The CB1 cannabinoid receptor mediates glutamatergic synaptic suppression in the hippocampus.
Cannabinoids have profound effects on synaptic function and behavior. Of the two cloned cannabinoid receptors, cannabinoid receptor 1 (CB1) is widely distributed in the CNS and accounts for most of the neurological effects of cannabinoids, while cannabinoid receptor 2 (CB2) expression in the CNS is very limited. The presence of additional receptors [i.e. cannabinoid receptor 3 (CB3)] is suggested by growing evidence of cannabinoid effects that are not mediated by CB1 or CB2. The most direct functional evidence for a CB3 comes from a study in hippocampus where deletion of CB1 was shown to have no effect on cannabinoid-mediated suppression of the excitatory synapse between Schaffer collateral/commissural fibers and CA1 pyramidal cells [Novel cannabinoid-sensitive receptor mediates inhibition of glutamatergic synaptic transmission in the hippocampus. Neuroscience 106:1-4]. In contrast, we report here that in extracellular field recordings, the cannabinoid agonist WIN 55,212-2 (5 microM) had no effect on Schaffer collateral/commissural fiber-CA1 pyramidal cell (Sch-CA1) synaptic transmission in slices from two independently made cannabinoid receptor 1-/- lines [Zimmer et al 1999 and Ledent et al 1999] while strongly suppressing Sch-CA1 synaptic transmission in CB1+/+ mice of the background strains. Also, we observed robust cannabinoid-mediated suppression of the Sch-CA1 synapse in pure C57BL/6 mice, contradicting a recent report that cannabinoid suppression of this synapse is absent in this strain [Hoffman AF, Macgill AM, Smith D, Oz M, Lupica CR (2005) Species and strain differences in the expression of a novel glutamate-modulating cannabinoid receptor in the rodent hippocampus. Eur J Neurosci 22:2387-2391]. Our results strongly suggest that cannabinoid-induced suppression of the Sch-CA1 synapse is mediated by CB1. Non-canonical cannabinoid receptors do not seem to play a major role in inhibiting transmitter release at this synapse.
Takahashi
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Department of Neuroscience, Albert Einstein College of Medicine of Yeshiva University, Kennedy Center Room 703, 1410 Pelham Parkway South, Bronx, NY 10461, USA.
Castillo
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PE
D000818:Animals; D048588:Benzoxazines; D002121:Calcium Channel Blockers / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D005260:Female; D005973:Glutamine / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009025:Morpholines / Q000494:pharmacology; D009281:Naphthalenes / Q000494:pharmacology; D009924:Organ Culture Techniques; D018408:Patch-Clamp Techniques; D043884:Receptor, Cannabinoid, CB1 / Q000187:drug effects / Q000378:metabolism*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*
D048588:Benzoxazines; D002121:Calcium Channel Blockers; D009025:Morpholines; D009281:Naphthalenes; D043884:Receptor, Cannabinoid, CB1; D005973:Glutamine; C070417:(3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone