Neuronal Synchrony Mediated by Astrocytic Glutamate through Activation of Extrasynaptic NMDA Receptors

Abstract

Fast excitatory neurotransmission is mediated by activation of synaptic ionotropic glutamate receptors. In hippocampal slices, we report that stimulation of Schaffer collaterals evokes in CA1 neurons delayed inward currents with slow kinetics, in addition to fast excitatory postsynaptic currents. Similar slow events also occur spontaneously, can still be observed when neuronal activity and synaptic glutamate release are blocked, and are found to be mediated by glutamate released from astrocytes acting preferentially on extrasynaptic NMDA receptors. The slow currents can be triggered by stimuli that evoke Ca2+ oscillations in astrocytes, including photolysis of caged Ca2+ in single astrocytes. As revealed by paired recording and Ca2+ imaging, a striking feature of this NMDA receptor response is that it occurs synchronously in multiple CA1 neurons. Our results reveal a distinct mechanism for neuronal excitation and synchrony and highlight a functional link between astrocytic glutamate and extrasynaptic NMDA receptors.

Supportive or information-processing functions of the mature protoplasmic astrocyte in the mammalian CNS? A critical appraisal

“…The data to date provides convincing evidence that vesicular release of glutamate can be obtained under some conditions, leading to increased EPSC frequency in granule cell neurons in the dentate of the rat hippocampus (Jourdain et al, 2007) and induction of a slow inward current (SIC) that increases action potential firing in the target neuron in the nucleus accumbens (D'Ascenzo et al, 2007). The SIC has been attributed to glutamate acting on NR2B subunit-containing extrasynaptic NMDA receptors (Fellin et al, 2004;D'Ascenzo et al, 2007).…”

Astrocytes in Alzheimer's Disease

“…These gliotransmitters include glutamate, ATP, D-serine, GABA, taurine, and mediate glialneuronal and glial-glial signaling. [97][98][99][100][101][102][103] The leading mechanism for gliotransmitters release is exocytotic, [104][105][106] although diffusion though large-pore plasmalemmal channels can also be involved. [107][108][109][110] 5) Glia and information processing in the brain.…”

Are astrocytes executive cells within the central nervous system?

“…There is feedback correspondence between the synapses and the astrocytes, so astrocytes increase their Ca ++ load and the value of their membrane potential when the synapses with which they are related are activated. Such behaviour allows astrocytes to modulate the neuronal and the astrocytic web in which they are situated by the generation of transmitters that are able to act at the neuronal synaptic receptors as well as on extra-synaptic receptors 36,37 .…”