Comparative ultrastructural features of excitatory synapses in the visual and frontal cortices of the adult mouse and monkey

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. The ultrastructure of excitatory synapses in the neuropil of layers 2–3 in mouse and monkey primary visual (V1) and frontal association (mouse FC, monkey LPFC) cortices were compared using 3D serial electron microscopy. The density and location of excitatory synapses on dendritic spines versus shafts were quantified in serial EM images and reconstructed in 3D to measure the volume of presynaptic (bouton) and postsynaptic elements (postsynaptic density, PSD, and spines). The authors show that the ultrastructural features of excitatory synapses of visual versus frontal cortices were markedly similar in the mouse but diverse in the monkey.