Reward and Stress is orchestrated by small ensembles of neurons in the midbrain.
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.
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.
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
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)
CONNECT Symposium 2025
One day of cutting-edge in vitro models: Jan. 10th 2025
You’re invited to discover the latest advances in brain organoid research and in vitro BBB models! For one day , the CONNECT Symposium will bring together leading scientists and professionals, including international keynote speakers Dr. Adrian Ranga (KU Leuven) and Dr. Roberto Villaseñor (Roche). Daily lunch, refreshments and a borrel is included.
Location:
Boothzaal, University Library Utrecht Science Park
Who can join?
PIs, PhDs and postdoc researchers; (co-) founders, junior and senior scientists from private industry; any professional or student enthused about in vitro modeling!
PhD course Neurodevelopment 2024
A new PhD course for Neurodevelopment will take place between the 18-22 November 2024! Organised by Cora Nijboer, Michael van der Kooij, Myrna Brandt, Carla Gomes da Silva, and Onur Basak of the UMC Brain Center, this course will combine multiple aspects of neurodevelopmental disorders. We will start by lectures on Autism Spectrum Disorder (day 1), dive into the recent developments on Neonatal Brain Injury (day 2), discuss how early priming of events can affect long term outcome (day 3) and see the state-of-the-art in pediatric neurooncology (day 4). These will be supplemented by journal clubs, career sessions, a wild card game to set the tone for student-designed project challenge (day 5)!
Who can join?
PhD Students enrolled at a Dutch University with great enthusiasm on Neurodevelopmental Disorders
Credits:
The course procides 1.5 ECTs
Registration:
Please contact the CEN secreteriaat (Cen-secretariaat@umcutrecht.nl) for registration. For more information, you can reach out to F.R. de Andrade (F.R.deAndrade-2@umcutrecht.nl).
Program:
Monday 18 November Autism Spectrum Disorders
- Keynote lectures by Prof. Em. Peter Burbach, Prof. Olga Penagarikano & Prof. Hilgo Bruining
- Roundtable & video analysis “Support housing for ASD patients”
- Welcome drinks & snacks
Tuesday 19 November Neonatal Brain Injury
- Keynote lectures by Dr. Jeroen Dudink, Dr. Daan Ophelders & Prof. Maria Cecilia Angulo
- Outreach: patenting your science and a workshop on designing graphical abstracts
Wednesday 20 November Early Priming and Long-Term Outcome
- Keynote lectures by Dr. Aniko Korosi, Dr. Jinte Middeldorp, Dr. Sharon Kolk & Dr. Ronald Poppe
- Journal club: decisions in storybuilding by 3 senior neuroscientists
- Life after science: speed-dating with PhD alumni that hold careers in education, valorization, government & industry (including drinks)
Thursday 21 November Pediatric Neuro-Oncology
- Keynote lectures by Prof. Marcel Kool, Dr. Benedetta Artegiani and others
- Game “keep your cards close”: new frontiers in neurodevelopment research
Friday 22 November Student pitches & more!
- Pitch your innovative project (team-competition)
- Writing & funding: interactive sessions with the editor-in-chief of Glia and the Dutch Brain Foundation
- Quiz
- Goodbye drinks & snacks
Daily lunch is included. Please let us know if you have any dietary requirements.
New gene for Parkinson’s disease discovered
In a new study published in Nature Genetics, Paul Hop and colleagues describe the discovery of a gene responsible for a heritable form of Parkinson’s disease. The study was an international collaboration coordinated by the Kenna lab and multiple partners in the US and Italy. The research team used the RVAT software package developed by the Kenna lab and specialized computational infrastructure to analyze DNA from over 2,100 patients with familial Parkinson’s disease and 70,000 volunteers. The partnership with project MinE, an independent initiative to unravel the genetic basis of amyotrophic lateral sclerosis made the scale of the analyses possible.
“We’re very excited about this finding. This was the largest genetic analysis of familial Parkinson’s disease to date, and we believe that the discovery of the RAB32 mutation and it’s effect on LRRK2 open up important new research lines” – Paul Hop
Paul Hop is a PhD student at the UMC Utrecht Brain Center under the supervision of Kevin Kenna and Jan Veldink. Paul is also a lead developer for the RVAT analysis package. His analysis revealed a mutation in the RAB32 gene that significantly increased the risk of Parkinson’s disease. Subsequent investigations of this mutation in laboratory grown cell models revealed that the mutation led to abnormal increases in the activity of a key Parkinson’s related protein called LRRK2. Such abnormal increases in LRRK2 activity are important in Parkinson’s disease. Furthermore, research community is already exploring this increase as a potential target for therapeutic intervention. Until now, only a handful of genes have been definitively implicated in heritable forms of Parkinson’s disease. The discovery of the RAB32 mutation and its effect on the LRRK2 protein are therefore an important step forward.
For more information about the study please see: