Cannabinoid receptor type 1 located on presynaptic terminals of principal neurons in the forebrain controls glutamatergic synaptic transmission.

1. J Neurosci. 2006 May 24;26(21):5794-9.

Cannabinoid receptor type 1 located on presynaptic terminals of principal neurons
in the forebrain controls glutamatergic synaptic transmission.

Domenici MR(1), Azad SC, Marsicano G, Schierloh A, Wotjak CT, Dodt HU,
Zieglgänsberger W, Lutz B, Rammes G.

Author information:
(1)Department of Clinical Neuropharmacology, Max Planck Institute of Psychiatry,
80804 Munich, Germany.

Erratum in
J Neurosci. 2006 Jun 14;26(24):table of contents.

It is widely accepted that cannabinoids regulate GABA release by activation of
cannabinoid receptor type 1 (CB1). Results obtained from a variety of brain
regions consistently indicate that cannabinoid agonists can also reduce
glutamatergic synaptic transmission. However, there are still conflicting data
concerning the role of CB1 in cannabinoid-induced inhibition of glutamatergic
transmission in cortical areas. Here, we provide direct evidence that activation
of CB1 on terminals of principal neurons controls excitatory synaptic responses
in the forebrain. In slices of the basolateral amygdala, the CA1 region of the
hippocampus, and the primary somatosensory cortex of wild-type mice, application
of the CB1 agonist
(R)-(+)-[2,3-dihydro-5-methyl-3-(4-morpholinylmethyl)pyrrolo[1,2,3-de]-1,4-benzox
azin-6-yl]-1-naphthalenylmethanone (WIN55,212-2; WIN) (5 mum) reduced evoked
excitatory postsynaptic responses. In contrast, in slices obtained from
conditional mouse mutants lacking CB1 in all principal forebrain neurons but not
in GABAergic interneurons (CB1(f/f;CaMKIIalphaCre)), WIN no longer affected
glutamatergic synaptic transmission in any of the brain regions tested.
Compatible with a presynaptic mechanism, WIN did not change the sensitivity to
focally uncaged l-glutamate. WIN reduced glutamatergic responses in slices
obtained from mice lacking CB1 exclusively in GABAergic neurons
(CB1(f/f;Dlx5/6-Cre)), thus excluding the involvement of CB1 expressed on
GABAergic neurons in this effect of the drug. The present data strongly indicate
that excitatory synaptic transmission in forebrain areas is directly modulated by
CB1 expressed on presynaptic axon terminals originating from glutamatergic
neurons.

DOI: 10.1523/JNEUROSCI.0372-06.2006
PMID: 16723537 [Indexed for MEDLINE]

Auteurs Bordeaux Neurocampus