In this ongoing collaboration with Antonio Sanz-Clemente at Northwestern University, we define an additional mechanism regulating the synaptic expression of the GluN2B subunit of NMDA receptors. Following synaptic activity, the GluN2B subunit is phosphorylated on the C-terminal PDZ ligand at S1480 but casein kinase 2 (CK2) resulting in the removal of GluN2B from the synapse. We now show that these extrasynaptic GluN2B subunits are dephosphorylated by PP1 in an activity-dependent manner resulting in the re-entry into the synapse.
See our paper at Cell Reports: https://doi.org/10.1016/j.celrep.2019.06.030
In this collaboration with the Swanson lab at UCSF, we show that NMDA-mediated superoxide production requires both a source of calcium influx and agonist binding to the glutamate site of the NMDA receptor (GluN2B subunit to be specific). Thus, both Ca2+ and agonist -binding are necessary, but neither is sufficient. This is the first report demonstrating this dual requirement and I predict this will be rule rather than the exception for NMDA receptor function.
MK801 is an open-channel blocker of the NMDA receptor pore. That is, when the receptor is activated and the channel opens, MK801 enters the pore and blocks it. Usually, MK801 is used extracellularly, but multiple studies have included it in the intracellular pipette solution during whole-cell patch clamp recordings. We show here that MK801 has a much lower effective affinity for NMDA receptors when used intracellularly, suggesting caution is needed when interpreting such studies.
Not just passed, apparently she destroyed it! Congrats to PhD Candidate Eden Barragan!
Exciting new collaborative publication with David Olson’s lab on the possibility that psychedelics may be rapid-acting antidepressants. Was fun to get back into studying 5-HT2A receptors after a long hiatus.
Covered by the press:
Wall Street Journal
After initial learning, subsequent learning is independent of NMDA receptor function, but requires mGluRs and increases in intrinsic excitability. New publication in collaboration with the Wiltgen Lab.
Excited to see the lab’s first original research publication in print and congrats to Jon Wong for his first scientific publication! It was even a featured article. PDF can be found here.
Shekib comes to us from Tom O’Dell’s lab at UCLA where he found unique NMDA receptor differences between ventral and dorsal hippocampus mediated by SK channels that account for differences in synaptic plasticity between those regions. We’re excited to have Shekib as part of the team!
We are excited to have MD/PhD student Ariel Jacobi rotating in the lab. As an undergraduate, Ariel worked with David Lynch at UPenn examining the novel possibility of postsynaptic D-serine and its biosynthetic enzyme, serine racemase. She then spent a year at the Max Planck Institute for Brain Research in Germany studying turtle brains in the laboratory of Gilles Laurent. Let’s do some patching!
Jon presents his poster “Postsynaptic serine racemase regulates NMDA receptors” at this year’s Society for Neuroscience (SfN) meeting in Washington, DC. His poster drew a good audience including multiple luminaries in the field (e.g. Jon Johnson, U Pitt, seen here). Congrats Jon for a job well done!