Presynaptic current changes at the mossy fiber-granule cell synapse of cerebellum during LTP

Arianna Maffei, Francesca Prestori, Paola Rossi, Vanni Taglietti, Egidio D'Angelo

Research output: Contribution to journalArticlepeer-review


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 N1a and N1b. Whereas N1a was part of the fiber volley (P1/N1a), N1b 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-Clkyn], 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 N1b) reduction. LTP was induced by θ-burst mossy fiber stimulation (8 trains of 10 impulses at 100 Hz separated by 150-ms pauses). Interestingly, during LTP, both N1 (or N1b) and N2/SN persistently increased, whereas P1 (or P1/N1a) 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-Daspartate 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 ̀M ω-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.

Original languageEnglish
Pages (from-to)627-638
Number of pages12
JournalJournal of Neurophysiology
Issue number2
Publication statusPublished - 2002

ASJC Scopus subject areas

  • Physiology
  • Neuroscience(all)


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