Multiple receptors coupled to phospholipase C gate long-term depression in visual cortex.
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.
Choi
Se-Young
SY
Mind/Brain Institute, Department of Neurosciences, Johns Hopkins University, Baltimore, Maryland 21218, USA.
Chang
Jeff
J
Jiang
Bin
B
Seol
Geun-Hee
GH
Min
Sun-Seek
SS
Han
Jung-Soo
JS
Shin
Hee-Sup
HS
Gallagher
Michela
M
Kirkwood
Alfredo
A
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*
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