Axonal Transport and Long-Term Memory Storage

描述（由申请人提供）：长期记忆（LTM）的存储需要重塑已有的突触和形成新的突触。虽然转录和突触蛋白合成在这些过程中的作用已经得到了很好的描述，但在LTM储存过程中，核和突触过程是如何协调的，这在很大程度上仍然未知。我们之前已经证明，通过基因产物的微管依赖性运输介导细胞核和突触之间通信的分子马达激酶在这一过程中起关键作用。我们已经发现，在海蜗牛应用中，驱动蛋白是诱导长期促进（LTF）的必要和充分条件，并且驱动蛋白运输多种蛋白质和蛋白质

DESCRIPTION (provided by applicant): Long-term memory (LTM) storage requires remodeling of pre-existing synapses and formation of new ones. While the roles of transcription and synaptic protein synthesis in these processes are well described, it remains largely unknown how nuclear and synaptic processes are coordinated during LTM storage. We have previously shown that kinesin, the molecular motor that mediates communication between nucleus and synapses through the microtubule-dependent transport of gene products, has a key role in this process. We have discovered that kinesins are necessary and sufficient to induce long-term facilitation (LTF) in marine snail Aplysia and that kinesin transport several protein and mRNA cargos that are relevant for learning. Our guiding hypothesis is that storage of LTM requires regulation of axonal transport of gene products in pre- and post-synaptic neurons of circuits involved in learning. In this proposal, we test our central hypothesis that kinesin mediated transport is differentially regulated in bidirectional plasticity during learning. We will perform our studies using the well-described pre-synaptic sensory and post-synaptic motor neurons of gill withdrawal reflex of Aplysia. The sensory and motor neuron synapses can be re-constituted in vitro and provide experimental flexibility to specifically manipulate these neurons to study regulation of transport in pre- and post-synaptic neurons. Specifically, we aim to understand how the three critical components of anterograde transport: the kinesin motor, cargo and microtubule tracks may be regulated to adjust delivery of cargo to synapses during LTM. An anticipated outcome of this proposed research is that once the molecular regulators of axonal transport are identified, they may be manipulated pharmacologically, producing new and innovative approaches to the treatment of disorders such as tauopathies in which axonal transport is affected.