Grants and Contributions:

Grant or Award spanning more than one fiscal year. (2017-2018 to 2022-2023)

Nerve cells communicate with each other via specialized intercellular junctions known as synapses. Synaptic plasticity, which means the strengthening and weakening of synapses, is an important feature of neuronal development as well as for learning and memory formation. Widely studied examples of vertebrate synaptic plasticity are long-term potentiation (persistent synaptic enhancement) and long-term depression (persistent synaptic weakening). Short-term events in synaptic plasticity are mediated by protein modifications, while later events require the synthesis of new proteins at the synapse. The finding that certain messenger RNAs are transported to and translated at the synapse led to the notion that long-term plasticity is implemented by spatially and temporarily restricted protein synthesis. However, the molecular signaling pathways leading to the induction of local translation remain largely elusive.

Our research proposal will investigate the effect of NMDA-receptor activation on local protein synthesis during synaptic plasticity. We will test whether proteins that regulate local translation are affected by NMDA-receptor activation, and whether these regulators of local translation affect the outcome of long-term potentiation or long-term depression in synapses. Characterizing the different signaling pathways that are regulated during synaptic plasticity and elucidating the control mechanisms for protein synthesis at the synapse will greatly enhance our knowledge of basic mechanisms underlying neuronal development as well as learning and memory.