Department Cellular Neuroscience
How does the brain learn, store, and recall specific locations and events?
And what causes these memory processes to malfunction in disease?
We study how neural computations on the cellular and circuit level underlie memory guided behavior and cognitive dysfunction.
- cracking the neuronal code
We want to understand how hippocampal neurons in the subiculum generate the neuronal code of action potential sequences that is transmitted to other brain regions such as the cortex. This action potential code is densely packed with information on the spatial position, self-motion, motivation, salience and is tuned by prior experience via synaptic plasticity. For cracking this hippocampal output code, we monitor synaptic input of multiple kinds during the behavior. We then use computational modeling to predict the conversion of input to output and finally test our predictions by recording directly from single neurons with synaptic resolution during behavior (supported by ERC consolidator grant SUB-D-Code). – Dennis Dalügge, Oliver Barnstedt, Pavol Bauer, Hiroshi Kaneko
- using artificial intelligence to detect features in neural activity and behavior
We are using machine vision and learning to classify behavior. The application of artificial intelligence based tools has the potential to revolutionize research on neural correlates of behavior. In particular, we classify the way an animal changes its pose and interacts with an environment in an unsupervised manner. We are convinced that high temporal resolution unsupervised behavioral classification will be a first step allowing us to correlate behavioral features with neural activity patterns. The second step is extracting scientific understanding and detecting causal relationships within these large behavior-correlated neural activity imaging data sets. In other words, we want to understand biological neural networks by using artificial neural networks as a tool. (supported by EFRE funding, Pavol Bauer, Kevin Luxem, Johannes Kürsch)
- understanding the diversity of neurons
For most brain areas a comprehensive understanding of the cell clusters forming the neural circuits is currently absent. In collaboration with Nelson Spruston (HHMI Janelia), Mark Cembrowski (University of Vancouver and the Janelia Quantitative Genomics Unit we use single-cell RNA sequencing and multiplexed in situ hybridization for transcriptomic profiling of cell types. A brain region of highest interest is the medial septum. It is a brain region that controls hippocampal memory circuits. We have set up an innovative framework of bioinformatics analyses to identify genetically-defined cell populations. In combination with viral tracing tools we further reveal specific hippocampus-projecting clusters and dissect their function during behavior (supported by HHMI Janelia Visitor Project) – Stefano Pupe
- understanding vulnerability and resilience of neural circuits to cognitive dysfunction
We are investigating how hippocampal memory circuits and individual neurons within these circuits respond to progressive pathological challenges. Here we have set a focus on the accumulation of amyloid beta, which can be observed in human Alzheimer patients and in advanced physiological aging. We found a computational principle explaining why reduced dendritic size in the response to pathology results in higher neuronal. By using computational modeling, we could understand how neuronal structural changes define electrical properties of dendrites and entire neurons. On the circuit level, we are investigating how hippocampal inhibitory and excitatory neurons interact in microcircuits and how altered interneuron function contributes to the malfunction of learning and memory processes (supported by SFB 1089 project B01) – Liudmila Sosulina, Hiroshi Kaneko
- investigating the subcortical modulation of memory circuits
Subcortical areas form the core of our brain, they are involved in complex activities such as memory, emotion, pleasure, arousal and hormone production. They act as hubs by relaying and modulating information passing to different areas of the brain including the hippocampus. We are trying to gain a better understanding on how hippocampal circuits are controlled by direct and indirect subcortical modulation from the medial septum, the locus coeruleus and the ventral tegmental area. The medial septum is a basal forebrain region that is reciprocally connected with the hippocampal formation, where it orchestrates microcircuit activation and oscillatory activity during different behavioral states. It is known as a main source of Acetylcholine, which is released by septo-hippocampal afferents during learning and memory processes. We have discovered that, in addition to cholinergic projections, glutamatergic and GABAergic septo-hippocampal projections play a key role in the control of activity levels of hippocampal neurons during memory guided navigation. The medial septum is an important network hub, it integrates behavioral state dependent input from locus coeruleus and channels specific information to the hippocampus and other memory-relevant brain regions. We want to better understand the multitude of medial septal functions during behavior (supported by SFB 1089 subproject C05) – Petra Mocellin, Liudmila Sosulina
The video shows a 3D-rendering of the medial septum and diagonal Band of Broca in a cleared mouse brain. VGluT2-positive neurons are labeled in red, green labeled neurons are retrogradely traced from MEC by using RABVΔG-EGFP.
Release of new preprint including research code
We are excited to share a new preprint entitled “Identifying Behavioral Structure from Deep Variational Embeddings of Animal Motion” that is available at BioRxiv.
In this work we present a novel machine learning framework for discovery of the latent structure of animal behavior given data from markerless pose estimation entitled Variational Animal Motion Embedding (VAME). VAME clusters the time series data into “behavioral motifs”, which are stereotypical behavioral patterns that occur repeatedly in free behavior. The structure of behavior is then represented in the distribution of motifs and the probability of transitions between them. In the preprint we show that this information is sensitive enough to serve as a basis for classification of mice according to its behavior phenotypes. This can be done even for subtle behavioral differences, which human experts are unable to detect from the video capture.
Since January 2020 Stefan Remy is the scientific director of the LIN and the head of the Department of Cellular Neuroscience. He is also appointed as Professor of Molecular and Cellular Neurobiology at the Otto von Guericke University, Medical Faculty in Magdeburg.
Stefan Remy’s department investigates how neural computations on the cellular and circuit level underlie memory guided behavior and cognitive dysfunction. Within the department biologists, mathematicians and computer scientists collaborate to extract scientific understanding from multidimensional behavioral and neurophysiological data sets.
He obtained the doctoral degree at the University of Bonn in 2003 and then worked from 2003-2005 as postdoc with Heinz Beck at the Department of Epileptology (Head: Christian E. Elger). As an Alexander-von-Humboldt fellow he joined the Department of Neurobiology and Physiology at Northwestern University, Evanston, in 2005. There he worked with Nelson Spruston on dendritic excitability and synaptic plasticity. In 2007 he continued his postdoctoral training with Heinz Beck in Bonn, where he started his own research group in 2009 funded by the state of NRW. From 2010 he headed a research group at the German Center of Neurodegenerative Diseases Bonn (Head: Pierluigi Nicotera) before moving to Magdeburg in 2020.
There are places I remember
All my life though some have changed
Some forever not for better
Some have gone and some remain
All these places have their moments
With lovers and friends I still can recall
Some are dead and some are living
In my life I've loved them all.
(John Lennon/ Paul McCartney)
My research philosophy is explained here in my inaugural lecture.
Head Prof. Dr. Stefan Remy +49 391 6263 92421, 92411, 93311 Stefan.Remy(at)lin-magdeburg.de Assistant Juliane Jäger +49 391 6263 92411 Juliane.Jaeger(at)lin-magdeburg.de
Research group leaders
Prof. Dr. Stefan Remy (Cells and Circuits)
+49 391 6263 92421, 92411, 93311 Stefan.Remy(at)lin-magdeburg.de
Dr. Pavol Bauer (Neural Data Science)
+49 391 6263 9 3361 Pavol.Bauer(at)lin-magdeburg.de
Dr. Oliver Barnstedt (DZNE Bonn)
Dr. Hiroshi Kaneko (staff scientist)
Dr. Stefano Pupe
Dr. Liudmila Sosulina (staff scientist)
Lab coordinators/Research Technicians
Silvia Vieweg +49 391 6263 _93481 vieweg(at)lin-magdeburg.de
Dr. Sanja Mikulovic (Swedish Research Council)
+49 391 6263_93171 Sanja.Mikulovic(at)lin-magdeburg.de
Other scientific contributors
Benedikt Auer (Stud. Hilfskraft)
Johannes Kürsch (Stud. Hilfskraft)
Dr. Falko Fuhrmann (Lab consultant)
Luxem K, Fuhrmann F, Kürsch J, Remy S, Bauer P. 2020. Identifying Behavioral Structure from Deep Variational Embeddings of Animal Motion. Available at BioRxiv. Doi: https://doi.org/10.1101/2020.05.14.095430
Schwarz MK, Remy S. 2019. Rabies virus-mediated connectivity tracing from single neurons. Journal of Neuroscience Methods. 325:108365. https://doi.org/10.1016/j.jneumeth.2019.108365
Widgren S, Bauer P, Eriksson R, Engblom S. 2019. SimInf: A Package for Data-Driven Stochastic Disease Spread Simulations. Journal of Statistical Software. 2019;91(12). doi: https://doi.org/10.18637/jss.v091.i12
Lindén J, Bauer P, Engblom S, Jonsson B. 2019. Exposing Inter-process Information for Efficient PDES of Spatial Stochastic Systems on Multicores. ACM Transactions in Modeling and Computer Simulation. 2019;29(2):1-25. doi: https://doi.org/10.1145/3301500
Luxem K, Fuhrmann F, Remy S, Bauer P. 2019. Hierarchical network analysis of behavior and neuronal population activity. In: 2019 Conference on Cognitive Computational Neuroscience. Berlin, Germany: Cognitive Computational Neuroscience; 2019. doi: https://doi.org/10.32470/CCN.2019.1261-0
Giovannetti E, Poll S, Justus D, Kaneko H, Fuhrmann F, Steffen J, Remy S, Fuhrmann M. 2018. Restoring memory by optogenetic synchronization of hippocampal oscillations in an Alzheimer’s disease mouse model. BioRXiv (preprint). https://doi.org/10.1101/363820
Dalügge D, Remy S. 2018. Human Cortical Dendrites: Stretched to Perform Better?. Cell. 175(3):635-637. https://doi.org/10.1016/j.cell.2018.09.052
Musial TF, Molina-Campos E, Bean LA, Ybarra N, Borenstein R, Russo ML, Buss EW, Justus D, Neuman KM, Ayala GD, Mullen SA, Voskobiynyk Y, Tulisiak CT, Fels JA, Corbett NJ, Carballo G, Kennedy CD, Popovic J, Ramos-Franco J, Fill M, Pergande MR, Borgia JA, Corbett GT, Pahan K, Han Y, Chetkovich DM, Vassar RJ, Byrne RW, Matthew Oh M, Stoub TR, Remy S, Disterhoft JF, Nicholson DA. 2018. Store depletion-induced h-channel plasticity rescues a channelopathy linked to Alzheimer's disease. Neurobiology of Learning and Memory. 154:141-157. https://doi.org/10.1016/j.nlm.2018.06.004
Müller C, Remy S. 2018. Septo–hippocampal interaction. Cell and Tissue Research. 373(3):565-575. https://doi.org/10.1007/s00441-017-2745-2
Müller C, Geis HR, Remy S. 2018. Visually Guided Single-Cell Recordings in the Hippocampus of Awake Mice. Manahan-Vaughan D, editor. In Handbook of in Vivo Neural Plasticity Techniques. Elsevier B.V. pp. 123-134. (Handbook of Behavioral Neuroscience). https://doi.org/10.1016/B978-0-12-812028-6.00006-9
Lindén J, Bauer P, Engblom S, Jonsson B. 2018. Fine-Grained Local Dynamic Load Balancing in PDES. In: Proceedings of the 2018 ACM SIGSIM Conference on Principles of Advanced Discrete Simulation - SIGSIM-PADS ’18. Rome, Italy: ACM Press; 2018:201-212. doi: https://doi.org/10.1145/3200921.3200928
Bauer P, Engblom S, Mikulovic S, Senek A. 2018. Multiscale modelling via split-step methods in neural firing. Mathematical and Computer Modelling of Dynamical Systems. 2018;24(4):426-445. doi: https://doi.org/10.1080/13873954.2018.1488740
Mikulovic S, Restrepo CE, Siwani S, Bauer P, Pupe S, Tort ABL, Kullander K, Leao RN. 2018. Ventral hippocampal OLM cells control type 2 theta oscillations and response to predator odor. Nature Communications. 2018;9(1):3638. doi: https://doi.org/10.1038/s41467-018-05907-w
Remy S, Poirazi P, Papoutsi A. 2017. Introduction to the Computational Neuroscience Special Section. European Journal of Neuroscience. 45(8):998-999. https://doi.org/10.1111/ejn.13562
Justus D, Dalügge D, Bothe S, Fuhrmann F, Hannes C, Kaneko H, Friedrichs D, Sosulina L, Schwarz I, Elliott DA, Schoch S, Bradke F, Schwarz MK, Remy S. 2017. Glutamatergic synaptic integration of locomotion speed via septoentorhinal projections. Nature Neuroscience. 20(1):16-19. https://doi.org/10.1038/nn.4447
Schmid LC, Mittag M, Poll S, Steffen J, Wagner J, Geis HR, Schwarz I, Schmidt B, Schwarz MK, Remy S, Fuhrmann M. 2016. Dysfunction of Somatostatin-Positive Interneurons Associated with Memory Deficits in an Alzheimer's Disease Model. Neuron. 92(1):114-125. https://doi.org/10.1016/j.neuron.2016.08.034
Müller C, Remy S. 2016. Slowly Building Excitement. Cell. 165(7):1568-1569. https://doi.org/10.1016/j.cell.2016.06.005
Bauer P, Engblom S, Widgren S. 2016. Fast event-based epidemiological simulations on national scales. The International Journal of High Performance Computing Applications. 2016;30(4):438-453. doi: https://doi.org/10.1177/1094342016635723
Widgren S, Engblom S, Bauer P, Frössling J, Emanuelson U, Lindberg A. 2016. Data-driven network modelling of disease transmission using complete population movement data: spread of VTEC O157 in Swedish cattle. BMC Veterinary Research. 2016;47(1):81. doi: https://doi.org/10.1186/s13567-016-0366-5
Wagner J, Krauss S, Shi S, Ryazanov S, Steffen J, Miklitz C, Leonov A, Kleinknecht A, Göricke B, Weishaupt JH, Weckbecker D, Reiner AM, Zinth W, Levin J, Ehninger D, Remy S, Kretzschmar HA, Griesinger C, Giese A, Fuhrmann M. 2015. Reducing tau aggregates with anle138b delays disease progression in a mouse model of tauopathies. Acta Neuropathologica. 130(5):619-631. https://doi.org/10.1007/s00401-015-1483-3
Fuhrmann F, Justus D, Sosulina L, Kaneko H, Beutel T, Friedrichs D, Schoch S, Schwarz MK, Fuhrmann M, Remy S. 2015. Locomotion, Theta Oscillations, and the Speed-Correlated Firing of Hippocampal Neurons Are Controlled by a Medial Septal Glutamatergic Circuit. Neuron. 86(5):1253-1264. https://doi.org/10.1016/j.neuron.2015.05.001
Bauer P, Lindén J, Engblom S, Jonsson B. 2015. Efficient Inter-Process Synchronization for Parallel Discrete Event Simulation on Multicores. In: Proceedings of the 3rd ACM Conference on SIGSIM-Principles of Advanced Discrete Simulation - SIGSIM-PADS ’15. London, United Kingdom: ACM Press; 2015:183-194. doi: https://doi.org/10.1145/2769458.2769476
Patra K, Lyons DJ, Bauer P, Hilscher MM, Sharma S, Leao RN, Kullander K. 2015. A role for solute carrier family 10 member 4, or vesicular aminergic-associated transporter, in structural remodelling and transmitter release at the mouse neuromuscular junction. European Journal of Neuroscienc. 2015;41(3):316-327. doi:https://doi.org/10.1111/ejn.12790
Milias-Argeitis A, Engblom S, Bauer P, Khammash M. 2015. Stochastic focusing coupled with negative feedback enables robust regulation in biochemical reaction networks. Journal of The Royal Society Interface. 2015;12(113):20150831. doi: https://doi.org/10.1098/rsif.2015.0831
Qi Y, Klyubin I, Harney SC, Hu NW, Cullen WK, Grant MK, Steffen J, Wilson EN, Do Carmo S, Remy S, Fuhrmann M, Ashe KH, Cuello AC, Rowan MJ. 2014. Longitudinal testing of hippocampal plasticity reveals the onset and maintenance of endogenous human Aß-induced synaptic dysfunction in individual freely behaving pre-plaque transgenic rats: Rapid reversal by anti-Aß agents. Acta neuropathologica communications. 2(1):175. https://doi.org/10.1186/s40478-014-0175-x
Šišková Z, Justus D, Kaneko H, Friedrichs D, Henneberg N, Beutel T, Pitsch J, Schoch S, Becker A, vonderKammer H, Remy S. 2014. Dendritic structural degeneration is functionally linked to cellular hyperexcitability in a mouse model of alzheimer's disease. Neuron. 84(5):1023-1033. https://doi.org/10.1016/j.neuron.2014.10.024
Pothmann L, Müller C, Averkin RG, Bellistri E, Miklitz C, Uebachs M, Remy S, de la Prida LM, Beck H. 2014. Function of inhibitory micronetworks is spared by Na+ channel-acting anticonvulsant drugs. Journal of Neuroscience. 34(29):9720-9735. https://doi.org/10.1523/JNEUROSCI.2395-13.2014
Müller C, Remy S. 2014. Dendritic inhibition mediated by O-LM and bistratified interneurons in the hippocampus. Frontiers in Synaptic Neuroscience. 6(SEP):23. https://doi.org/10.3389/fnsyn.2014.00023
Bauer P, Engblom S. 2014. Sensitivity Estimation and Inverse Problems in Spatial Stochastic Models of Chemical Kinetics. Lecture Notes in Computational Science and Engineering; 2015:519-527. https://doi.org/10.1007/978-3-319-10705-9_51
Müller C, Remy S. 2013. Fast micro-iontophoresis of glutamate and GABA: a useful tool to investigate synaptic integration. Journal of visualized experiments : JoVE. (77). https://doi.org/10.3791/50701
Müller C, Beck H, Coulter D, Remy S. 2012. Inhibitory Control of Linear and Supralinear Dendritic Excitation in CA1 Pyramidal Neurons. Neuron. 75(5):851-864. https://doi.org/10.1016/j.neuron.2012.06.025
Krueppel R, Remy S, Beck H. 2011. Dendritic integration in hippocampal dentate granule cells. Neuron. 71(3):512-528. https://doi.org/10.1016/j.neuron.2011.05.043
Chen S, Su H, Yue C, Remy S, Royeck M, Sochivko D, Opitz T, Beck H, Yaari Y. 2011. An increase in persistent sodium current contributes to intrinsic neuronal bursting after status epilepticus. Journal of Neurophysiology. 105(1):117-129. https://doi.org/10.1152/jn.00184.2010
Park JY, Remy S, Varela J, Cooper DC, Chung S, Kang HW, Lee JH, Spruston N. 2010. A post-burst afterdepolarization is mediated by group I metabotropic glutamate receptor-dependent upregulation of Cav2.3 R-type calcium channels in CA1 pyramidal neurons. PLoS Biology. 8(11):e1000534. https://doi.org/10.1371/journal.pbio.1000534
Remy S, Beck H, Yaari Y. 2010. Plasticity of voltage-gated ion channels in pyramidal cell dendrites. Current Opinion in Neurobiology. 20(4):503-509. https://doi.org/10.1016/j.conb.2010.06.006
Remy S, Csicsvari J, Beck H. 2009. Activity-Dependent Control of Neuronal Output by Local and Global Dendritic Spike Attenuation. Neuron. 61(6):906-916. https://doi.org/10.1016/j.neuron.2009.01.032
Royeck M, Horstmann MT, Remy S, Reitze M, Yaari Y, Beck H. 2008. Role of axonal NaV1.6 sodium channels in action potential initiation of CA1 pyramidal neurons. Journal of Neurophysiology. 100(4):2361-2380. https://doi.org/10.1152/jn.90332.2008
Remy S, Spruston N. 2007. Dendritic spikes induce single-burst long-term potentiation. Proceedings of the National Academy of Sciences of the United States of America. 104(43):17192-17197. https://doi.org/10.1073/pnas.0707919104
Remy S, Beck H. 2006. Molecular and cellular mechanisms of pharmacoresistance in epilepsy. Brain. 129(Pt 1):18-35. https://doi.org/10.1093/brain/awh682
Heinemann U, Kann O, Remy S, Beck H. 2006. Novel mechanisms underlying drug resistance in temporal lobe epilepsy. Advances in neurology. 97:85-95.
Yue C, Remy S, Su H, Beck H, Yaari Y. 2005. Proximal persistent Na+ channels drive spike afterdepolarizations and associated bursting in adult CA1 pyramidal cells. Journal of Neuroscience. 25(42):9704-9720. https://doi.org/10.1523/JNEUROSCI.1621-05.2005
Remy C, Remy S, Beck H, Swandulla D, Hans M. 2004. Modulation of voltage-dependent sodium channels by the δ-agonist SNC80 in acutely isolated rat hippocampal neurons. Neuropharmacology. 47(7):1102-1112. https://doi.org/10.1016/j.neuropharm.2004.06.034
Ellerkmann RK, Remy S, Chen J, Sochivko D, Elger CE, Urban BW, Becker A, Beck H. 2003. Molecular and functional changes in voltage-dependent Na+ channels following pilocarpine-induced status epilepticus in rat dentate granule cells. Neuroscience. 119(2):323-333. https://doi.org/10.1016/S0306-4522(03)00168-4
Remy S, Urban BW, Elger CE, Beck H. 2003. Anticonvulsant pharmacology of voltage-gated Na+ channels in hippocampal neurons of control and chronically epileptic rats. European Journal of Neuroscience. 17(12):2648-2658. https://doi.org/10.1046/j.1460-9568.2003.02710.x
Remy S, Gabriel S, Urban BW, Dietrich D, Lehmann TN, Elger CE, Heinemann U, Beck H. 2003. A novel mechanism underlying drug resistance in chronic epilepsy. Annals of Neurology. 53(4):469-479. https://doi.org/10.1002/ana.10473
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