On Tuesday, March 7, the Neuroscience Graduate Program welcomed Dr. Haining Zhong from the Vollum Institute. The independent research institute is affiliated with Oregon Health and Science University in Portland, Oregon. Dr. Zhong is a senior scientist and professor at the Vollum Institute and has been working with the institute since 2010.
Dr. Sika Zheng, University of California, Riverside’s (UCR) Professor of Biomedical Sciences and Director of the Center for Ribonucleic Acid and Biology and Medicine, introduced Dr. Zhong at the beginning of the Seminar. Dr. Zheng complimented Dr. Zhong by stating, “What impressed me the most was his ingenuity and passion for science.”
In his introduction, Dr. Zheng commended Dr. Zhong’s numerous publications and awards, prefaced his larger findings and shared a few memories. He applauded Dr. Zhong’s success in developing imaging techniques and optical sensors for cyclic adenosine 3, 5-monophosphate (cAMP) signaling and “protein kinase a” (PKA) activity, as well as a fruitful career at “one of the best neuroscience institutions.”
When Dr. Zhong took the floor, he stated that he was “very impressed by the work done at UCR,” and declared it an “honor to share [his] work here.” He shared his presentation “Imaging Neuronal cAMP and PKA Signaling in Space and Time.”
The Zhong lab research primarily studies how the brain functions and changes to succeed in a dynamic environment. They focus on the regulation of neuromodulation and experience-dependent plasticity. Neuromodulation is used to coordinate changes in biological states, thus controlling brain function. Irregularities with neuromodulation are linked with neurological diseases and neurodegenerative disorders. Experience-dependent plasticity is important for learning and memory and is dependent on neuronal circuits.
During their research endeavors, the lab was not impressed with the current imaging technology that is used to monitor brain activity. Thus, Dr. Zhong and his colleagues developed endogenous protein labeling and biosensors for subcellular signaling pathways and microscopy to investigate cAMP and PKA pathways within neurons.
Dr. Zhong and his colleagues are investigating movement and motivation behind the action on a cellular level. He states that the inputs into the cell, chemical and electrical, converge to regulate neuronal function. He focuses on the cAMP pathway, which is a vital second messenger for various biological pathways. When cAMP is used as a second messenger, it helps the cell fire a greater signal, otherwise known as an action potential, with specific circumstances. He affirms “After 50 years of research, the cyclic AMP- PKA pathway touches almost every aspect of neural function. And that cyclic AMP-PKA signaling is associated with neurodegenerative and neurological diseases.”
Though he did recognize that cAMP and PKA pathways have been studied for half a century, Dr. Zhong presented how his research is focused on the “spatial-temporal activity dynamics in the cyclic AMP and PKA pathway.” The lab studies the pathways at different levels to gain a “comprehensive” understanding of the pathway. He studies both, at a cellular level and at a behavioral level to gain a sense of the overall function.
In the first half of the presentation, Dr. Zhong went over the methods of the experiment at a cellular level. He also explained the background information of what is already known about the pathway, such as the mechanism behind cell signaling and function. The cyclic AMP subunits bind to catalytic subunits which leads to a cascading effect of other processes to create cell signaling and function. They found that if the PKA binding site is deleted, then they can still activate the PKA catalytic units, which move into the spines of the neuron’s dendrites, which is the receiving end of the neuron. He also explains that PKA catalytic subunits are associated with the membrane upon activation via myristoylation, which is when myristic acid is added to the protein subset. The subunit has an intrinsic affinity for the membrane, which makes a difference in the function of the PKA pathway.
The second part of the seminar was dedicated to the in-vivo portions of his experiment. Dr. Zhong reminded the attendees that different biological states affect the resulting behavior. He explained how the lab uses neuromodulation to dynamically control the circuit.
In the in-vivo portions, the lab found that PKA activity in indirect spiny neuron pathways is possibly driven by an acute accumulation of extracellular adenosine through the Adenosine A2a receptors because of the accumulation found in the striatum during locomotion assays. Another potential mechanism is that PKA activity is both increased in direct and indirect spiny neuron pathways which may increase synaptic transmission and neuronal excitability.
Dr. Zhong explained how “Dopamine is like the gas in the system, and adenosine is the brake.” His analogy is meant to explain how dopamine drives movement while adenosine is supposed to suppress action. But, both must work in tandem to modulate locomotor behavior.
The new evidence of the build-up of adenosine in the striatum will help determine specific striatal functions and how dopamine and adenosine coordinate within the striatum to produce animal movement. Thus, producing new insights into the actions of dopamine in the striatum. With dopamine being a major player in neurological motor diseases, such as Parkinson’s Disease, understanding the function pathways in-depth will only enhance the progress in treating such illnesses.
For more information on Zhong’s lab and their current developments and experiments, visit their website. There, a complete list of publications, research and lab members can be found.
