Bergmann glial ensheathment of dendritic spines regulates synapse number without affecting spine motility

Abstract

In the cerebellum, lamellar Bergmann glial (BG) appendages wrap tightly around almost every Purkinje cell dendritic spine. The function of this glial ensheathment of spines is not entirely understood. The development of ensheathment begins near the onset of synaptogenesis, when motility of both BG processes and dendritic spines are high. By the end of the synaptogenic period, ensheathment is complete and motility of the BG processes decreases, correlating with the decreased motility of dendritic spines. We therefore have hypothesized that ensheathment is intimately involved in capping synaptogenesis, possibly by stabilizing synapses. To test this hypothesis, we misexpressed GluR2 in an adenoviral vector in BG towards the end of the synaptogenic period, rendering the BG α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) Ca2+-impermeable and causing glial sheath retraction. We then measured the resulting spine motility, spine density and synapse number. Although we found that decreasing ensheathment at this time does not alter spine motility, we did find a significant increase in both synaptic pucta and dendritic spine density. These results indicate that consistent spine coverage by BG in the cerebellum is not necessary for stabilization of spine dynamics, but is very important in the regulation of synapse number.

Cell Biology of Astrocyte-Synapse Interactions

“…A single mouse cortical astrocyte is estimated to contact over 100,000 synapses; whereas a human astrocyte can contact up to 2,000,000 synapses (Bushong et al, 2002; Oberheim et al, 2009). A similar tile-like organization of other astrocyte-like radial glia cells have also been observed for cerebellar Bergmann glia, which ensheath Purkinje cell synapses, and retinal Muller Glia, which ensheath synapses within the inner and outer plexiform layers (Lippman Bell et al, 2010; Lippman et al, 2008; Wang et al, 2017). These observations indicate that astrocytes, through their fine processes, have the ability to sense and adhere to synapses and coordinate with the neighboring astrocytes to tile and completely cover the neuropil.…”

Chemical labelling for visualizing native AMPA receptors in live neurons

“…It is generally known that glial cells including astrocytes tightly wrap synapses from the post-synaptic side in brain tissues51. In the hippocampus of mature animals, approximately 57% of synapses are sheathed.…”

Morphological plasticity of astroglia: Understanding synaptic microenvironment

“…Very fine, and apparently highly mobile, astrocytic processes have been reported in organotypic brain slices using a membrane‐bound GFP (Benediktsson et al, 2005). Furthermore, co‐labeling of dendritic spines and PAPs in hippocampal (Halassa et al, 2007a; Perez‐Alvarez et al, 2014; Verbich et al, 2012) and cerebellar slices (Lippman Bell et al, 2010; Lippman et al, 2008) as well as in vivo (Bernardinelli et al, 2014b; Perez‐Alvarez et al, 2014) suggested that PAPs are highly dynamic structures that engage and disengage with dendritic spines, also responding to the induction of synaptic plasticity (Bernardinelli et al, 2014b; Perez‐Alvarez et al, 2014). …”

“…Furthermore, blocking Rac‐1 and interfering with PAP motility leads to enhanced number of dendritic filopodia (Nishida and Okabe, 2007). Similarly, in the cerebellum Bergmann glia coverage is required for synapse stabilization and regulation (Lippman Bell et al, 2010; Lippman et al, 2008). …”