Spine Ca2+ signaling in spike-timing-dependent plasticity.
Calcium is a second messenger, which can trigger the modification of synaptic efficacy. We investigated the question of whether a differential rise in postsynaptic Ca2+ ([Ca2+]i) alone is sufficient to account for the induction of long-term potentiation (LTP) and long-term depression (LTD) of EPSPs in the basal dendrites of layer 2/3 pyramidal neurons of the somatosensory cortex. Volume-averaged [Ca2+]i transients were measured in spines of the basal dendritic arbor for spike-timing-dependent plasticity induction protocols. The rise in [Ca2+]i was uncorrelated to the direction of the change in synaptic efficacy, because several pairing protocols evoked similar spine [Ca2+]i transients but resulted in either LTP or LTD. The sequence dependence of near-coincident presynaptic and postsynaptic activity on the direction of changes in synaptic strength suggested that LTP and LTD were induced by two processes, which were controlled separately by postsynaptic [Ca2+]i levels. Activation of voltage-dependent Ca2+ channels before metabotropic glutamate receptors (mGluRs) resulted in the phospholipase C-dependent (PLC-dependent) synthesis of endocannabinoids, which acted as a retrograde messenger to induce LTD. LTP required a large [Ca2+]i transient evoked by NMDA receptor activation. Blocking mGluRs abolished the induction of LTD and uncovered the Ca2+-dependent induction of LTP. We conclude that the volume-averaged peak elevation of [Ca2+]i in spines of layer 2/3 pyramids determines the magnitude of long-term changes in synaptic efficacy. The direction of the change is controlled, however, via a mGluR-coupled signaling cascade. mGluRs act in conjunction with PLC as sequence-sensitive coincidence detectors when postsynaptic precede presynaptic action potentials to induce LTD. Thus presumably two different Ca2+ sensors in spines control the induction of spike-timing-dependent synaptic plasticity.
Nevian
Thomas
T
Department of Cell Physiology, Max-Planck Institute for Medical Research, D-69120 Heidelberg, Germany. nevian@pyl.unibe.ch
Sakmann
Bert
B
D000200:Action Potentials / Q000502:physiology*; D000818:Animals; D002118:Calcium / Q000502:physiology; D020746:Calcium Channels, L-Type / Q000502:physiology; D020013:Calcium Signaling / Q000502:physiology*; D049229:Dendritic Spines / Q000502:physiology*; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D017774:Long-Term Potentiation / Q000502:physiology; D009473:Neuronal Plasticity / Q000502:physiology*; D017966:Pyramidal Cells / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000502:physiology*; D013997:Time Factors
D020746:Calcium Channels, L-Type; D002118:Calcium