Comparative ultrastructural features of excitatory synapses in the visual and frontal cortices of the adult mouse and monkey
Open accessAbstract
The excitatory glutamatergic synapse is the principal site of communication between cortical pyramidal neurons and their targets, a key locus of action of many drugs, and highly vulnerable to dysfunction and loss in neurodegenerative disease. A detailed knowledge of the structure of these synapses in distinct cortical areas and across species is a prerequisite for understanding the anatomical underpinnings of cortical specialization and, potentially, selective vulnerability in neurological disorders. We used serial electron microscopy to assess the ultrastructural features of excitatory (asymmetric) synapses in the layers 2-3 (L2-3) neuropil of visual (V1) and frontal (FC) cortices of the adult mouse and compared findings to those in the rhesus monkey (V1 and lateral prefrontal cortex [LPFC]). Analyses of multiple ultrastructural variables revealed four organizational features. First, the density of asymmetric synapses does not differ between frontal and visual cortices in either species, but is significantly higher in mouse than in monkey. Second, the structural properties of asymmetric synapses in mouse V1 and FC are nearly identical, by stark contrast to the significant differences seen between monkey V1 and LPFC. Third, while the structural features of postsynaptic entities in mouse and monkey V1 do not differ, the size of presynaptic boutons are significantly larger in monkey V1. Fourth, both presynaptic and postsynaptic entities are significantly smaller in the mouse FC than in the monkey LPFC. The diversity of synaptic ultrastructural features demonstrated here have broad implications for the nature and efficacy of glutamatergic signaling in distinct cortical areas within and across species.
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Quantitative analyses of synapses in the neuropil have shown that most synapses on dendritic shafts are AS (~80%), with relatively few being SS (~20%).
“In fact, quantitative analyses of synapses in the neuropil have shown that most synapses on dendritic shafts are AS (∼80%), with relatively few being SS (∼20%) (Beaulieu et al., 1992; Peters et al., 2008; Hsu et al., 2017; Calì et al., 2018; Santuy et al., 2018b; Domínguez-Álvaro et al., 2019, 2021a,b; Yakoubi et al., 2019b; Montero-Crespo et al., 2020, 2021; Cano-Astorga et al., 2021, 2023;”
From Unambiguous identification of asymmetric and symmetric synapses using volume electron microscopy (2024) · cites this paper as Hsu et al., 2017
The Results section (‘Postsynaptic targets, location and distribution of asymmetric synapses’; page unavailable) quantifies asymmetric synapses on dendritic shafts in mouse and monkey cortex. It does not report the proportion of all shaft synapses that are asymmetric versus symmetric, so the claimed ~80%/~20% split is unsupported by this paper. (LLM, conf=0.83)
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- Authors
- Hsu, A., Luebke, J. I., & Medalla, M.
- Affiliations
- Boston University (US)
- Corresponding author
- Medalla, Maria
- Venue
- Journal of Comparative Neurology
- Publisher
- Wiley
- Published
- 2017-03-26
- Volume
- 525
- Issue
- 9
- Pages
- 2175-2191
- ISSN
- 0021-9967 (ISSN-L)
- 1096-9861
- PMC
- PMC6296778
- OpenAlex
- W2592450516
- Cited by
- 68
- References
- 98
- Citations by year
- 2026: 4 · 2025: 8 · 2024: 13 · 2023: 5 · 2022: 5 · 2021: 8 · 2020: 10 · 2019: 5 · 2018: 7 · 2017: 3
- FWCI
- 3.35
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- The Journal of Comparative Neurology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (K99 and R00 MH101234)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural dynamics and brain function
- Keywords
- excitatory synapses, glutamatergic synapses, synaptic ultrastructure, visual cortex, frontal cortex, primary visual cortex, lateral prefrontal cortex, presynaptic terminals, postsynaptic structures, mice, rhesus monkeys, comparative neuroanatomy, cortical specialization
- MeSH terms
- Analysis of Variance, Animals, Female, Frontal Lobe, Macaca mulatta, Male, Neurons, Species Specificity, Synapses, Visual Cortex, Microscopy, Immunoelectron, Presynaptic Terminals, Neuropil, Imaging, Three-Dimensional, Mice
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