Accumulating evidence indicates the existence of bidirectional communication between astrocytes and neurons. However, the effects of astrocytes on action potential-evoked synaptic transmission at single synapse level are largely unknown. We investigated the neuromodulatory role of astrocytes on synaptic physiology at single hippocampal synapses. Using electrophysiological and Ca²⁺ imaging techniques on rat hippocampal slices, we performed paired recordings from CA1 pyramidal neurons and single astrocytes. Astrocytes were loaded with the Ca²⁺ indicator Fluo 4 (50 mM) and the Ca²⁺-cage NP-EGTA (5mM) and were selectively stimulated by UV-flash photolysis (2Hz, 5s). Single synapses of Schaffer collaterals were stimulated at 0.5 Hz.

We found that:

The selective elevation of Ca²⁺ in single astrocytes transiently increased the synaptic efficacy due to the potentiation of the probability of transmitter release, without affecting the amplitude of synaptic currents.

This form of short-term plasticity was due to SNARE protein- and Ca²⁺-dependent release of glutamate from astrocytes, that activates presynaptic type I metabotropic glutamate receptors (mGluRs).

The concurrent activity of astrocyte Ca²⁺ elevation and postsynaptic neuron caused the persistent potentiation of synaptic transmission. Therefore, the temporal coincidence of neuronal and astrocytic signals induced the long-term potentiation (LTP) of hippocampal synaptic transmission.

LTP was independent of NMDA receptor activation and postsynaptic intracellular Ca²⁺. However, LTP was prevented by blockage of presynaptic type I of mGluRs and synthesis of nitric oxide.

We conclude that astrocytes potentiate synaptic transmission playing an active role in the transfer and storage of synaptic information by the nervous system.

Supported by: MICINN (BFU2007-64764) and European Union (Health-F2-2007-202167).