Kelsey Martin

martin_10_18Experience changes the strength and number of synaptic connections in the brain. This process, known as synaptic plasticity, provides a cellular mechanism for memory storage. While short-term forms of plasticity involve localized, transient changes in synaptic efficacy, persistent forms of synaptic plasticity, such as those underlying long-term memory, have been shown to require new RNA and protein synthesis. This means that signals are transported from the synapse, where they are generated, to the nucleus, where they alter gene expression. The newly synthesized gene products must then be transported from the cell soma to the synapse to produce enduring changes in synaptic strength. Our lab is interested in both aspects of communication between the synapse and the nucleus during synaptic plasticity in neurons, focusing on 1) signaling from synapse to nucleus and 2) mRNA localization and regulated translation. We study these questions in cultured Aplysia sensory-motor neurons and in cultured rodent hippocampal neurons using cell biological, molecular biological and electrophysiological techniques. We are beginning to develop tools to study these processes in more complex circuits in living animals.

Transport of molecules from the synapse to the nucleus of neurons is particularly challenging because synapses are often very far from the cell body.  Our lab has described a role for importin-mediate active transport of signals from synapse to nucleus during long-term plasticity. Current research is aimed at 1) identifying synaptically localized cargoes that undergo stimulus-induced nuclear import during neuronal plasticity, 2) understanding how synaptic stimulation triggers their nuclear import, and 3) characterizing the cell biological pathways mediating the long-distance retrograde transport from synapse to nucleus. We are also focused on identifying the specific changes in transcription that are required for long-term plasticity, and on understanding the function of transcriptional changes in gene expression in synaptic plasticity.

Since each neuron has a single nucleus but can form thousands of synaptic connections, the requirement for transcription during synaptic plasticity raises the question of how the products of gene expression can be targeted to alter synaptic strength at select synapses made by a given neuron. We have found that one important mechanism involves the translation of synaptically localized mRNAs. Current research addresses the following questions: 1) what is the population of localized mRNAs in neurons? 2) how do mRNAs localize to synapses—what are the cis-acting RNA localization elements and the trans-acting RNA binding proteins? 3) how does synapse formation and/or synaptic stimulation regulate either the trafficking or the translation of localized transcripts? 4) what is the function of local translation in memory formation? From a broad perspective, we would like to understand how gene expression can be spatially and temporally regulated at the level of the synapse, and how this local translational regulation is coordinated and integrated with transcriptional changes in the neuron.

Kelsey Martin is at UC Los Angeles | Lab Website