This work is incisive. The analysis was done on single dendritic spines of CA1 pyramidal cells in the hippocampi of water maze-trained rats versus controls. The role of CA1 pyramidal cells in reconciling local-interceptive stimuli and formation of long-term memory has been noted. The observation is that following learning, there is a memory-specific increase in the number of mushroom spines with synaptic contacts structurally differentiated from numbers of filopodia, stubby, or thin spines. This effect was improved with a PKC activator (bryostatin, an experimental Alzheimer's therapeutic) which increased postsynaptic densities, numbers of presynaptic vesicles, and occurrence of double-synapse presynaptic terminal boutons, mushroom spines (i.e., suggested to be the site of storage for long-term associative memory and genesis of memory-specific synapses). This is a good example of a structural level of analysis.

From a functional standpoint, age-related cognitive decline is found to be related to excitatory-inhibitory imbalances in the synaptic discharges of pyramidal neurons....  Read more

This work is incisive. The analysis was done on single dendritic spines of CA1 pyramidal cells in the hippocampi of water maze-trained rats versus controls. The role of CA1 pyramidal cells in reconciling local-interceptive stimuli and formation of long-term memory has been noted. The observation is that following learning, there is a memory-specific increase in the number of mushroom spines with synaptic contacts structurally differentiated from numbers of filopodia, stubby, or thin spines. This effect was improved with a PKC activator (bryostatin, an experimental Alzheimer's therapeutic) which increased postsynaptic densities, numbers of presynaptic vesicles, and occurrence of double-synapse presynaptic terminal boutons, mushroom spines (i.e., suggested to be the site of storage for long-term associative memory and genesis of memory-specific synapses). This is a good example of a structural level of analysis.

From a functional standpoint, age-related cognitive decline is found to be related to excitatory-inhibitory imbalances in the synaptic discharges of pyramidal neurons. Majdi et al. (2007) wanted to find whether aging and cognitive status are related to the numbers of excitatory and inhibitory presynaptic boutons. They analyzed the density of excitatory and inhibitory presynaptic inputs in the rat’s cerebral cortex in young and aged male Fisher rats. They grouped aged animals into cognitively impaired and cognitively unimpaired and used a Morris water maze task. With immunohistochemistry they showed a slow decline in the density of excitatory and inhibitory presynaptic terminals in the young to cognitively unimpaired to cognitively impaired. There was no significant change in the ratio of excitatory to inhibitory presynaptic terminals bouton densities. The density of excitatory and inhibitory postsynaptic receptor sites showed significant changes, however. The ratios of excitatory to inhibitory postsynaptic densities were altered in the cognitively impaired when compared to young rats.

The contradiction is evident in the structural and functional analysis of pre-postsynaptic densities of normal aged and cognitively impaired aged animals. The finding that postsynaptic densities are altered in the cognitively impaired and that the presynaptic storage terminals remain intact is suggestive that learning ability and long-term memory storage remain somewhat intact in the Alzheimer patients. And the difference between presynaptic and postsynaptic potentials can denote learning and memory versus that of performance at least in the water maze task entailing proximal and introceptive stimuli.

References:
Hongpaisan J, Alkon DL. A structural basis for enhancement of long-term associative memory in single dendritic spines regulated by PKC. Proc Natl Acad Sci U S A. 2007 Dec 4 ; 104(49):19571-6. Abstract

Maryam Majdi, Alfredo Ribeiro-da-Silva, A. Claudio Cuello (2007). Cognitive impairment and transmitter-specific pre- and postsynaptic changes in the rat cerebral cortex during ageing. European Journal of Neuroscience 26 (12), 3583–3596.

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