Excited that Eden has decided to join the Gray Lab! Eden graduated from UC Irvine where she worked in the lab of Diane O’Dowd studying how mutations in the gene for the voltage-gated sodium channel NaV1.1 lead to epilepsy.
Let’s do some fun science together!
Gray JA, Zito K, and Hell JW (2016). Non-ionotropic signaling by the NMDA receptor: controversy and opportunity. F1000Research, 5(F1000 Faculty Rev): 1010.
In collaboration with Karen Zito and Johannes Hell, I recently reviewed the emerging literature on possible non-ionotropic signaling by the NMDA receptor, which is classically a ligand-gated ion channel. This conformational-based signaling remains controversial but, if validated, could open the doors for a new era of understanding ion channels and synapse function.
Happy to have Eden Barragan from the Neuroscience Graduate Group rotating in the lab!
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.
Stein IS, Gray JA, and Zito K (2015). Non-ionotropic NMDA receptor signaling drives activity-induced dendritic spine shrinkage. Journal of Neuroscience, 35(35): 12303-12308
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.
Saw this little foot sticking out from under the fridge in my office… hey little guy. Was able to scare him out into the hall, catch him, and release him outside. Be free!
Finally got the first photo of the lab.
L-to-R: Meaghan, Aaron, Jon, John
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!
After some delays, the air tables have arrived, microscopes and manipulators assembled, time to get the rigs up and functional!