ArticleNature communications2025
Synaptic signatures and disease vulnerabilities of layer 5 pyramidal neurons.
Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed.
- Review
- Increased excitability of layer 5 neocortical pyramidal neurons and its contribution to seizure activity in Gabrg2 gene-deficient mice.iScience · 2026Article
- Human Neocortical Glutamatergic Neurons Revealed Through Multimodal Profiling.bioRxiv : the preprint server for biology · 2026Article
- Neuroinflammatory stress preferentially impacts synaptic MAPK signaling and mitochondria in excitatory neurons.Molecular neurodegeneration advances · 2026Article
- Autism-associatedProceedings of the National Academy of Sciences of the United States of America · 2025Article
- An integrated transcriptomic and proteomic map of the mouse hippocampus at synaptic resolution.Nature communications · 2025Article
- The Role of Astrocytes in the Molecular Pathophysiology of Schizophrenia: Between Neurodevelopment and Neurodegeneration.Biomolecules · 2025Review
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Authors and funding
9 authors.
Funding
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Abstract
Cortical layer 5 (L5) intratelencephalic (IT) and pyramidal tract (PT) neurons are embedded in distinct information processing pathways. Their morphology, connectivity, electrophysiological properties, and role in behavior have been extensively analyzed. However, the molecular composition of their synapses remains largely uncharacterized. Here, we dissect the protein composition of the excitatory postsynaptic compartment of mouse L5 neurons in intact somatosensory circuits, using an optimized proximity biotinylation workflow with high spatial accuracy. We find distinct synaptic signatures of L5 IT and PT neurons that are defined by proteins regulating synaptic organization and transmission, including cell-surface proteins (CSPs), neurotransmitter receptors and ion channels. In addition, we find a differential vulnerability to disease, with a marked enrichment of autism risk genes in the synaptic signature of L5 IT neurons compared to PT neurons. These results align with human studies and suggest that the excitatory postsynaptic compartment of L5 IT neurons is susceptible in autism. Our approach is versatile and can be broadly applied to other neuron types to create a protein-based, synaptic atlas of cortical circuits.
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Registered trials
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