Cannabinoid CB1 receptor deficiency increases contextual fear memory under highly aversive conditions and long-term potentiation in vivo.
Neurobiology of Learning and Memory. 2012-07-01; 98(1): 47-55
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1. Neurobiol Learn Mem. 2012 Jul;98(1):47-55. doi: 10.1016/j.nlm.2012.04.008. Epub
2012 May 8.
Cannabinoid CB1 receptor deficiency increases contextual fear memory under highly
aversive conditions and long-term potentiation in vivo.
Jacob W(1), Marsch R, Marsicano G, Lutz B, Wotjak CT.
(1)Max Planck Institute of Psychiatry, Kraepelinstrasse 2, D-80804 Munich,
The cannabinoid receptor type 1 (CB1) is abundantly expressed in the central
nervous system where it negatively controls the release of several
neurotransmitters. CB1 activity plays a crucial role in learning and memory and
in synaptic plasticity. In the present study, the role of CB1 was investigated in
three different hippocampus-dependent memory tasks and in in vivo hippocampal
synaptic plasticity in knockout (CB1-ko) and wildtype mice. There was no
difference in short-term and long-term social and object recognition memory
between CB1-ko and wildtype mice. In contrast, in background contextual fear
conditioning CB1-ko mice showed enhanced freezing levels in the conditioning
context and increased generalised contextual fear after a high-intensity
conditioning foot shock of 1.5 mA, but not after 0.7 mA. In in vivo field
potential recordings in the dentate gyrus, CB1-ko mice displayed a decreased
paired-pulse facilitation of the populations spikes, suggesting an altered
inhibitory synaptic drive onto hippocampal granule cells. Furthermore, CB1-ko
mice displayed significantly higher levels of in vivo long-term potentiation
(LTP) in the dentate gyrus. In conclusion, CB1 deficiency leads to enhanced
contextual fear memory and altered synaptic plasticity in the hippocampus,
supporting the key role of endocannabinoid signalling in learning and memory, in
particular following highly aversive encounters.
Copyright © 2012 Elsevier Inc. All rights reserved.
PMID: 22579951 [Indexed for MEDLINE]