Haining Zhong, Ph.D., and Tianyi Mao, Ph.D., assistant scientists with OHSU’s Vollum Institute, were awarded a grant as part of the Brain Research through Advancing Innovative Neurotechnologies (BRAIN) initiative. The grant given to OHSU — an award totaling $1,156,556 over three years from the National Institute of Neurological Disorders and Stroke within the NIH — will allow the investigators to further explore their research in neuromodulation, a key mode of chemical communication between neurons in the brain.
This research has great relevance to potential treatments for diseases associated with defects in neuromodulation including Parkinson’s, schizophrenia, addiction, and depression. Because neuromodulation originates from a small group of cells without redundant pathways that would allow surrounding areas to compensate, damage to these cells can have devastating consequences. Parkinson’s disease is perhaps the most dramatic example of this disease process, where the loss of neurons that produce dopamine, a key neuromodulator, influence the entire cortex leading to progressively debilitating symptoms.
Neuromodulation events, which regulate neuronal excitability and plasticity, have been extensively studied from the standpoint of individual neurons, but their actions and effects on systems are poorly understood because there is no effective way to record these events in living animals. The purpose of the research team’s study, “A novel approach to examine slow synaptic transmission in vivo,” is to create a method for visualizing the signaling events induced by neuromodulators in vivo, thereby gaining a mechanistic understanding of the neural circuitry.
To accomplish this, the team aims to combine and improve several lines of multi-disciplinary cutting-edge technology including novel mouse genetic strategy and advanced imaging. First, they will create transgenic mice by inserting DNA that encodes a fluorescent sensor of neuromodulatory signaling targeting neuromodulators such as norepinephrine and dopamine. They will then use 2-photon fluorescent microscopy which the team predicts will enable more precise imaging than traditional methods. This will enable the team to see how cells receiving neuromodulator input behave in normal situations, what the dynamics are, and how their motor behaviors change. By establishing a baseline, researchers can then compare normal functioning with what transpires when diseases slow transmission, paving the way for potential treatments.