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Protein is key to forming short-term memories

Synapses from the brainstem.

Synapses from the brainstem.

Short-term memory is essential for everyday life — whether remembering a phone number while dialing, carrying on a conversation, or forming the basis of long-term memories. Neuroscientists think that short-term memory is based on changes in both the properties of brain cells and the connections, called synapses, between them.

Now Diasynou Fioravante, formerly of Harvard Medical School and now at the UC Davis Center for Neuroscience, and colleagues have identified a sensor that plays a key role in modifying neurons and synapses to create short-term memories. The work was published Aug. 5 in the journal eLife.

Brain function depends on signals jumping across synapses. When an electrical signal is generated by the cell before the synapse, calcium ions flow into the cell and trigger release of molecules called neurotransmitters which cross the synapse to the next cell, producing an electrical signal. The size of the signal is a measure of synaptic strength.

Synaptic strength can change over both the short-term (tens of seconds) and long-term. A short-term increase in strength called post-tetanic potentiation is thought to underlie formation of short-term memory. It amplifies the signal across the synapse by increasing the amount of neurotransmitter released in response to each electrical impulse, and it is triggered by an increase of calcium in the presynaptic cell.

Protein kinase C (green stain) on synapses (red). Yellow color shows PKC on synapses.

Protein kinase C (green stain) on synapses (red). Yellow color shows PKC on synapses.

Fioravante and colleagues now show that an enzyme called protein kinase C is responsible for this effect. They found that genetically modified mice that lack protein kinase C do not show this short-term potentiation, but that it could be restored by reintroducing the enzyme. A version of protein kinase C that lacks the ability to bind calcium was unable to trigger post-tetanic potentiation.

The work could provide tools to manipulate brain plasticity and study how memories are formed, Fioravante said. It could also eventually provide new ways to improve short-term memory function in patients with memory deficits.

The researchers think that protein kinase C is likely the first of a new class of sensors that make short-term, local modifications to how brain cells work and connect with each other.

Coauthors on the paper are: YunXiang Chu, Arthur de Jong, Pascal Kaeser and Wade Regehr at Harvard Medical School, and Michael Leitges at the University of Oslo. The work was funded by the National Institutes of Health.

Read the full paper online here.

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