Researchers Characterize Thousands of RNA Sequences Linked to Memory Storage

Neurobiologists working with the sea slug Aplysia have identified 5,657 unique sequences consisting of both coding and noncoding RNAs that are involved in long-term memory storage.

When threatened, Aplysia species release clouds of ink to blind the attacker. A quick neural response is necessary for speedy reaction to danger by the animal. Since its siphon-withdrawal response is mediated by electrical synapses, which allow several neurons to fire synchronously, and as Aplysia has only about 20,000 neurons, it has become a favorite subject for investigation by neuroscientists.

To determine which RNAs were linked to memory retention investigators at The Scripps Research Institute (Jupiter, FL, USA) devised a new approach for studying the process in Aplysia.

The approach, which was based on the characterization of RNA transport complexes carried by the molecular motor kinesin, offered four distinct advantages over previously described methods: (i) it allowed the identification of RNAs based on their association with transport machinery that was destined for synapses; (ii) it reflected dynamically regulated RNAs; (iii) it allowed for identification of the targeted RNAs; and (iv) it could be used in different regions of the central nervous system (CNS), thereby facilitating genomic characterization of synaptic transcriptome of the entire CNS or region of the CNS.

Results published in the April 15, 2013, online edition of the journal Proceedings of the National Academy of Sciences of the United States of America (PNAS) described the identification of 5,657 unique sequences consisting of both coding and noncoding RNAs from the Aplysia CNS. Several of these RNAs played key roles in the maintenance of synaptic function and growth. One of these RNAs, myosin heavy chain, was required specifically for the induction of long-term facilitation (LTF) at sensory and motor neuron synapses.

“Our analyses suggest that the transported RNAs are surprisingly diverse,” said first author Sathya Puthanveettil, assistant professor of neuroscience at The Scripps Research Institute. “It also brings up an important question of why so many different RNAs are transported to synapses. One reason may be that they are stored there to be used later to help maintain long-term memories.”

“New protein synthesis is a prerequisite for maintaining long term memory,” said Dr. Puthanveettil, “but you do not need this kind of transport forever, so it raises many questions that we want to answer. What molecules need to be synthesized to maintain memory? How long is this collection of RNAs stored? What localized mechanisms come into play for memory maintenance? ”

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