This year, our group successfully implemented transsynaptic retrograde tracing (cTRIO) using a modified Rabies virus. This approach allowed us to identify a specific group of lateral septum (LS) interneurons that connect directly to enkephalinergic neurons involved in controlling affective states. This finding offers a potential mechanism explaining why global LS stimulation—observed in human DBS studies and mouse optogenetics—induces positive affective behaviors through inhibition of these neurons. Initial experiments using AAV-hDlx and RV CreOFF-FlipON strategies demonstrated selective expression of hDlx, marking a key step forward in targeting these neurons.

An unexpected challenge arose when testing monocyte inhibition using Gi-DREADDs in a Parkinson’s disease model: animals surprisingly died within minutes of treatment. Repeating the experiment in non-Parkinsonian mice yielded the same result, prompting a deeper investigation. This surprising outcome led us to collaborate with Vladimir Matchkow’s group, where we discovered that monocyte inhibition causes cardiac arrest, revealing an unexpected link between the innate immune system and heart function. Additional collaborations with Søren Degn and DTU were established to apply multiomic screening for inflammatory markers, aiming to uncover new mechanisms underlying immune-to-brain interactions.

In 2025, we plan to embrace “big data” approaches to integrate findings across projects. Collaborating with Boris Hefiets at Stanford University, we will pursue whole-brain analyses and multiomics to deepen our understanding of affective resilience and Parkinson’s disease models. We also aim to further explore single-cell sequencing data from microglial activation studies and begin functional testing of newly identified targets. This next phase holds great promise for discovery, blending opportunity with the excitement of exploring uncharted scientific territory.

This year, our group released a developmental atlas of the mouse hypothalamus and prethalamus, now available as a preprint with accompanying datasets. The atlas links key transcriptional regulators to neurogenesis and to human traits such as metabolic disease and cognition. We also began developing a cost-effective, multiplexed smFISH platform for 3D spatial transcriptomics in whole cleared mouse brains, and initiated new collaborations within the Nordic-EMBL network.

A major challenge in 2024 was the unexpected relocation of our lab in November due to facility damage. Despite the disruption, the team coordinated the move swiftly and effectively, minimizing impact on ongoing experiments. A personally rewarding milestone was stepping outside of core expertise to apply a new technique successfully—highlighting the team’s adaptability and growth.

In 2025, we aim to publish our first lab-led manuscript, expand our spatial transcriptomic work to disease models, and deepen collaborations in human developmental modeling and clinical translation. Our team continues to grow in independence and technical skill, now routinely executing complex protocols with confidence.

This year, our group made substantial advances in uncovering the genetic regulation of memory formation across specific brain regions and cell types. By implementing cutting-edge single-cell multiomics technologies, we began identifying key regulatory genes involved in this process. Additionally, we completed a proof-of-principle for a novel history-tracing genomics technology, which holds promise as a major technological breakthrough in neurobiology. Our efforts have directly contributed to DANDRITE’s mission by pioneering integrated single-cell datasets that link chromatin state, gene expression, and receptor signaling within individual neurons.

A significant technical challenge in 2024 was the integration of diverse genomics approaches—such as ATAC-seq, RNA-seq, and history-tracing modalities—at single-cell resolution. To overcome these complexities, we leveraged a new infrastructure grant from the Novo Nordisk Foundation, which allowed us to upgrade our workflows and improve both library preparation and data analysis pipelines. These enhancements greatly accelerated our experimental throughput and data quality. A personal highlight was seeing the team evolve: postdocs took on independent leadership roles, and our PhD student expanded into computational analysis, elevating the entire group’s scientific maturity.

In 2025, our priority is to implement the next generation of genomics technologies to address some of the most pressing questions in neurobiology. We will continue refining our multiomic strategies and build new collaborations that integrate our findings into broader translational research. As the team grows in confidence and capability, we remain focused on producing impactful science that bridges molecular mechanisms with brain function.

This year, our group made significant progress in understanding synaptic protein homeostasis. We developed a systematic approach to analyze degradation signals for thousands of synaptic proteins. A major driver of this work was the adoption of subcellular ubiquitylomics, a mass spectrometry-based technique that enabled us to study protein degradation in neuronal synapses. This was achieved through a fruitful collaboration with the University of Southern Denmark. Our contributions directly support the translational goals of DANDRITE and the Nordic EMBL Partnership.

One key challenge in 2024 was implementing mouse behavior assays, a new direction for our lab. Thanks to strong collaborative support from colleagues within DANDRITE, we were able to overcome this hurdle and successfully integrate these assays into our research. It was also a particularly rewarding year as several team members received competitive fellowships and grants, reflecting the strength and potential of the group.

In 2025, we aim to further investigate the degradation signals of synaptic proteins and their role in synaptic plasticity. As our team continues to grow in size and diversity, we remain committed to fostering a collaborative and innovative research environment.

This year, our group identified significant physiological changes in the gut of zebrafish exposed to a drug associated with elevated autism risk. These findings may help explain the gastrointestinal symptoms observed in individuals with autism and in other animal models. We also adapted high-throughput methods to monitor brain activity and morphology across large numbers of zebrafish, enabling faster hypothesis testing and broader functional insights.

A major challenge in 2024 was adapting to new regulations that made it more difficult to import zebrafish lines into the Nordic region. In response, we began developing strategies to generate the necessary mutant lines in-house. Despite these logistical hurdles, the team remained focused and resilient. A particularly rewarding moment was when postdoc Dr. Andersen-Civil was awarded a Lundbeck Postdoctoral Fellowship—an important milestone for both her and the group.