Acute changes in short-term plasticity at synapses with elevated levels of neuronal calcium sensor-1.
Short-term synaptic plasticity is a defining feature of neuronal activity, but the underlying molecular mechanisms are poorly understood. Depression of synaptic activity might be due to limited vesicle availability, whereas facilitation is thought to result from elevated calcium levels. However, it is unclear whether the strength and direction (facilitation versus depression) of plasticity at a given synapse result from preexisting synaptic strength or whether they are regulated by separate mechanisms. Here we show, in rat hippocampal cell cultures, that increases in the calcium binding protein neuronal calcium sensor-1 (NCS-1) can switch paired-pulse depression to facilitation without altering basal synaptic transmission or initial neurotransmitter release probability. Facilitation persisted during high-frequency trains of stimulation, indicating that NCS-1 can recruit 'dormant' vesicles. Our results suggest that NCS-1 acts as a calcium sensor for short-term plasticity by facilitating neurotransmitter output independent of initial release. We conclude that separate mechanisms are responsible for determining basal synaptic strength and short-term plasticity.
Sippy
Tanya
T
Department of Neurobiology and The Brain Research Institute, David Geffen School of Medicine at UCLA, 650 Charles E. Young Drive South, Los Angeles, California 90095, USA.
Cruz-Martín
Alberto
A
Jeromin
Andreas
A
Schweizer
Felix E
FE
D019870:1-Phosphatidylinositol 4-Kinase / Q000378:metabolism; D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D002118:Calcium / Q000378:metabolism / Q000494:pharmacology; D015220:Calcium Channels / Q000502:physiology; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology*; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D004558:Electric Stimulation; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D049452:Green Fluorescent Proteins; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008164:Luminescent Proteins; D051580:Neuronal Calcium-Sensor Proteins; D009473:Neuronal Plasticity / Q000502:physiology*; D009479:Neuropeptides / Q000235:genetics / Q000378:metabolism*; D018377:Neurotransmitter Agents / Q000378:metabolism; D017729:Presynaptic Terminals / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D009435:Synaptic Transmission / Q000502:physiology*; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
D015220:Calcium Channels; D002135:Calcium-Binding Proteins; D008164:Luminescent Proteins; D051580:Neuronal Calcium-Sensor Proteins; D009479:Neuropeptides; D018377:Neurotransmitter Agents; C101464:frequenin calcium sensor proteins; D049452:Green Fluorescent Proteins; D019870:1-Phosphatidylinositol 4-Kinase; D002118:Calcium