Connexin 30 sets synaptic strength by controlling astroglial synapse invasion

Abstract

Astrocytes play active roles in brain physiology by dynamic interactions with neurons. Connexin 30, one of the two main astroglial gap-junction subunits, is thought to be involved in behavioral and basic cognitive processes. However, the underlying cellular and molecular mechanisms are unknown. We show here in mice that connexin 30 controls hippocampal excitatory synaptic transmission through modulation of astroglial glutamate transport, which directly alters synaptic glutamate levels. Unexpectedly, we found that connexin 30 regulated cell adhesion and migration and that connexin 30 modulation of glutamate transport, occurring independently of its channel function, was mediated by morphological changes controlling insertion of astroglial processes into synaptic clefts. By setting excitatory synaptic strength, connexin 30 plays an important role in long-term synaptic plasticity and in hippocampus-based contextual memory. Taken together, these results establish connexin 30 as a critical regulator of synaptic strength by controlling the synaptic location of astroglial processes.

Astrocyte Reactivity and Reactive Astrogliosis: Costs and Benefits

“…However, astrocyte functions in unchallenged CNS go far beyond assistance and support (170,247). Astrocytes were shown to control formation, maintenance, function, and removal of neuronal synapses (45,68,168,228,237,238); help to control blood flow (104,120,153,207,276); and together with pericytes regulate the bloodbrain barrier (1,11,17,133). A single protoplasmic astrocyte in the human brain accommodates within its domain as many as two million neuronal synapses (161).…”

Astroglial connexin 43 sustains glutamatergic synaptic efficacy

“…We recently found that there was a non-channel function of Cx30 which, by controlling the astroglial coverage of synapses, sets synaptic strength through alteration of astroglial glutamate transport [18]. While a few Cx43 functions in astrocyte biology and brain development have been described involving intercellular communication, release of gliotransmitters through hemichannels, and neuroglial proliferation and migration through adhesive properties [4,13], the specific role of Cx43 in synaptic transmission is currently unknown.…”

New advances on glial activation in health and disease

“…These structural changes can be detected not only at the level of their cell body and proximal processes, but more importantly, through their fine, lamellate distal processes that surround synapses and ensheath axonal nodes [86] . Effective regulation of the perisynaptic space is attributed, in part, to astrocyte morphology [87] , and perturbations in fine morphology of these glial cells can ultimately contribute to synaptic dysfunction and disrupted neurotransmission [88] .…”