Area-Specific Synapse Structure in Branched Posterior Nucleus Axons Reveals a New Level of Complexity in Thalamocortical Networks

Abstract

Thalamocortical posterior nucleus (Po) axons innervating the vibrissal somatosensory (S1) and motor (MC) cortices are key links in the brain neuronal network that allows rodents to explore the environment whisking with their motile snout vibrissae. Here, using fine-scale high-end 3D electron microscopy, we demonstrate in adult male C57BL/6 wild-type mice marked differences between MC versus S1 Po synapses in (1) bouton and active zone size, (2) neurotransmitter vesicle pool size, (3) distribution of mitochondria around synapses, and (4) proportion of synapses established on dendritic spines and dendritic shafts. These differences are as large, or even more pronounced, than those between Po and ventro-posterior thalamic nucleus synapses in S1. Moreover, using single-axon transfection labeling, we demonstrate that the above differences actually occur on the MC versus the S1 branches of individual Po cell axons that innervate both areas. Along with recently-discovered divergences in efficacy and plasticity, the synaptic structure differences reported here thus reveal a new subcellular level of complexity. This is a finding that upends current models of thalamocortical circuitry, and that might as well illuminate the functional logic of other branched projection axon systems.

Cortico-Thalamo-Cortical Circuits of Mouse Forelimb S1 Are Organized Primarily as Recurrent Loops

“…For the forelimb S1-projecting PO neurons studied here, we targeted adjacent forelimb M1 as a functionally relevant candidate site of dual branches from their axonal arbors, but such branches could have been located elsewhere in a highly focal manner. Consistent with this possibility, anatomical evidence supports the idea that at least some TC axons branch in two or more cortical areas in a dual or multifocal pattern, rather than a broadly diffuse manner (Kuramoto et al, 2009(Kuramoto et al, , 2015Clascá et al, 2012;Ohno et al, 2012;Rodriguez-Moreno et al, 2020;Winnubst et al, 2019).…”

Variation of connectivity across exemplar sensory and associative thalamocortical loops in the mouse

“…To begin identifying whether the functional divergence observed across the MD →PL and MGB →A1 pathways may be partly explained by gross structural features ( Casas-Torremocha et al, 2019 ; Rodriguez-Moreno et al, 2020 ), we anterogradely labeled small populations of axons originating from the lateral MD or the ventral division of the MGB. To this end, we iontophoretically delivered biotinylated dextran amine (BDA) into these areas ( Figure 2A,D ; Figure 2—figure supplement 1 ; see Materials and methods for details).…”

Synaptic Organization of the Human Temporal Lobe Neocortex as Revealed by High-Resolution Transmission, Focused Ion Beam Scanning, and Electron Microscopic Tomography

“…Both experimental approaches allowed the estimation of structural parameters representing morphological correlates of synaptic transmission and plasticity that can be used to correlate structure with function directly. In addition, a direct comparison with findings from different animal species and brain regions where the quantitative data of synaptic structures are already available is now possible [ 31 , 32 , 37 , 38 , 39 , 47 , 54 ]. Furthermore, the quantitative 3D models of SBs could be used for numerical and/or Monte Carlo simulations of various synaptic parameters still not assessable for experiments, at least in humans.…”