Koch Group

Netzwerkeigenschaften und Mikrostruktur des menschlichen Gehirns

Das menschliche Gehirn muss ständig die kontinuierliche, elektrische Aktivität anpassen, welche die Grundlage von Informationsverarbeitung und der Gedächtnisbildung darstellt. Eine Fehlregulation dieses Gleichgewichts kann die neuronalen Netze in einen übererregten Zustand versetzen, was zu sogenannten epileptischen Anfällen führt, die eine Störung der betroffenen Hirnregionen verursacht. Die Ursache von epileptischer Hirnaktivität kann sehr unterschiedlich sein und die Mechanismen, die an der Entstehung und Entwicklung einer epileptischen Störung beteiligt sind, sind sehr komplex. Das Ziel unserer Arbeitsgruppe ist es, die Erregbarkeit kortikaler Verschaltungen und die Plastizität menschlicher Neurone und neuronaler Netzwerke zu untersuchen, auch inwieweit sie an der Epileptogenese beteiligt sind. Die Identifizierung potenzieller molekularer und zellulärer Signalwege, die an der Regulierung der Erregbarkeit der kortikalen Netzwerke beteiligt sind, könnte neue Ansatzpunkte für eine frühzeitige Intervention bei der Behandlung von Epilepsie aufdecken.

Porträtfoto eines Mannes mit kurzen Haaren. Er trägt ein gestreiftes Hemd.

Dr. Henner Koch
hkochukaachende

Address
Dept. of Neurology, Section Epileptology
University of Aachen
Pauwelsstrasse 30
52074 Aachen, Germany
Tel. +49-(0)241- 80-80576

 

Team

Porträtfoto eines Mannes mit kurzen Haaren. Er trägt ein gestreiftes Hemd.

Dr. Henner Koch
hkochukaachende

Address
Dept. of Neurology, Section Epileptology
University of Aachen
Pauwelsstrasse 30
52074 Aachen, Germany

Tel. +49-(0)241-80-80576

 

Porträtfoto eines Mannes schwarzen Haaren und Schnurrbart. Er trägt einen weißen Kittel.

Sebastian Maruri
smaruripazmiukaachende

Address
Dept. of Neurology, Section Epileptology
University of Aachen
Pauwelsstrasse 30
52074 Aachen, Germany

Tel. +49-(0)241-80675

 

Porträtfoto einer Frau mit langen dunkelblonden Haaren. Sie trägt eine weiße Bluse.

Birgit Gittel (lead technician)
bgittelukaachende

Address
Dept. of Neurology, Section Epileptology
University of Aachen
Pauwelsstrasse 30
​​​​​​​52074 Aachen, Germany

Tel. +49-(0)241-80-38611

 

Porträtfoto einer lächelnden Frau mit braunen langen Haareb

Lisa Josephine Korn
lkornukaachende

Address
Dept. of Neurology, Section Epileptology
University of Aachen
Pauwelsstrasse 30
​​​​​​​52074 Aachen, Germany

 

Research projects and techniques

Aging and Neurodegeneration in a Human Brain Tissue Model

  • Studying and manipulating the mature human brain at a cellular level has historically been challenging. Recent success involves long-term culturing of surgically resected human brain tissue while preserving its mature structure and neuronal activity.
  • Recent research highlights the critical role of glia cells in neurodegenerative diseases.
  • The project combines expertise in brain slice cultures and immunology to create a novel tool for exploring neurodegenerative disease dynamics and molecular mechanisms.
  • This innovative system has the potential to bridge the gap between animal and human studies, serving as a primary tool for investigating neurodegenerative disease processes and testing new therapeutics.

Epilepsy and the respiratory control of breathing – Implication for SUDEP

  • SUDEP is the leading epilepsy-related cause of death, affecting all ages and epilepsy severities. While ASMs control seizures for many patients, they don't cure epilepsy and can have severe side effects.
  • Roughly 30% of ASM-resistant epilepsy patients face ongoing seizures and higher SUDEP risk, necessitating safer treatments.
  • Targeting new molecular anti-seizure treatments may yield novel drugs and early diagnosis biomarkers.
  • Cardiorespiratory dysfunction post-seizures may be SUDEP's common mechanism. Brainstem involvement due to epilepsy activity can cause SUDEP. Mouse models and advanced tech allow precise brain network investigations.
  • A critical need persists for understanding epilepsy and SUDEP mechanisms. Mouse models and precise methods are vital for translating findings into preventive and therapeutic strategies.
  • Promising therapies often fail to transition from preclinical models to human treatments.
  • New therapy options are primarily developed and tested in non-human systems.
  • Utilize human ex vivo brain systems to bridge the gap between preclinical and clinical research in epilepsy.
  • Characterize and optimize viral vectors for gene therapy in human brain tissue, apply viral vector-mediated CRISPR techniques to model epilepsy causes in human samples, and use these insights to enhance promoter-driven gene therapy approaches for epilepsy. The ultimate goal is to improve treatment approaches for patients with epilepsy by gaining more accurate insights into disease mechanisms within a human context.

https://elifesciences.org/articles/48417

https://www.nature.com/articles/s41598-017-12527-9

https://www.biorxiv.org/content/10.1101/2023.10.10.561508v1

  • Epilepsy involves synchronized depolarizations of neuron groups leading to seizures, with various causes. The electrophysiological and micro-anatomical aspects of seizures are poorly understood.
     
  • To investigate epileptic discharges at a micro-network level we utilize innovative culturing methods for human brain slices and employ micro-electrode arrays (MEA) for spatio-temporal electrophysiological recordings.
     
  • MEA recordings are instrumental in studying neuronal activity in human neocortical and hippocampal slices, providing insights into synchronized network activities. This approach aids in better understanding neuronal network dynamics and simulating physiological and disease-related brain processes.

Publications

10 Selected publications:

Schwarz N, Uysal B, Welzer M, Bahr JC, Layer N, Löffler H, Stanaitis K, Pa H, Weber YG, Hedrich UB, Honegger JB, Skodras A, Becker AJ, Wuttke TV, Koch H : 'Long-term adult human brain slice cultures as a model system to study human CNS circuitry and disease.' last (senior) eLife, 2019 Sep 9 doi: doi: 10.7554/eLife.48417

Koch H, Weber YG : 'The glucose transporter type 1 (Glut1) syndromes.' first Epilepsy & behavior : E&B, 2019 Feb doi: doi: 10.1016/j.yebeh.2018.06.010

Schwarz N, Hedrich UBS, Schwarz H, P A H, Dammeier N, Auffenberg E, Bedogni F, Honegger JB, Lerche H, Wuttke TV, Koch H : 'Human Cerebrospinal fluid promotes long-term neuronal viability and network function in human neocortical organotypic brain slice cultures.' last (senior) Scientific reports, 2017 Sep 25 doi: doi: 10.1038/s41598-017-12527-9

Schünemann KD, Hattingh RM, Verhoog MB, Yang D, Bak AV, Peter S, van Loo KMJ, Wolking S, Kronenberg-Versteeg D, Weber Y, Schwarz N, Raimondo JV, Melvill R, Tromp SA, Butler JT, Höllig A, Delev D, Wuttke TV, Kampa BM, Koch H : 'Comprehensive analysis of human dendritic spine morphology and density.' last (senior) Journal of neurophysiology, 2025 Apr 1 doi: doi: 10.1152/jn.00622.2024

Qi G, Yang D, Bak A, Hucko W, Delev D, Hamou H, Feldmeyer D, Koch H : 'Transport-related effects on intrinsic and synaptic properties of human cortical neurons: A comparative study.' last (senior) The Journal of physiology, 2026 Mar doi: doi: 10.1113/JP288111

Koch H, Caughie C, Elsen FP, Doi A, Garcia AJ 3rd, Zanella S, Ramirez JM : 'Prostaglandin E2 differentially modulates the central control of eupnoea, sighs and gasping in mice.' first The Journal of physiology, 2015 Jan 1 doi: doi: 10.1113/jphysiol.2014.279794

Bak A, Schmied K, Jakob ML, Bedogni F, Squire OA, Gittel B, Jesinghausen M, Schünemann KD, Weber Y, Kampa B, van Loo KMJ, Koch H : 'Temporal dynamics of neocortical development in organotypic mouse brain cultures: a comprehensive analysis.' last (senior) Journal of neurophysiology, 2024 Sep 1 doi: doi: 10.1152/jn.00178.2024

Koch H, Huh SE, Elsen FP, Carroll MS, Hodge RD, Bedogni F, Turner MS, Hevner RF, Ramirez JM : 'Prostaglandin E2-induced synaptic plasticity in neocortical networks of organotypic slice cultures.' first The Journal of neuroscience : the official journal of the Society for Neuroscience, 2010 Sep 1 doi: doi: 10.1523/JNEUROSCI.4665-09.2010

Koch H, Zanella S, Elsen GE, Smith L, Doi A, Garcia AJ 3rd, Wei AD, Xun R, Kirsch S, Gomez CM, Hevner RF, Ramirez JM : 'Stable respiratory activity requires both P/Q-type and N-type voltage-gated calcium channels.' first The Journal of neuroscience : the official journal of the Society for Neuroscience, 2013 Feb 20 doi: doi: 10.1523/JNEUROSCI.6390-11.2013

Layer N, Brandes J, Lührs PJ, Wuttke TV, Koch H : 'The effect of lamotrigine and other antiepileptic drugs on respiratory rhythm generation in the pre-Bötzinger complex.' last (senior) Epilepsia, 2021 Nov doi: doi: 10.1111/epi.17066

Further publications
 
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