Basic Science Research

Microdialysis Diagram

CIRCADIAN RHYTHMS: One of the main research projects in our lab has been to understand how circadian rhythms are generated and coordinated temporally and spatially and how nocturnal light intrusion impacts physiology in health and disease. These circadian studies are driven by a powerful approach perfected in our laboratory: long-term (up to 100 days) pineal microdialysis to sample melatonin release at high-resolution (every 10-20 min) in freely moving animals. Using this technique, the lab has been able to uncover novel features of circadian rhythms that were previously unknown, including identification of rats with extreme chronotypes (rats with very early and very late melatonin onset). These studies will lead to a better understanding of basic properties of circadian timing. They will also provide clues on how jet lag, shift-work, and light-at-night impact our circadian rhythms and health. Currently, we are focused on understanding the impact of chronic shift of the light:dark cycle, which simulates shiftwork in humans, on cardiac functions as well as cortical functions using various investigative tools.

ENDOGENOUS HALLUCINOGENS: It has been proposed that exceptional states of consciousness in humans such as psychosis may involve the brain synthesis of serotonin analogs exhibiting potent psychoactive properties. One such compound, N,N-dimethyltryptamine (DMT), has been found naturally in several plants, in the bodily fluids of animals including humans, and in elevated levels in psychiatric patients. Exogenously administered DMT elicits intense visual and mental hallucinations in healthy humans. Our lab demonstrated the natural presence of DMT within the living rodent pineal gland and occipital cortex. More recently, we have begun to analyze regulatory mechanisms of endogenous DMT synthesis, secretion, and signaling. In addition, we plan to examine functional impact of exogenous DMT administration on electrical oscillations in mammalian brain. These studies will further the understanding of exceptional states of consciousness and pathophysiological mental states like schizophrenia, wherein hallucinations are reported.

NEUROBIOLOGY OF THE DYING BRAIN: One of the newest projects in our lab is to define electrical oscillations of the brain at the systems level in distressed animals. This new line of research utilizes physical principles of vibrations and waves and mathematical modeling of brain oscillations, and requires skills in Matlab and signal processing. These studies aim to provide a better understanding of how the brain processes information during both normal and abnormal states, and may lead to a better understanding of human near-death experiences.

BRAIN-HEART CONNECTION: How does the heart of a healthy individual cease to function within just a few minutes in the absence of oxygen? We addressed this issue by simultaneously examining the heart and the brain in animal models during asphyxiation and found that asphyxia markedly stimulates neurophysiological and neurochemical activities of the brain. Furthermore, previously unidentified corticocardiac coupling showed increased intensity as the heart deteriorated. Blocking efferent input to the heart markedly increased survival time of both the heart and the brain. The results show that targeting the brain’s outflow may be an effective strategy to delay the death of the heart and the brain from asphyxia. One of our ongoing studies focuses on the role of brain efferent signaling in accelerating cardiac demise in neurological crisis including stroke.