Was excited to be able to contribute to an elegant study from the Zito Lab showing that NMDA receptor-mediated spine shrinkage requires glutamate binding but not ion flux through the channel, supporting recent studies showing that the NMDA receptor can signal in an non-ionotropic manner in response to agonist binding.
Our proposal entitled “Genetic ‘Saturation’ of the NMDA Receptor Glycine Co-Agonist Site” was selected for a NARSAD Young Investigator Grant from the Brain and Behavior Research Foundation. We are interested in understanding the fundamental basis for the unique requirement of NMDA receptors to bind both glutamate and a co-agonist (either glycine or D-serine). Even though our understanding is quite limited, in schizophrenia and other neuropsychiatric disorders, significant efforts have been made to clinically enhance NMDA receptor activity though this co-agonist site, either directly by high-dose administration of glycine, D-serine or D-cycloserine (a partial agonist) or indirectly though inhibition of glycine transporters or D-amino acid oxidase. We’re hoping that a deeper understanding of the mechanisms of NMDA receptor function and synapse biology will allow us to develop improved treatments for schizophrenia.
The Brain and Behavior Research Foundation is a leading non-profit dedicating to mental illness, please consider donating to this worthwhile charity.
I just received the exciting news that I have received a pilot project grant from the UC Davis Alzheimer’s Disease Center.
Hippocampal synapse loss is an early finding in Alzheimer’s disease that is associated with elevated levels of soluble amyloid-β (Aβ) oligomers. These Aβ oligomers induce synaptic depression in the hippocampus in an NMDA receptor-dependent manner, but the mechanism remains unclear. My pilot project entitled “NMDA Receptor Subunit Dependence of Amyloid Beta-Induced Synaptic Depression” will use genetic approaches to examine the role of NMDA receptor GluN2 subunits in this Aβ-induced synaptic depression. The long-term goal is to understand the fundamental pathophysiology of Alzheimer’s disease at the earliest stages to allow for hypothesis-driven development of novel trajectory-altering treatments.
I am really excited to Meaghan joining the lab, my first postdoc! She comes from Gabriela Popescu’s laboratory at the University at Buffalo, where she published a series of elegant studies that contributed significantly to our understanding of the structure/function relationships within the NMDA receptor through detailed single-channel analysis. Meaghan’s work described how bupivacaine, a local anesthetic that is primarily a sodium channel blocker, also acts as an antagonist at NMDA receptors and, thus, may have some benefit in preventing the central sensitization that causes chronic pain. In addition, she published work describing how closure of the agonist binding clefts on the NMDA receptor relate to agonist efficacy. Her publications can be found here. Welcome Meaghan!
I’m so pleased that Jon decided to join my lab! My first graduate student, oh boy. But seriously, Jon really impressed me during his rotation. Eager to do experiments, Jon very eagerly got an old rig up and operational after only a few weeks of troubleshooting (the life of an electrophysiologist!). And now, we’re off and running.
Welcome Jon Wong… sorry I don’t have a rig set up yet. Thanks to Kim McAllister for allowing us the use one of her rigs so it can be a worthwhile rotation!!
Jon, a first year PhD student in the Neuroscience Graduate Group, had the unique opportunity for a student at a liberal arts college (Calvin College) to gain experience with patch clamp electrophysiology. Using a mouse model of corpus collosum agenesis, he found that the Probst bundle, a collection of aberrant axons that forms in these mice, makes functional connections to the posterior cortex. I’m excited to have him rotating in my lab!
Lab renovations are finally complete (-ish). Divider wall was taken down, new plumbing and dedicated electrical circuits were installed, and black-out curtain hung.
Time to move start moving in! Special thanks to my dad who was visiting from Ohio for helping me unpack and break down a few hundred boxes. Also for helping me install the stick-on white board.