Cellular mechanisms of burst firing-mediated long-term depression in rat neocortical pyramidal cells.
During wakefulness and sleep, neurons in the neocortex emit action potentials tonically or in rhythmic bursts, respectively. However, the role of synchronized discharge patterns is largely unknown. We have recently shown that pairings of excitatory postsynaptic potentials (EPSPs) and action potential bursts or single spikes lead to long-term depression (burst-LTD) or long-term potentiation, respectively. In this study, we elucidate the cellular mechanisms of burst-LTD and characterize its functional properties. Whole-cell patch-clamp recordings were obtained from layer V pyramidal cells in somatosensory cortex of juvenile rats in vitro and composite EPSPs and EPSCs were evoked extracellularly in layers II/III. Repetitive burst-pairings led to a long-lasting depression of EPSPs and EPSCs that was blocked by inhibitors of metabotropic glutamate group 1 receptors, phospholipase C, protein kinase C (PKC) and calcium release from the endoplasmic reticulum, and that required an intact machinery for endocytosis. Thus, burst-LTD is induced via a Ca2+- and phosphatidylinositol-dependent activation of PKC and expressed through phosphorylation-triggered endocytosis of AMPA receptors. Functionally, burst-LTD is inversely related to EPSP size and bursts dominate single spikes in determining the sign of synaptic plasticity. Thus burst-firing constitutes a signal by which coincident synaptic inputs are proportionally downsized. Overall, our data thus suggest a mechanism by which synaptic weights can be reconfigured during non-rapid eye movement sleep.
Czarnecki
Antonny
A
Department of Physiology, University of Bern, Bühlplatz 5, 3012 Bern, Switzerland .
Birtoli
Barbara
B
Ulrich
Daniel
D
D000818:Animals; D001952:Bridged-Ring Compounds / Q000494:pharmacology; D002614:Chelating Agents / Q000494:pharmacology; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D004705:Endocytosis / Q000187:drug effects / Q000502:physiology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D006493:Heparin / Q000494:pharmacology; D007189:Indans / Q000494:pharmacology; D017774:Long-Term Potentiation / Q000502:physiology; D036881:Long-Term Synaptic Depression / Q000187:drug effects / Q000502:physiology*; D019579:Neocortex / Q000166:cytology / Q000502:physiology*; D009473:Neuronal Plasticity / Q000187:drug effects; D009636:Norbornanes; D018408:Patch-Clamp Techniques; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D017966:Pyramidal Cells / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D018091:Receptors, AMPA / Q000378:metabolism; D012430:Ruthenium Red / Q000494:pharmacology; D019837:Ryanodine Receptor Calcium Release Channel / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013003:Somatosensory Cortex / Q000166:cytology / Q000502:physiology; D013859:Thiocarbamates; D013871:Thiones / Q000494:pharmacology; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors
C095756:1-aminoindan-1,5-dicarboxylic acid; D001952:Bridged-Ring Compounds; D002614:Chelating Agents; D018691:Excitatory Amino Acid Antagonists; D007189:Indans; D009636:Norbornanes; D010726:Phosphodiesterase Inhibitors; D018091:Receptors, AMPA; D019837:Ryanodine Receptor Calcium Release Channel; D013859:Thiocarbamates; D013871:Thiones; D012430:Ruthenium Red; D004533:Egtazic Acid; C046498:tricyclodecane-9-yl-xanthogenate; D006493:Heparin; D010738:Type C Phospholipases; C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid