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The endocannabinoid system controls key epileptogenic circuits in the hippocampus.
- Source :
-
Neuron [Neuron] 2006 Aug 17; Vol. 51 (4), pp. 455-66. - Publication Year :
- 2006
-
Abstract
- 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.
- Subjects :
- Analysis of Variance
Animals
Behavior, Animal drug effects
Benzoxazines
Calcium Channel Blockers pharmacology
Calcium-Calmodulin-Dependent Protein Kinase Type 2
Calcium-Calmodulin-Dependent Protein Kinases genetics
Epilepsy chemically induced
Epilepsy genetics
Gene Expression physiology
Glutamic Acid genetics
Glutamic Acid metabolism
Hippocampus drug effects
Hippocampus physiopathology
Kainic Acid toxicity
Male
Membrane Potentials drug effects
Membrane Potentials genetics
Membrane Potentials radiation effects
Mice
Mice, Inbred C57BL
Mice, Transgenic
Morpholines pharmacology
Naphthalenes pharmacology
Nerve Net drug effects
Nerve Net physiopathology
Pyramidal Cells physiology
Pyramidal Cells radiation effects
Receptor, Cannabinoid, CB1 deficiency
Reverse Transcriptase Polymerase Chain Reaction methods
Vesicular Glutamate Transport Protein 1 metabolism
gamma-Aminobutyric Acid genetics
Cannabinoid Receptor Modulators physiology
Endocannabinoids
Epilepsy pathology
Epilepsy physiopathology
Hippocampus pathology
Nerve Net pathology
Subjects
Details
- Language :
- English
- ISSN :
- 0896-6273
- Volume :
- 51
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Neuron
- Publication Type :
- Academic Journal
- Accession number :
- 16908411
- Full Text :
- https://doi.org/10.1016/j.neuron.2006.07.006