NSF Award
0212189
Nerve cells, or neurons, extend complex branches that communicate with many other neurons by sending and capturing signals at functional contacts called synapses, specialized small sites where membranes of two nerve cells are very close together. When the presynaptic cell is active, chemical neurotransmitters are released to act on the post-synaptic cell membrane, to excite or inhibit activity in the postsynaptic cell. A single neuron can have thousands of synapses with hundreds or thousands of other neurons in the brain, and each synapse is potentially capable of changing its efficacy in transmitting signals. It is believed that a fundamental mechanism underlying neural functions such as memory formation is a strengthening of synapses through repeated activity. That strengthening requires synthesis of new proteins, which probably remodel the synapse. Recently a subcellular neuronal organelle called an RNA granule has been suggested to harbor messenger RNA (mRNA) molecules that provide templates for such remodeling proteins, with translocation and release of this mRNA locally at activated synapses in response to neural depolarization. This project uses molecular biological techniques on cultured neurons to define the functional roles of specific RNA granule proteins in a novel conceptual framework. First, the new RNAi (RNA-interference) technique allows selective inactivation or 'knock-down' of specific gene expression, and is used to investigate the role of a particular granule protein called Staufen, to see how it is involved in granule assembly. Second, micro-RNAs (miRNA) are a type of short RNA that can regulate gene expression post-transcriptionally, so miRNAs in the granule will be identified to see how they might modify the local protein synthesis. <br/> This project has some technological risks, but potentially very high impact, because results will be important for understanding molecular mechanisms of modifying neural functions, and so of networks involved in memory and learning. The impact is likely to extend beyond neuroscience to cell biology and physiology in general. The project also continues active involvement of this highly regarded PI with training a postdoctoral researcher, with international collaborations, and with public outreach.
