An integrated transcriptomic and proteomic map of the mouse hippocampus at synaptic resolution

Eva Kaulich, Quinn Waselenchuk, Nicole Fürst, Kristina Desch, Janus Mosbacher, Elena Ciirdaeva, Marcel Juengling, Roshni Ray, Belquis Nassim-Assir, Georgi Tushev, Julian D. Langer and Erin M. Schuman ()
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Eva Kaulich: Max Planck Institute for Brain Research
Quinn Waselenchuk: Max Planck Institute for Brain Research
Nicole Fürst: Max Planck Institute for Brain Research
Kristina Desch: Max Planck Institute for Brain Research
Janus Mosbacher: Max Planck Institute for Brain Research
Elena Ciirdaeva: Max Planck Institute for Brain Research
Marcel Juengling: Max Planck Institute for Brain Research
Roshni Ray: Max Planck Institute for Brain Research
Belquis Nassim-Assir: Max Planck Institute for Brain Research
Georgi Tushev: Max Planck Institute for Brain Research
Julian D. Langer: Max Planck Institute for Brain Research
Erin M. Schuman: Max Planck Institute for Brain Research

Nature Communications, 2025, vol. 16, issue 1, 1-22

Abstract: Abstract Understanding the brain’s molecular diversity requires spatially resolved maps of transcripts and proteins across regions and compartments. Here, we performed deep spatial molecular profiling of the mouse hippocampus, combining microdissection of 3 subregions and 4 strata with fluorescence-activated synaptosome sorting, transcriptomics, and proteomics. This approach revealed thousands of locally enriched molecules spanning diverse receptor, channel, metabolic, and adhesion families. Integration of transcriptome and proteome data highlighted proteins tightly linked to or decoupled from mRNA availability, in part due to protein half-life differences. Incorporation of translatome data identified roles for protein trafficking versus local translation in establishing compartmental organization of pyramidal neurons, with distal dendrites showing increased reliance on local protein synthesis. Classification of CA1 synapses revealed contributions from kinases, cytoskeletal elements, and adhesion molecules in defining synaptic specificity. Together, this study provides a molecular atlas of the hippocampus and its synapses (syndive.org), and offers insights into spatial transcript-protein relationships.

Date: 2025
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DOI: 10.1038/s41467-025-63119-5

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