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Research Group Lippmann

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Research

Function-to-structure analysis of synapses to understand presynaptic vesicular dynamics and plasticity


Synaptic transmission is fundamental for nerve cell communication, brain activity and cognition. Brain activity and cognition are not static but dynamic processes subserving learning and environmental adaptation. Until recently, it was possible to study synaptic transmission only either functionally by using electrophysiology, with which one can measure synaptic currents in nerve cells, or by imaging snapshots of synaptic structures using high-resolution electron microscopy. By using a technique called zap-and-freeze, biological tissue like acute brain slices can be electrically stimulated and subsequently high-pressure frozen within milliseconds. Highly dynamic processes, such as presynaptic vesicle fusion and endocytosis can thus be resolved spatiotemporally with electron microscopy. Using this approach in acute brain slices, we investigate vesicular dynamics, such as occurring during presynaptic plasticity, in space and time. Electron tomography further enables us to three-dimensionally reconstruct larger parts of synapses for in-depth analyses of vesicular docking states and fusion pits.​​

Cellular mechanisms underlying network oscillations in epilepsy-related diseases

carl-ludwig-institut-rglippmann-research1-medizinische-fakultaet-leipzig.pngHippocampal network oscillations, such as gamma oscillations and sharp wave ripples, are fundamental for information perception, processing and memory consolidation in the brain. In epilepsy-related diseases, network oscillations are often disrupted and could thus contribute to cognitive dysfunctions of patients. We aim to better understand the cellular mechanisms underlying impaired hippocampal network oscillations in acquired and congenital epilepsy-related diseases. For this, we use patch-clamp electrophysiology for studying synaptic and intrinsic cellular activities as well as local field potential recordings to characterize changes in network oscillations in acute brain slices and in vivo. We are particularly interested in functional changes of parvalbumin-positive fast-spiking interneurons (PV-IN), inhibitory neurons that are key players for generating gamma oscillations and sharp wave ripples as well as for promoting epileptic activity in case of their dysfunction.​

Funding

​carl-ludwig-institut-rg-lippmann-funding-mbl-medizinische-fakultaet-leipzig.jpeg​Whitman Fellowship
Marine Biological Laboratory,
Woods Hole, MA, USA
​Universität_Leipzig_Logo.png​Junior Research Grant
Medical Faculty, Leipzig University
​the_grass_foundation_logo.png​Grass Fellowship
Grass Foundation, USA

Team

​carl-ludwig-institut-lippmann-medizinische-fakultaet-leipzig.jpg​Dr. Kristina Lippmann
Group ​Leader
Kristina.Lippmann@medizin.uni-leipzig.de​
​carl-ludwig-institut-burkart-medizinische-fakultaet-leipzig.jpgMarie Elisabeth Burkart

MD Student
Marie-Elisabeth.Burkart@medizin.uni-leipzig.de
Modulation of GABAergic drive and network oscillations in the hippocampal area CA1

​carl-ludwig-institut-kurzke-medizinische-fakultaet-leipzig.jpgJosephine Kurzke
MD Student
Josephine.Kurzke@medizin.uni-leipzig.de
Cognitive impairment underlying DEND syndrome - Modulation of hippocampal gamma activity by the KATP activating mutation V59M
​carl-ludwig-institut-jacobi-medizinische-fakultaet-leipzig.jpg​Robert Jacobi
MD Student, University of Würzburg
Robert.Jacobi@stud-mail.uni-wuerzburg.de

Positions

We are looking for talented, ambitious and creative students, who are interested in joining our team. We are offering doctoral research projects for medical students and bachelor or master thesis projects for life science students interested in neuroscience.​

Publications

Articles
(* equal contribution; # shared correspondence)


In preparation

Lippmann K.
Post-stroke epileptogenesis diminishes hippocampal presynaptic GABAergic release.


Published

Lippmann, K. 2024
A Reduction in the Readily Releasable Vesicle Pool Impairs GABAergic Inhibition in the Hippocampus after Blood–Brain Barrier Dysfunction.
Int. J. Mol. Sci. 25:6862. https://doi.org/10.3390/ijms25136862

Burkart ME*, Kurzke J*, Vera J, Ashcroft FM, Eilers JE,​​ Lippmann K. 2023
​KATP​ channel mutation disrupts hippocampal network activity and nocturnal gamma shifts.
Brain, awae157, https://doi.org/10.1093/brain/awae157

Lippmann K, Klaft ZJ, Salar S, Hollnagel JO, Maslarova A. 2022
​Status epilepticus induces chronic silencing of burster and dominance of regular ​firing neurons during sharp wave-ripples in the mouse subiculum.
Neurobiol Dis 175:105929. Online ahead of print.

Köhler S, Winkler U, Junge T, Lippmann K, Eilers J, Hirrlinger J. 2022
Gray and white matter astrocytes differ in basal metabolism but respond similarly to neuronal activity.
Glia. 2022 Sep 5. doi: 10.1002/glia.24268. Online ahead of print.

Vera J., Lippmann K.*
Post-stroke epileptogenesis is associated with altered intrinsic properties of hippocampal pyramidal neurons leading to increased theta resonance.
*These authors contributed equally
Neurobiol Dis. 2021; 156:105425

Kusick G.F., Chin M., Raychaudhuri S., Lippmann K.*, Adula KP.*, Hujber E*., Vu T.*, Davis M.W., Jorgensen E.M., Watanabe S.
Synaptic vesicles transiently dock to refill release sites.
*These authors contributed equally
Nat Neurosci 2020 Nov; 23(11):1329-1338 doi: 10.1038/s41593-020-00716-1.

Wagner W.*, Lippmann K.*, Hornig S., Lombino F., Roesler M., Schweizer M., Polo S., Schwarz J.R., Eilers J. and Kneussel M.,
Myosin VI plays dual roles for AMPA receptor targeting in Purkinje cells and is critical for cerebellar long-term depression.
*These authors contributed equally
Cell Rep. 2019 Jul 2;28(1):11-20.e9

Naumann G, Lippmann K, Eilers J
Photophysical properties of Na+ - indicator dyes suitable for quantitative two-​photon fluorescence-lifetime measurements.
J Microsc. 2018 Nov; 272(2):136-144

Kim SY, Senatorov VV Jr, Morrissey CS, Lippmann K, Vazquez O, Milikovsky DZ, Gu F, Parada I, Prince DA, Becker AJ, Heinemann U, Friedman A, Kaufer D
TGFß signaling is associated with changes in inflammatory gene expression and perineural net degradation around inhibitory neurons following various neurological insults.
Sci Rep. 2017 Aug 9;7(1):7711

Milikovsky DZ, Weissberg I, Solomon-Kamintsky L, Lippmann K, Schefenbauer O, Frigerio F, Rizzi M, Sheintuch L, Zelig D, Ofer J, Vezzani A, Friedman A.
Electrocorticographic dynamics as a novel biomarker in five models of epileptogenesis.
J Neurosci. 2017; pii: 2446-16. doi: 10.1523/JNEUROSCI.2446-16.2017. [Epub ahead of print]

Lippmann K, Kamintsky L, Kim SY, Lublinsky S, Prager O, Nichtweiß J, Salar S, Kaufer D, Heinemann U, Friedman A.
Epileptiform activity and spreading depolarization in the blood-brain barrier-disrupted peri-infarct hippocampus are associated with impaired GABAergic inhibition and synaptic plasticity.
J Cereb Blood Flow Metab. 2016; pii: 0271678X16652631. [Epub ahead of print]

Salar S, Lapilover EG, Müller J, Hollnagel JO, Lippmann K, Friedman A, Heinemann U.
Synaptic plasticity in area CA1 of rat hippocampal slices following intraventricular application of albumin.
Neurobiol Dis. 2016; 91:155-65

Maslarova A, Lippmann K, Salar S, Rösler A, Heinemann U.
Differential participation of pyramidal cells in generation of spontaneous sharp wave-ripples in the mouse subiculum in vitro.
Neurobiol Learn Mem. 2015; 125:113-119

Salar S, Maslarova A, Lippmann K, Nichtweiss J, Weissberg I, Sheintuch L, Kunz WS, Shorer Z, Friedman A, Heinemann U
Blood-brain barrier dysfunction can contribute to pharmacoresistance of seizures.
Epilepsia 2014; 55:1255-63

Lapilover EG, Lippmann K, Salar S, Maslarova A, Dreier JP, Heinemann U, Friedman A.
Peri-infarct blood-brain barrier dysfunction facilitates induction of spreading depolarization associated with epileptiform discharges.
Neurobiol Dis. 2012; 48:495-506

Other publications:

Wübbeler M, Lippmann K, Wünsch D, Docter D (Ed.) 2019
Lost in Translation? Translationsforschung in den Lebenswissenschaften.
Schriftenreihe der Jungen Akademie der Wissenschaften und der Literatur | Mainz, Band 3. Franz Steiner Verlag, ISBN: 978-3-515-12284-9​

Contact

​Dr. Kristina Lippmann

Carl-Ludwig-Institut für Physiologie, Room E207
Liebigstr. 27, 04103 Leipzig, Germany

phone: +49 (0) 341 15570​
​email: Kristina.Lippmann@medizin.uni-leipzig.de​

Liebigstraße 27, Haus E
04103 Leipzig
Phone:
+49 (0) 341 - 97 15500
Fax:
+49 (0) 341 - 97 15509
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