Martin Hruska, PhD
PO Box 9303
108 Biomedical Road
Morgantown, WV 26505
Synapses in the CNS are fundamental structures that regulate the information transfer in the brain and enable the brain's plasticity. By adapting their shape, size, and patterns of connectivity – known as structural plasticity, synapses modulate circuit function and the information storage in the brain. These structural changes are accompanied by modifications of the molecular composition and nano-organization of pre-synaptic and post-synaptic compartments. Plasticity decreases with aging, and defects in synaptic processing lead to learning and memory deficits linked to Alzheimer's disease. Deciphering how the complex biology of synapses underlies normal brain function and how defects in these processes might cause neurological disorders is the long-term goal of our work. We use high resolution imaging, including the state-of-the-art Stimulated Emission Depletion (STED) nanoscopy, in combination with molecular and biochemical approaches to investigate the development and plasticity of synapses in health and disease. We focus on answering the following fundamental questions:
- Is there a molecular code of neuronal connectivity?
- How do synapses change during sleep?
- How are synapses remodeled after injury?
- Hruska, M., Cain, R.E. & Dalva, M.B. "Nanoscale rules governing the organization of glutamate receptors in spine synapses are subunit specific." Nat Commun 13, 920 (2022).
- Henderson, N., Marchand, S., Hruska, M., Hippenmeyer, S., Luo, L., Dalva, M. “Ephrin-B3 controls excitatory synapse density through cell-cell competition for EphBs.” eLife (2019) 8(), e41563.
- Barber, K., Hruska, M., Bush, K., Martinez, J., Fei, H., Levitan, I., Dalva, M., Wairkar, Y. “Levels of Par-1 kinase determine the localization of Bruchpilot at the Drosophila neuromuscular junction synapses.” Scientific Reports (2018), 8(1), 16099.
- Hruska, M., Henderson, N., Le Marchand, S.J., Jafri, H. and Dalva, M.B. “Synaptic nanomodules underlie the organization and plasticity of spine synapses.” Nature Neuroscience (2018) May; 21(5): 671-682.
- Hruska, M., Henderson, N.T., Xia, N., Le Marchand, S.J. and Dalva, M.B. “Anchoring and synaptic stability of PSD-95 is driven by ephrin-B3.” Nature Neuroscience (2015) Oct; 18(11): 1594-1604.
- Dai, J., Buhusi, M., Demyanenko, G., Brennaman, L., Hruska, M., Dalva, M., and Maness, P. “Neuron Glia-Related Cell Adhesion Molecule (NrCAM) Promotes Topographic Retinocollicular Mapping.” PloS One. (2013) July 8 (9): e73000.
- Hruska, M. & Dalva, M.B. “Ephrin regulation of synapse formation, function and plasticity.” Molecular and Cellular Neurosciences (2012) 50, 35–44. Review.
- Nolt, M.J., Lin, Y., Hruska, M., Murphy, J., Sheffler-Colins, S.I., Kayser, M.S, Passer, J., Bennett, M.V., Zukin, R.S. and Dalva, M.B. “EphB controls NMDA receptor function and synaptic targeting in a subunit-specific manner.” J Neurosci. (2011) Apr 6; 31(14): 5353-64.
- Kayser, M.S., Lee, A.C., Hruska, M. and Dalva, M.B. “Preferential control of basal dendritic protrusions by EphB2.” PLoS One. (2011) Feb 25; 6(2): e17417.
- McClelland, A.C.*, Hruska, M.*, Coenen, A.J., Henkemeyer, M and Dalva, M.B. “Transsynaptic EphB2-ephrin-B3 interaction regulates excitatory synapse density by inhibition of postsynaptic MAPK signaling.” Proc Natl Acad Sci U S A. (2010) May 11; 107(19): 8830-5. *Equal author contribution.
- Nishi, R., Stubbusch, J., Hulce, J.J., Hruska, M., Pappas, A., Bravo, M.C., Huber, L.P., Bakondi, B., Soltys, J. and Rohrer, H. “The cortistatin gene PSS2 rather than the somatostatin gene PSS1 is strongly expressed in developing avian autonomic neurons.” J Comp Neurol. (2010) Mar 15; 518(6): 839-50.
- Hruska, M., Keefe, J., Wert, D., Tekinay, A.B., Hulce, J.J., Iba.ez-Tallon, I. and Nishi, R. “Prostate stem cell antigen is an endogenous lynx1-like prototoxin that antagonizes alpha7- containing nicotinic receptors and prevents programmed cell death of parasympathetic neurons.” J. Neurosci. (2009) Nov 25; 29(47): 14847-54.
- Hruska, M. and Nishi, R. “Cell-Autonomous Inhibition of α7-Containing Nicotinic Acetylcholine Receptors Prevents Death of Parasympathetic Neurons during Development.” J. Neurosci. (2007) 27(43): 11501-11509.