The role of dendritic action potentials and Ca2+ influx in the induction of homosynaptic long-term depression in hippocampal CA1 pyramidal neurons.
Long-term depression (LTD) of synaptic efficacy at CA1 synapses is believed to be a Ca(2+)-dependent process. We used high-speed fluorescence imaging and patch-clamp techniques to quantify the spatial distribution of changes in intracellular Ca2+ accompanying the induction of LTD at Schaffer collateral synapses in CA1 pyramidal neurons. Low-frequency stimulation (3 Hz), which was subthreshold for action potentials, produced small changes in [Ca2+]i and failed to elicit LTD. Increasing the stimulus strength so that action potentials were generated produced both robust LTD and increases in [Ca2+]i. Back-propagating action potentials at 3 Hz in the absence of synaptic stimulation also produced increases in [Ca2+]i, but failed to induce LTD. When subthreshold synaptic stimulation was paired with back-propagating action potentials, however, large increases in [Ca2+]i were observed and robust LTD was induced. The LTD was blocked by the N-methyl-D-aspartate receptor (NMDAr) antagonist APV, and stimulus-induced increases in [Ca2+]i were reduced throughout the neuron under these conditions. The LTD was also dependent on Ca2+ influx via voltage-gated Ca2+ channels (VGCCs), because LTD was severely attenuated or blocked by both nimodipine and Ni2+. These findings suggest that back-propagating action potentials can exert a powerful control over the induction of LTD and that both VGCCs and NMDArs are involved in the induction of this form of plasticity.
Christie
B R
BR
Division of Neuroscience, Baylor College of Medicine, Houston, Texas 77030, USA.
Magee
J C
JC
Johnston
D
D
D000200:Action Potentials / Q000502:physiology; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000502:physiology; D003712:Dendrites / Q000502:physiology*; D004594:Electrophysiology; D006624:Hippocampus / Q000166:cytology / Q000502:physiology*; D066298:In Vitro Techniques; D015640:Ion Channel Gating / Q000502:physiology; D017774:Long-Term Potentiation / Q000502:physiology*; D017966:Pyramidal Cells / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology; D013569:Synapses / Q000502:physiology*
D015220:Calcium Channels; D016194:Receptors, N-Methyl-D-Aspartate; D002118:Calcium