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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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Amyloid, APP, and Electrical Activity of the Brain. Neuroscientist. 2020 Jun;26(3):231-251. doi: 10.1177/1073858419882619. Epub 2019 Nov 29.

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Selective inhibition of mitochondrial respiratory complexes controls the transition of microglia into a neurotoxic phenotype in situ. Brain Behav Immun. 2020 May 21. pii: S0889-1591(20)30209-9. doi: 10.1016/j.bbi.2020.05.052. [Epub ahead of print]

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Synchronicity of excitatory inputs drives hippocampal networks to distinct oscillatory patterns. Hippocampus. 2020 May 15. doi: 10.1002/hipo.23214. [Epub ahead of print]

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Vascular Signaling in Allogenic Solid Organ Transplantation - The Role of Endothelial Cells. Front Physiol. 2020 May 8;11:443. doi: 10.3389/fphys.2020.00443. eCollection 2020. Review.

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Plant "intelligence" changes nothing. EMBO Rep. 2020 May 6;21(5):e50395. doi: 10.15252/embr.202050395. Epub 2020 Apr 16.

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Inhibition of cardiac Kv4.3 (Ito) channel isoforms by class I antiarrhythmic drugs lidocaine and mexiletine. Eur J Pharmacol. 2020 Apr 29:173159. doi: 10.1016/j.ejphar.2020.173159. [Epub ahead of print]

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Functional association of a CD40 gene single nucleotide polymorphism with the pathogenesis of coronary heart disease. Cardiovasc Res. 2020 May 1;116(6):1214-1225. doi: 10.1093/cvr/cvz206. Epub 2019 Aug 2.

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Risk and protective factors for post-thrombotic syndrome after deep venous thrombosis. J Vasc Surg Venous Lymphat Disord. 2020 May;8(3):390-395. doi: 10.1016/j.jvsv.2019.10.012. Epub 2019 Dec 14.

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Marfan-Syndrom: Eine therapeutische Herausforderung für die Langzeitbehandlung (1/3). Medinlux. 2020 Apr;4:18-22. Review.

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AAV-mediated TIMP-1 overexpression in aortic tissue reduces the severity of allograft vasculopathy in mice. J Heart Lung Transplant. 2020 Apr;39(4):389-398. doi: 10.1016/j.healun.2020.01.1338. Epub 2020 Jan 30.

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Endothelial CD40 Mediates Microvascular von Willebrand Factor-Dependent Platelet Adhesion Inducing Inflammatory Venothrombosis in ADAMTS13 Knockout Mice. Thromb Haemost. 2020 Mar;120(3):466-476. doi: 10.1055/s-0040-1702228. Epub 2020 Mar 5.

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Mild metabolic stress is sufficient to disturb the formation of pyramidal cell ensembles during gamma oscillations. J Cereb Blood Flow Metab. 2019 Dec 16:271678X19892657. doi: 10.1177/0271678X19892657. [Epub ahead of print

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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]


Institute of
Physiology and Pathophysiology

Heidelberg University

Im Neuenheimer Feld 326

69120 Heidelberg

Germany

Phone:+49 6221 54-4056
Fax:+49 6221 54-6364
E-mail:susanne.bechtel@
physiologie.uni-heidelberg.de