Ca2+ requirements for cerebellar long-term synaptic depression: role for a postsynaptic leaky integrator.
Photolysis of a caged Ca(2+) compound was used to characterize the dependence of cerebellar long-term synaptic depression (LTD) on postsynaptic Ca(2+) concentration ([Ca(2+)](i)). Elevating [Ca(2+)](i) was sufficient to induce LTD without requiring any of the other signals produced by synaptic activity. A sigmoidal relationship between [Ca(2+)](i) and LTD indicated a highly cooperative triggering of LTD by Ca(2+). The duration of the rise in [Ca(2+)](i) influenced the apparent Ca(2+) affinity of LTD, and this time-dependent behavior could be described by a leaky integrator process with a time constant of 0.6 s. A computational model, based on a positive-feedback cycle that includes protein kinase C and MAP kinase, was capable of simulating these properties of Ca(2+)-triggered LTD. Disrupting this cycle experimentally also produced the predicted changes in the Ca(2+) dependence of LTD. We conclude that LTD arises from a mechanism that integrates postsynaptic Ca(2+) signals and that this integration may be produced by the positive-feedback cycle.
Tanaka
Keiko
K
Department of Neurobiology, Duke University Medical Center, Box 3209, Durham, NC 27710, USA.
Khiroug
Leonard
L
Santamaria
Fidel
F
Doi
Tomokazu
T
Ogasawara
Hideaki
H
Ellis-Davies
Graham C R
GC
Kawato
Mitsuo
M
Augustine
George J
GJ
D000814:Aniline Compounds; D000818:Animals; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000502:physiology*; D002525:Cerebellar Cortex / Q000166:cytology / Q000502:physiology*; D003712:Dendrites / Q000378:metabolism / Q000648:ultrastructure; D004533:Egtazic Acid / Q000031:analogs & derivatives; D005246:Feedback / Q000502:physiology; D005452:Fluoresceins; D007202:Indicators and Reagents; D036881:Long-Term Synaptic Depression / Q000502:physiology*; D008564:Membrane Potentials / Q000502:physiology; D051379:Mice; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D009924:Organ Culture Techniques; D018408:Patch-Clamp Techniques; D011493:Protein Kinase C / Q000378:metabolism; D011689:Purkinje Cells / Q000166:cytology / Q000378:metabolism*; D051381:Rats; D013569:Synapses / Q000378:metabolism*; D013570:Synaptic Membranes / Q000378:metabolism; D009435:Synaptic Transmission / Q000502:physiology*; D013997:Time Factors
D000814:Aniline Compounds; D005452:Fluoresceins; D007202:Indicators and Reagents; C503942:Oregon green 488 BAPTA-1; C117677:dimethoxynitrophenyl-EGTA-4; D004533:Egtazic Acid; D011493:Protein Kinase C; D019950:Mitogen-Activated Protein Kinase 1; D002118:Calcium