RT Journal Article SR Electronic T1 The Concentration of Synaptically Released Glutamate Outside of the Climbing Fiber–Purkinje Cell Synaptic Cleft JF The Journal of Neuroscience JO J. Neurosci. FD Society for Neuroscience SP 5265 OP 5274 DO 10.1523/JNEUROSCI.19-13-05265.1999 VO 19 IS 13 A1 Jeffrey A. Dzubay A1 Craig E. Jahr YR 1999 UL http://www.jneurosci.org/content/19/13/5265.abstract AB AMPA receptors and glutamate transporters expressed by cerebellar Bergmann glial cells are activated by neurotransmitter released from climbing fibers (Bergles et al., 1997). Based on anatomical evidence, this is most likely the result of glutamate diffusing out of the climbing fiber–Purkinje cell synaptic clefts (Palay and Chan-Palay, 1974). We used the change in the EC50 of the Bergmann glia AMPA receptors produced by cyclothiazide (CTZ) to estimate the concentration of glutamate reached at the glial membrane. The decrease of the EC50 gives rise to a concentration-dependent potentiation of the AMPA receptor-mediated responses (Patneau et al., 1993). By comparing the increase in amplitude of the AMPA receptor response in the Bergmann glia (840 ± 240%; n= 8) with the shift in the glutamate dose–response curve measured in excised patches (EC50, 1810 μm in control vs 304 μm in CTZ), we estimate that the extrasynaptic transmitter concentration reaches 160–190 μm. This contrasts with the concentration in the synaptic cleft, thought to rapidly rise above 1 mm, but is still high enough to activate glutamate receptors. These results indicate that the sphere of influence of synaptically released glutamate can extend beyond the synaptic cleft.