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Everything we see and do is regulated by electrical signals in our nerves and muscles. The focus of my research over the last decade has been to understand how the proteins that generate and transform these electrical signals in cells actually work. Ion channels, which function like tiny pores in the cell membrane, are crucial for sensing and generating electrical signals. My laboratory uses human disease causing mutations in ion channels as a scientific "compass" to direct our inquiries into how ion channels and their molecular partners control cellular activity in neurons. Ion channel research was catalyzed by the invention of glass electrodes to measure electrical signals in cell membranes. However, the average neuron in a human brain sends electrical signals across cables or axons that are only 1/1000th the width of a human hair while also sometimes spanning a meter in length. Progress in the field of neurobiology has been stymied by the fact that the axon is far too small and delicate for measuring ion channel function with electrodes. In principle, these measurements could be achieved with light in the proper setting. Thus, my laboratory at Dartmouth College focuses on devising and refining optical techniques to measure ion channel activity at the nanometer scale within live neurons using genetically-encoded optical indicators. Combining this optical approach with rodent genetics has allowed us to discover and publish novel modulators of synaptic transmission. Our goal is to expand this area of knowledge and potentially identify critical regulators of human disease in synaptic transmission for future therapeutic avenues.measure physiological outputs from neurons using optogenetic indicators in combinations with genetic and biochemical approaches. As such our future projects are trying to determine the following, please contact us for more details:
Panzera, L.C., Johnson, B., Quinn, J.A., Cho, I.H., Tamkun, M.M., Hoppa, M.B. (2022) Activity-dependent endoplasmic reticulum Ca2+ uptake depends on Kv2.1-mediated endoplasmic reticulum/plasma membrane junctions to promote synaptic transmission. Proc Natl Acad Sci U S A. 2022 Jul 26;119(30):e2117135119. doi: 10.1073/pnas.2117135119. Epub 2022 Jul 21. PMID: 35862456
Ralowicz, A.J., Hoppa, M.B. (2022) Dividing communication, at the nanoscale. Elife. 2022 May 24;11:e79446. doi: 10.7554/eLife.79446. PMID: 35608410
Jordan T, Newcomb JM, Hoppa MB, Luke GP. (2022) Focused ultrasound stimulation of an ex-vivo Aplysia abdominal ganglion preparation. J Neurosci Methods. Apr 15;372:109536. doi: 10.1016/j.jneumeth.2022.109536. Epub 2022 Feb 25. PMID: 35227740
Cho, I.H., Panzera, L.C., Chin, M., Alpizar, S.A., Olveda, G.E., Hill, R.A., Hoppa, M.B. (2020) The potassium channel subunit Kvβ1 serves as a major control point for synaptic facilitation. Proceedings of the National Academy of Sciences., USA. 2020 Nov 24;117(47):29937-29947
The Photoconvertible Fluorescent Probe, CaMPARI, Labels Active Neurons in Freely-Moving Intact Adult Fruit Flies. Frontiers in Neural Circuits., 2020 May 8;14:22
Perez-Alvarez, A., Fearey, B., Schulze,C., O'Toole, R.J., Moeyaert, B., Mohr, M.A., Arganda-Carreras, I., Yang, W., Wiegert, J.S., Schreiter, E.R., Gee, C.E., Hoppa, M.B., Oertner, T.G. Freeze-frame imaging of synaptic activity using SynTagMA. Nature Communications., 2020 May 18;11(1):2464.
Panzera, L.C., Hoppa, M.B. (2019) Genetically Encoded Voltage Indicators Are Illuminating Subcellular Physiology of the Axon. Frontiers in Cellular Neuroscience., 2019 Mar 1;13:52.