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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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The mitochondrial calcium uniporter is crucial for the generation of fast cortical network rhythms. J Cereb Blood Flow Metab. 2019 Nov 13:271678X19887777. doi: 10.1177/0271678X19887777. [Epub ahead of print]

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Shaping the heart: Structural and functional maturation of iPSC-cardiomyocytes in 3D-micro-scaffolds. Biomaterials. 2020 Jan;227:119551. doi: 10.1016/j.biomaterials.2019.119551. Epub 2019 Oct 19.

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Simulation Strategies for Calcium Microdomains and Calcium Noise. Adv Exp Med Biol. 2020;1131:771-797. doi: 10.1007/978-3-030-12457-1_31.

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Somatic mutations and promotor methylation of the ryanodine receptor 2 is a common event in the pathogenesis of head and neck cancer. Int J Cancer. 2019 Dec 15;145(12):3299-3310. doi: 10.1002/ijc.32481. Epub 2019 Jun 19.

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Persistent increase in ventral hippocampal long-term potentiation by juvenile stress: A role for astrocytic glutamine synthetase. Glia. 2019 Dec;67(12):2279-2293. doi: 10.1002/glia.23683. Epub 2019 Jul 17.

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4.2 Kreislauf. In: Physiologie hoch2 (Gründer S, Schlüter KD, eds.) Urban & Fischer Verlag/Elsevier GmbH 2019, pp. 192-225. ISBN 978-3-437-43461-7

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The neuronal oxygen-sensing pathway controls postnatal vascularization of the murine brain. FASEB J. 2019 Nov;33(11):12812-12824. doi: 10.1096/fj.201901385RR. Epub 2019 Aug 30.

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TRPC channels are not required for graded persistent activity in entorhinal cortex neurons. Hippocampus. 2019 Nov;29(11):1038-1048. doi: 10.1002/hipo.23094. Epub 2019 Apr 19.

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The C-terminal HCN4 variant P883R alters channel properties and acts as genetic modifier of atrial fibrillation and structural heart disease. Biochem Biophys Res Commun. 2019 Oct 29;519(1):141-147. doi: 10.1016/j.bbrc.2019.08.150. Epub 2019 Aug 31.

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Endothelial cell modulation of cardiomyocyte gene expression. Exp Cell Res. 2019 Oct 15;383(2):111565. doi: 10.1016/j.yexcr.2019.111565. Epub 2019 Aug 20.

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Pacemaker cell characteristics of differentiated and HCN4-transduced human mesenchymal stem cells. Life Sci. 2019 Sep 1;232:116620. doi: 10.1016/j.lfs.2019.116620. Epub 2019 Jul 7.

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Reduction of Transplant Vasculopathy by Intraoperative Nucleic Acid-based Therapy in a Mouse Aortic Allograft Model. Thorac Cardiovasc Surg. 2019 Sep;67(6):503-512. doi: 10.1055/s-0038-1673633. Epub 2018 Oct 23.

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Functional association of a CD40 gene single nucleotide polymorphism with the pathogenesis of coronary heart disease. Cardiovasc Res. 2019 Aug 2. pii: cvz206. doi: 10.1093/cvr/cvz206. [Epub ahead of print]


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