Intracellular calcium regulation by burst discharge determines bidirectional long-term synaptic plasticity at the cerebellum input stage.
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 [Ca2+]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 <250 ms), and long-term potentiation (LTP) was found with a large [Ca2+]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.
Gall
David
D
Department of Cellular-Molecular Physiological and Pharmacological Sciences, University of Pavia, I-27100 Pavia, Italy.
Prestori
Francesca
F
Sola
Elisabetta
E
D'Errico
Anna
A
Roussel
Celine
C
Forti
Lia
L
Rossi
Paola
P
D'Angelo
Egidio
E
D000200:Action Potentials / Q000502:physiology* / Q000528:radiation effects; D000818:Animals; D000831:Animals, Newborn; D019540:Area Under Curve; D002118:Calcium / Q000378:metabolism*; D002531:Cerebellum / Q000166:cytology*; D004307:Dose-Response Relationship, Radiation; D004558:Electric Stimulation / Q000379:methods; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D005110:Extracellular Space / Q000378:metabolism*; D021621:Imaging, Three-Dimensional / Q000379:methods; D066298:In Vitro Techniques; D008274:Magnesium / Q000494:pharmacology; D009434:Neural Pathways / Q000502:physiology / Q000528:radiation effects; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D009474:Neurons / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D018408:Patch-Clamp Techniques / Q000379:methods; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D013569:Synapses / Q000502:physiology / Q000528:radiation effects; D009435:Synaptic Transmission / Q000502:physiology / Q000528:radiation effects; D019284:Thapsigargin / Q000494:pharmacology; D013997:Time Factors
D004791:Enzyme Inhibitors; D018691:Excitatory Amino Acid Antagonists; D019284:Thapsigargin; D008274:Magnesium; D011188:Potassium; D002118:Calcium