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The endocannabinoid system controls key epileptogenic circuits in the hippocampus.

Neuron | Aug 17, 2006

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.

Pubmed ID: 16908411 RIS Download

Mesh terms: Analysis of Variance | Animals | Behavior, Animal | Benzoxazines | Calcium Channel Blockers | Calcium-Calmodulin-Dependent Protein Kinase Type 2 | Calcium-Calmodulin-Dependent Protein Kinases | Cannabinoid Receptor Modulators | Endocannabinoids | Epilepsy | Gene Expression | Glutamic Acid | Hippocampus | Kainic Acid | Male | Membrane Potentials | Mice | Mice, Inbred C57BL | Mice, Transgenic | Morpholines | Naphthalenes | Nerve Net | Pyramidal Cells | Receptor, Cannabinoid, CB1 | Reverse Transcriptase Polymerase Chain Reaction | Vesicular Glutamate Transport Protein 1 | gamma-Aminobutyric Acid

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Associated grants

  • Agency: NIDA NIH HHS, Id: DA00286
  • Agency: NIDA NIH HHS, Id: DA11322
  • Agency: NIDA NIH HHS, Id: DA15916
  • Agency: NIDA NIH HHS, Id: K02 DA000286
  • Agency: NIMH NIH HHS, Id: MH065670
  • Agency: NIMH NIH HHS, Id: MH49428
  • Agency: NIDA NIH HHS, Id: R01 DA011322
  • Agency: Biotechnology and Biological Sciences Research Council, Id: S19916

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