The hallmark of myelinated axons is their organization into molecularly distinct domains, a pre-requisite for the rapid propagation of actionpotentials. The paranodal domains establish the axo-glial septate junctions (AGSJs) through interactions involving axonal Contactin-associated protein (Caspr), Contactin (Cont), and glial Neurofascin NF155. The nodal domain is organized by neuronal NF186, voltage gated sodium (Nav) channels, and Ankyrin G (AnkG), a cytoskeletal adaptor protein.

Chronic stress is a factor in many psychiatric diseases, such as depression, PTSD and other anxiety disorders. The brain noradrenergic (NE) system is important in arousal and acute stress reactivity, and is implicated in the etiology of stress-related psychiatric disorders. In the previus grant period, we showed that increasing NE transmission acutely in the prefrontal cortex (PFC) of rats facilitates cognitive flexibility on an attentional setshifting test (AST). By contrast, chonic unpredictable stress (CUS) compromised cognitive flexibility.

3-aminobutyric acid, or GABA, is the main inhibitory neurotransmitter in the mammalian brain. Dysfunctions in GABA-mediated inhibition have been implicated in the etiology of a variety of brain disorders. Furthermore, GABA receptors are targets for a host of therapeutic and endogenous modulators such as benzodiazepines, barbiturates, and neurosteroids. Key to understanding the etiology of these diseases and the molecular mechanisms of these modulators, is a detailed understanding of the activation mechanism of the GABA receptor.

Opioid receptor agonists remain the drugs of choice to treat moderate to severe pain, but their use is limited by adverse effects including tolerance, dependence, abuse, and respiratory depression. A recent increase in overdoses and deaths is fueling concerns about opioids that further limit their legitimate medical use. A growing body of evidence indicates that the therapeutic window of an opioid can be increased by combining it with another drug, such that smaller doses of the opioid (in combination with another drug) produce the desired therapeutic effect.

Basic Research

Basic Research

Basic Research

Basic Research

Basic Research

Basic Research