Martin Hruska, PhD

Research Interests

Synapses in the central nervous system (CNS) are fundamental for regulating information transfer and enabling brain plasticity through structural adaptations in shape, size, and connectivity, known as structural plasticity. These changes modulate circuit function and information storage, accompanied by modifications in the molecular composition and nano-organization of pre-synaptic and post-synaptic compartments. However, plasticity decreases with aging, and defects in synaptic processing are linked to learning and memory deficits associated with Alzheimer's disease.

Our overarching goal is to decipher the complex biology of synapses and its implications for neurological disorders. To achieve this, we employ a multidisciplinary approach that integrates molecular and biochemical methods with state-of-the-art Stimulated Emission Depletion (STED) microscopy. We focus on three core domains:

1. Nanoscale Molecular Organization: Unraveling the intricate molecular architecture of active zones and post-synaptic densities.
2. Synaptic Plasticity Mechanisms: Investigating the dynamic processes underlying synaptic adaptation and plasticity.
3. Neurological Disorder Pathogenesis: Exploring how synaptic dysfunction contributes to the development of neurological disorders.

Through this comprehensive approach, we aim to elucidate how synaptic biology supports normal brain function and how disruptions in these processes may lead to neurological diseases.

Publications

[2024]

• Manning A., Bender P.T.R, Boyd-Pratt H., Mendelson B. Z., Hruska M., Anderson C.T.  Trans-synaptic association of vesicular zinc transporter 3 and Shank3 supports synapse-specific dendritic spine structure and function in mouse auditory cortex. J. Neurosci. e0619242024 (2024) doi:10.1523/jneurosci.0619-24.2024.

[2022]

• 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). 

[2019]

• 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.

[2018]

• 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. 

[2015]

• 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.

[2013]

• 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.

[2012]

• Hruska, M. & Dalva, M.B. “Ephrin regulation of synapse formation, function and plasticity.” Molecular and Cellular Neurosciences (2012) 50, 35–44. Review.

[2011]

• 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.

[2010]

• 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.

[2009]

• 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. 

[2007]

• 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.