Anna-Sophia Wahl – Neuronal Repair and Rewiring

Although the last decades have been very successful in developing acute treatment options for patients suffering from stroke, we still cannot provide specific and causative therapies for the chronic consequences of strokes such as long-term motor impairment or cognitive decline. A prerequisite for developing novel therapeutic approaches, is to improve our understanding, how the brain itself deals with structural damage on different levels- from a network, to a cellular and subcellular level. We know from clinical studies and animal models, that an injury to the brain induces plastic mechanisms and initiates intrinsic repair processes. However, in our own work we have shown, that interacting with this intrinsic repair machinery is not trivial. Thus, the goal of our work is, to uncover the principles of neuronal repair and rewiring to identify new targets for restoring impaired neuronal activity and for promoting recovery of lost function after brain injury. Specifically, we would like to understand, how some nerve cells are chosen to participate in repair processes while others maintain their old function.

We also examine how surviving nerve cells form new connections, how old connections are strengthened, which neuronal circuits reorganize, stabilize or disintegrate and how neuronal remodeling contributes to the functional outcome.

Elucidating causal connections between neuronal rewiring and functional outcome

We use different imaging methods (wide field and multiphoton calcium imaging) in the behaving animal (performing grasping tasks, running on a running wheel or in a virtual reality environment) during learning and after the induction of different stroke models. We also apply opto- and chemogenetics, sophisticated behavioral assessments for sensorimotor and cognitive functions as well as deep learning algorithms to explore causal relationships between neuronal rewiring- from a cellular resolution till a network level- and the behavioral phenotype.

Studying neuronal microcircuits for sensorimotor dysfunction and recovery after stroke

We study how individual surviving neurons in the cortex rewire and recode to take over lost- or impaired motor function after a photothrombotic stroke targeting the sensorimotor cortex. We use chronic 2-photon calcium imaging in active animals following the same region of interest in the cortex during learning of the motor task and after stroke. We hope to reveal (i) how the computation of individual neurons and neuronal ensembles adapt to injury and how this is related to motor recovery, (ii) how different layers of the motor cortex contribute to the rewiring processes ,(iii) if mechanisms of spontaneous recovery can be further promoted by appropriate external treatment approaches (e.g. pharmacology or rehabilitation).

Studying the pathomechanisms of cognitive decline on a microcircuit level after stroke

Almost 20% of stroke patients develop forms of cognitive decline months but also years after the ischemic event. The underlying mechanisms are not understood. A critical area of memory formation but also memory degeneration is the hippocampus. Hippocampal neurons are in particular known to be highly vulnerable to ischemic injury. Using chronic 2-photon calcium imaging in the hippocampus during learning of a spatial memory task (mice learn to navigate in a virtual reality set-up) and after induction of micro-strokes we hope to elucidate (i) how micro-strokes impair the local neuronal circuitry in the hippocampus affecting memory, (ii) how surviving neurons and functional ensembles of neurons rewire to compensate for the damage and (iii) if neuronal rewiring can be further enhanced by the appropriate stimulation paradigm or neuro-cognitive rehabilitation schedule.

Anna-Sophia Wahl, Principal investigator

I am a board certified psychiatrist with both clinical training in neurology and psychiatry as well as a neuroscientist with expertise in neuronal repair, stroke and dementia. In 2019 I started to build my own team as junior group leader at the Brain Research Institute, University of Zurich. Since 07/2022 I have accepted an associate professorship for neuroanatomy at LMU Munich with a dual affiliation as principal investigator at the ISD. With my team I am developing animal models – using a combination of chronic in-vivo 2photon imaging in mice and deep learning to unveil causal relationships between neuronal coding and the behavioural phenotype in health and disease.

We still know very little of the complex spatial and temporal dynamics of the brain state after stroke and this has prevented us from developing successful treatment options which are able to causally interact with intrinsic repair mechanisms to restore lost or impaired function after stroke. With our research we provide an experimental pipeline to break the ground – not only revealing novel pharmacological targets but also for studying the efficiency of different pharmaceutical compounds or translational stimulation approaches to promote neuronal repair and rewiring after CNS injury such as stroke.

Personal data:

Anna-Sophia Wahl, MD PhD

Academic training

2012: American Medical State Examination USMLE Step II

2010: Final year rotation at the Department of Neurology, Columbia University, New York, USA

2010: Final year rotation in internal medicine/ cardiology at the Swiss Heart Center, Bern, Switzerland

2009: Department of Neurology, Massachusetts General Hospital (MGH), Harvard Medical School, Boston, USA

2007-2011: Participant of the MD/PhD Program at Heidelberg University, studying biology to a bachelor`s equivalent

2004 – 2011: Medical Studies at Heidelberg University

Academic and scientific degrees

2011-2014: PhD (summa cum laude) at the Brain Research Institute, ETH and University, Zurich, Switzerland; Supervisor: Prof. Dr. M. Schwab

2007-2009: MD thesis (magna cum laude) at the Interdisciplinary Center of Neurosciences, Heidelberg; Supervisor: Prof. Dr. H. Bading

Professional career since graduation:

Since 07/2022: Professor for neuroanatomy (W2, tenure track) at LMU Munich

Since 01/2019: Junior Group Leader at the Brain Research Institute, Department Neurophysiology (Head: Prof. F. Helmchen), University of Zurich; Principal Investigator at the Center for Neuroscience Zurich;

2016-2020: Resident in Psychiatry/ Clinical scientist at the Central Institute of Mental Health (ZI), Mannheim, University of Heidelberg (Head: Prof. Andreas Meyer-Lindenberg); Board certified psychiatrist and psychotherapist since 02/2021;

2015-2016: Postdoctoral fellow at the Brain Research Institute, ETH and University Zurich, Group Prof. Martin Schwab

2015: Resident in Neurology, University Hospital Zurich

Honors:

2022: SyNergy Professorship “Neuroanatomy”, Munich Cluster for Systems Neurology

2021: Research Grant Synapsis Foundation, Demenz Forschung Schweiz

2020: Research Grant Hurka Foundation, Zurich, Switzerland

2020: Research Grant Swiss Natonal Science Foundation (No. 192678)

2019: Research Grant Novartis Foundation for biomedical research

2018: Wrangell-Habilitation Scholarship

2018: Branco Weiss Fellowship

2017: Junior Research Award of the Journal Brain Sciences.

2015: Finalist of the FENS-Kavli PhD Prize

2014: Prize of the Faculty of Science, University of Zurich for an excellent PhD thesis

2014: Best publication award 2014 of the Swiss Society of Neuroscience

2012-2014: Several travel grants of the Center for Neuroscience Zurich (ZNZ), Swiss Physiological society and Swiss Society of Neuroscience (SSN) for neuroscience conferences.

2007-2011: Scholarship of the German National Academic Foundation (Studienstiftung des Deutschen Volkes)

2007: Participation in the Lindau Nobel Laureate Meeting 2007 upon nomination by the Medical Faculty of Heidelberg and a selection process of 20 000 applicants worldwide, sponsored by the Boehringer Ingelheim Foundation.

2005-2011: Scholarship of the Konrad-Adenauer-Foundation

2004: Prize of the German Physical Society for excellent achievements in physics in the A-level, School prize for German and the Natural Sciences in the A-level

Anna-Sophia Wahl – Neuronal Repair and Rewiring

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