Neuroscience. 2006 Mar 7; [Epub ahead of print]
The CB1 cannabinoid receptor mediates glutamatergic synaptic suppression in the hippocampus.
Takahashi KA, Castillo PE.
Department of Neuroscience, Albert Einstein College of Medicine of Yeshiva University, Kennedy Center Room 703, 1410 Pelham Parkway South, Bronx, NY 10461, USA.
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 [Hajos N, Ledent C, Freund TF (2001) 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 (5muM) 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; 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. |
