Our Aim
Traumatic, ischemic and inflammatory lesions to the spinal cord lead to the transection of descending and ascending axonal tract systems. If these lesions are complete – i.e. if all axons in the spinal cord are transected – severe and persistent functional deficits ensue. If however the lesions are incomplete and some axonal tracts are spared, some recovery of function can be observed. We are studying the anatomical, functional and molecular mechanisms underlying the recovery process in an attempt to develop new therapeutic strategies that can support spinal cord repair in neurological disease caused by trauma, ischemia or inflammation.
Our Approach
Over the recent years we have used various axonal tracts – ascending and descending pathways – to study how axonal connections remodel in response to injury. We could identify the de novo formation of intraspinal detour circuits as a key remodelling process that mediates recovery of function. We are currently using (i) anterograde, retrograde and trans-synaptic tracing techniques in combination with confocal microscopy to reveal the anatomy of spinal detour circuits, (ii) genetic and pharmacological manipulations to dissect the molecular interactions that regulate detour circuit formation and (iii) electrophysiological recordings and behavioural testing to assess effects on functional recovery.
Some of our current projects
Regulation of synapse formation and elimination following spinal cord injury
The incidence of Spinal Cord Injury (SCI) in Germany is estimated at about 36 cases per million of the population, which translates to about 3000 new spinal cord injured patients per year. Most of these patients are young adults injured at work or during traffic accidents who will have to live the rest of their life disabled due to the limited repair capacity of severed central axons. Recently, therapeutic options have emerged that can promote some level of axonal outgrowth after SCI. However, our work emphasizes that axonal outgrowth is in itself insufficient and that regrowing axons have to be integrated into reorganized intraspinal networks to promote functional recovery. To achieve this aim we address the following questions: (i) How do regrowing axons find the correct path to their targets and how do they make appropriate synaptic connections? (ii) how are newly formed intraspinal circuits refined over time to foster functional recovery and which cells contribute to the shaping of circuits? (iii) Which therapeutic strategies can support appropriate synapse formation/elimination?
Activity-dependent regulation of axonal plasticity following spinal cord injury
The transection of axonal connections leads to motor and sensory deficits in many traumatic, ischemic and inflammatory conditions of the central nervous system (CNS). Despite the fact that axonal regeneration generally fails in the CNS, dramatic functional recovery can be observed in particular after incomplete lesions to brain and spinal cord. Our recent work indicates that spontaneous recovery of motor function can be mediated by the formation of intraspinal detour circuits. Detour circuits are formed in the following steps: First, a subpopulation of transected projection neurones forms new collaterals that contact intraspinal relay neurones. Initially these collaterals contact relay neurones irrespective of their projection pattern. However over the following weeks only those sprouts which contact neurones that connect to the original target area are maintained while other sprouts are eliminated. Electrophysiological and behavioural experiments confirm that intraspinal detour circuits are key anatomical substrates of functional recovery. To understand when and where detour circuits can be formed and which regulatory principles guide their formation we study: (i) how neuronal activity guides the formation and stabilization of newly formed connections and (ii) whether we can design therapies based on enhanced activity paradigms to promote the formation of detour circuits and thereby improve functional recovery after CNS injury.
Acute and long term effects of mild repetitive traumatic brain injury
Traumatic brain injury (TBI) is a leading cause of mortality and morbidity worldwide, particularly among younger adults. In Germany, traumatic brain injury occurs with a frequency of 323 per 100,000 inhabitants annually. Among all brain injuries, it is now recognized that repeated concussions, a mild form of brain injury, are by far the most frequent forms of brain injury. They often occur in the context of sport and have the potential for long-term neurological impairments. A comprehensive understanding of the underlying neurobiological mechanisms associated with repeated concussive and sub-concussive head impacts is essential to identify points of intervention and potential drug targets. Hence in this project we address the following questions: (i) which neuronal, glial and immune responses follow mild repeated brain injury? (ii) which potential therapies can alleviate the structural and functional consequences of synapse loss following mild repetitive brain injury?
2024
Todorov-Völgyi, K., González-Gallego, J., Müller, S. A., Beaufort, N., Malik, R., Schifferer, M., Todorov, M. I., Crusius, D., Robinson, S., Schmidt, A., Körbelin, J., Bareyre, F., Ertürk, A., Haass, C., Simons, M., Paquet, D., Lichtenthaler, S. F., & Dichgans, M. (2024). Proteomics of mouse brain endothelium uncovers dysregulation of vesicular transport pathways during aging. Nature aging, 4(4), 595–612.
2023
Tai YH, Engels D, Locatelli G, Emmanouilidis I, Fecher C, Theodorou D, Müller SA, Licht-Mayer S, Kreutzfeldt M, Wagner I, de Mello NP, Gkotzamani SN, Trovò L, Kendirli A, Aljović A, Breckwoldt MO, Naumann R, Bareyre FM, Perocchi F, Mahad D, Merkler D, Lichtenthaler SF, Kerschensteiner M, Misgeld T. (2023) Targeting the TCA cycle can ameliorate widespread axonal energy deficiency in neuroinflammatory lesions. Nat Metab. 5(8):1364-1381.
Aljović A, Jacobi A, Marcantoni M, Kagerer F, Loy K, Kendirli A, Bräutigam J, Fabbio L, Van Steenbergen V, Pleśniar K, Kerschensteiner M, Bareyre FM. Synaptogenic gene therapy with FGF22 improves circuit plasticity and functional recovery following spinal cord injury. EMBO Mol Med. 2023 Jan 5:e16111.
Van Steenbergen V, Burattini L, Trumpp M, Fourneau J, Aljović A, Chahin M, Oh H, D'Ambra M, Bareyre FM. Coordinated neurostimulation promotes circuit rewiring and unlocks recovery after spinal cord injury. J Exp Med. 2023 Mar 6;220(3):e20220615.
Chovsepian A, Empl L, Bareyre FM. Plasticity of callosal neurons in the contralesional cortex following traumatic brain injury. Neural Regen Res. 2023 Jun;18(6):1257-1258.
2022
Laura Empl, Alexandra Chovsepian, Maryam Chahin, Wing Yin Vanessa Kan, Julie Fourneau, Valérie Van Steenbergen, Sanofer Weidinger, Maite Marcantoni, Alexander Ghanem, Peter Bradley, Karl Klaus Conzelmann, Ruiyao Cai, Alireza Ghasemigharagoz, Ali Ertürk, Ingrid Wagner, Mario Kreutzfeldt, Doron Merkler, Sabine Liebscher & Florence M. Bareyre. Selective plasticity of callosal neurons in the adult contralesional cortex following murine traumatic brain injury. Nat Commun 13, 2659 (2022).
Aljovic A, Zhao S, Chahin M, de la Rosa C, Van Steenbergen V, Kerschensteiner M, Bareyre FM. A deep learning-based toolbox for Automated Limb Motion Analysis (ALMA) in murine models of neurological disorders. Commun Biol. 2022 Feb 15;5(1):131.
Fourneau J, Bareyre FM. Semaphorin7A: its role in the control of serotonergic circuits and functional recovery following spinal cord injury. Neural Regen Res. 2022 May;17(5):959-962.
2021
Van Steenbergen V, Bareyre FM. Chemogenetic approaches to unravel circuit wiring and related behavior after spinal cord injury. Exp Neurol. 2021 Nov;345:113839.
Loy K, Fourneau J, Meng N, Denecke C, Locatelli G, Bareyre FM. Semaphorin 7A restricts serotonergic innervation and ensures recovery after spinal cord injury. Cell Mol Life Sci. 2021 Mar;78(6):2911-2927.
2020
Granier C, Schwarting J, Fourli E, Laage-Gaupp F, Hennrich AA, Schmalz A, Jacobi A, Wesolowski M, Conzelmann KK, Bareyre FM. Formation of somatosensory detour circuits mediates functional recovery following dorsal column injury. Sci Rep. 2020 Jul 2;10(1):10953.
2019
Denecke CK, Aljović A, Bareyre FM. Combining molecular intervention with in vivo imaging to untangle mechanisms of axon pathology and outgrowth following spinal cord injury. Exp Neurol. 2019 Aug;318:1-11.
Bradley PM, Denecke CK, Aljovic A, Schmalz A, Kerschensteiner M, Bareyre FM. Corticospinal circuit remodeling after central nervous system injury is dependent on neuronal activity. J Exp Med. 2019 Nov 4;216(11):2503-2514.
Loy K, Bareyre FM. Rehabilitation following spinal cord injury: how animal models can help our understanding of exercise-induced neuroplasticity. Neural Regen Res. 2019 Mar;14(3):405-412.
2018
Loy K, Schmalz A, Hoche T, Jacobi A, Kreutzfeldt M, Merkler D, Bareyre FM. Enhanced Voluntary Exercise Improves Functional Recovery following Spinal Cord Injury by Impacting the Local Neuroglial Injury Response and Supporting the Rewiring of Supraspinal Circuits. J Neurotrauma. 2018 Dec 15;35(24):2904-2915.
2017
Chovsepian A, Empl L, Correa D, Bareyre FM. Heterotopic Transcallosal Projections Are Present throughout the Mouse Cortex. Front Cell Neurosci. 2017 Feb 21;11:36.
2015
Jacobi A, Bareyre FM. Regulation of axonal remodeling following spinal cord injury. Neural Regen Res. 2015 Oct;10(10):1555-7.
Jacobi A, Loy K, Schmalz AM, Hellsten M, Umemori H, Kerschensteiner M, Bareyre FM. FGF22 signaling regulates synapse formation during post-injury remodeling of the spinal cord. EMBO J. 2015 May 5;34(9):1231-43
Prof. Dr. Florence Bareyre, Principal Investigator
Read more about the PI on the next tab.
Almir Aljović, post-doctoral fellow
I am born in Serbia, but most of my life I lived in Sarajevo, Bosnia and Herzegovina. I have a broad interest in science, that’s why I studied Psychology at the University of Sarajevo and Genetics and bioengineering at International Burch University. I did my master’s degree at the University of Strasbourg, obtaining a degree in Neuroscience. Studying neuroscience allowed me to fuse my interest in understanding behavior with my interest in molecular genetics. I started my Ph.D. in the Bareyre lab in October 2018, where I have a chance to study adaptation mechanisms of neurons following traumatic injuries of the nervous system. Outside the lab, I enjoy spending time with my friends, reading, and watching good movies. Sometimes I just stare at the ceiling for hours and do nothing (help) #JK.
Maryam Chahin, PhD student
After achieving the EMN master degree from University de Bordeaux in France, I pursued my studies as a PhD student in PD. Dr. Bareyre´s lab. My work aim to understand how the brain react after receiving repetitive mild traumatic brain injury and if therapeutically those outcomes can be alleviated. When I am not in the lab, I spend most of my times in art related activities.
Fritz Kagerer, PhD student
Being born in Regensburg I made my way to yet another Bavarian city Erlangen, where I did my bachelor's degree in Integrated Life Sciences (Biophysics and Biomathematics). During that, I realized that life sciences and the scientific thinking behind them are what I love and want to pursue.Neurosciences as a specific topic became apparent to me in several courses I took in my Erasmus semester in Stockholm. The interdisciplinary nature of this subject makes it incredibly interesting and exciting for me. Because of that I started my Master's degree at TUM in „Biomedical Neurosciences“ and found the Bareyre Lab for a lab rotation. Since I liked both work and the environment, it looks like they are stuck with me now and I’m not gonna leave any time soon… My project involves the interaction of immune cells and neurons in the autoimmune disease Multiple Sclerosis (MS). When I’m not at the lab bench doing western blots, I'm usually with friends or smashing Almir and Michele in table tennis :^)
Adna Smajkan, PhD student
Both my Bachelor's and Master's degrees were earned at the International University of Sarajevo, Faculty of Engineering and Natural Sciences, in the field of Genetics and Bioengineering. I got the opportunity to work on my Master's thesis project at the Ludwig Maximilian University of Munich, Department of Pharmacy - Center for Drug Research. In the course of my research, I examined novel tools for genome editing and regulation using a modified CRISPR-Cas9 system, designed primarily to circumvent the limited packaging capacity of rAAV vectors, the gold-standard delivery tools utilized in gene therapy. In October 2022 I started an internship in the Bareyre lab, where I focused on investigating the role of glial cells in circuit remodeling in aging mice following incomplete spinal cord injury. As a way to keep my brain functioning while doing research, I do a lot of sports in my free time. The outdoors is my favorite place to be, whether I'm running, hiking, or just enjoying nature :)
Stefani Dzhuleva, HIWI student
I was born in Bulgaria and have lived there my whole life. After high school, I decided to follow a Bachelor in Biomedical Sciences at VU Amsterdam. The university has a particular focus on Natural Sciences and the program itself offers variety of courses and allows for exploration of many different subfields. My favourite one was undoubtedly Neuroscience and after following this course I was determined that this is the field I want to pursue in the future. I have always been fascinated by the brain and have always wanted to broaden my knowledge regarding all mechanisms influencing human behaviour. At a later stage, I wanted to explore the technical side of my program as well. For this reason I decided to apply for an exchange semester at ETH Zurich, where I spent 5 months and studied Health Sciences and Technology with a particular focus on Analytics and Imaging. Throughout my stay in Switzerland I applied for an internship at PD. Dr. Bareyre's lab due to my interest in brain pathology, treatment and recovery, which fully matched the project she is currently working on. In my free time I am usually with my friends, have a small road trip to a nearby city that I am eager to visit, go for a hike to admire nature or just stay home and enjoy a nice movie afternoon.
Tomal Matt, Technical Assistant
Born in Munich, I decided to do an apprenticeship as a Biology Laboratory Technician at the TUM Institute of Pathology in the field of Neuropathology, which introduced me to the field of Neuroscience. Wanting to stay in the field after finishing my apprenticeship, I applied for a Technical Assistant position at PD Dr. Bareyre's lab. Outside of the lab, I love to spend time with friends, explore new places, and travel whenever possible. I enjoy hiking, biking, and spending time in nature, whether it's at nearby parks or on longer trips to the mountains or lakes. I also enjoy trying out new restaurants and cuisines, cooking at home with friends, reading books, and watching movies.
Hannah Peedle, PhD student
I completed my bachelor’s degree in Neuroscience at the University of St Andrews in my home country of Scotland. During my degree I became particularly interested in the biomedical aspect of neuroscience, specifically neurodegeneration and the role of neuroimmune interactions in health and disease. I knew that I wanted to continue my studies in the vast and exciting field of neuroscience and so I was delighted when I was accepted onto the GSN master’s program at the LMU, and I am now in my second year. I began an internship in the Bareyre lab in November 2023, which involved investigating the role of microglia and complement 3 in spinal cord injury and I enjoyed the working environment and research so much that I will now stay for my master’s thesis. When I’m not in the lab I’m likely playing sports such as tennis, football or volleyball, and I also love hiking in the mountains!
Rozaria Jeleva, Visiting medical doctor
Nigar Manifova, Master student
Alumni
Jonas Bräutigam, medical student, LMU Munich
Valérie Van Steenbergen, Post-doctoral scientist, Novartis, Basel.
Julius Mutschler, medical student, LMU Munich
Romane Bordeaux, medical student, LMU Munich
Jennifer Schmitt, medical student, LMU, Munich
Michele Trumpp, medical student, LMU, Munich
Laura Burattini, medical student, LMU, Munich
Luca Fabbio, master student
Leidy Reyes Jimenez, medical student, LMU, Munich
Alexandra Chovsepian, post-doctoral fellow, LMU, Munich
Laura Empl, Patent examiner, EPO, Munich
Carmen Denecke, scientist
Claudia Lang, scientist plant and food research, NZ
Anne Jacobi, Scientist, Roche, Basel.
Julian Schwarting, medical doctor, LMU, Munich
Fabian Laage Gaup, medical resident, Yale University, USA
Nathalie Garzorz, medical doctor, Munich
Katarzyna Plesniar, Medical student, Ireland
Julie Fourneau, Patent examiner, France
Marta D'Ambra
Maximilian Springer
Hanseul Oh
Prof. Dr. rer. nat. Florence Bareyre
I have been working on brain and spinal cord injuries for more than 20 years and my goal is to understand how innate plasticity can be harvested to foster functional recovery following injury. Key research achievements include the first reports that the spinal cord can spontaenously undergo plastic remodelings following traumatic lesion (Nature Neuroscience 2004 and Nature Medicine 2005). Recent key work demonstrated that the transcription factor STAT3 iinitiates axonal regeneration (PNAS, 2011), that presynaptogenic organizers such as FGF22 are necessary to post-injury synapse formation (EMBO J, 2015) and that neuronal activity is a key process that drives plasticity in the injured spinal cord (JEM, 2019).
Training
1992 – 1994 Bachelor Biochemistry, University Paris VII, France
1994 – 1996 Master Biochemistry, University Paris VII, France
1996 –1997 Post Master Pharmacology, University Marne-la-Vallée, France
2003 Ph.D (Medal of excellence)
2003 – 2004 Postdoctoral fellow at the Dept. of Anatomy and Neurobiology, Washington University School of Medicine, St. Louis, USA
2004 –2005 Postdoctoral fellow at the Dept. of Molecular and Cellular Biology, Harvard University, Cambridge, USA
Academic positions & appointments
2003 Ph.D., Brain Research Institute, Swiss Federal Institute of Technology (ETH) Zurich, Switzerland with the “Medal of Excellence”.
2003 – 2005 Post-Doc, Dept. of Anatomy and Neurobiology, Washington University and Dept. of Molecular and Cellular Biology, Harvard University, Boston, USA
2005 – 2007 Post-Doc, Institute of Clinical Neuroimmunology, LMU Munich, Germany
2008 – 2014 Leader of a BMBF Young Investigator Group, Institute of Clinical Neuroimmunology, LMU Munich, Germany
since 2012 Principial investigator of the Excellence Cluster, Munich Cluster for Systems Neurology (SyNergy), Munich, Germany
2014 Habilitation in Neuroimmunology, LMU Munich, Germany
since 2015 Member and research group leader at the Biomedical Center, LMU Munich, Germany
2024 APL Professorship, LMU Munich, Germany
Collaborative Research
since 2010 Member and PI of the Collaborative Research Center 870 “Neuronal Circuits”
since 2011 Core Faculty Member of the Graduate School of Systemic Neurosciences funded by the DFG Excellence Initiative
since 2012 Member and PI of the DFG-funded Excellence Cluster “Munich Cluster for Systems Neurology” (SyNergy)
since 2014 Board Member of the Collaborative Research Center 870 “Neuronal Circuits”
since 2019 Member and PI of the Collaborative Research Center 274 “Checkpoints of CNS recovery”
Awards & honors
2003 Dissertation Medal of Excellence, ETH Zürich
2003 – 2005 Postdoctoral fellowship from the Swiss National Foundation (SNF)
2005 – 2007 EMBO long-term fellowship
2007 Sobek junior price for multiple sclerosis research (German MS Foundation)
2008 – 2014 Independent group leader award, Neuroscience program of the Federal Ministry of Education and Research (BMBF)
5 key papers
Bradley PM, Denecke CK, Aljovic A, Schmalz A, Kerschensteiner M, Bareyre FM. Corticospinal circuit remodeling after central nervous system injury is dependent on neuronal activity. J Exp Med. 2019 Nov 4;216(11):2503-2514.
Jacobi A, Loy K, Schmalz AM, Hellsten M, Umemori H, Kerschensteiner M, Bareyre FM. FGF22 signaling regulates synapse formation during post-injury remodeling of the spinal cord. EMBO J. 2015 May 5;34(9):1231-43
Bareyre FM, Garzorz N, Lang C, Misgeld T, Büning H, Kerschensteiner M. In vivo imaging reveals a phase-specific role of STAT3 during central and peripheral nervous system axon regeneration. Proc Natl Acad Sci U S A. 2011 Apr 12;108(15):6282-7.
Bareyre FM, Kerschensteiner M, Misgeld T and Sanes JR. (2005) Transgenic tracing of the corticospinal tract: a new tool to study axonal regeneration and remodeling. Nat Med 11(12):1355-1360
Bareyre FM, Kerschensteiner M, Raineteau O, Mettenleiter TC, Weinmann O and Schwab ME. (2004) Spontaneous formation of a new axonal circuit in the rat injured spinal cord. Nat Neurosci. 2004 Mar;7(3):269-77.
Christmas 2022 - So many presents :)
Christmas 2022
Christmas 2022
Fall 2022: Goodbye Julie
Fall 2022
Fall 2022
Oktoberfest 2022
Oktoberfest 2022
Oktoberfest 2022
November 2022: Lab retreat - Bareyre & Kerschensteiner labs
Fall 2022: The netrin team!
Oktoberfest 2022
Klinikum soccer cup 2022 - We tookthe second place!!
Klinikum soccer cup
Summer 2022: Goodbye party for Marta and Hanseul
Summer BBQ 2021
Summer party 2021 - Good bye Luca!
July 2020: Laura‘s PhD: Congrats Laura!!
Medieval Christmas Market 2019
1st INIM Soccer cup - 2021 - Bareyre Lab won!!
September 2020: Lab Life with Corona…
Lab 2019
Oktoberfest 2019
Lab impressions
We gratefully acknowledge support for our work by the following agencies:
Collaborative Research Center 870 – German Research Foundation (DFG)
Wings for Life Foundation
Munich Cluster for Systems Neurology (SyNergy)
Collaborative Research Center 274– German Research Foundation (DFG)
International Foundation for Research in Paraplegia
Förderprogramm für Forschung und Lehre (FöFoLe) der Medizinischen Fakultät der LMU
Alexander Von Humboldt Foundation
Prof. Dr. rer. nat. Florence Bareyre
Florence.Bareyre@med.uni-muenchen.de
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