Environmental insults alter brain function and behaviour inboth rodents and people. One putative underlying mechanism that has receivedsubstantial attention recently is the gut microbiota, the ecosystem ofsymbiotic microorganisms that populate the intestinal tract, which is known toplay a role in brain health and function via the gut-brain axis. Two keyenvironmental insults known to affect both brain function and behaviour, andthe gut microbiome, are poor diet and psychological stress. While there isstrong evidence for interactions between the microbiome and host physiology inthe context of chronic stress, little is known about the role of the microbiomein the host response to acute stress. Determining the underlying mechanisms bywhich stress may provoke functional changes in the gut and brain is criticalfor developing therapeutics to alleviate adverse consequences of traumaticstress.

The Arnsten lab studies molecular influences on the higher cognitive circuits of the dorsolateral prefrontal cortex (dlPFC), in order to understand mechanisms affecting working memory at the cellular and behavioral levels, with the overarching aim of identifying the actions that render the dlPFC so vulnerable in cognitive disorders. Her lab has shown that the dlPFC has unique neurotransmission and neuromodulation compared to the classic actions found in the primary visual cortex, including mechanisms to rapidly weaken PFC connections during uncontrollable stress. Reduced regulation of these stress pathways due to genetic or environmental insults contributes to dlPFC dysfunction in cognitive disorders, including calcium dysregulation and tau phosphorylation in the aging association cortex. Understanding these unique mechanisms has led to the development of a new treatment, IntunivTM, for a variety of PFC disorders.