Abstract
Perisynaptic astrocytic processes (PAPs) carry out several different functions, from metabolite clearing to control of neuronal excitability and synaptic plasticity. All these functions are likely orchestrated by complex cellular machinery that resides within the PAPs and relies on a fine interplay between multiple subcellular components. However, traditional transmission electron microscopy (EM) studies have found that PAPs are remarkably poor of intracellular organelles, failing to explain how such a variety of PAP functions are achieved in the absence of a proportional complex network of intracellular structures. Here, we use serial block-face scanning EM to reconstruct and describe in three dimensions PAPs and their intracellular organelles in two different mouse cortical regions. We described five distinct organelles, which included empty and full endosomes, phagosomes, mitochondria, and endoplasmic reticulum (ER) cisternae, distributed within three PAPs categories (branches, branchlets, and leaflets). The majority of PAPs belonged to the leaflets category (~60%), with branchlets representing a minority (~37%). Branches were rarely in contact with synapses (<3%). Branches had a higher density of mitochondria and ER cisternae than branchlets and leaflets. Also, branches and branchlets displayed organelles more frequently than leaflets. Endosomes and phagosomes, which accounted for more than 60% of all the organelles detected, were often associated with the same PAP. Likewise, mitochondria and ER cisternae, representing ~40% of all organelles were usually associated. No differences were noted between the organelle distribution of the somatosensory and the anterior cingulate cortex. Finally, the organelle distribution in PAPs did not largely depend on the presence of a spine apparatus or a pre-synaptic mitochondrion in the synapse that PAPs were enwrapping, with some exceptions regarding the presence of phagosomes and ER cisternae, which were slightly more represented around synapses lacking a spine apparatus and a presynaptic mitochondrion, respectively. Thus, PAPs contain several subcellular organelles that could underlie the diverse astrocytic functions carried out at central synapses.
Highlights
Over the last decades, astrocytes have been assigned an increasing number of functions, from neurovascular coupling and metabolite clearing, to control of neuronal excitability and synaptic plasticity (Nuriya and Hirase, 2016; Papouin et al, 2017; Mestre et al, 2020)
We found that the fraction of synapses contacted by a Perisynaptic astrocytic processes (PAPs) at the post-synaptic site was 78.6 ± 6.3% for anterior cingulate (AC) and 79.4 ± 2.1% for SS (p = 0.8), while the fraction of synapses contacted by PAP at the synaptic cleft was 50.39 ± 1.27% for AC and 53.79 ± 3.09% for SS (p = 0.1; Figure 1F)
We found that the extent of PAP coverage around the post-synaptic element was comparable between the two cortical regions (AC: 0.14 ± 0.01 μm2; SS: 0.15 ± 0.04 μm2; p = 0.65; Figure 1G)
Summary
Astrocytes have been assigned an increasing number of functions, from neurovascular coupling and metabolite clearing, to control of neuronal excitability and synaptic plasticity (Nuriya and Hirase, 2016; Papouin et al, 2017; Mestre et al, 2020). Astrocytes display a spongiform shape and are equipped with processes that infiltrate the neural tissue reaching out to synapses that tend to encapsulate (Reichenbach et al, 2010) Such processes can be morpho-functionally classified into branches, branchlets, leaflets, and endfeet, depending on size and location. It has been estimated that up to 75% of cortical and 65% of hippocampal axo-spinous synapses are contacted by astrocytic processes (Witcher et al, 2007; Lushnikova et al, 2009; Bernardinelli et al, 2014) This close anatomical relationship with synapses is necessary to allow astrocytes to sense and modulate the synaptic environment (Reichenbach et al, 2010; Bernardinelli et al, 2014; Heller and Rusakov, 2015). It is worth noting that synapses can be contacted by branchlets and branches
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