Physiology of neural circuits

Physiology of Neural Circuits

 

Research Interests

The main scientific interest of our laboratory is to understand the mechanisms underlying in vivo function of neural networks. The major research lines include 

  • Characterization of the endogenous brain rhythms during early postnatal development, in the adulthood and during ageing/neurodegenerative diseases 
  • Elucidation of the mechanisms underlying processing of sensory signals 
  • Understanding the rules governing the integration of neurons in the preexisting neural networks
  • Interactions between nervous and immune systems of the brain Interactions between nervous and immune systems of the brain

 

Methods

Cellular activity is often associated with an increase in the intracellular calcium concentration. We use this property of neural, neuroglial and immune cells for monitoring their function in vivo by means of two-photon calcium imaging. In combination with state-of-the art electrophysiological, optical and molecular biological techniques (multi-color two-photon microscopy, expression of function-modifying proteins, cell attached and whole-cell patch clamp recordings) this approach allows to study function of multi-cellular networks at single cell or even subcellular resolution. 

 

Projects

  • Mechanisms underlying processing of sensory signals in the visual cortex and the olfactory bulb
  • Mechanisms governing migration and integration of adult stem cells in the preexisting neural networks
  • Neuroglial function in the aging and diseased brain
  • Understanding the cause of neuroglial hyperactivity in mouse models of Alzheimer's disease

 

 

Selected Publications

  • Figarella K., Wolburg H., Garaschuk O., Duszenko M. 2019 Microglia in neuropathology caused by protozoan parasites. Biol. Rev. in press. Figarella K., Wolburg H., Garaschuk O., Duszenko M. 2019 Microglia in neuropathology caused by protozoan parasites. Biol. Rev. in press.     
  • Garaschuk O., Semchyshyn H.M., Lushchak V.I. 2018 Healthy brain aging: interplay between reactive species, inflammation and energy supply. Ageing Res. Rev. 43: 26-45.
  • Lerdkrai C., Asavapanumas N., Brawek B., Kovalchuk Y., Mojtahedi N., Olmedillas del Moral M., Garaschuk O. 2018 Intracellular Ca2+ stores control in vivo neuronal hyperactivity in a mouse model of Alzheimer’s disease. PNAS USA 115: E1279-E1288.
  • Askew K, Li K, Olmos-Alonso A, Garcia-Moreno F, Liang Y, Richardson P, Tipton T, Chapman MA, Riecken K, Beccari S, Sierra A, Molnár Z, Cragg MS, Garaschuk O, Perry VH, Gomez-Nicola D. 2017 Coupled proliferation and apoptosis maintain the rapid turnover of microglia in the adult brain. Cell Reports 18: 391-405.
  • Liang Y, Li K., Riecken K, Maslyukov A, Gomez-Nicola D, Kovalchuk Y, Fehse B, Garaschuk O. 2016 Long-term in vivo single cell tracking reveals the switch of migration patterns in adult-born juxtaglomerular cells of the mouse olfactory bulb. Cell Research 26: 805-821.
  • Osswald M, Jung E, Sahm F, Solecki G, Venkataramani V, Blaes J, Weil S, Horstmann H, Wiestler B, Syed M, Huang L, Ratliff M, Karimian-Jazi K, Kurz FT, Schmenger T, Lemke D, Gömmel M, Pauli M, Liao Y, Häring P, Pusch S, Herl V, Steinhäuser C, Krunic D, Jarahian M, Miletic H, Berghoff AS, Griesbeck O, Kalamakis G, Garaschuk O, Preusser M, Weiss S, Liu H, Heiland S, Platten, M Huber PE, Deimling T, Wick W, Winkler F. 2015 Brain tumor cells interconnect to a functional and resistant network. Nature 528: 93-98.
  • Kirmse K, Kummer M, Kovalchuk Y, Witte OW, Garaschuk O, Holthoff K. 2015 GABA depolarizes immature neurons and inhibits network activity in the neonatal neocortex in vivo. Nature Communications 6, 7750.
  • Heneka MT, Carson MJ, El Khoury J, Landreth GE, Brosseron F, Feinstein DL, Jacobs AH, Wyss-Coray T, Vitorica J, Ransohoff RM, Herrup K, Frautschy SA, Finsen B, Brown GC, Verkhratsky A, Yamanaka K, Koistinaho J, Latz E, Halle A, Petzold GC, Town T, Morgan D, Shinohara ML, Perry VH, Holmes C, Bazan NG, Brooks DJ, Hunot S, Joseph B, Deigendesch N, Garaschuk O, Boddeke E, Dinarello CA, Breitner JC, Cole GM, Golenbock DT, Kummer MP. 2015 Neuroinflammation in Alzheimer's Disease. Lancet Neurology 14:388-405
  • Kovalchuk Y, Homma R, Liang Y, Maslyukov A, Hermes M, Thestrup T, Griesbeck O, Ninkovic J, Cohen LB, Garaschuk O. 2015 In vivo odorant response properties of migrating adult-born neurons in the mouse olfactory bulb. Nature Communications 6, 6349. 
  • Maier FC, Wehrl HF, Schmid AM, Mannheim JG, Wiehr S, Lerdkrai C, Calaminus C, Stahlschmidt A, Ye L, Burnet M, Stiller D, Sabri O, Reischl G, Staufenbiel M, Garaschuk O, Jucker M, Pichler BJ. 2014 Longitudinal PET/MRI reveals β-amyloid deposition and rCBF dynamics, and connects vascular amyloidosis to quantitative loss of perfusion. Nature Medicine 20: 1485-1492.
  • Brawek B, Schwendele B, Riester K, Kohsaka S, Lerdkrai C, Liang Y, Garaschuk O. (2014) Impairment of in vivo calcium signaling in amyloid plaque-associated microglia. Acta Neuropathol. 127, 495-505
  • Thestrup T, Litzlbauer J, Bartholomäus I, Mues M, Russo L, Dana H, Kovalchuk Y, Liang Y, Kalamakis G, Laukat Y, Becker S, Witte G, Geiger A, Allen T, Rome LC, Chen TW, Kim DS, Garaschuk O, Griesinger C, Griesbeck O. 2014 Optimized ratiometric calcium sensors for functional in vivo imaging of neurons and T lymphocytes. Nature Methods 11: 175-182
  • Varvel NH, Grathwohl SA, Baumann F, Liebig C, Brawek B, Thal DR, Charo IF, Heppner FL, Aguzzi A, Garaschuk O, Ransohoff RM, Jucker M. 2012 Microglial repopulation model reveals a robust homeostatic process for replacing CNS myeloid cells. PNAS USA 109: 18150-18155
  • Rochefort* NL, Garaschuk* O, Milos*, RI, Narushima M, Marandi N, Pichler B, Kovalchuk Y, Konnerth A. 2009 Sparsification of neuronal activity in the visual cortex at eye-opening. PNAS USA 106: 15049-15054. *Equal contribution
  • Busche MA, Eichhoff G, Adelsberger H, Abramowski D, Wiederhold KH, Haass C, Staufenbiel M, Konnerth A, Garaschuk O. 2008 Clusters of hyperactive neurons near amyloid plaques in a mouse model of Alzheimer’s disease. Science 321: 1686-1689.
  • Heim N*, Garaschuk O*, Friedrich MW, Mank M, Milos RI, Kovalchuk Y, Konnerth A, Griesbeck O. 2007 Improved calcium imaging in transgenic mice expressing a Troponin-C based FRET sensor. Nature Methods 4: 127-129. *Equal contribution
  • Garaschuk O, Milos RI & Konnerth A. 2006 Targeted bulk-loading of fluorescent indicators for two-photon brain imaging in vivo. Nature Protocols 1, 380-386
  • Adelsberger H*, Garaschuk O*, Konnerth A. 2005 Cortical calcium waves in resting newborn mice. Nature Neuroscience 8: 988-990. *Equal contribution
  • Stosiek C*, Garaschuk O*, Holthoff K, Konnerth A. 2003 In vivo two-photon calcium imaging using multi-cell bolus loading. PNAS USA 100: 7319-7324. *Equal contribution.
  • Garaschuk O, Linn J, Eilers J, Konnerth A. 2000 Large-scale oscillatory calcium waves in the immature cortex. Nature Neuroscience 3: 452-459
  • Airaksinen M. S, Eilers J, Garaschuk O, Thoenen H, Konnerth A & Meyer M. 1997 Ataxia and altered dendritic calcium signalling in mice carrying a targeted nullmutation of the calbindin D28k gene. PNAS USA 94, 1488-1493

Group Leader and Further Information

Olga Garaschuk
Physiology of Neural Circuits
Werner Reichardt Centre for Integrative Neuroscience
Otfried-Mueller-Str. 25
72076 Tübingen
Germany

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