Journal article
Regulation of fear extinction by long-term depression: the roles of endocannabinoids and brain derived neurotrophic factor
Behavioural Brain Research, Vol.319, pp.148-164
2017
Abstract
The extinction of a conditioned fear response is of great interest in the search for a means of ameliorating adverse neurobiological changes resulting from stress. The discovery that endocannibinoid (EC) levels are inversely related to the extent of such stress, and that the amygdala is a primary site mediating stress, suggests that ECs in this brain region might play a major role in extinction. Supporting this are the observations that the basolateral complex of the amygdala shows an increase in ECs only during extinction and that early clinical trials indicate that cannabinoid-like agents, when taken orally by patients suffering from post traumatic stress disorder (PTSD), reduce insomnia and nightmares. In order to optimize the potential of these agents to ameliorate symptoms of PTSD four important questions need to be answered: first, what is the identity of the cells that release ECs in the amygdala during extinction; second, what are their sites of action; third, what roles do the ECs play in the alleviation of long- depression (LTD), a process central to extinction; and finally, to what extent does brain derived neurotrophic factor (BDNF) facilitate the release of ECs? A review of the relevant literature is presented in an attempt to answer these questions. It is suggested that the principal cell involved in EC synthesis and release during extinction is the so-called excitatory extinction neuron in the basal nucleus of the amygdala. Furthermore that the main site of action of the ECs is the adjacent calcitonin gene-related peptide inhibitory interneurons, whose normal role of blocking the excitatory neurons is greatly diminished. The molecular pathways leading (during extinction trials) to the synthesis and release of ECs from synaptic spines of extinction neurons, that is potentiated by BDNF, are also delineated in this review. Finally, consideration is given to how the autocrine action of BDNF, linked to the release of ECs, can lead to the sustained release of these, so maintaining extinction over long times.
Details
- Title
- Regulation of fear extinction by long-term depression: the roles of endocannabinoids and brain derived neurotrophic factor
- Authors
- Maxwell Bennett (Author) - University of SydneyJonathon Arnold (Author) - University of SydneySean N Hatton (Author) - University of SydneyJim Lagopoulos (Author) - University of the Sunshine Coast
- Publication details
- Behavioural Brain Research, Vol.319, pp.148-164
- Publisher
- Elsevier BV
- Date published
- 2017
- DOI
- 10.1016/j.bbr.2016.11.029
- ISSN
- 0166-4328
- Copyright note
- Copyright © 2017. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/
- Organisation Unit
- University of the Sunshine Coast, Queensland; Thompson Institute
- Language
- English
- Record Identifier
- 99451289602621
- Output Type
- Journal article
Metrics
146 File views/ downloads
735 Record Views
InCites Highlights
These are selected metrics from InCites Benchmarking & Analytics tool, related to this output
- Collaboration types
- Domestic collaboration
- Web Of Science research areas
- Behavioral Sciences
- Neurosciences
UN Sustainable Development Goals (SDGs)
This output has contributed to the advancement of the following goals:
Source: InCites