Pull-push neuromodulation of LTP and LTD enables bidirectional experience-induced synaptic scaling in visual cortex

Neuron. 2012 Feb 9;73(3):497-510. doi: 10.1016/j.neuron.2011.11.023.

Abstract

Neuromodulatory input, acting on G protein-coupled receptors, is essential for the induction of experience-dependent cortical plasticity. Here we report that G-coupled receptors in layer II/III of visual cortex control the polarity of synaptic plasticity through a pull-push regulation of LTP and LTD. In slices, receptors coupled to Gs promote LTP while suppressing LTD; conversely, receptors coupled to Gq11 promote LTD and suppress LTP. In vivo, the selective stimulation of Gs- or Gq11-coupled receptors brings the cortex into LTP-only or LTD-only states, which allows the potentiation or depression of targeted synapses with visual stimulation. The pull-push regulation of LTP/LTD occurs via direct control of the synaptic plasticity machinery and it is independent of changes in NMDAR activation or neuronal excitability. We propose these simple rules governing the pull-push control of LTP/LTD form a general metaplasticity mechanism that may contribute to neuromodulation of plasticity in other cortical circuits.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adrenergic Agonists / pharmacology
  • Adrenergic Antagonists / pharmacology
  • Analysis of Variance
  • Animals
  • Animals, Newborn
  • Biophysics
  • Drug Administration Schedule
  • Drug Interactions
  • Electric Stimulation
  • Excitatory Amino Acid Agonists / pharmacology
  • Excitatory Amino Acid Antagonists / pharmacology
  • Excitatory Postsynaptic Potentials / drug effects
  • In Vitro Techniques
  • Inhibitory Postsynaptic Potentials / drug effects
  • Isoproterenol / pharmacology
  • Long-Term Potentiation / drug effects
  • Long-Term Potentiation / physiology*
  • Long-Term Synaptic Depression / drug effects
  • Long-Term Synaptic Depression / physiology*
  • Methoxamine / pharmacology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • N-Methylaspartate / pharmacology
  • Neurons / drug effects
  • Neurons / physiology*
  • Patch-Clamp Techniques
  • Photic Stimulation
  • Propranolol / pharmacology
  • Rats
  • Rats, Long-Evans
  • Receptors, AMPA / deficiency
  • Synapses / drug effects
  • Synapses / physiology*
  • Valine / analogs & derivatives
  • Valine / pharmacology
  • Visual Cortex / cytology*
  • Visual Cortex / drug effects
  • Visual Cortex / physiology*
  • Visual Pathways / drug effects
  • Visual Pathways / physiology

Substances

  • Adrenergic Agonists
  • Adrenergic Antagonists
  • Excitatory Amino Acid Agonists
  • Excitatory Amino Acid Antagonists
  • Receptors, AMPA
  • N-Methylaspartate
  • 2-amino-5-phosphopentanoic acid
  • Propranolol
  • Valine
  • Methoxamine
  • Isoproterenol
  • glutamate receptor ionotropic, AMPA 1