The Journal of Neurophysiology Vol. 88 No. 2 August 2002, pp. 627-638
Copyright ©2002 by the American Physiological Society

Presynaptic Current Changes at the Mossy Fiber-Granule Cell Synapse of Cerebellum During LTP

 ¹Department of Molecular/Cellular Physiology and Instituto Nazionale Fisica della Materia, University of Pavia, 27100 Pavia, Italy; and  ²Department of Evolutionary and Functional Biology, University of Parma, 43100 Parma, Italy

Maffei, Arianna, Francesca Prestori, Paola Rossi, Vanni Taglietti, and Egidio D'Angelo. Presynaptic Current Changes at the Mossy Fiber-Granule Cell Synapse of Cerebellum During LTP. J. Neurophysiol. 88: 627-638, 2002. The involvement of presynaptic mechanisms in the expression of long-term potentiation (LTP), an enhancement of synaptic transmission suggested to take part in learning and memory in the mammalian brain, has not been fully clarified. Although evidence for enhanced vesicle cycling has been reported, it is unknown whether presynaptic terminal excitability could change as has been observed in invertebrate synapses. To address this question, we performed extracellular focal recordings in cerebellar slices. The extracellular current consisted of a pre- (P₁/N₁) and postsynaptic (N₂/SN) component. In ~50% of cases, N₁ could be subdivided into N_1a and N_1b. Whereas N_1a was part of the fiber volley (P₁/N_1a), N_1b corresponded to a Ca²⁺-dependent component accounting for 40-50% of N₁, which could be isolated from individual mossy fiber terminals visualized with fast tetramethylindocarbocyanine perchlorate (DiI). The postsynaptic response, given its timing and sensitivity to glutamate receptor antagonists [N₂ was blocked by 10 µM [1,2,3,4-tetrahydro-6-nitro-2,3-dioxo-benzo[f]quinoxaline-7-sulfonamide disodium (NBQX) and SN by 100 µM APV +50 µM 7-Cl-kyn], corresponded to granule cell excitation. N₂ and SN could be reduced by 1) Ca²⁺ channel blockers, 2) decreasing the Ca²⁺ to Mg²⁺ ratio, 3) paired-pulse stimulation, and 4) adenosine receptor activation. However, only the first two manipulations, which modify Ca²⁺ influx, were associated with N₁ (or N_1b) reduction. LTP was induced by -burst mossy fiber stimulation (8 trains of 10 impulses at 100 Hz separated by 150-ms pauses). Interestingly, during LTP, both N₁ (or N_1b) and N₂/SN persistently increased, whereas P₁ (or P₁/N_1a) did not change. Average changes were N₁ = 38.1 ± 31.9, N₂ = 49.6 ± 48.8, and SN = 59.1 ± 35.5%. The presynaptic changes were not observed when LTP was prevented by synaptic inhibition, by N-methyl-D-aspartate and metabotropic glutamate receptor blockage, or by protein kinase C blockage. Moreover, the presynaptic changes were sensitive to Ca²⁺ channel blockers (1 mM Ni²⁺ and 5 µM -CTx-MVIIC) and occluded by K⁺ channel blockers (1 mM tetraethylammmonium). Thus regulation of presynaptic terminal excitability may take part in LTP expression at a central mammalian synapse.