Bareyre Lab – Neuronal Repair

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.

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.

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?

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.

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?

Dr. Julie Fourneau, Postdoctoral fellow

I studied Cell Biology and Physiology and obtained a Master in Biology and Health Research in Lille (France). In 2018, I obtained my PhD in Neurosciences with Dr Erwan Dupont and Pr Marie-Hélène Canu (URePSSS, University of Lille) working on the molecular and functional repercussions of a sensorimotor restriction. Wanting to continue in the field of sensorimotor plasticity, I moved to Munich and joined Dr. Florence Bareyre's group as a postdoctoral researcher. Now I work on the remodeling of the central nervous system following partial spinal cord lesions, and on the identification and understanding of the role of glial cells in this remodeling. Besides science and the lab walls, I love to eat and explore new restaurants... and to get rid of the calories, I really like to go hiking, biking or bouldering. Whenever I have the opportunity, I enjoy traveling around the world and visiting new places.

Dr. Valérie van Steenbergen, Postdoctoral fellow

After my studies in Biomedical sciences, I embarked on a PhD project at KU Leuven to understand how molecular changes in neuronal microtubules can affect mitochondrial transport and how we can image these changes using label-free imaging. I thoroughly enjoyed gaining expertise in in vitro work and advanced imaging techniques and decided to gain new skills related to in vivo studies for my postdoc, allowing me to combine the best of both worlds. I therefore traded Belgian chocolates and beer for the Weisswurst and (almost equally good) German beer and joined the team of Florence Bareyre in Munich early 2020. My main project focusses on activity-dependent remodeling of spinal circuits after spinal cord injury using gene therapy, anatomy analysis and behavioural tests. My weekends are spent hiking, snowboarding or just enjoying a lazy afternoon at one of Bavaria’s beautiful lakes.

Almir Aljović, PhD student

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.

Julius Mutschler, Medical student

Growing up in a rural area by the Lake of Constance, I got fascinated by nature and the ground-lying science early on. This led me to the decision to study medicine as I felt like it would be a perfect mix including all the different facets of science and social aspects. In class, I quickly discovered to like Neuroscience, Immunology and Oncology. So for my doctoral thesis, I decided to further focus on the actual research regarding Neuroimmunology joining the Bareyre Lab in March 2021. Here, my project focuses on defining cellular and molecular responses to repetitive mild Traumatic Brain Injury (rmTBI) with the perspective on finding first therapeutical approaches.

When I am not in the lab, I try to be outside as often as I can; whether this means biking to the lake with friends, climbing in the mountains surrounding Munich or summiting high peaks like the Mont Blanc.

Romane Bordeaux, Medical student

Born in France and raised in Munich, I started my medical studies at the Ludwig-Maximilians-Universität München in 2017, during which I gradually developed an interest in the field of neuroscience. I joined the Bareyre Lab in April 2021 for my medical doctoral thesis. My MD project focuses on the role of microglia in the control of neuronal activity and shaping of rewired circuits following incomplete spinal cord injury. In my free time I enjoy spending time with my family and friends, discovering new series and traveling.

Hanseul Oh, Master student

First moving to Germany in 2017, I finished my Bachelor’s degree in Medical Natural Sciences at Jacobs University Bremen in 2020. Then, captivated by the enormous plasticity of our brain, I came to Munich and am currently studying masters in Neuroscience at GSN-LMU. I joined Bareyre Lab in May 2021, and my research focus lies on the activity-dependent circuit reorganisation in mice after the spinal cord injury. Besides lab work and academics, I like going out for sports, photography or Münchner beer or sending out a handwritten card to my family back in South Korea or my friends all over the place!

Joelle Metzger, Master student

I was born in a small town near Basel, Switzerland and moved to Zurich after high school for my studies. At ETH Zurich I studied Health Sciences and Technology with a focus on Neuro- and Sportscience, as I was always very interested in what happens between muscles and neurons. During my studies I developed a broad interest in spinal cord injury. This is why I came to Munich to conduct my master thesis here at AG Bareyre where I investigate the role of astrocytes in synapse removal and circuit rewiring following spinal cord injury. Outside the lab, I like spending time with friends and family, playing volleyball, snowboarding or hiking.

Marta d'Ambra, Master student

I was born in San Francisco, U.S. by Italian and Ethiopian parents, an improbable couple. I went on to complete a bachelor's in Biological Sciences and a second bachelor's in Psychology, and searched for a Master´s to consolidate the two subjects. I began my Master´s in neuroscience at the University of Trieste in Italy, and have joined the Bareyre lab as part of my master's thesis. I will partake in research delving into the subject of neuronal rewiring after spinal cord injury. Specifically, we will look at how stimulation better affects the process of rewiring via detour circuits, and downstream behavioral effects.

Michele Rosso, Medical student

After growing up in a German-speaking region in the Italian Alps, I moved to Munich in 2018 to pursue my medical studies. Neuroscience, in its basic and clinical aspects, sparked my curiosity from the very first lectures. Therefore in 2019, I seized the opportunity to work in the Bareyre Lab on a research project investigating motor recovery after spinal cord injury. Over time, fascinating immunological pathways caught my eye, leading me to combine them with my interest in neuroscience as I pursue my medical doctorate in which I focus on the immune response that follows spinal cord injuries. If I´m not in the lab you will most likely find me working on med school and healthcare related EdTech projects or on the handball playing field.

Alumni

Jennifer Schmitt, medical student, LMU, Munich

Michele Trumpp, medical student, LMU, Munich

Laura Burattini, medical student, LMU, Munich

Luca Fabbio, scientist

Leidy Reyes Jimenez, medical student, LMU, Munich

Alexandra Chovsepian, post-doctoral fellow, LMU, Munich

Laura Empl, SFB274 scientific coordinator, Munich

Carmen Denecke, scientist

Claudia Lang, scientist plant and food research, NZ

Anne Jacobi, post-doctoral fellow, Harvard, USA

Julian Schwarting, medical doctor, LMU, Munich

Fabian Laage Gaup, medical resident, Yale University, USA

Nathalie Garzorz, medical doctor, Munich

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

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)

Bareyre Lab – Neuronal Repair

Our Aim

Our Approach

Some of our current projects

Regulation of synapse formation and elimination following spinal cord injury

Activity-dependent regulation of axonal plasticity following spinal cord injury

Acute and long term effects of mild repetitive traumatic brain injury

Contact

PD. Dr. rer. nat. Florence Bareyre

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

Alexander Von Humboldt Foundation

Contact

Partners