Brief dendritic calcium signals initiate long-lasting synaptic depression in cerebellar Purkinje cells.
We have performed experiments designed to test the hypothesis that long-term depression (LTD) of excitatory synaptic transmission in the cerebellar cortex is caused by a rise in postsynaptic Ca concentration. These experiments combined measurements of synaptic efficacy, performed with the thin slice patch clamp technique, with fura-2 measurements of intracellular Ca concentration ([Ca]i) in single cerebellar Purkinje cells. Simultaneous activation of the climbing fiber and parallel fibers innervating single Purkinje cells caused a LTD of transmission of the parallel fiber-Purkinje cell excitatory synapse. This LTD was associated with large and transient rises in [Ca]i in the Purkinje cell and apparently was due to Ca entry through voltage-gated Ca channels in the Purkinje cell dendrites. The rise in [Ca]i produced by climbing fiber activity was necessary for LTD, because addition of the Ca chelator bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetate (BAPTA) to the interior of the Purkinje cell blocked LTD. Further, elevation of [Ca]i, produced by depolarizing pulses delivered in conjunction with parallel fiber activation, induced a depression of synaptic activity that closely resembled LTD in both time course and magnitude. Thus, a rise in [Ca]i appears to be sufficient to initiate LTD. From these results, we conclude that LTD of the parallel fiber-Purkinje cell synapse is initiated by a brief, climbing fiber-mediated rise in postsynaptic [Ca]i and that LTD is maintained by other, longer-lived processes that are triggered by the rise in postsynaptic [Ca]i.
Konnerth
A
A
Max-Planck-Institut für biophysikalische Chemie, Göttingen, Germany.
Dreessen
J
J
Augustine
G J
GJ
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology*; D002525:Cerebellar Cortex / Q000502:physiology; D003712:Dendrites / Q000502:physiology*; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D066298:In Vitro Techniques; D007700:Kinetics; D011689:Purkinje Cells / Q000502:physiology*; D051381:Rats; D013569:Synapses / Q000502:physiology*; D009435:Synaptic Transmission; D013997:Time Factors
D015220:Calcium Channels; D004533:Egtazic Acid; C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid; D002118:Calcium