Characterization of AMPA Receptors Targeted by the Climbing Fiber Transmitter Mediating Presynaptic Inhibition of GABAergic Transmission at Cerebellar Interneuron-Purkinje Cell Synapses

Abstract

-permeable AMPARs, philanthotoxin-433, did not affect the CF-induced inhibition but suppressed AMPAR-mediated currents in Bergmann glia. A low-affinity GluR antagonist, ␥-Dglutamylglycine, or retardation of neurotransmitter diffusion by dextran reduced the inhibitory action of CF-stimulation, whereas blockade of glutamate transporters enhanced the CF-induced inhibition. The results suggest that the CF transmitter released after repeated stimulation overwhelms local glutamate uptake and thereby diffuses from the release site to reach GluR2/GluR3 AMPARs on nearby interneuron terminals. Double immunostaining showed that GluR2/3 subunits and glutamate decarboxylase or synaptophysin are colocalized at the perisomatic GABAergic processes surrounding PCs. Finally, electron microscopy detected specific immunoreactivity for GluR2/3 at the presynaptic terminals of symmetric axosomatic synapses on the PC. These findings demonstrate that the CF transmitter directly inhibits GABA release from interneurons to the PC, relying on extrasynaptic diffusion and local heterogeneity in AMPAR subunit compositions.

Expression of SV2 in the Seveloping Chick Cerebellum: Comparison with Calbindin and AMPA Glutamate Receptors 2/3

“…The colocalization of GluR 2/3 and the presynaptic markers GAD65 or synaptophysin in basket cell axon terminals at Purkinje cell somata support this interpretation of presynaptic AMPA receptors in the cerebellum (Satake et al, 2006). The obtained expression pattern of postsynaptic GluR 2/3 immunoreactivity in Purkinje and granule cell dendrites was present from embryonic stages on and can be detected throughout all posthatched stages.…”

Synaptic Mechanism for the Sustained Activation of Oculomotor Integrator Circuits in the Rat Prepositus Hypoglossi Nucleus: Contribution of Ca2+-Permeable AMPA Receptors

“…4 E4 ). A similar effect of NAS on EPSC responses was observed using 10 M philanthotoxin 433 (PhTx) (Eldefrawi et al, 1988), which is a different blocker of CP-AMPA receptors and is also used for the blockade of CP-AMPA receptor-mediated currents (Washburn and Dingledine, 1996;Tó th and McBain, 1998;Plant et al, 2006;Satake et al, 2006). The duration, EPSC frequency, and charge transfer in the presence of PhTx (1.0 Ϯ 0.2 s; 7.5 Ϯ 2.0 Hz; 1.2 Ϯ 0.8 pC; n ϭ 6) were significantly smaller than in controls (2.4 Ϯ 0.6 s, p Ͻ 0.01; 19.7 Ϯ 8.4 Hz, p Ͻ 0.01; 2.6 Ϯ 1.4 pC, p Ͻ 0.05).…”

Intracerebellar Transplantation of Neural Stem Cells into Mice with Neurodegeneration Improves Neuronal Networks with Functional Synaptic Transmission

“…Especially GluR2, 3 are abundant in Purkinje neuron [8]. Moreover GluR2, 3 are main mediators involving synaptic transmission in not only interaction of Basket cells and Purkinje neurons but also that of climbing fibers and Purkinje neurons [24]. GABA A receptor 2 is also one of the principal synaptic transmitter receptor components.…”