Grin2a Dysfunction Impairs Cognitive Flexibility by Disrupting LC Modulation of mPFC Circuits
Research Summary:
This study investigated how the loss of the Grin2a gene, which encodes the GluN2A subunit of NMDA receptors, affects working memory and hippocampal function in mice. Using behavioral tests (8-arm radial maze), Hassan and his team found that Grin2a- deficient mice had impaired spatial working memory.
Electrophysiological recordings of the Grin2a- deficient mice showed disrupted theta-gamma oscillation coupling in the hippocampus, a pattern important for memory processing. Additionally, the mutants had an abnormal increase in parvalbumin-expressing interneurons, leading to an imbalance in excitatory and inhibitory (E/I) inputs to pyramidal neurons.
This imbalance may underlie the observed memory deficits. Overall, the study emphasizes the essential role of GluN2A in maintaining hippocampal network stability and cognitive function, with implications for disorders like schizophrenia and epilepsy.
Mightex’s Contribution:
Using Mightex’s PolyEcho and Polygon, Hassan and his team were able to deliver highly precise and targeted light stimulation to specific engrams within the brain. This level of precision and real-time control facilitated by our PolyScan software allowed them to modulate neural activity dynamically, enabling deeper investigation into the functional connectivity and dynamics of the hippocampal circuits.
Mightex’s technology enhanced the resolution and flexibility of the experiments, contributing to the broader goal of developing potential therapeutic strategies for neuropsychiatric disorders.
Hassan is a Master’s student at the University of Michigan, specializing in pharmacology and neuroscience. His research investigates how disruptions in neural circuitry contribute to schizophrenia, focusing on working memory, emotional regulation, and decision-making. Using multi-electrode arrays, optogenetics, and closed-loop perturbation, he explored hippocampal network dynamics in Grin2a mutant models. Hassan’s work bridges neuroscience and clinical neuropharmacology, aiming to inform future therapeutic strategies.