Glial cells of the nervous system directly influence neuronal and synaptic activities by releasing transmitters. However, the physiological consequences of this glial transmitter release on brain information processing remain poorly understood. We demonstrate here in hippocampal slices of 2-to 5-week-old rats that glutamate released from glial cells generates slow transient currents (STCs) mediated by the activation of NMDA receptors in pyramidal cells. STCs persist in the absence of neuronal and synaptic activity, indicating a nonsynaptic origin of the source of glutamate. Indeed, STCs occur spontaneously but can also be induced by pharmacological tools known to activate astrocytes and by the selective mechanical stimulation of single nearby glial cells. Bath application of the inhibitor of the glutamate uptake DL-threo-␤-benzyloxyaspartate increases both the frequency of STCs and the amplitude of a tonic conductance mediated by NMDA receptors and probably also originated from glial glutamate release. By using dual recordings, we observed synchronized STCs in pyramidal cells having their soma distant by Ͻ100 m. The degree of precision (Ͻ100 msec) of this synchronization rules out the involvement of calcium waves spreading through the glial network. It also indicates that single glial cells release glutamate onto adjacent neuronal processes, thereby controlling simultaneously the excitability of several neighboring pyramidal cells. In conclusion, our results show that the glial glutamate release occurs spontaneously and synchronizes the neuronal activity in the hippocampus.

Fig. 3. Decision tree for hybrid sequencing strategy. For organisms with a small genome size (Ͻ3 Mb) and͞or a small number of gaps and͞or high levels of repetitive structure inducing physical ends, we found 8ϫ Sanger sequencing to be the most cost-effective approach. For organisms with a large genome size, many sequencing gaps, and͞or hard stops, we found initial sequencing of 5.3ϫ Sanger data followed by the addition of two 454 runs to be the most cost-effective approach.

The hair cell's mechanoreceptive organelle, the hair bundle, is highly sensitive because its transduction channels open over a very narrow range of displacements. The synchronous gating of transduction channels also underlies the active hair-bundle motility that amplifies and tunes responsiveness. The extent to which the gating of independent transduction channels is coordinated depends on how tightly individual stereocilia are constrained to move as a unit. Using dual-beam interferometry in the bullfrog's sacculus, we found that thermal movements of stereocilia located as far apart as a bundle's opposite edges display high coherence and negligible phase lag. Because the mechanical degrees of freedom of stereocilia are strongly constrained, a force applied anywhere in the hair bundle deflects the structure as a unit. This feature assures the concerted gating of transduction channels that maximizes the sensitivity of mechanoelectrical transduction and enhances the hair bundle's capacity to amplify its inputs.The high sensitivity of sensory systems requires an efficient use of the energy in stimuli to bias the open probability of ion channels. For a hair cell of the inner ear, mechanical forces directly gate transduction channels atop stereocilia, the rod-like constituents of the mechanosensitive hair bundle 1 . A hair bundle's sensitivity is determined by the relation between the applied force and the number of channels opened: the narrower the force range over which gating occurs, the greater the sensitivity. The coordinated gating of transduction channels is also thought to underlie active hair-bundle motility, a component of the active process that amplifies and tunes the responses of hair cells 2 .Because mechanical stimuli are ordinarily applied at the tall edge of a hair bundle, channel gating depends upon the propagation of mechanical force across the array of stereocilia. Each stereocilium possesses a basal rootlet of actin filaments that tends to hold the process upright; as measured at the hair bundle's tip, the combined stiffness of these stereociliary pivots is about 200 μN·m −1 (ref.3). In addition, the successive stereocilia in each file are joined by tip links that are thought to represent the gating springs attached to transduction channels at one or both ends. For large bundle deflections and in the presence of a physiological concentration of Ca 2+ , the combined stiffness of these gating springs is typically 1000 μN·m −1 (ref. HHMI Author Manuscript HHMI Author Manuscript HHMI Author Manuscriptsprings-the phenomenon of gating compliance-to a value comparable to that of the pivots, or even lower 4,5 .The stereocilia of a hair bundle appear at first glance to be connected in a series-parallel configuration such that a force applied to the tallest stereocilium in each file would first deflect that process alone (Fig. 1a). Movement of the tallest stereocilium would then tighten the tip link and perhaps other filaments connecting it to the second, deflecting that process; the second stereoc...