David A Morilak, Ph.D.

We study the negative impact of stress, and mechanisms for better treatment of stress-related psychiatric disorders. Our research addresses a) regulation and integration of the acute behavioral, cognitive and endocrine responses to stress; b) adaptive and maladaptive responses to chronic stress; and c) regulatory mechanisms of action of psychotherapeutic drugs and other types of therapeutic interventions, including behavioral therapies, and d) cognitive impairment after cancer therapy and its treatment. One focus of our research over the years has been on norepinephrine (NE), an important neuromodulatory transmitter that plays a critical role in the acute response to stress by enhancing arousal and sensorimotor response capabilities, and by integrating autonomic and endocrine responses with behavior. We study the modulation of behavioral and neuroendocrine responses to acute stress, and strategies to enhance higher-order cognitive processes mediated in the prefrontal cortex related to cognitive flexibility and coping behavior. Our techniques span the range from molecular, cellular and neural circuit to whole animal behavior and cognition. We study structural, functional and regulatory changes in prefrontal circuits that underly neuronal plasticity, the basis of both stress-induced pathology and therapeutic efficacy. Our work is relevant to understanding stress-related pathology underlying illnesses such as depression, PTSD or anxiety disorders, and the beneficial effects of antidepressant and anxiolytic therapies. Experimental approaches include behavioral tests of cognition, arousal, anxiety and defensive responses; intracerebral drug microinjections; DiOlistic labeling with morphometric analysis of dendrites and spines; in situ hybridization, immunohistochemistry and receptor autoradiography; radioimmunoassay for plasma hormone measures; electrophysiology to assess plasticity in ascending and descending corticolimbic circuits; viral-based chemo- and optogenetics, western blots, IP assays and other measures of protein regulation and signal transduction; and the application of chronic metabolic and psychogenic stressors.

Research Area/Field of Study: Neuroscience

Sub-Field of Study: Stress neurobiology, cognitive function, neural circuits, antidepressants, animal models, cognitive impairment after cancer treatment, novel therapeutics, prefrontal cortex

Associated Diseases: Depression, PTSD, anxiety disorders, age-related cognitive impairment, cancer chemobrain

Techniques Used: Molecular biology (rt pcr, IP), biochemistry (western blots, ELISA, RIA), chemogenetics, optogenetics, electrophysiology, neuropharmacology, in situ hybridization, DiOlistic labeling, neuroanatomy, behavioral pharmacology, cognitive testing