Neurobiology Lecture


Age-based models to study synaptic dysfunction

Luísa V. Lopes
Instituto de Medicina Molecular
Lisbon, Portugal

While neuronal loss has long been considered as the main contributor to age-related cognitive decline, these alterations are currently attributed to gradual synaptic dysfunction driven by calcium dyshomeostasis and alterations in ionotropic/metabotropic receptors. Given the key role of the hippocampus in encoding, storage, and retrieval of memory, the morpho- and electrophysiological alterations that occur in the major synapse of this network deserve special attention. A link between regular consumption of caffeine - an adenosine receptor blocker - to decreased risk of Alzheimer’s disease (AD) in humans is well established, while the mechanisms responsible have only now been uncovered.

We have compelling evidence from humans and animal models that implicate adenosine A2A receptors (A2AR) upsurge as a crucial mediator of age-related synaptic dysfunction. The relevance of this mechanism in patients was very recently demonstrated in the form of a significant association of the A2AR-encoding gene with hippocampal volume (synaptic loss) in mild cognitive impairment and AD. Novel pathways implicate A2AR in the control of mGluR5-dependent NMDAR activation and subsequent Ca2+ dysfunction upon aging. The nature of this receptor makes it particularly suited for long-term therapies, as an alternative for regulating aberrant mGluR5/NMDAR signaling in aging and disease, without disrupting their crucial constitutive activity.


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Heidelberg researchers investigate new approaches to treating neurodegenerative diseases

Bading2MauceripicProtecting nerve cells from losing their characteristic extensions, the dendrites, can reduce brain damage after a stroke. Neurobiologists from Heidelberg University have demonstrated this by means of research on a mouse model. The team, led by Prof.Dr. Hilmar Bading in cooperation with Junior Professor Dr. Daniela Mauceri, is investigating the protection of neuronal architecture to develop new approaches to treating neurodegenerative diseases. The current research findings were published in the journal “Proceedings of the National Academy of Sciences”.

Brain nerve cells possess many arborised dendrites, which can make connections with other neurons. The highly complex, ramified structure of neurons is an important precondition for their ability to connect with other nerve cells, in order to enable the brain to function normally. In earlier studies, the Heidelberg researchers identified the signal molecule VEGFD – Vascular Endothelial Growth Factor D – as a central regulator for maintaining and restoring neuronal structures. “Our current research results demonstrate that a stroke as a consequence of an interruption of the blood supply to the brain leads to a reduction of VEGFD levels. That causes the nerve cells to lose part of their dendrites. They shrink and this leads to impairments of the cognitive and motor abilities,” explains Prof. Bading.

Based on these findings, the researchers at the Interdisciplinary Centre for Neurosciences explored the question of whether the reduction of neuronal structures after a stroke can be prevented by restoring the VEGFD levels. More...

SchuetzZum Tod von Günther Schütz, IZN Alumnus

Das Deutsche Krebsforschungszentrum trauert um Günther Schütz, einen großen Wissenschaftler und hoch angesehen ehemaligen Kollegen, der am 28. Mai im Alter von 80 Jahren verstorben ist. Mehr...

What determines the identity of cells?

MallScientists from the Hector Institute for Translational Brain Research and Stanford University showed in mice how so-called pioneer factors determine the identity of nerve and muscle cells. During embryonic development, these factors ensure that the various body cells can form. In laboratory experiments, pioneer factors can even be used to transform cell types, for example skin cells into nerve cells. This allows scientists to obtain specific cell types for their research.

Moritz Mall at the German Cancer Research Center (DKFZ, HITBR) and Qian Yi Lee at Stanford University compared two transcription factors that are structurally similar but induce completely different cell types. The factor Ascl1 can program skin cells into nerve cells, while Myod1 can convert skin cells into muscle cells.

Since transcription factors normally exert their effect by binding certain gene switches, the researchers first investigated the DNA binding sites of both factors. Although Ascl1 and Myod1 induce very different cell types, both surprisingly bind to largely overlapping recognition sequences in the mouse genome. This is true both during reprogramming and during normal cell differentiation. "For us, this was an indication that other mechanisms must be involved to ensure that only the desired genes are regulated," explains Mall. In fact, further analyses showed that despite the overlap, Ascl1 and Myod1 each attached to specific regions of the genome with stronger binding power. More...

An epigenetic factor in memory-encoding neurons improves the ability to remember

AnaoliveiraIt is currently thought that memories are represented within the neurons that are activated when we acquire new information and that the retrieval of a memory requires the reactivation of this subset of neuons. The group led by Dr. Ana Oliveira now found that, increasing a protein called Dnmt3a2, that is responsible for establishing chemical marks on the DNA, specifically in hippocampal memory-encoding cells is sufficient to boost memory in mice and to modulate the precision of the reactivation of the memory-encoding cells.

The scientists trained laboratory mice in a Pavlovian-conditioning task, and labelled the cells of the hippocampus that encode the memory for that experience (around 5% of the whole hippocampus). When they increased Dnmt3a2 levels selectively in these memory-encoding cells, they observed that the mice had improved memory performance. This was associated with better reactivation of the “correct” memory-encoding cells during memory recall. Remarkably, the same protein was previously shown to restore aging-related cognitive dysfunctions, and to facilitate the erasure of traumatic memories in mice. Therefore, this study opens a new gate for future studies aimed at designing new therapeutic approaches based on targeting memory-encoding cells, to modulate the duration of memories.

Related article: Neuronal ensemble-specific DNA methylation strengthens engram stability Externer Inhalt


Open positions at the IZN

  • A postdoc/scientific assistant position is offered in the Research Group 'General Neurophysiology' (Prof. Dr. Oliver Kann) at the Institute of Physiology and Pathophysiology, University of Heidelberg. The group focuses on (i) mitochondria and energy metabolism during neuronal activity, and (ii) the impact of activated microglia (brain macrophages) on neuronal activity and neurodegeneration. Adobe
    Posted 07.2020

  • Two positions for postdoctoral or doctoral researchers in the department of Functional Neuroanatomy (Prof T. Kuner) are available in a consortium which aims to visualize multi-protein networks in nervous tissue with near-molecular optical resolution. Adobe
    Posted 02.2020

  • The research group of Dr. Kevin Allen is seeking a highly motivated PhD student to work on the neuronal basis of spatial behavior. The student will use a wide array of techniques to study system neuroscience, including in vivo tetrode and silicon probe recordings in mice, optogenetics, behavioral testing, analysis of large databases and histological analysis. Adobe
    Posted 11.2019




Managing Director:
Prof. Dr. Hilmar Bading
IZN-Neurobiology, University of Heidelberg
Im Neuenheimer Feld 366, 1.OG
D-69120 Heidelberg, Germany


Phone:  +49 - 6221 - 54 16500
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email:  Bading@nbio.uni-heidelberg.de




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IZN-Neurobiology, University of Heidelberg
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D-69120 Heidelberg, Germany


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Fax:  +49 - 6221 - 54 16524
email:  Braeunling@nbio.uni-heidelberg.de




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Herr Ferhat Dikmen
IZN-Neurobiology, University of Heidelberg
Im Neuenheimer Feld 366, 1.OG
D-69120 Heidelberg, Germany


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email:  Sekretariat@nbio.uni-heidelberg.de


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Latest Revision: 2020-08-04
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