postulated to reflect the insertion of AMPARs and to represent a structural correlate of the conversion of postsynaptically silent synapses into functional ones. An attractive line of future investigations would be to use quantitative immunogold electron microscopy for elucidating learning-induced alterations in both the area of PSDs and the AMPAR immunoreactivity. Interestingly, a recent study has demonstrated that associative auditory fear conditioning drives GluR1 subunit of AMPARs into thalamo-amygdala synapses

Synaptic Plasticity Electron Microscopy

Figure 23.3. Schematic Demonstrating the Patterns of Changes in Axospinous Synapses that are most Frequently Observed at the Electron Microscopic Level in the Mammalian Brain Following Learning. As compared with controls (A), behavioral learning promotes synaptogenesis manifested by an addition of axospinous synapses established by single-synapse boutons (B) and by an increase in the number of multisynapse boutons (C). Additionally, behavioral learning is also associated with the restructuring of existing synapses that involves an enlargement of their PSD area (D).

Figure 23.3. Schematic Demonstrating the Patterns of Changes in Axospinous Synapses that are most Frequently Observed at the Electron Microscopic Level in the Mammalian Brain Following Learning. As compared with controls (A), behavioral learning promotes synaptogenesis manifested by an addition of axospinous synapses established by single-synapse boutons (B) and by an increase in the number of multisynapse boutons (C). Additionally, behavioral learning is also associated with the restructuring of existing synapses that involves an enlargement of their PSD area (D).

while blockade of synaptic GluR1-receptor incorporation disrupts fear memory47. It would be advantageous, therefore, to use immunogold electron microscopy for quantifying the expression of the GluR1 subunit, and perhaps associated scaffolding and trafficking molecules like SAP-97 and stargazin in synapses, as well as possible changes in PSD area following various forms of learning.

To elucidate what kind of structural synaptic modifications are likely to account for synaptic plasticity associated with learning and memory, numerous studies have examined alterations in synapse number and structure following the induction of NMDA receptor-dependent hippocampal long-term potentiation (LTP), which is viewed as a synaptic model of memory. One of the most consistent observations of such studies is that LTP elicits the formation of additional perforated axospinous synapses in the hippocampal dentate gyrus48 and CA1 region49,50. This process proceeds rapidly, but is transient. In CA1, for example, the proportion of perforated synapses gradually increases at 5, 15, and 30 min after cessation of potentiating stimulation; then it decreases at 45 min and returns to control values at 60 min50. It is not surprising, therefore, that no change in the proportion of perforated synapses is detected in CA1 at 2 h following LTP induction51. The LTP-related addition of perforated synapses is largely due to an increase in the number of their subtype that exhibits a segmented, completely partitioned PSD52,53. Such synapses are distinguished from other axospinous junctions by the highest content of AMPA receptors11 and may contribute thereby to a marked enhancement of synaptic transmission soon after LTP induction. It has been proposed that LTP induction leads to the conversion of existing nonperforated synapses into segmented, completely partitioned ones7. This would explain why additional synapses of the latter subtype appear within a time frame that is unlikely to be long enough to allow the assembly of new excitatory hippocampal synapses54. In any case, the formation of segmented, completely partitioned synapses may represent an efficient way of rapidly and transiently augmenting synaptic transmission before other, perhaps permanent, forms of synaptic plasticity can emerge. Future studies will show if a similar pattern of synapse restructuring is also characteristic of early stages of the learning process.

Defeat Drugs Death

Defeat Drugs Death

This Book Is One Of The Most Valuable Resources In The World When It Comes To Helpful Info On Avoiding And Beating A Fatal Drug Addiction!

Get My Free Ebook


Post a comment