Interplay between synaptic endocannabinoid signaling and metaplasticity in neuronal circuit function and dysfunction.
Synaptic neuromodulation acts across different functional domains to regulate cognitive processing and behavior. Recent challenges are related to elucidating the molecular and cellular mechanisms through which neuromodulatory pathways act on multiple time scales to signal state-dependent contingencies at the synaptic level or to stabilise synaptic connections during behavior. Here, we present a framework with the synaptic neuromodulators endocannabinoids (eCBs) as key players in dynamic synaptic changes. Modulation of various molecular components of the eCB pathway yields interconnected functional activation states of eCB signaling (prior, tonic, and persistent), which may contribute to metaplastic control of synaptic and behavioral functions in health and disease. The emerging picture supports aberrant metaplasticity as a contributor to cognitive dysfunction associated with several pathological states in which eCB signaling, or other neuromodulatory pathways, are deregulated.
Department of Biomedical Sciences, Division of Neuroscience and Clinical Pharmacology, University of Cagliari, Cagliari, Italy.
Miriam
M
Melis
Barbara
B
Greco
Raffaella
R
Tonini
D000818:Animals; D063388:Endocannabinoids / Q000378:metabolism*; D006801:Humans; D009473:Neuronal Plasticity; D013569:Synapses / Q000378:metabolism* / Q000502:physiology; D009435:Synaptic Transmission
D063388:Endocannabinoids
behavioral plasticity; endocannabinoids; experience-dependent plasticity; metaplasticity; synapse modulation