Tomáš Hromádka, MD, PhD
Two major pathological features of Alzheimer’s disease (AD) – neurofibrillary tangles and neuritic plaques – lead to progressive neuronal loss and also influence synaptic and neuronal properties and play a role in controlling activity in larger neuronal networks. Determining the relationship between pathological changes at the level of molecules, synapses, neurons, circuits, networks, and cognition represents the biggest challenge in understanding neurodegeneration.
To understand the impact of AD on brain activity and function we use transgenic mouse models of AD expressing truncated tau, as well as mouse models directly “infected” with purified tau fibrils. Using a combination of electrophysiological, optical, molecular, and optogenetic tools in-vivo we determine the impact of neurodegeneration on activity and function of well-defined classes of cortical neurons and neuronal circuits.
Current projects in the department focus on the role of inhibitory cortical interneurons in the early stages of neurodegeneration, rescue of synaptic dysfunction, and the changes in cortical vasculature and function of the blood-brain barrier in delivering therapeutics to the brain tissue.
- Gréta Vargová (PhD student)
- Thomas Vogels (PhD student)
Projects – funding
Inhibitory cortical circuits mediating cognitive dysfunction in Alzheimer’s disease. (2020-2023) APVV-19-0585
SyDAD – Synaptic Dysfunction in Alzheimer’s Disease. (2015–2019) MSCA-ITN2015-ETN – Marie Skłodowska-Curie Innovative Training Networks (ITN-ETN), Horizon2020, Grant agreement ID 676144
Functional impact of Alzheimer’s disease on cortical neurons. (2016–2018) VEGA 2/0148/16
Zimová, I., Brezováková, V., Hromádka, T., Weisová, P., Cubínková, V., Valachová, B., Filipčík, P., Jadhav, S., Smolek, T., Novák, M., and Žilka, N. (2016) Human truncated tau induces mature neurofibrillary pathology in a mouse model of human tauopathy. J Alzheimer Dis 54(2): 831–843
Novák, O., Zelenka, O., Hromádka, T., and Syka, J. (2016) Immediate manifestation of acoustic trauma in the auditory cortex is layer specific and cell type dependent. Journal of Neurophysiology 115:1860–1874
Hromádka, T., Zador, A. M., and DeWeese, M. R. (2013). Up states are rare in awake auditory cortex. Journal of Neurophysiology 109:1989–1995
Hromádka, T. and Zador, A. M. (2009). Representations in auditory cortex. Current Opinion in Neurobiology 19:430–433
Lima, S. Q., Hromádka, T., Znamenskiy, P., and Zador, A. M. (2009).
PINP: A new method of tagging neuronal populations for identification during in vivo electrophysiological recording. PLoS ONE4:e6099
Koulakov, A. A., Hromádka, T., and Zador, A. M. (2009). Correlated connectivity and the distribution of firing rates in the neocortex.
Journal of Neuroscience 29:3685–3694
Hromádka, T., DeWeese, M. R., and Zador, A. M. (2008). Sparse representation of sounds in the unanesthetized auditory cortex. PLoS Biology 6:e16
Huber, D., Petreanu, L., Ghitani, N., Ranade, S., Hromádka, T., Mainen, Z., and Svoboda, K. (2008). Sparse optical microstimulation in barrel cortex drives learned behaviour in freely moving mice. Nature 451:61–64.