Activation of alpha 7-containing nicotinic receptors on astrocytes triggers AMPA receptor recruitment to glutamatergic synapses

作者：Wang Xulong; Lippi Giordano; Carlson David M; Berg Darwin K^*

来源：Journal of Neurochemistry, 2013, 127(5): 632-643.

DOI：10.1111/jnc.12436

• AMPA receptors
• astrocytes
• cholinergic
• glutamatergic
• nicotinic
• synapse formation

Astrocytes, an abundant form of glia, are known to promote and modulate synaptic signaling between neurons. They also express 7-containing nicotinic acetylcholine receptors (7-nAChRs), but the functional relevance of these receptors is unknown. We show here that stimulation of 7-nAChRs on astrocytes releases components that induce hippocampal neurons to acquire more -amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors post-synaptically at glutamatergic synapses. The increase is specific in that no change is seen in synaptic NMDA receptor clusters or other markers for glutamatergic synapses, or in markers for GABAergic synapses. Moreover, the increases in AMPA receptors on the neuron surface are accompanied by increases in the frequency of spontaneous miniature synaptic currents mediated by the receptors and increases in the ratio of evoked synaptic currents mediated by AMPA versus NMDA receptors. This suggests that stimulating 7-nAChRs on astrocytes can convert silent' glutamatergic synapses to functional status. Astrocyte-derived thrombospondin is necessary but not sufficient for the effect, while tumor necrosis factor- is sufficient but not necessary. The results identify astrocyte 7-nAChRs as a novel pathway through which nicotinic cholinergic signaling can promote the development of glutamatergic networks, recruiting AMPA receptors to post-synaptic sites and rendering the synapses more functional.

• 出版日期2013-12