Metaplastic control of the endocannabinoid system at inhibitory synapses in hippocampus.
The modifiability of neuronal response plasticity is called "metaplasticity." In suppressing synaptic inhibition and facilitating induction of long-term excitatory synaptic plasticity, endocannabinoids (eCBs) act as agents of metaplasticity. We now report the discovery of a calcium-dependent mechanism that regulates eCB mobilization by metabotropic glutamate receptor (mGluR) activation. The switch-like mechanism primes cells to release eCBs and requires a transient rise in intracellular Ca2+ concentration ([Ca2+]i) but not concurrent activation of mGluRs. Conversely, short-term, [Ca2+]i-dependent eCB release can be persistently enhanced by mGluR activation. Hence, eCBs are also objects of metaplasticity, subject to higher levels of physiological control.
Edwards
David A
DA
Department of Physiology, Program in Neuroscience, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
Zhang
Longhua
L
Alger
Bradley E
BE
D000818:Animals; D001692:Biological Transport; D020013:Calcium Signaling; D063385:Cannabinoid Receptor Modulators / Q000502:physiology*; D063388:Endocannabinoids; D004789:Enzyme Activation; D006624:Hippocampus / Q000201:enzymology / Q000502:physiology*; D008071:Lipoprotein Lipase / Q000378:metabolism; D036881:Long-Term Synaptic Depression; D008297:Male; D009473:Neuronal Plasticity / Q000502:physiology*; D051381:Rats; D043884:Receptor, Cannabinoid, CB1 / Q000378:metabolism; D018094:Receptors, Metabotropic Glutamate / Q000378:metabolism; D013569:Synapses / Q000201:enzymology / Q000502:physiology*; D010738:Type C Phospholipases / Q000378:metabolism
D063385:Cannabinoid Receptor Modulators; D063388:Endocannabinoids; D043884:Receptor, Cannabinoid, CB1; D018094:Receptors, Metabotropic Glutamate; D008071:Lipoprotein Lipase; D010738:Type C Phospholipases