Astrocytes generate Na ⁺ -mediated metabolic waves

Abstract

Glutamate-evoked Na ؉ increase in astrocytes has been identified as a signal coupling synaptic activity to glucose consumption. Astrocytes participate in multicellular signaling by transmitting intercellular Ca 2؉ waves. Here we show that intercellular Na ؉ waves are also evoked by activation of single cultured cortical mouse astrocytes in parallel with Ca 2؉ waves; however, there are spatial and temporal differences. Indeed, maneuvers that inhibit Ca 2؉ waves also inhibit Na ؉ waves; however, inhibition of the Na ؉ ͞glutamate cotransporters or enzymatic degradation of extracellular glutamate selectively inhibit the Na ؉ wave. Thus, glutamate released by a Ca 2؉ wave-dependent mechanism is taken up by the Na ؉ ͞glutamate cotransporters, resulting in a regenerative propagation of cytosolic Na ؉ increases. The Na ؉ wave gives rise to a spatially correlated increase in glucose uptake, which is prevented by glutamate transporter inhibition. Therefore, astrocytes appear to function as a network for concerted neurometabolic coupling through the generation of intercellular Na ؉ and metabolic waves.

Activity-Dependent Structural Plasticity of Perisynaptic Astrocytic Domains Promotes Excitatory Synapse Stability

“…This is likely to occur at individual synapses, as LTP-induced PAP motility selectively modified the structural organization and spine coverage around potentiated synapses, which in turn was associated with an increased stability of synapses. Thus, in addition to regulating glutamate transport [40], the release of gliotransmitters [41], and neurometabolic coupling [42], astrocytic Ca 2+ dynamics are important to regulate PAP motility and thereby the stability of the tripartite synapse. These results provide a new mechanism through which synaptic activation can control the physical interactions between PAPs and excitatory synapses, and they demonstrate an important structural role of PAPs as active partners in the regulation of activity-dependent synaptic remodeling.…”

Morphological plasticity of astroglia: Understanding synaptic microenvironment

“…This does not necessarily imply that elegant experimental manipulations with astroglial Ca 2+ within a certain dynamic range by triggering certain cellular cascades should reproduce such effects (Agulhon et al, 2010; Fiacco et al, 2007; Petravicz et al, 2008) (see (Rusakov et al, 2014; Volterra et al, 2014) for discussion). In addition to the much debated astrocyte‐neuron exchange, Ca 2+ rises in astrocytes could also boost the expression level of glutamate transporters (Devaraju et al, 2013), re‐position mitochondria closer to glutamate transporters (Jackson et al, 2014; Ugbode et al, 2014), and regulate neuro‐metabolic coupling with neurons (Bernardinelli et al, 2004; Porras et al, 2008). Recent findings suggest that such Ca 2+ signals could be required for morphological changes in PAPs (Molotkov et al, 2013; Tanaka et al, 2013).…”

Differential Effects of NMDA and AMPA Glutamate Receptors on Functional Magnetic Resonance Imaging Signals and Evoked Neuronal Activity during Forepaw Stimulation of the Rat

“…The metabolic response, on the one hand, is probably mediated by glial transport of glutamate and its recycling through mechanisms involving changes in intracellular Na ϩ concentration (Pellerin and Magistretti, 1994;Chatton et al, 2000;Bernardinelli et al, 2004). This hypothesis has received in vivo experimental support from both magnetic resonance spectroscopy studies (for review, see Rothman et al, 2003) and recent findings that increases in cerebral glucose utilization after somatosensory or visual stimulation are markedly reduced in knock-out mice deficient for each of the two glial glutamate transporters GLAST and GLT-1 (Voutsinos-Porche et al, 2003a,b;Herard et al, 2005).…”