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.
Department of Physiology, Program in Neuroscience, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
David A
DA
Edwards
Longhua
L
Zhang
Bradley E
BE
Alger
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