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Institute of Physiology and Pathophysiology

Research Areas

Fast Network Oscillations


Rhythmic activity is a key functional feature of the brain, as evident from the well-known EEG-rhythms. Meanwhile, many neuroscientists agree that such network oscillations are «meaningful» and provide an important background for temporal coding of information. In our group we focus on one type of network oscillations in the rodent hippocampus, namely «ripples» at ~200 Hz as originally described by John O´Keefe, G. Buszáki and others. We want to elucidate the precise mechanisms by which neurons are entrained to fire at high precision within these short (5 ms) cycles. Moreover, we would like to find out why certain neurons participate in this network while others do not.

Function of GABAergic Synapses

The complex organisation of central synapses offers multiple mechanisms for regulation and modulation of synaptic strength. We focus on inhibitory synapses in the mammalian CNS which use GABA (gamma-aminobutyric acid) as transmitter. The availability of GABA is regulated by its synthesis, degradation and after release-uptake. In situations of over-excitability, the GABA-synthetizing enzyme GAD is up-regulated while a decrease of neuronal activity leads to a down-regulation of GAD. Thus, cellular GABA content seems to be an activity-dependent, variable parameter. We propose that the presynaptic GABA metabolism is a true and autonomous mechanism of synaptic plasticity. We are presently testing this hypothesis using various electrophysiological, histological and biochemical techniques.

Synaptic Physiology and Pharmacology of Epilepsy


Epilepsy is characterized by a chronic state of recurrent pathological hypersynchronous electrical activity in the brain or parts of the brain. A very simple pathophysiologcal concept could ascribe epilepsy to a disturbed balance between excitation and inhibition in the affected circuits. Certainly, this idea is a gross over-simplification. Nevertheless, some of the most efficient anticonvulsant drugs act by strengthening synaptic inhibition. We are interested in the mechanisms of action of such drugs at the synaptic, cellular and network level. Moreover, we search for changes in synaptic innervation of hippocampal neurons in models of temporal lobe epilepsy. Such efforts should help to clarify why epileptic seizures alter the hippocampal circuitry in a way which promotes further epileptogenesis, contributing to the chronic (and often progressive) nature of this frequent disease.


Recent Publications

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Impact of carbonylation on glutathione peroxidase-1 activity in human hyperglycemic endothelial cells. Redox Biol. 2018 Jun;16:113-122. doi: 10.1016/j.redox.2018.02.018. Epub 2018 Mar 1.

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Improving electrical properties of iPSC-cardiomyocytes by enhancing Cx43 expression. J Mol Cell Cardiol. 2018 May 16. pii: S0022-2828(18)30171-8. doi: 10.1016/j.yjmcc.2018.05.010. [Epub ahead of print]

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Early Blood-Brain Barrier Disruption in Ischemic Stroke Initiates Multifocally Around Capillaries/Venules. Stroke. 2018 May 14. pii: STROKEAHA.118.020927. doi: 10.1161/STROKEAHA.118.020927. [Epub ahead of print]

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In silico assessment of the conduction mechanism of the Ryanodine Receptor 1 reveals previously unknown exit pathways. Sci Rep. 2018 May 2;8(1):6886. doi: 10.1038/s41598-018-25061-z.

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Parallel detection of theta and respiration-coupled oscillations throughout the mouse brain. Sci Rep. 2018 Apr 24;8(1):6432. doi: 10.1038/s41598-018-24629-z.

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Stability and Function of Hippocampal Mossy Fiber Synapses Depend on Bcl11b/Ctip2. Front Mol Neurosci. 2018 Apr 5;11:103. doi: 10.3389/fnmol.2018.00103. eCollection 2018.

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Glycyrrhetinic Acid Antagonizes Pressure-Induced Venous Remodeling in Mice. Front Physiol. 2018 Apr 4;9:320. doi: 10.3389/fphys.2018.00320. eCollection 2018.

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Respiration-Entrained Brain Rhythms Are Global but Often Overlooked. Trends Neurosci. 2018 Apr;41(4):186-197. doi: 10.1016/j.tins.2018.01.007. Epub 2018 Feb 9.

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Hypertension-evoked RhoA activity in vascular smooth muscle cells requires RGS5. FASEB J. 2018 Apr;32(4):2021-2035. doi: 10.1096/fj.201700384RR. Epub 2018 Jan 5.

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VCAM-1 expression is upregulated by CD34+/CD133+-stem cells derived from septic patients. PLoS One. 2018 Mar 30;13(3):e0195064. doi: 10.1371/journal.pone.0195064. eCollection 2018.

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Carnosine Catalyzes the Formation of the Oligo/Polymeric Products of Methylglyoxal. Cell Physiol Biochem. 2018 Apr;46(2):713-726. doi: 10.1159/000488727. Epub 2018 Mar 29.

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Making room for new memories. Science. 2018 Mar 30;359(6383):1461-1462. doi: 10.1126/science.aat1493.

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Bringing European physiologists together. Acta Physiol (Oxf). 2018 Apr;222(4):e13043. doi: 10.1111/apha.13043. Epub 2018 Feb 15.

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Endothelial progenitor cells accelerate endothelial regeneration in an in vitro model of Shigatoxin-2a-induced injury via soluble growth factors. Am J Physiol Renal Physiol. 2018 Mar 7. doi: 10.1152/ajprenal.00633.2017. [Epub ahead of print]

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Astrocytic glutamine synthetase is expressed in the neuronal somatic layers and down-regulated proportionally to neuronal loss in the human epileptic hippocampus. Glia. 2018 May;66(5):920-933. doi: 10.1002/glia.23292. Epub 2018 Jan 19.

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Expansion of functional personalized cells with specific transgene combinations. Nat Commun. 2018 Mar 8;9(1):994. doi: 10.1038/s41467-018-03408-4.


Institute of
Physiology and Pathophysiology

Heidelberg University

Im Neuenheimer Feld 326

69120 Heidelberg

Germany

Phone:+49 6221 54-4035
Fax:+49 6221 54-4038
E-mail:sekretariat.hecker@
physiologie.uni-heidelberg.de