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Outreach and Awards IZN/Chica and Heinz Schaller Young Investigator Neuroscience Award

For the best first author publication by a young scientist in the Interdisciplinary Center for Neurosciences

The IZN/Chica and Heinz Schaller Young Investigator Neuroscience Award is an annual prize offered by the Chica and Heinz Schaller Foundation and is given in recognition of an outstanding first-author research publication in any aspect of neuroscience. Candidates must be current members of IZN research groups or have been members while the relevant work was performed. IZN principal investigators are excluded unless the work was clearly done during their post-doctoral or doctoral period at the IZN. Self-nomination of candidates is encouraged.

Deadline for nominations for the 2025 award is May 30, 2025 and the award winner will be notified at the end of June 2025. The prize money of 1000 € may be divided between equally contributing first authors and is to be used at the winner’s or winners’ discretion. The prize will be presented at an award ceremony during the annual IZN Retreat at Kloster Schöntal.

Applications should include:

  • CV
  • Scientific justification (one page, single spaced, Arial 11)
  • Summary of the significance of the work in lay terms (half page, single spaced, Arial 11)
  • Original paper published or accepted for publication in 2024 or before May 30, 2025

Please email your application to the chair of the selection committee, Dr. Ana Oliveira:  Ana.Oliveira@zi-mannheim.de.

Past Winners

2024  

Frédéric Fiore and Khaleel Alhalaseh (Agarwal Lab)

Fiore, F., Alhalaseh, K., Dereddi, R. R., Bodaleo Torres, F., Çoban, I., Harb, A., & Agarwal, A. (2023). Norepinephrine regulates calcium signals and fate of oligodendrocyte precursor cells in the mouse cerebral cortex. Nature communications, 14(1), 8122. https://doi.org/10.1038/s41467-023-43920-w

OPCs constitute around 10% of all cells in the central nervous system, yet remain surprisingly understudied despite their relative abundance and perceived importance. This is largely due to the fact that OPCs are elusive cells that are not easily targeted by conventional methods (like recombinant AAVs, for example). As a result, we still know very little about the physiology of these cells, especially in vivo. The introduction of our novel triple transgenic mouse line (NG2-GCaMP6f;tdTomato), which now allows accurate dual-color labelling of OPCs in a time-restricted manner, constitute a significant step towards resolving some of the issues that have hindered progress in the field of OPC biology until now. As a result, this study is amongst the very first to present awake in vivo Ca2+ imaging data from mouse OPCs, yielding key, previously unavailable information on the behavior of these cells in their natural environment. To our knowledge, this is also one of the first study to combine morphological and functional data to highlight differences in physiological properties across the oligodendrocyte lineage. Perhaps even more importantly, we discovered that increased brain-wide NE release promotes the differentiation of OPCs into mature oligodendrocytes. This is highly relevant, as it could serve as the basis for new therapeutic strategies in the treatment of diseases like Multiple Sclerosis (MS), in which the loss of oligodendrocytes and demyelination are important features. This could potentially be done using existing SNRIs (Serotonin and Norepinephrine Reuptake Inhibitors) currently used in the treatment of depression and anxiety.

2023

Alexander Hodapp and Martin E. Kaiser (Both Lab)

Hodapp, A., Kaiser, M. E., Thome, C., Ding, L., Rozov, A., Klumpp, M., Stevens, N., Stingl, M., Sackmann, T., Lehmann, N., Draguhn, A., Burgalossi, A., Engelhardt, M., & Both, M. (2022). Dendritic axon origin enables information gating by perisomatic inhibition in pyramidal neurons. Science (New York, N.Y.), 377(6613), 1448–1452. https://doi.org/10.1126/science.abj1861 

The brain is made out of many different types of electrically excitable cells that are able to communicate by generating action potentials. These cells are called neurons. While highly specialized with a wide variety in shape, size and electrochemical properties, nearly all of them encompass the same base components consisting of a cell body, one or many dendrites, which can be described as the input structure to the cell, and a single axon, which can be described as the output structure of the cell. The interplay of thousands, even millions of these neurons leads to oscillations, periodic variations of network activity, expressed as coordinated rises and tides of overall electrical activity and an orchestrated interplay of excitatory and inhibitory forces. During network oscillations there are phases of high perisomatic inhibition, leading to a reduction of the firing rate and phases of low inhibition doing the opposite. While the majority of excitatory neurons, meaning those that cause an increase in firing rate of other cells, stay silent during phases of high inhibition, some do not or even appear to get activated by this mechanism. They form coordinated activity patterns. This so called selective recruitment is believed to be one of the hallmarks of neural networks, the ability of neurons to interconnect to carry out a specific function.
In our work we describe a mechanism based on a specific neural morphology in combinationwith perisomatic inhibition that extends the classical view of how neurons are specifically recruited into ensembles of cells: in many cells the axon emerges out of a dendrite instead of the cell body. We could show that this leads to a reduction in the effect of perisomatic inhibition on these cells, resulting in a much higher rate of participation during network events. This is accomplished by the ability to escape inhibition through electrical isolation from the cell body. We also indicate the preferential treatment of inputs to this Axon-carrying dendritic branch compared to inputs to other dendrites that are not in a preferential isolated position from perisomatic inhibition. In this way the network can reliably and precisely regulate participation of specific cells into activity patterns, which is essential for the execution of different tasks or the coding of specific memories. We believe that this mechanism helps us in a deeper understanding of how the brain processes information, especially with respect to cognition and memory. Hopefully, this will lead to further scientific discoveries.

2022

Vijayan Gangadharan (R. Kuner Lab)

Gangadharan, V., Zheng, H., Taberner, F. J., Landry, J., Nees, T. A., Pistolic, J., Agarwal, N., Männich, D., Benes, V., Helmstaedter, M., Ommer, B., Lechner, S. G., Kuner, T., & Kuner, R. (2022). Neuropathic pain caused by miswiring and abnormal end organ targeting. Nature, 606(7912), 137–145. https://doi.org/10.1038/s41586-022-04777-z

Pain is an unpleasant emotional and sensory experience, which serves as a mechanism to protect our bodies from various damaging conditions, such as heat, chemicals and parasites. When pain becomes chronic, it develops into a debilitating disease that results in suffering, disability and a poor quality of life. What’s worse – the treatment options for chronic pain are very limited. In this study, we tracked peripheral sensory nerve fibers at a high-resolution using chronic, in vivo, non-invasive imaging of touch-sensing and pain-sensing peripheral nerves in mice models of neuropathic pain models before and after nerve injury over a period of 10 months. Multi-photon imaging was done in combination with sensory behavior, including the analysis of evoked as well as spontaneous pain. We found that upon partial nerve injury (which is a common type of injury in humans), the skin area that is innervated by injured nerves becomes numb with complete degeneration of severed nerves. Within a few weeks after nerve injury, uninjured nerves began to sprout into the adjacent, denervated skin area, which slowly restored sensitivity. However, about 20-24 weeks after nerve injury, mice started showing hypersensitivity to light touch. Our multi-photon imaging showed that only pain-sensing fibers collaterally sprouted into the denervated area but not touch-sensing fibers. Our ultrastructural analyses using 3-dimensional electron microscopy revealed that the collaterally sprouted nociceptors do not innervate the skin as free nerve endings as they would in a physiological state, but rather innervated the Meissner corpuscles, a touch-sensing end-organ in skin. Furthermore, our electrophysiological analyses revealed that these collaterally sprouted nociceptors have lowered thresholds, suggesting that light touch stimuli become painful. Overall, we discovered a novel miswiring and abnormal targeting of touch-sensing Meissner corpuscles by pain-sensing fibers. This gives novel mechanistic evidence of how pain-sensing fibers can hijack touch-sensing apparatus in the skin to develop chronic pain. We hope that this mechanistic understanding of chronic pain development will help design new therapeutic strategies for chronic pain and vastly minimize the unwanted side effects.

2021

Jing Yan (Bading Lab)

Yan, J., Bengtson, C. P., Buchthal, B., Hagenston, A. M., & Bading, H. (2020). Coupling of NMDA receptors and TRPM4 guides discovery of unconventional neuroprotectants. Science (New York, N.Y.), 370(6513), eaay3302. https://doi.org/10.1126/science.aay3302

XXX

2020

Kübra Gülmez-Karaca (Oliveira Lab)

Gulmez Karaca, K., Kupke, J., Brito, D. V. C., Zeuch, B., Thome, C., Weichenhan, D., Lutsik, P., Plass, C., & Oliveira, A. M. M. (2020). Neuronal ensemble-specific DNA methylation strengthens engram stability. Nature communications, 11(1), 639. https://doi.org/10.1038/s41467-020-14498-4

Without memories, you would not remember why you read this text, where you are and even who you are. Memories define our personal history, and are indispensable for survival as evidenced by the devastating consequences of memory-related pathologies. Recent evidence demonstrates that each memory leaves a unique footprint in the brain termed the memory engram created by the neurons that are activated during a new experience (i.e., neuronal ensembles) and re-activated, at least in part, during memory recall to retrieve this memory. These findings strongly suggest that those neurons activated by learning actually hold the
representations of each memory, and thus point that understanding how neuronal ensembles are retained in memory engrams is essential to understand how the brain stores and recalls memories. However, we have surprisingly limited understanding of how and what regulates neuronal ensembles mainly due to a lack of tools that allow for alterations in those neurons. In our work, we used the state-of-the-art technology that permits the selective manipulation of those neurons activated during learning, and investigated how these neurons, once becoming a part of the memory engram, are regulated to support a successful memory recall. We trained
laboratory mice in a form of Pavlovian-like conditioning in which they link a fearful experience to a certain environment. This kind of memory involves the activation of the hippocampus, a brain region that records what happened where and when. Hence, we manipulated only the neuronal ensembles located in the hippocampus (around 5% of the hippocampus). We showed that increasing the levels of a certain protein only in those neurons activated during learning, but not in other “irrelevant” neurons, was sufficient to boost memory in mice. Furthermore, this delicate manipulation enhanced the brain’s ability to re-activate more of the originally activated neuronal ensembles to support memory recall, indicating a more stable memory engram. The protein we increased (termed DNA methyltransferase 3a2, Dnmt3a2) is an epigenetic factor that induces chemical modifications on the DNA. We found that Dnmt3a2 preferentially modified DNA sections relevant for the communication and connectivity of neurons, suggesting a mechanism on how more Dnmt3a2 in neuronal ensembles might have impacted memory. Altogether, our findings provide the first hint that epigenetic factors within the neurons that actually encode memories can regulate the stability of memory engrams, as well as memory strength, opening an exciting territory to further understand how and where the brain stores memories and to treat memory dysfunctions characterized by disrupted memory engrams.

2019

Max Richter (Müller Lab)

Richter, M. C., Ludewig, S., Winschel, A., Abel, T., Bold, C., Salzburger, L. R., Klein, S., Han, K., Weyer, S. W., Fritz, A. K., Laube, B., Wolfer, D. P., Buchholz, C. J., Korte, M., & Müller, U. C. (2018). Distinct in vivo roles of secreted APP ectodomain variants APPsα and APPsβ in regulation of spine density, synaptic plasticity, and cognition. The EMBO journal, 37(11), e98335. https://doi.org/10.15252/embj.201798335

Increasing evidence suggests that the synaptic functions of the amyloid precursor protein, that is key to Alzheimer pathogenesis, may be carried out by its secreted ectodomains. Here, we discovered a receptor for APPsα, which paves the way for new treatment approaches for Alzheimer's disease. Alzheimer's disease is triggered by insoluble protein aggregates that are found as extracellular deposits in patients’ brains. The main component is the β-amyloid peptide (Aβ), which damages and eventually kills the nerve cells. This small peptide is a cleavage product of a substantially larger precursor protein, the amyloid precursor protein (APP). Alzheimer's was long assumed to be caused mainly by the overproduction of the β-amyloid peptide. New studies show, however, that APPsα levels drop over the course of the disease. It seems that in Alzheimer's disease, there is a misregulation in APP cleavage whereby too little APPsα is produced. Here, using Adeno-associated virus (AAV) mediated intracranial expression, we studied the specific in vivo roles of APPs fragments generated by non‐amyloidogenic or amyloidogenic APP processing. We were able to demonstrate that APPsα but not APPsβ increases the number of synaptic contacts between nerve cells. This was associated with more efficient nerve cell communication and improved memory in learning tests. Using further electrophysiological experiments, we could show that APPsα facilitates synaptic plasticity (LTP). We could also show that the C-terminal 16 amino acids of APPsα are sufficient for this function. Pharmacological analysis showed that APPsα acts on synapses containing a certain subtype of receptors. These receptors use the neurotransmitter acetylcholine, which is one of the most important messenger molecules for transmitting signals between nerve cells. We demonstrated that the protein fragment APPsα potentiates signal transmission by acetylcholine receptors (α7‐nAChR) and increases their natural responsiveness towards the endogenous ligand acetylcholine. This is the first time that a physiological, in vivo relevant receptor for APPsα has been identified. These results point towards new approaches to treat Alzheimer's disease, such as increasing the amount of APPsα in the brain.

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