Pull-push neuromodulation of LTP and LTD enables bidirectional experience-induced synaptic scaling in visual cortex.
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.
The Mind/Brain Institute, Johns Hopkins University, Baltimore, MD 21218, USA.
ShiYong
S
Huang
Mario
M
Treviño
Kaiwen
K
He
Alvaro
A
Ardiles
Roberto de
Rd
Pasquale
Yatu
Y
Guo
Adrian
A
Palacios
Richard
R
Huganir
Alfredo
A
Kirkwood
D000322:Adrenergic Agonists / Q000494:pharmacology; D018674:Adrenergic Antagonists / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D001703:Biophysics; D004334:Drug Administration Schedule; D004347:Drug Interactions; D004558:Electric Stimulation; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D066298:In Vitro Techniques; D053444:Inhibitory Postsynaptic Potentials / Q000187:drug effects; D007545:Isoproterenol / Q000494:pharmacology; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology*; D036881:Long-Term Synaptic Depression / Q000187:drug effects / Q000502:physiology*; D008729:Methoxamine / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016202:N-Methylaspartate / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D018408:Patch-Clamp Techniques; D010775:Photic Stimulation; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D020318:Rats, Long-Evans; D018091:Receptors, AMPA / Q000172:deficiency; D013569:Synapses / Q000187:drug effects / Q000502:physiology*; D014633:Valine / Q000031:analogs & derivatives / Q000494:pharmacology; D014793:Visual Cortex / Q000166:cytology* / Q000187:drug effects / Q000502:physiology*; D014795:Visual Pathways / Q000187:drug effects / Q000502:physiology
D000322:Adrenergic Agonists; D018674:Adrenergic Antagonists; D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D007545:Isoproterenol; D008729:Methoxamine; D016202:N-Methylaspartate; D011433:Propranolol; D018091:Receptors, AMPA; D014633:Valine; C056639:2-amino-5-phosphopentanoic acid