Details

Autor(en) / Beteiligte

• Ko, BumJin
• Yoo, Jong-Yeon
• Yoo, Taesik
• Choi, Woochul
• Dogan, Rumeysa
• Sung, Kibong
• Um, Dahun
• Lee, Su Been
• Kim, Hyun Jin
• Lee, Sangjun
• Beak, Seung Tae
• Park, Sang Ki
• Paik, Se-Bum
• Kim, Tae-Kyung
• Kim, Joung-Hun

Titel

Npas4-mediated dopaminergic regulation of safety memory consolidation

Ist Teil von

• Cell reports (Cambridge), 2023-07, Vol.42 (7), p.112678-112678, Article 112678

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2023

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• Amygdala circuitry encodes associations between conditioned stimuli and aversive unconditioned stimuli and also controls fear expression. However, whether and how non-threatening information for unpaired conditioned stimuli (CS−) is discretely processed remains unknown. The fear expression toward CS− is robust immediately after fear conditioning but then becomes negligible after memory consolidation. The synaptic plasticity of the neural pathway from the lateral to the anterior basal amygdala gates the fear expression of CS−, depending upon neuronal PAS domain protein 4 (Npas4)-mediated dopamine receptor D4 (Drd4) synthesis, which is precluded by stress exposure or corticosterone injection. Herein, we show cellular and molecular mechanisms that regulate the non-threatening (safety) memory consolidation, supporting the fear discrimination. [Display omitted] •Synaptic depotentiation of the LA-to-aBA pathway reduces fear expression toward CS−•Upregulation of Npas4-Drd4 axis mediates the consolidation of CS− memory•Consolidation of CS− memory can be disrupted by exposure to stressors or enhanced CORT level•A subset of LA neurons, which express Npas4, regulate fear expression in response to CS− Ko et al. identified cellular and molecular mechanisms underlying fear discrimination between CS− and CS+. Specifically, a subpopulation of amygdala neurons expressing Npas4 induce synaptic depotentiation in the LA-to-aBA pathway by safety signal-dependent induction of Npas4 and subsequent upregulation of its downstream target Drd4, which offsets fear expression to CS−.