Researchers at the Max Planck Institute for Brain Research have mapped the molecular landscape of the mouse hippocampus, a region central to learning and memory. By combining RNA and protein profiling with advanced methods to isolate brain regions and synapses, the team identified thousands of molecules with distinct spatial patterns.
The study, published in Nature Communications, shows how local protein production and synaptic diversity shape hippocampal function and provides a freely accessible resource for the research community.
Understanding the complexity of the brain requires detailed maps of both messenger RNAs (mRNAs) and proteins across regions, cell types, and compartments. While recent studies have profiled either transcripts or proteins in specific brain areas, few have systematically integrated both molecular classes in parallel.
In this new work, Dr. Eva Kaulich, Quinn Waselenchuk, and colleagues in the Schuman Lab at the Max Planck Institute for Brain Research in Frankfurt present the first integrated transcriptomic and proteomic atlas of the mouse hippocampus at synaptic resolution. The hippocampus—a region central to learning and memory—was chosen for its well-characterized structure, function, and connectivity.
The researchers combined RNA sequencing (RNA-seq) and liquid chromatography-tandem mass spectrometry (LC-MS/MS) with precision microdissection of hippocampal subregions and layers, as well as Fluorescence-Activated Synaptosome Sorting (FASS). This combination allowed them to systematically map more than 17,000 mRNAs and 10,000 proteins, uncovering thousands with distinct enrichment patterns, including receptors, ion channels, adhesion molecules, and metabolic regulators.
Integrating the datasets revealed complex regulatory relationships: while some proteins closely mirrored their mRNA levels, others did not, reflecting additional control by protein half-lives and local translation. Analysis of pyramidal neuron compartments further showed that distal dendrites likely rely more heavily on local protein synthesis to maintain their molecular identity.
“Our atlas provides an unprecedented view of how RNAs and proteins are organized in the hippocampus. This opens up new opportunities to study how molecular diversity supports brain function and plasticity,” says co-lead author Eva Kaulich, Postdoctoral Researcher in the Schuman Lab.
“By integrating transcriptomic and proteomic data at subcellular resolution, we can now better understand how neurons regulate their molecular machinery locally, especially at synapses,” adds co-first author Quinn Waselenchuk, graduate student in the labs of Erin Schuman and Julian Langer at the Max Planck Institute for Brain Research and the Max Planck Institute of Biophysics.
“The hippocampus has long served as a model system in neuroscience. By making this atlas accessible, we aim to provide a tool that will help the community investigate how molecular organization shapes neuronal and synaptic function,” concludes Schuman.
More information:
Eva Kaulich et al, An integrated transcriptomic and proteomic map of the mouse hippocampus at synaptic resolution, Nature Communications (2025). DOI: 10.1038/s41467-025-63119-5
The atlas is publicly available through syndive.org.
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Max Planck Institute for Brain Research
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