Intracellular calcium regulation by burst discharge determines bidirectional long-term synaptic plasticity at the cerebellum input stage

David Gall, Francesca Prestori, Elisabetta Sola, Anna D'Errico, Celine Roussel, Lia Forti, Paola Rossi, Egidio D'Angelo

Research output: Contribution to journalArticle

Abstract

Variations in intracellular calcium concentration ([Ca2+] i) provide a critical signal for synaptic plasticity. In accordance with Hebb's postulate (Hebb, 1949), an increase in postsynaptic [Ca 2+]i can induce bidirectional changes in synaptic strength depending on activation of specific biochemical pathways (Bienenstock et al., 1982; Lisman, 1989; Stanton and Sejnowski, 1989). Despite its strategic location for signal processing, spatiotemporal dynamics of [Ca2+]i changes and their relationship with synaptic plasticity at the cerebellar mossy fiber (mf)-granule cell (GrC) relay were unknown. In this paper, we report the plasticity/[Ca2+]i relationship for GrCs, which are typically activated by mf bursts (Chadderton et al., 2004). Mf bursts caused a remarkable [Ca2+]i increase in GrC dendritic terminals through the activation of NMDA receptors, metabotropic glutamate receptors (probably acting through IP3-sensitive stores), voltage-dependent calcium channels, and Ca2+-induced Ca2+ release. Although [Ca2+]i increased with the duration of mf bursts, long-term depression was found with a small [Ca2+]i increase (bursts 2+]i increase (bursts >250 ms). LTP and [Ca2+]i saturated for bursts >500 ms and with theta-burst stimulation. Thus, bursting enabled a Ca2+-dependent bidirectional Bienenstock-Cooper-Munro-like learning mechanism providing the cellular basis for effective learning of burst patterns at the input stage of the cerebellum.

Original languageEnglish
Pages (from-to)4813-4822
Number of pages10
JournalJournal of Neuroscience
Volume25
Issue number19
DOIs
Publication statusPublished - May 11 2005

Keywords

  • Calcium
  • Cerebellum
  • Granule cells
  • LTD
  • LTP
  • Synaptic plasticity

ASJC Scopus subject areas

  • Neuroscience(all)

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