Circuitry for associative plasticity in the amygdala involves endocannabinoid signaling.

1. J Neurosci. 2004 Nov 3;24(44):9953-61.

Circuitry for associative plasticity in the amygdala involves endocannabinoid
signaling.

Azad SC(1), Monory K, Marsicano G, Cravatt BF, Lutz B, Zieglgänsberger W, Rammes
G.

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

Endocannabinoids are crucial for the extinction of aversive memories, a process
that considerably involves the amygdala. Here, we show that low-frequency
stimulation of afferents in the lateral amygdala with 100 pulses at 1 Hz releases
endocannabinoids postsynaptically from neurons of the basolateral amygdala of
mice in vitro and thereby induces a long-term depression of inhibitory GABAergic
synaptic transmission (LTDi) via a presynaptic mechanism. Lowering inhibitory
synaptic transmission significantly increases the amplitude of excitatory
synaptic currents in principal neurons of the central nucleus, which is the main
output site of the amygdala. LTDi involves a selective mGluR1 (metabotropic
glutamate receptor 1)-mediated calcium-independent mechanism and the activation
of the adenylyl cyclase-protein kinase A pathway. LTDi is abolished by the
cannabinoid type 1 (CB1) receptor antagonist SR141716A and cannot be evoked in
CB1 receptor-deficient animals. LTDi is significantly enhanced in mice lacking
the anandamide-degrading enzyme fatty acid amide hydrolase. The present findings
show for the first time that mGluR activation induces a retrograde
endocannabinoid signaling via activation of the adenylyl cyclase-protein kinase A
pathway and the release of anandamide. Furthermore, the results indicate that
anandamide decreases the activity of inhibitory interneurons in the amygdala.
This disinhibition increases the activity of common output neurons and could
provide a prerequisite for extinction by formation of new memory.

DOI: 10.1523/JNEUROSCI.2134-04.2004
PMID: 15525780 [Indexed for MEDLINE]

Auteurs Bordeaux Neurocampus