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Translational Neuroscience

The research mission of the Department of Translational Neuroscience is to discover and delineate mechanisms and processes which are fundamental to the development of neural systems and to the control of behavior as well as to translate these to pathogenesis and disease models. We use cutting edge technology, disease models as well as computational tools to achieve these goals.

Our teaching mission is to raise the next generation scientists and clinicians with state-of-the-art knowledge, technical expertise and vision in the field of neuroscience. As a part of this effort, we teach in several Bachelor courses, coordinate the Neuroscience and Cognition master program of the Utrecht University and offer doctoral and postdoctoral training.

News

May 19, 2025 / Grants

New Woelse Waard grant for Elly Hol: reactive gliosis in Parkinson’s Disease

PI Elly Hol with PhD student Hanne Twenhöfel

Unravelling the role of glial cells in brain disease

Glial cells are crucial for brain function, providing essential support to neurons, yet they remain understudied in the context of brain diseases. When an inflammatory response known as ‘reactive gliosis’ occurs, these cells may lose their neuron-supportive functions and contribute to disease onset. A research team from UMC Utrecht, led by Professor Elly Hol, has secured a Woelse Waard grant to study glial cells in the context of Parkinson’s Disease.

Parkinson’s Disease (PD) is a neurodegenerative brain disease in which midbrain dopaminergic neurons, necessary for coordinating movement, gradually degenerate. The new research project, dubbed ‘GliaPark’, strives to uncover how glia are involved. This is a crucial stepping stone to developing therapeutics to halt this neurodegenerative process and utilizing glial cells as a new target in PD and other brain diseases.

Targeting astrocytes

One specific type of glial cell is the astrocyte. In PD, astrocytes have been significantly less researched than dopaminergic neurons. Elly Hol, professor of Glia biology of brain diseases, explains: “Astrocytes are known to undergo reactive gliosis in PD. The change in astrocytes will contribute to neurodegeneration and can lead to an early loss of dopaminergic neurons. Therefore, targeting astrocytes might help to prevent neuron loss.”

Organoids

The new study is spearheaded by Elly Hol. She will carry out the project together with Translational Neuroscience researchers Jeroen Pasterkamp, Frank Meye, and PhD student Hanne Twenhöfel, alongside a patient researcher from the Parkinson’s Association. The team will use in vitro models derived from Parkinson’s patients to examine how these cells behave under reactive gliosis conditions, aiming to shed new light on neurodegenerative mechanisms and potential therapeutic strategies.

To achieve this, the researchers will create 2D and 3D co-culture models using human induced pluripotent stem cell (iPSC)-derived dopaminergic neurons and astrocytes, incorporating varying PD mutations. They will then assess differences in cell activity, reactive gliosis, morphology, neuropathology, and RNA expression across these cultures and controls.

Deeper insights

Ultimately, the researchers want to create assembloids: interconnected midbrain and striatum organoids (implementing a protocol by Jürgen Knoblich). The midbrain is normally connected to the striatum, providing dopaminergic input for movement control. In PD, when midbrain dopaminergic neurons degenerate, the striatum loses that input. With these assembloids, the team can investigate how a PD midbrain organoid affects a control striatum organoid, and vice versa, to gain deeper insights into neurodegenerative processes.

Follow-up project

In the next few years, Elly plans to initiate a follow-up project to expand upon the results found and, wherever possible, to conduct valorization by working together with a company on possible further development of medication targeting astrocytes. By uncovering how astrocytes contribute to neurodegeneration, these studies could lay the groundwork for new therapies for PD and potentially other brain diseases.

Consortia

Among the researchers, there are strong interactions with the following consortium projects: the BrainScapes program (gravity subsidy – dopaminergic system), spanning the VU, Amsterdam UMC, LUMC, and TU Delft; and MODEM (dementia program ZonMW – neuron-glia interactions), spanning the VU, Amsterdam UMC, LUMC, TU Delft, Radboud UMC, UMCG, and MUMC.

Vrienden UMC Utrecht & Wilhelmina Kinderziekenhuis

This research project is made possible thanks to the support granted by Stichting Woelse Waard to Stichting Vrienden UMC Utrecht & Wilhelmina Children’s Hospital, the charity of the (children’s) hospital. If you would like to contribute to our research, please contact Stichting Vrienden by phone at 088 756 10 10, or go to https://vriendenumcutrecht-wkz.nl/.

April 9, 2025 / News, Research paper

Reward and Stress is orchestrated by small ensembles of neurons in the midbrain.

A. The VTA is comprised of different neurotransmitter-defined neuronal subtypes. B. Distinct, non-overlapping ensembles composed of these different neuronal subtypes were activated for positive valence experiences vs. negative valence experiences.

How do small groups of neurons decide whether we approach a reward or avoid a threat? In a study published April 2nd 2025 in Nature Communications, Frank Meye’s lab at UMC Utrecht shows that distinct neuronal clusters (i.e. neuronal ensembles) in the ventral tegmental area (VTA) are essential for encoding positive and negative experiences.

First author Ioannis Koutlas and colleagues used an innovative approach in transgenic mice where they tagged neurons in the VTA which, based on immediate early gene expression, had become active in response to a particular environmental stimulus. They first established that acute exposure to a rewarding opioid or to a stressful social confrontation triggered opposite behavioral outcomes (approach vs avoidance). They then showed that these two distinct experiences tagged two largely non-overlapping ensembles of neurons in the VTA. These sets were of approximately similar small size (10% of VTA neurons). Moreover, each ensemble comprised multiple neurotransmitter-defined neuronal cell types, and the compositions thereof were similar between the ensembles. This indicates that neurotransmitter-based identities are not sufficient to parse neurons in functional terms.

The researchers then stimulated or inhibited these small ensembles to assess their role in behavior. By selectively activating these groups with opto- or chemogenetics, the researchers drove strong reward-seeking (reward ensemble) or avoidance responses (stress ensemble). Instead, targeted inhibition of these small ensembles fully blocked adaptive behaviors such as stress-driven avoidance, and reward-driven approach behaviors. These experiments identify the crucial role of VTA ensembles of specific cell types in processes of aversion and reward.

An operant task, in which the mouse can choose to optogenetically stimulate the positive valence ensemble by poking its nose into the active port.

Immunohistochemical staining shows the expression of TH, CoChR-GFP, and 2 implanted fiber optic cannulae in the VTA, which can optogenetically stimulate selectively tagged ensembles.

Perturbations in processing such valence processes are a fundamental problem in various brain disorders, not only including psychiatric conditions such as eating disorders, drug addiction and depression, but also neurological disorders like dementia and Parkinson’s disease. The results from this study are therefore an important stepping stone towards understanding, with further research, which exact neuronal cell types contribute to pervasive aversion/reward problems across brain diseases.

“Our findings shed light on the organization of the VTA into valence-specific ensembles, which is key to orchestrating adaptive behavioral responses,” says first author Ioannis Koutlas.

The work was carried out at the Translational Neuroscience Department at the UMC Utrecht Brain Center. Please read the full publication here.

November 13, 2024 / News, Research paper

Special issue: The Shapeshifters; Plasticity from Cells to Society

An Open Call to submit manuscripts for a special issue about Plasticity for Interdisciplinary Science Reviews

The shapeshifter symposium — The shapeshifters symposium, organized by the plasticity consortium, was the prelude to this special issue.

Plasticity, the ability to be molded in various forms while maintaining a core identity, is a term that is increasingly used within various fields of science, e.g. neuroscience, plant- and cell biology, and within the humanities. However, the meaning and use of plasticity varies between different fields. What type of epistemological work does the term plasticity do in different scholarly fields? Can a general theory of plasticity be developed that will encompass some core features but also allow space for unique usages? These are the questions that this special issue poses, and will try to provide and answer from various interdisciplinary perspectives.

Guest editors

This special issue is edited by the members of the Plasticity consortium, which was formed to perform interdisciplinary research as part of the Centre for Unusual Collaborations.

Loai Abdelmohsen (Eindhoven University, The Netherlands).

Onur Başak (Utrecht Medical Center, The Netherlands).

Yaron Caspi (National Taiwan University, Taipei, Taiwan).

Jeff Diamanti (University of Amsterdam, The Netherlands).

Esmee Geerken, (University of Utrecht, The Netherlands).

Tamalone van den Eijnden (University of Twente, The Netherlands).

Keywords: Plasticity, emergence, resilience, robustness, adaptation, metabolism, capacity and ability to change, system sciences, system change, complexity, tipping points, social transitions, transformation, affordances, circular causality, permissive causality, intentionality/volition, meta plasticity, meaning making, disruptive plasticity

Plasticity Special Issue Information

This special Issues, on the theme of “plasticity” explores the concept of plasticity across academic domains and beyond. The guest editors for this issue are group of scholars from different fields, from neuroscience, to cell biology, earth sciences, social sciences, media studies, environmental humanities and arts. We are united by a fascination for what the concept of plasticity means within, between and beyond our field of research.

We invite researchers from all disciplines, societal stakeholders, and the arts to come to question what it means to be a shape within a shapeshifting process, a form within a form – changing, adapting, evolving, or mutating, along with its environment, and to submit these thoughts, formulated within manuscripts, to this special issue; The Shapeshifters; plasticity from cells to society.

Specifically, we invite scholars as individual or as collectives from all disciplines to submit manuscripts that connect, bridge and define plasticity within and between various fields; we are especially keen on ideas exploring how plasticity may be of use in fields that currently do not use the term.

Scholars are invited (but not restricted) to think along four interdisciplinary themes, that has been discussed in four dedicated panel discussions during a symposium organized in Amsterdam, May 30th /31st, 2024. These are: (I) Complexity and Circular Causation, (ii) Environment, (iii)Time, and (iv) Epistemic Cultures. For a full description of the symposium, see the Shapeshifters Symposium Footage may be found here: Shapeshifters Symposium Recording.

The shapeshifters symposium was a blast! We were challenged to go across the boundaries of disciplines not as mere tourists, by as migrating researchers who brought their disciplinary culture and attempted to synthesize it with the new concepts that we come across. The special issue, which will be led by a white paper, will reflect the ideas that sprout out of these two day think tank. [Onur Başak]

Manuscript submission information

Submission Deadline: You are invited to submit your manuscript at any time before the submission deadline of 1st of April, 2025.

We invite and encourage authors to submit their original and high-quality manuscripts to this special issue. All submissions will undergo a rigorous peer-review process by at least two independent reviewers to ensure high-quality contributions and scientific validity. Papers will be published on-line immediately after acceptance.

Please submit your manuscript through the journal manuscript submission system. Importantly, once submission on the electronic platform was completed, please send an email to the guest editor: e.geerken@uu.nl to inform about the manuscript submission. Manuscripts must be submitted exclusively through the above-mentioned link on the journal’s submission system. Any submissions made through other channels, or ones where the guest editors was not informed, will not be considered for inclusion in this special issue.

Please ensure you read the Guide for Authors before writing your manuscript. Any submissions lacking the correct formatting, declarations, ethical approvals, or related materials will not be allowed to proceed to the review stage. If the manuscripts fail to meet the standards in terms of English language, content, or relevance, they will be declined. For any inquiries about the appropriateness of contribution topics, please contact the following corresponding Guest Editors, Dr. Yaron Caspi or Dr. Esmee Geerken, E-mails: e.geerken@uu.nl; ycaspi@ntu.edu.tw

PLASTICITY SPONSORS

This special issue is made possible with the support of:

The Alliance (Wageningen University, Technical University Eindhoven, Utrecht University, Utrecht Medical Centre Utrecht)

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Vacancies

We welcome open applications from PhD candidates and postdocs.