Astroglial connexin 43 sustains glutamatergic synaptic efficacy

Abstract

Astrocytes dynamic interactions with neurons play an active role in neurotransmission. The gap junction (GJ) subunits connexins 43 and 30 are strongly expressed in astrocytes and have recently been shown to regulate synaptic activity and plasticity. However, the specific role of connexin 43 in the morphological and electrophysiological properties of astrocytes in situ as well as in synaptic transmission remains unknown. Here, we show that connexin 43, a major determinant of astroglial GJ coupling, regulates astrocyte cell volume, but has no impact on astroglial passive membrane properties. Furthermore, we demonstrate that connexin 43 modulates glutamatergic synaptic activity of hippocampal CA1 pyramidal cells. This regulation involves changes in synaptically released glutamate, with no alteration in neuronal excitability or postsynaptic function. These results reveal connexin 43 as a critical player in neuroglial interactions by supporting synaptic efficacy.

Connexin Type and Fluorescent Protein Fusion Tag Determine Structural Stability of Gap Junction Plaques

“…Cx43 and Cx30 were recently shown to have differential tissue distribution in the mouse visual cortex, and this distribution is correlated with functional organization of cortical brain tissue, at least in layer IV of this region of the cerebral cortex (56). Deletion of astrocyte Cx30 alone and deletion of both Cx43 and Cx30 were shown to have opposite effects on synaptic transmission and plasticity (57,58). These differences in neuronal activity were ascribed to channel-independent effects of the Cx30 CT. Additionally, Cx43 and Cx30 are highly localized to the astrocyte process that wraps specifically around brain vasculature (known as the astrocyte endfoot domain).…”

Morphological plasticity of astroglia: Understanding synaptic microenvironment

“…Astrocytes are connected through the gap junction molecules connexin 43 (Cx43) and Cx30 (Anders et al, 2014; Chever et al, 2014; Pannasch and Rouach, 2013; Pannasch et al, 2011). Gap junctions might be involved directly or indirectly in synapse‐glia signaling (Houades et al, 2008).…”

“…Astrocytes devoid of the gap junction protein invade the synaptic cleft, leading to decreased AMPAR‐mediated synaptic transmission as glutamate was taken up by the astrocytes before it reached the postsynapse (Pannasch et al, 2014). Moreover, astrocytes lacking Cx43, or Cx30 and Cx43 (Chever et al, 2014; Lutz et al, 2009; Pannasch et al, 2011) but not Cx30 alone (Pannasch et al, 2014) appear swollen, which suggests a mechanism for controlling the astrocyte volume and PAP displacement.…”

Connexin and pannexin signaling pathways, an architectural blueprint for CNS physiology and pathology?

“…The latter observation was based on the use of hippocampal slices derived from astrocytespecific Cx43 KO mice. As such, the mechanism of action, channel-dependent or channel-independent, has not been clarified yet [273]. Panx1 channels equally respond to [Ca 2? ]…”