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Publication : The endocannabinoid system controls key epileptogenic circuits in the hippocampus.

First Author  Monory K Year  2006
Journal  Neuron Volume  51
Issue  4 Pages  455-66
PubMed ID  16908411 Mgi Jnum  J:122066
Mgi Id  MGI:3713054 Doi  10.1016/j.neuron.2006.07.006
Citation  Monory K, et al. (2006) The endocannabinoid system controls key epileptogenic circuits in the hippocampus. Neuron 51(4):455-66
abstractText  Balanced control of neuronal activity is central in maintaining function and viability of neuronal circuits. The endocannabinoid system tightly controls neuronal excitability. Here, we show that endocannabinoids directly target hippocampal glutamatergic neurons to provide protection against acute epileptiform seizures in mice. Functional CB1 cannabinoid receptors are present on glutamatergic terminals of the hippocampal formation, colocalizing with vesicular glutamate transporter 1 (VGluT1). Conditional deletion of the CB1 gene either in cortical glutamatergic neurons or in forebrain GABAergic neurons, as well as virally induced deletion of the CB1 gene in the hippocampus, demonstrate that the presence of CB1 receptors in glutamatergic hippocampal neurons is both necessary and sufficient to provide substantial endogenous protection against kainic acid (KA)-induced seizures. The direct endocannabinoid-mediated control of hippocampal glutamatergic neurotransmission may constitute a promising therapeutic target for the treatment of disorders associated with excessive excitatory neuronal activity.
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