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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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Marfan syndrome: A therapeutic challenge for long-term care. Biochem Pharmacol. 2019 Jun;164:53-63. doi: 10.1016/j.bcp.2019.03.034. Epub 2019 Mar 27.

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Characterization of the Subventricular-Thalamo-Cortical Circuit in the NP-C Mouse Brain, and New Insights Regarding Treatment. Mol Ther. 2019 May 16. pii: S1525-0016(19)30222-9. doi: 10.1016/j.ymthe.2019.05.008. [Epub ahead of print]

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TRPC channels are not required for graded persistent activity in entorhinal cortex neurons. Hippocampus. 2019 Apr 19. doi: 10.1002/hipo.23094. [Epub ahead of print]

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Angioneurins-key regulators of blood-brain barrier integrity during hypoxic and ischemic brain injury. Prog Neurobiol. 2019 Apr 7. pii: S0301-0082(19)30039-5. doi: 10.1016/j.pneurobio.2019.03.004. [Epub ahead of print] Review.

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Chronic hypoxia changes gene expression profile of primary rat carotid body cells: consequences on the expression of NOS isoforms and ET-1 receptors. Physiol Genomics. 2019 Apr 1;51(4):109-124. doi: 10.1152/physiolgenomics.00114.2018. Epub 2019 Mar 1.

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Determination of the Maximum Velocity of Filaments in the in vitro Motility Assay. Front Physiol. 2019 Mar 27;10:289. doi: 10.3389/fphys.2019.00289. eCollection 2019.

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Priming of microglia with IFN-γ slows neuronal gamma oscillations in situ. Proc Natl Acad Sci U S A. 2019 Feb 19. pii: 201813562. doi: 10.1073/pnas.1813562116. [Epub ahead of print]

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Reduction of Transplant Vasculopathy by Intraoperative Nucleic Acid-based Therapy in a Mouse Aortic Allograft Model. Thorac Cardiovasc Surg. 2018 Oct 23. doi: 10.1055/s-0038-1673633. [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