Cellular Mechanisms of Long Term Memory Storage

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Dr. Menahem Segal, head of the Laboratory of Neuronal Plasticity at the Weizmann Institute of Science in Israel, studies the neuronal basis of long term memory in the brain. Of particular interest are conditions that are associated with deterioration of memory systems, such as those occurring in Alzheimer’s disease patients and mentally retarded children.

Dr. Segal’s lab recently published a study investigating the cellular machinery involved in long-term memory storage, focusing specifically on dendritic spines: small protrusions from the cell body, less than a mm in length, onto which synapses are made [1].

Neurons, or nerve cells, are the primary cell type in an animal’s nervous system. Their most distinguishing feature is the ability to conduct signals along their length. These signals can be transmitted via electrical messengers, like the voltage changes accomplished by the movement of charged particles including sodium, potassium, calcium and chloride in and out of the cells; or via chemical messengers, neurotransmitters such as dopamine and serotonin.

Dendrites are long thin structures that arise from the cell body branch multiple times. The cell body of a neuron frequently gives rise to multiple dendrites; these function to receive electrical signals from neighboring neurons and conduct them to the cell body from which they originate.

Dendrite spines are protrusions that extend out of the dendrite. Each spine can receive signals, and the more signaling that occurs through a particular spine, the more it grows. This growth is thought to be important in learning and memory formation. The dendrites of a single neuron can contain hundreds to thousands of spines, thus increasing the number of contacts between neurons.

The great variety of dendritic spine shapes, sizes, and density of distribution on the parent dendrites of a single neuron, as well as the apparent persistence of spines throughout the life of each neuron, suggest that these spines are involved in memory formation and storage. While this view prevailed throughout the 20th century, supporting evidence for it is rather scarce because the small size of the spine prevents systematic electrophysiological analysis.

It has been known for some time that a particular enzyme known as protein kinase C, zeta form (PKMz or PRKCZ) is important for long-term memory storage. Indeed, last year during Brain Awareness Week, we reported that memory enhancement had been achieved in rats; one of the studies discussed utilized PRKCZ to enhance the rats’ long-term memories of a conditioned taste aversion.  What hasn’t been understood, however, is how PRKCZ — also called PKMz — maintains or enhances memory. Dr. Segal and the members of his lab thus put extra copies of PKMz into rat neurons growing in tissue culture dishes and examined what happened to their dendritic spines. Using time lapse photography of these living cultured neurons in a confocal laser scanning microscope, they showed that the extra PKMz did not change the number of spines or the number of branches each spine had, which indicates the number of synapses it can form. However, it did reduce the length of the spines, making them stubbier and more mushroom-like; this is a hallmark of more mature spines. These spines are more stable than longer and thinner spines, which represent newly formed synapses and can appear and disappear within days.

The researchers concluded that PKMz accumulates in pre-existing dendritic spines and helps them mature, and that it uses this mechanism to play its previously known but not yet elucidated role in maintaining or enhancing long-term memory. In future studies, Dr. Segal and his team hope to begin to uncover the cellular basis of the neuroplasticity exhibited by developing brains.

References

1. Ron et al. Overexpression of PKMz Alters Morphology and Function of Dendritic Spines in Cultured Cortical Neurons. Cereb Cortex. 2011 Nov 28. [Epub ahead of print]
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