All animals use their brains and sensory organs to learn about the location of potential predators and their calls, food resources, suitable mates, etc. At any given moment, the environmental information enters the brain—via the sensory organs—and activates a subset of neurons. These neurons then store this information by adjusting the strength of their synapses. The synapse refers to the point of contact, or the site of information transfer, between neurons, and synaptic plasticity refers to the cellular mechanism by which neurons adjust the strength of the synaptic connection. Generally speaking, there are two forms of synaptic plasticity. Synapses can either be strengthened, in a process known as long-term potentiation (LTP), or weakened, in a process known as long-term depression (LTD). Following the induction of LTP or LTD, synapses activate a complex set of intracellular signaling events which work together to insert or remove ionotropic glutamatergic receptors from the postsynaptic membrane. My research lab studies the molecular mechanisms responsible for the stabilization of ionotropic glutamatergic receptors at synapses. It is essential to understand these molecular mechanisms as their dysregulation gives rise to brain disorders affecting memory systems. Thus, understanding how neurons process these signals is of utmost importance. We aim to answer three main research questions. One of our goals is to determine the mechanisms by which proline phosphorylation regulates the stability of postsynaptic spines. The second goal of my laboratory is to determine the role of m6A mRNA methylation in neuronal excitability. Our third goal is to use single-molecule imaging studies to understand the behavior of the individual molecules at the synapse. We are studying the cellular mechanisms mentioned previously using a multidisciplinary approach that combines mouse genetics, animal behavior, molecular biology, whole-cell electrophysiology, computer simulations, and high-resolution microscopy techniques.
Delgado J.Y., (2021) Lack of support for surface diffusion of postsynaptic AMPARs in tuning synaptic transmission. Biophys J. Aug 17;120(16):3409-3417.
Delgado J.Y., (2020) An Alternative Pin1 Binding and Isomerization Site in the N-Terminus Domain of PSD-95. Frontiers of Molecular Neuroscience. Mar 18; 13:31.
Delgado J.Y., Nall D.L. and Selvin P.R. (2020) Pin1 Binding to Phosphorylated PSD-95 Regulates the Number of Functional Excitatory Synapses. Frontiers of Molecular Neuroscience. Mar 13; 13:10.
Delgado J.Y., Fink A., Grant S., O'Dell T.J., Opazo P. (2018) Rapid homeostatic downregulation of LTP by extrasynaptic GluN2B receptors. J. of Neurophysiology, Aug 15
Shi H., Zhang X., Weng Y.L., Lu Z., Liu Y., Lu Z., Li J., Hao P., Zhang Y., Zhang F., Wu Y., Delgado J.Y., Su Y., Patel M., Cao X., Shen B., Huang X., Ming G.L., Zhuang X., Song H., He C., Zhou T. (2018) m6A facilitates hippocampus-dependent learning and memory through Ythdf1. Nature; 563, 249–253