TY - JOUR
T1 - Maintenance of High-Frequency Transmission at Purkinje to Cerebellar Nuclear Synapses by Spillover from Boutons with Multiple Release Sites
AU - Telgkamp, Petra
AU - Padgett, Daniel E.
AU - Ledoux, Veronica A.
AU - Woolley, Catherine S.
AU - Raman, Indira M.
N1 - Funding Information:
We thank Dr. Bill Russin of the Northwestern Biological Imaging Facility for his technical expertise on electron microscopy, Renee May for help with 3D reconstructions, Dr. Larry Trussell for the diffusion program, and Drs. Chinfei Chen and Larry Trussell for helpful comments. I.M.R. is especially grateful to the Searle Scholars Program for their support. Also supported by NIH NS39395 (I.M.R.) and NS37324 (C.S.W.).
PY - 2004/1/8
Y1 - 2004/1/8
N2 - Cerebellar Purkinje neurons maintain high firing rates but their synaptic terminals depress only moderately, raising the question of how vesicle depletion is minimized. To identify mechanisms that limit synaptic depression, we evoked 100 Hz trains of GABAergic inhibitory postsynaptic currents (IPSCs) in cerebellar nuclear neurons by stimulating Purkinje axons in mouse brain slices. The paired-pulse ratio (IPSC2/IPSC1) of the total IPSC was ∼1 and the steady-state ratio (IPSC20/IPSC1) was ∼0.5, suggesting a high response probability of postsynaptic receptors, without an unusually high release probability. Three-dimensional electron microscopic reconstructions of Purkinje boutons revealed multiple active zones without intervening transporters, suggestive of "spillover"-mediated transmission. Simulations of boutons with 10-16 release sites, in which transmitter from any site can reach all receptors opposite the bouton, replicated multiple-pulse depression during normal, high, and low presynaptic Ca influx. These results suggest that release from multiple-site boutons limits depletion-based depression, permitting prolonged, high-frequency inhibition at corticonuclear synapses.
AB - Cerebellar Purkinje neurons maintain high firing rates but their synaptic terminals depress only moderately, raising the question of how vesicle depletion is minimized. To identify mechanisms that limit synaptic depression, we evoked 100 Hz trains of GABAergic inhibitory postsynaptic currents (IPSCs) in cerebellar nuclear neurons by stimulating Purkinje axons in mouse brain slices. The paired-pulse ratio (IPSC2/IPSC1) of the total IPSC was ∼1 and the steady-state ratio (IPSC20/IPSC1) was ∼0.5, suggesting a high response probability of postsynaptic receptors, without an unusually high release probability. Three-dimensional electron microscopic reconstructions of Purkinje boutons revealed multiple active zones without intervening transporters, suggestive of "spillover"-mediated transmission. Simulations of boutons with 10-16 release sites, in which transmitter from any site can reach all receptors opposite the bouton, replicated multiple-pulse depression during normal, high, and low presynaptic Ca influx. These results suggest that release from multiple-site boutons limits depletion-based depression, permitting prolonged, high-frequency inhibition at corticonuclear synapses.
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U2 - 10.1016/S0896-6273(03)00802-X
DO - 10.1016/S0896-6273(03)00802-X
M3 - Article
C2 - 14715139
AN - SCOPUS:0347948470
VL - 41
SP - 113
EP - 126
JO - Neuron
JF - Neuron
SN - 0896-6273
IS - 1
ER -