AG BioImaging

Die Arbeitsgruppe BioImaging beschäftigt sich mit zwei Forschungsschwerpunkten. Zum einen werden die zellulären Grundlagen von Lernern und Gedächtnis untersucht. Insbesondere interessieren wir uns für die Mechanismen, die an den Kontaktstellen zwischen den Nervenzellen, den sogenannten Synapsen, die Übertragung von Information modulieren können. Diese synaptische Plastizität wird als eine zelluläre Grundlage für Lernen und Gedächtnis im Gehirns angesehen. Zum anderen untersuchen wir die Netzwerkaktivität von Neuronen im Gehirn unter physiologischen und pathophysiologischen Bedingungen. Wir möchten verstehen, wie neuronale Netze im Gehirn Informationen verarbeiten und  welche Mechanismen bei verschiedenen Erkrankungen wie Epilepsie oder Schlaganfall zu einer gestörten Verarbeitung führen.

Die zentrale experimentelle Kompetenz unserer Arbeitsgruppe liegt auf dem Gebiet moderner optischer Methoden. Neben der 2-Photonen Mikroskopie setzen wir die schnelle konfokale Fluoreszenzmikroskopie ein, um die Vorgänge bei der Informationsübertragung zwischen Nervenzellen und die Netzwerkaktivität von Neuronen zu untersuchen. Ergänzt werden diese optischen Methoden durch elektrophysiologische Ableitungen mit Hilfe der patch-clamp Technik.

Publikationen: Pubmed

1. Flossmann et al., Somatostatin Interneurons Promote Neuronal Synchrony in the Neonatal Hippocampus, Cell Re-
   ports (2019), https://doi.org/10.1016/j.celrep.2019.02.061
2. Haselmann H, Mannara F, Werner C, Planaguma J, Miguez-Cabalo F, Schmidl L, Grünewald B, Petit-Pedrol M, Kirmse K, Classen J, Demir F, Klöcker N, Soto D, Doose S, Dalmau J, Hallermann S and Geis C (2018) Human autoantibodies against the AMPA receptor subunit GluA2 induce receptor reorganisation and memory dysfunction. Neuron DOI: 10.1016/j.neuron.2018.07.048.
3. Lukas M, Holthoff K, Egger V (2018) Long-Term Plasticity at the Mitral and Tufted Cell to Granule Cell Synapse of the Olfactory Bulb Investigated with a Custom Multielectrode in Acute Brain Slice Preparation. Methods Mol Biol 1820:157-167. doi: 10.1007/978-1-4939-8609-5_13.
4. Rahmati V, Kirmse K, Holthoff K, Kiebel SJ (2018) Ultra-Fast Accurate Reconstruction of Spiking Activity from Calcium Imaging Data. J Neurophysiol doi: 10.1152/jn.00934.2017.
5. Rahmati V, Kirmse K, Holthoff K, Schwabe L, Kiebel SJ (2017) Developmental Emergence of Sparse Coding: A Dynamic Systems Approach. Sci Rep 7:13015. DOI:10.1038/s41598-017-13468-z.
6. Kirmse K, Hübner CA, Isbrandt D, Witte OW, Holthoff K (2017) GABAergic Transmission during Brain Development: Multiple Effects at Multiple Stages. The Neuroscientist. DOI: 10.1177/1073858417701382
7. Kirmse K und Holthoff K (2017) Funktionen der GABAergen Übertragung im unreifen Gehirn. Neuroforum 23(1):30–37.
8. Kummer M, Kirmse K, Zhang C, Haueisen J, Witte OW, Holthoff K (2016) Column-like Ca2+ clusters in the mouse neonatal neocortex revealed by three-dimensional two-photon Ca2+ imaging in vivo. Neuroimage 138, 64-75. doi:10.1016/j.neuroimage.2016.05.050.
9. Rahmati V, Kirmse K, Markovic D, Holthoff K, Kiebel SJ (2016) Inferring neuronal dynamics from calcium imaging data using biophysical models and Bayesian inference. PLoS Comput Biol 12(2): e1004736. doi:10.1371/journal.pcbi.1004736
   
10. Kummer M, Kirmse K, Witte OW, Haueisen J, Holthoff K (2015) A method to quantify accuracy of position feedback signals of a three-dimensional two-photon laser-scanning microscope. Biomed Opt Express 6(10):3678-3693.
11. Popovic M, Vogt K, Holthoff K, Konnerth A, Salzberg BM, Grinvald A, Antic SD, Canepari M, Zecevic D (2015) Imaging Submillisecond Membrane Potential Changes from Individual Regions of Single Axons, Dendrites and Spines. Adv Exp Med Biol 859:57-101. doi: 10.1007/978-3-319-17641-3_3
12. 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. Nat Commun 6:7750, doi:10.1038/ncomms8750
13. Joerk A, Seidel RA, Walter S, Wiegand A, Kahnes M, Klopfleisch M, Pohnert G, Westerhausen M, Witte OW, Holthoff K (2014) Impact of heme and heme degradation products on vascular diameter in mouse visual cortex, JAHA, doi: 10.1161/JAHA.114.001220.
14. Hübner CA and Holthoff K (2013) Anion transport and GABA signaling. Front Cell Neurosci 7:177. doi: 10.3389/fncel.2013.00177
15. Kummer M, Kirmse K, Witte OW, Holthoff K (2012) Reliable in vivo identification of both GABAergic and glutamatergic neurons using Emx1-Cre driven fluorescent reporter expression, Cell Calcium 52: 182-189.
16. Kirmse K, Witte OW, Holthoff K (2011) GABAergic depolarization during early cortical development and implications for anticonvulsive therapy in neonates, Epilepsia 52:1532-1543.
17. Kirmse K, Witte OW, Holthoff K (2010) GABA depolarizes immature neocortical neurons in the presence of the ketone body ß-hydroxybutyrate, J Neurosci 30: 16002-16007.
18. Holthoff K, Canepari M, Vogt C, Konnerth A, Zecevic D (2010) Dendritic voltage imaging, Imaging in Neuroscience and Development: A laboratory manual, Rafael Yuste, Fred Lanni and Arthur Konnerth (Eds.), Cold Spring Harbor Laboratory Press, in press.
19. Canepari M, Popovic M, Vogt C, Holthoff K, Konnerth A, Salzberg BM, Grinvald A, Antic S, Zecevic D (2010) Imaging submillisecond membrane potential changes from individual regions of single axons, dendrites and spines, Membrane Potential Imaging in the Nervous System, Marco Canepari and Dejan Zecevic (Eds.), Springer, in press.
20. Holthoff K,  Secevic D*, Konnerth A (2010) Rapid time-course of action potentials in spines and remote dendrites of mouse visual cortex neurons, J Physiol588: 1085-1096. (see Perspectives)
21. Holthoff K* (2009) Calcium Imaging of dendrites and spines, Calcium Measurement Methods, Series: Neuromethods 43, Alexei Verkhratsky and Ole H. Petersen (Eds.), Humana Press.
22. Holthoff K*, Sagnak E, Witte OW (2007) Functional mapping of cortical areas with optical imaging, Neuroimage 37: 440-448.
23. Johenning F, Holthoff K* (2007) Nuclear Calcium signals during L-LTP induction do not predict the degree of synaptic potentiation, Cell Calcium 41: 271-83.
24. Holthoff K*, Kovalchuk Y, Konnerth A (2006) Dendritic spikes and activity-induced synaptic plasticity, Cell Tissue Res 326: 369-77.
25. Holthoff K, Kovalchuk Y, Yuste R* , Konnerth A (2004) Single-shock LTD by local dendritic spikes, J Physiol 560: 27-36.
26. Kovalchuk Y, Holthoff K, Konnerth A* (2004) Neurotrophin action on a rapid time scale, Curr Opin Neurobiol 14: 558-563.
27. Holthoff K* (2004) Dendritic spikes and synaptic plasticity, Curr Neurovasc Res 1 (4): 269-281.
28. Stosiek C, Garaschuk O, Holthoff K, Konnerth A* (2003) In vivo two-photon calcium imaging of neuronal networks. Proc Natl Acad Sci U S A 100: 7319-7324.
29. Ludwig A, Budde T, Stieber J, Moosmang S, Wahl C, Holthoff K, Langebartels A, Wotjak C, Munsch T, Zong X, Feil S, Feil R, Lancel M, Chien KR, Konnerth A, Pape HC, Biel M, Hofmann F* (2003)  Absence epilepsy and sinus dysrhythmia in mice lacking the pacemaker channel HCN2. EMBO J 22: 216-224.
30. Holthoff K*, Tsay D (2002) Calcium dynamics in spines: Link to synaptic plasticity, Exp Physiol  87.6, 725-731.
31. Holthoff K*, Tsay D, Majewska A, Yuste R (2002) Response to 'Raising the speed limit - Fast calcium handling in dendritic spines', Trends Neurosci 25: 441.
32. Goldberg J*, Holthoff K, Yuste R (2002) A Problem with Hebb and local spikes. Trends Neurosci 25: 433-435.
33. Holthoff K*, Tsay D, Yuste R (2002) Calcium dynamics in spines depend on their dendritic location. Neuron, 33:425-437.
34. Witte OW*, Niermann H, Holthoff K (2001) Cell swelling and ion redistribution assessed with intrinsic optical signals. An Acad Bras Cienc 73: 337-35.
35. Niermann H, Amiry-Moghaddam M, Holthoff K, Witte OW, Ottersen OP* (2001) A novel role of vasopressin in the brain: modulation of a radial, activity dependent water flux in the neocortex. J Neurosci, 21:3045-3051.
36. Yuste R, Miller RB, Holthoff K, Zhang S, Miesenbock G* (2000) Synapto-pHluorins: chimeras between pH-sensitive mutants of green fluorescent protein and synaptic vesicle membrane proteins as reporters of neurotransmitter release. Methods Enzymol 327:522-546.
37. Yuste R*, Majewska A, Holthoff K (2000) From form to function: calcium compartmentalization in dendritic spines. Nat Neurosci 3(7): 653-659.
38. Holthoff K, Witte OW* (2000) Directed spatial potassium redistribution in rat neocortex. Glia,  29:288-292.
39. Holthoff K, Witte OW* (1998) Intrinsic optical signals in vitro: a tool to measure alterations in extracellular space with two-dimensional resolution. Brain Res Bull 47:649-655.
40. Holthoff K, Witte OW* (1997) Recording of neuronal network properties with near infrared dark field microscopy and microelectrodes. Electrochim Acta 42:3241-3246.
41. Holthoff K, Witte OW* (1996) Intrinsic optical signals in rat neocortical slices measured with near-infrared dark-field microscopy reveal changes in extracellular space. J Neurosci 16:2740-2749.
42. Holthoff K, Dodt HU, Witte OW* (1994) Changes in intrinsic optical signal of rat neocortical slices following afferent stimulation. Neurosci Lett 180:227-230.
43. Ott D, Holthoff K, Lades M, and Eckmiller R* (1990) Scanning laser ophthalmoscopy (SLO) - a new tool in vision and oculomotor research. SPIE 1357:218-227.
44. Ott D, Lades M, Holthoff K, Eckmiller R* (1990) A general numerical method evaluating three-dimensional eye rotations by scanning laser ophthalmoscopy. Ophthalmic Physiol Opt 10:286-290.

* Korrespondierender Autor

Förderungen der Arbeitsgruppe: https://www.uniklinikum-jena.de/bioimaging/F%C3%B6rderung.html

Team der Arbeitsgruppe: https://www.uniklinikum-jena.de/bioimaging/Gruppe.html

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