Activation of CB1 specifically located on GABAergic interneurons inhibits LTD in the lateral amygdala.
Learning & Memory. 2008-02-22; 15(3): 143-152
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1. Learn Mem. 2008 Mar 5;15(3):143-52. doi: 10.1101/lm.741908. Print 2008 Mar.
Activation of CB1 specifically located on GABAergic interneurons inhibits LTD in
the lateral amygdala.
Azad SC(1), Kurz J, Marsicano G, Lutz B, Zieglgänsberger W, Rammes G.
(1)Max-Planck-Institute of Psychiatry, Clinical Neuropharmacology, 80804 Munich,
Previously, we found that in the lateral amygdala (LA) of the mouse, WIN55,212-2
decreases both glutamatergic and GABAergic synaptic transmission via activation
of the cannabinoid receptor type 1 (CB1), yet produces an overall reduction of
neuronal excitability. This suggests that the effects on excitatory transmission
override those on inhibitory transmission. Here we show that CB1 activation by
WIN55,212-2 and Delta(9)-THC inhibits long-term depression (LTD) of basal
synaptic transmission in the LA, induced by low-frequency stimulation (LFS; 900
pulses/1 Hz). The CB1 agonist WIN55,212-2 blocked LTD via G(i/o) proteins,
activation of inwardly rectifying K+ channels (K(ir)s), inhibition of the
adenylate cyclase-protein kinase A (PKA) pathway, and PKA-dependent inhibition of
voltage-gated N-type Ca2+ channels (N-type VGCCs). Interestingly, WIN55,212-2
effects on LTD were abolished in CB1 knock-out mice (CB1-KO), and in conditional
mutants lacking CB1 expression only in GABAergic interneurons, but were still
present in mutants lacking CB1 in principal forebrain neurons. LTD induction per
se was unaffected by the CB1 antagonist SR141716A and was normally expressed in
CB1-KO as well as in both conditional CB1 mutants. Our data demonstrate that
activation of CB1 specifically located on GABAergic interneurons inhibits LTD in
the LA. These findings suggest that CB1 expressed on either glutamatergic or
GABAergic neurons play a differential role in the control of synaptic
transmission and plasticity.
PMID: 18323569 [Indexed for MEDLINE]