Sci. STKE, 9 December 2003
NEUROBIOLOGY Of Plasticity and Purinergic Suppression
Most synapses display activity-dependent changes in synaptic efficacy that influence the likelihood that a particular neuronal pathway will fire; different types of synapses, however, can show marked differences in their responses to repetitive firing, and these differences depend on mechanisms that are incompletely understood. Zhang et al. uncovered an intriguing bidirectional conversation between neurons and astrocytes that mediates a novel form of use-dependent heterosynaptic inhibition (see Preview by Pascual and Haydon). The authors used pharmacologic manipulation in combination with electrophysiological analysis of cocultures of hippocampal neurons and astrocytes to show that endogenous adenosine triphosphate (ATP), acting through presynaptic purinergic P2Y receptors, tonically suppressed glutamatergic transmission. Repetitive stimulation of glutamatergic neurons led to heterosynaptic suppression of nearby neurons, which depended on the sequential activation of P2Y and non-N-methyl-D-aspartate glutamate receptors. Using pharmacologic analysis, separate neuronal and astrocyte cultures, and bioluminescence detection of released ATP, the authors demonstrated that this suppression depended on the release of ATP from glutamate-stimulated astrocytes. The ATP metabolite adenosine mediated a similar heterosynaptic suppression of glutamatergic synapses on CA1 pyramidal neurons in rat hippocampal slices. Pharmacologic analysis, combined with calcium imaging and measurement of ATP release, indicated that this adenosine derived at least in part from ATP released from glia. In a separate study, Moore et al. demonstrated that the dramatic paired-pulse facilitation, frequency facilitation, and an unusual form of long-term potentiation characteristic of hippocampal mossy fiber synapses depended on tonic inhibition through presynaptic adenosine A1 receptors of basal transmitter release. Pharmacologic blockade of A1 receptors or degradation of extracellular adenosine in rat or mouse hippocampal slices enhanced the basal synaptic response and suppressed these use-dependent responses, as did A1 knockout. Both studies emphasize the importance of the local environment--and of adenosine in particular--in modulating activity-dependent changes in synaptic function.
J. Zhang, H. Wang, C. Ye, W. Ge, Y. Chen, Z. Jiang, C. Wu, M. Poo, S. Duan, ATP released by astrocytes mediates glutamatergic activity-dependent heterosynaptic suppression. Neuron 40, 971-982 (2003). [Online Journal]
O. Pascual, P. G. Haydon, Synaptic inhibition mediated by glia. Neuron 40, 873-875 (2003). [Online Journal]
Citation: Of Plasticity and Purinergic Suppression. Sci. STKE 2003, tw476 (2003).
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