Concluding Remarks: Excitatory inputs in the hippocampus can feedback onto inhibitory synapses and induce long-term changes in GABAergic synaptic efficacy via retrograde endocannabinoid signaling (I-LTD). The disinhibition caused by synaptically-driven release of endocannabinoids not only enhances excitability (Chevaleyre and Castillo, 2003) but also mediates metaplasticity. These findings highlight the relevance of endocannabinoids in activity-dependent synaptic plasticity and reveal the variety of mechanisms by which these messengers may contribute to the storage of information in the brain. The profound repercussion of THC exposure on endocannabinoid-mediated synaptic plasticity in the hippocampus provides a mechanism by which cannabis derivatives may alter cognitive functions.
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