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Neural substrates for the opposing effects of distinct presynaptic group III metabotropic glutamate receptors on extinction of contextual fear conditioning in mice.

Dobi, Alice and Sartori, Simone and Busti, Daniela and Flor, Peter and Van Der Putten, P. Herman and Singewald, Nicolas and Shigemoto, Ryuichi and Ferraguti, Francesco (2012) Neural substrates for the opposing effects of distinct presynaptic group III metabotropic glutamate receptors on extinction of contextual fear conditioning in mice. Neuropharmacology. pp. 1-16. ISSN 0028-3908

Abstract

Activation of mGlu7 or mGlu8 receptors through specific agonists, administered intra-amygdala before extinction training, produced different effects on extinction of contextual fear conditioning. The mGlu7 receptor agonist AMN082 facilitated extinction, whereas activation of mGlu8 receptors by (S)-3,4-DCPG prevented the reduction of the freezing behaviour normally observed after the re-exposure of the animals to the conditioning context in the absence of the US. Despite the relatively similar distribution of the immunoreactivity for mGlu7a and mGlu8a receptors within the BLA and ITCs, our anatomical analysis at the ultrastructural level revealed how these two receptors are to a significant extent segregated to different inputs. In particular, mGlu7a receptors were located primarily onto glutamatergic afferents either intrinsic to the BLA or extrinsic and arising from the thalamus, but not the mPFC. On the other hand, mGlu8a showed a more restricted distribution than mGlu7a receptors in the BA and appeared absent from the three pathways that have been examined in this study. The identified segregation of these two group III mGlu receptors into primarily distinct afferents corroborates the marked pharmacological difference caused by their respective agonists on extinction expression.

Item Type: Article
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Additional Information: This is a RoMEO green journal: can archive pre-print and post-print or publisher's version/PDF.
Keywords: mGluR7 mGluR8 fear circuit amygdala
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Date Deposited: 13 Oct 2015 13:14
Last Modified: 13 Oct 2015 13:14
URI: https://oak.novartis.com/id/eprint/6832

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