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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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Hypertension-evoked RhoA activity in vascular smooth muscle cells requires RGS5. FASEB J. 2017 Dec 5. pii: fj.201700384RR. doi: 10.1096/fj.201700384RR. [Epub ahead of print]

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Modulation of glutathione peroxidase activity by age-dependent carbonylation in glomeruli of diabetic mice. J Diabetes Complications. 2017 Nov 22. pii: S1056-8727(17)31094-2. doi: 10.1016/j.jdiacomp.2017.11.007. [Epub ahead of print]

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Sensitive mass spectrometric assay for determination of 15-deoxy-Δ12,14-prostaglandin J2 and its application in human plasma samples of patients with diabetes. Anal Bioanal Chem. 2017 Nov 16. doi: 10.1007/s00216-017-0748-1. [Epub ahead of print]

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Role of protein carbonylation in diabetes. J Inherit Metab Dis. 2017 Nov 6. doi: 10.1007/s10545-017-0104-9. [Epub ahead of print]

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AP-1 Oligodeoxynucleotides Reduce Aortic Elastolysis in a Murine Model of Marfan Syndrome. Mol Ther Nucleic Acids. 2017 Dec 15; 9: 69–79. Epub 2017 Sep 20. doi: 10.1016/j.omtn.2017.08.014

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Allosteric inhibition of carnosinase (CN1) by inducing a conformational shift. J Enzyme Inhib Med Chem. 2017 Dec;32(1):1102-1110. doi: 10.1080/14756366.2017.1355793.

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Transcription factor decoy technology: a therapeutic update. Biochem Pharmacol. 2017 Nov 15;144:29-34. doi: 10.1016/j.bcp.2017.06.122. Epub 2017 Jun 19. Review.

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Local oxygen homeostasis during various neuronal network activity states in the mouse hippocampus. J Cereb Blood Flow Metab. 2017 Nov 3; 271678X17740091. doi: 10.1177/0271678X17740091

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Subtype-specific differentiation of cardiac pacemaker cell clusters from human induced pluripotent stem cells. Stem Cell Res Ther. 2017 Oct 16;8(1):229. doi: 10.1186/s13287-017-0681-4.

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Heteromeric channels formed by TRPC1, TRPC4 and TRPC5 define hippocampal synaptic transmission and working memory. EMBO J. 2017 Sep 15;36(18):2770-2789. doi: 10.15252/embj.201696369. Epub 2017 Aug 8


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