Fig. 8: A scheme is showing the effect of CR on synaptic microenvironment and plasticity.

The growth of thin astrocytic processes triggered by CR increases astrocyte volume fraction in hippocampal neuropil and reduces the escape of K+ and glutamate from the synaptic cleft (spillover). Fewer extrasynaptic N2B-NMDA receptors are activated by glutamate spillover during high-frequency synaptic stimulation. Reduced activation of extrasynaptic N2B-NMDA, in turn, increases the magnitude of LTP. Growth of astroglial perisynaptic leaflets is associated with the downregulation of Cx43 expression and reduced gap-junction coupling of the cells in the network. Fewer channels balance astrocyte input resistance increase produced by larger astrocyte membrane surface.