Abstracts

Summary: The endocanabinoid system is an important neuromodulatory system that regulates cognition, learning and memory, motor behavior and pain perception. Upon depolarization of a postsynaptic neuron, endocannabinoids are released in the synaptic cleft, bind to the presynaptic type 1 cannabinoid receptor (CBR1) leading to a decrease in neuronal excitability. This mechanism is a key regulator of neurotransmission in the normal brain but might play a critical role in providing on-demand protection against pathologic hyperexcitability and seizures. Several recent studies seem to confirm the anticonvulsant role of the endocannabinoid system and reported that a neuroprotective machinery involving endocannabinoids is impaired in the hippocampus of human epileptic patients leading to the hypothesis that the downregulation of CBR1 and related molecular components of the endocannabinoid system may increased network excitability. One focus of this workshop will be to clarify the present knowledge of the distribution of CBR1 in the brain of healthy human subjects and how the availability of these receptors changes both in epileptic patients and in animal models of temporal lobe epilepsy. Furthermore, in animal models of temporal lobe epilepsy the endocannabinoid system was shown to undergo time-dependent changes related to the evolution of seizure activity. Altogether, data using imaging, neuropathologic and molecular approaches will be presented. Finally, these data will be discussed in light of the major functional characteristics of endocannabinoid signaling in the modulation of synaptic activity in the normal and epileptic brain. A better knowledge of how this system regulates neuronal excitability might lead to new therapeutic avenues for the treatment of drug-resistant epilepsy.