Neurons in the brain analyze the sensory world by making appropriate neural connections during development despite an ever-changing environment. This process occurs during a sensitive period of early brain development and requires specialized receptors found at the synapses (connections) between neurons. The NMDA receptor is one such critical receptor. Although this receptor has traditionally been thought to function only at postsynaptic sites, recent evidence suggests an importance for NMDARs at presynaptic sites. Currently, the role of presynaptic NMDA receptors is poorly understood. The goal of this project is to determine how presynaptic NMDA receptors regulate neurotransmitter release and why this regulation is important for the development of appropriate neural connections. The proposed studies will specifically test the central hypothesis that plasticity mediated by presynaptic NMDA receptors is required for the normal development of early sensory functions within the brain. By demonstrating that presynaptic NMDA receptors contribute to early forms of neural plasticity, and that their contributions may shift with development, the findings from this proposal are expected to define a novel property of synaptic plasticity in emerging cortical circuits. Moreover, a fundamental understanding of the unique differences between presynaptic and postsynaptic NMDA receptors will aid future pharmacological manipulations that target NMDA receptors for the treatment of neurological disorders. The goals of this proposal will be met through promoting the involvement of underrepresented minorities in this intensive neuroscience research project.
