title: Multiple receptors coupled to phospholipase C gate long-term depression in visual cortex.
abstract: Long-term depression (LTD) in sensory cortices depends on the activation of NMDA receptors. Here, we report that in visual cortical slices, the induction of LTD (but not long-term potentiation) also requires the activation of receptors coupled to the phospholipase C (PLC) pathway. Using immunolesions in combination with agonists and antagonists, we selectively manipulated the activation of alpha1 adrenergic, M1 muscarinic, and mGluR5 glutamatergic receptors. Inactivation of these PLC-coupled receptors prevents the induction of LTD, but only when the three receptors were inactivated together. LTD is fully restored by activating any one of them or by supplying intracellular D-myo-inositol-1,4,5-triphosphate (IP3). LTD was also impaired by intracellular application of PLC or IP3 receptor blockers, and it was absent in mice lacking PLCbeta1, the predominant PLC isoform in the forebrain. We propose that visual cortical LTD requires a minimum of PLC activity that can be supplied independently by at least three neurotransmitter systems. This essential requirement places PLC-linked receptors in a unique position to control the induction of LTD and provides a mechanism for gating visual cortical plasticity via extra-retinal inputs in the intact organism.
authors.affiliation: Mind/Brain Institute, Department of Neurosciences, Johns Hopkins University, Baltimore, Maryland 21218, USA.
authors.forename: Se-Young
authors.initials: SY
authors.lastname: Choi
authors.forename: Jeff
authors.initials: J
authors.lastname: Chang
authors.forename: Bin
authors.initials: B
authors.lastname: Jiang
authors.forename: Geun-Hee
authors.initials: GH
authors.lastname: Seol
authors.forename: Sun-Seek
authors.initials: SS
authors.lastname: Min
authors.forename: Jung-Soo
authors.initials: JS
authors.lastname: Han
authors.forename: Hee-Sup
authors.initials: HS
authors.lastname: Shin
authors.forename: Michela
authors.initials: M
authors.lastname: Gallagher
authors.forename: Alfredo
authors.initials: A
authors.lastname: Kirkwood
mesh_terms: D000818:Animals; D015640:Ion Channel Gating / Q000502:physiology*; D036881:Long-Term Synaptic Depression / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D051381:Rats; D020318:Rats, Long-Evans; D064529:Receptor, Metabotropic Glutamate 5; D043643:Receptor, Muscarinic M1 / Q000378:metabolism*; D018340:Receptors, Adrenergic, alpha-1 / Q000378:metabolism*; D018094:Receptors, Metabotropic Glutamate / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D010738:Type C Phospholipases / Q000378:metabolism*; D014793:Visual Cortex / Q000378:metabolism*
chemical_list: C578936:Grm5 protein, mouse; C578937:Grm5 protein, rat; D064529:Receptor, Metabotropic Glutamate 5; D043643:Receptor, Muscarinic M1; D018340:Receptors, Adrenergic, alpha-1; D018094:Receptors, Metabotropic Glutamate; D010738:Type C Phospholipases