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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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Inhibition of cardiac Kv4.3 (Ito) channel isoforms by class I antiarrhythmic drugs lidocaine and mexiletine. Eur J Pharmacol. 2020 Aug 5;880:173159. doi: 10.1016/j.ejphar.2020.173159. Epub 2020 Apr 29.

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Brain energy rescue: an emerging therapeutic concept for neurodegenerative disorders of ageing. Nat Rev Drug Discov. 2020 Jul 24. doi: 10.1038/s41573-020-0072-x. Online ahead of print.

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Lactate Attenuates Synaptic Transmission and Affects Brain Rhythms Featuring High Energy Expenditure. iScience. 2020 Jul 24;23(7):101316. doi: 10.1016/j.isci.2020.101316. Epub 2020 Jun 27.

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A Global Cndp1-Knock-Out Selectively Increases Renal Carnosine and Anserine Concentrations in an Age- and Gender-Specific Manner in Mice. Int J Mol Sci. 2020 Jul 10;21(14):4887. doi:10.3390/ijms21144887.

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Neuronal gamma oscillations and activity-dependent potassium transients remain regular after depletion of microglia in postnatal cortex tissue. J Neurosci Res. 2020 Jul 7. doi: 10.1002/jnr.24689. Online ahead of print.

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Marfan-Syndrom: Eine therapeutische Herausforderung für die Langzeitbehandlung (3/3). Medinlux. 2020 Jun;6:16-20. Review.

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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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Marfan-Syndrom: Eine therapeutische Herausforderung für die Langzeitbehandlung (2/3). Medinlux. 2020 May;5:16-23. Review.

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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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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