Astrocyte- and NMDA receptor-dependent slow inward currents differently contribute to synaptic plasticity in an age-dependent manner in mouse and human neocortex

Slow inward currents (SICs) are known as excitatory events of neurons elicited by astrocytic glutamate via activation of extrasynaptic NMDA receptors. By using slice electrophysiology, we tried to provide evidence that SICs can elicit synaptic plasticity. Age dependence of SICs and their impact on synaptic plasticity was also investigated in both on murine and human cortical slices. It was found that SICs can induce a moderate synaptic plasticity, with features similar to spike timing-dependent plasticity. Overall SIC activity showed a clear decline with aging in humans and completely disappeared above a cutoff age. In conclusion, while SICs contribute to a form of astrocyte-dependent synaptic plasticity both in mice and humans, this plasticity is differentially affected by aging. Thus, SICs are likely to play an important role in age-dependent physiological and pathological alterations of synaptic plasticity.

Automated summary

This study used slice electrophysiology to provide evidence that slow inward currents (SICs) can elicit synaptic plasticity by activating extrasynaptic NMDA receptors. The age dependence of SICs and their impact on synaptic plasticity were investigated in both murine and human cortical slices. The findings showed that SICs can induce moderate synaptic plasticity similar to spike timing-dependent plasticity, with a clear decline in SIC activity with aging and complete disappearance above a certain age cutoff. In conclusion, SICs likely play an important role in age-dependent physiological and pathological alterations of synaptic plasticity.