The Arnsten Lab studies molecular influences on the higher cognitive circuits of the prefrontal cortex (PFC), with the overarching goal of developing rational treatments for cognitive disorders in aging and mental illness.
The lab uses a multi-disciplinary approach to understand mechanisms influencing working memory at the cellular and behavioral levels. Research has focused on how neuromodulators such as norepinephrine (NE), dopamine (DA) and acetycholine (Ach), dynamically modulate PFC network strength through intracellular signaling mechanisms that open or close potassium channels near glutamate NMDA receptor synapses on dendritic spines.
We have termed this rapid form of neuroplasticity Dynamic Network Connectivity (DNC). Our data explains how exposure to stress causes the rapid loss of PFC cognitive abilities, and how genetic mutations in molecules that regulate these pathways can lead to symptoms of mental illness. Dysregulation of these pathways with advancing age also contributes to loss of PFC neuronal firing, cognitive deficits and vulnerability for degeneration in Alzheimer’s Disease. Understanding these mechanisms has already led to successful new treatments, including the use of guanfacine (Intuniv™) for a variety of PFC disorders.