Accumulating evidence indicates the existence of bidirectional communication between astrocytes and neurons, in which astrocytes exchange information with the synaptic elements. 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 microM) and the Ca²⁺ cage NP-EGTA (5mM) to be selectively stimulated by UV-flash photolysis (2Hz, 5s). We stimulated Schaffer collaterals (0.5 Hz) using the minimal stimulation technique that activates single synapses.

We found that:

The 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 Ca ²⁺ dependent release of glutamate from astrocytes.

Astrocytes potentiated synaptic transmission through activation of type I metabotropic glutamate receptors. When the astrocytic Ca²⁺ elevation was paired with a transient mild depolarization of the postsynaptic neuron the transient potentiation became persistent. Therefore, the temporal coincidence of neuronal and astrocytic signals induced the long-term potentiation (LTP) of hippocampal synaptic transmission.

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 MEC (BFU 2004-00448) and CAM (200620M083).