Some beautiful work [original article] by Oliet’s lab in a recent issue of Cell demonstrates the importance of glia in synaptic plasticity. The show a system where D-serine and not glycine controls the NMDA receptor in a coagonist role (or perhaps glutamate is really the coagonist…) and show how similar pairing protocols can have opposite effects (LTD vs. LTP) depending on D-serine modulation by astrocytes. Yet more hidden factors in plasticity are being revealed!
Here’s the key figure:
More details from the News & Views summary after the jump.
From the N&V summary cited above:
A growing body of work, including a beautiful study in this issue of Cell (Panatier et al., 2006), argues for a revision of our old textbook ideas about glial cells, NMDA receptors, and D-serine as a link between them. Fluorescence imaging studies from a number of groups indicate that astrocytes respond to neurotransmitter not with action potentials, like most neurons, but with propagating waves of intracellular calcium ions thought to elicit release of “gliotransmitters” such as ATP, glutamate, and D-serine (Haydon, 2001 and Mothet et al., 2005). In the meantime, mounting evidence indicates that the NMDA receptor’s glycine site often is not saturated under physiological conditions (Danysz and Parsons, 1998), and that, at some synapses, the endogenous ligand for the glycine site is actually D-serine (Schell et al., 1995). A report that astrocytes release D-serine when stimulated by glutamate (Mothet et al., 2005) lends support to the hypothesis that glia may actively modulate NMDA receptor-mediated transmission (Schell et al., 1995) and, consequently, synaptic plasticity.
In their new study, Panatier et al. (2006) address this idea in brain slices with electrophysiological recordings from neurons in the supraoptic nucleus (SON) of the rat hypothalamus. This neuroendocrine region controls numerous homeostatic systems throughout the body. When the hormone oxytocin is released in the SON during lactation, there is a reduction in the extent to which astrocytic processes surround excitatory synapses (Oliet et al., 2001). In earlier studies, Oliet and colleagues examined this system from a more neurocentric perspective. They showed that reduced glial coverage during lactation permits greater neurotransmitter diffusion beyond the immediate vicinity of the synapse, enhancing glutamate crosstalk between synapses and modulation of transmission by neuronal metabotropic glutamate receptors (Oliet et al., 2001 and Piet et al., 2004). In the present study, they show that glia do more than simply provide background for the neuronal melody—astrocytes actually conduct the orchestra, using D-serine as a baton.