Neural circuit and molecular mechanisms for noradrenergic modulation of fear learning and memory

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K21620
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Basic / Social brain science; Neurochemistry/Neuropharmacology
• Research Institution: Institute of Physical and Chemical Research
• Principal Investigator: Tan Bao Zhen 国立研究開発法人理化学研究所, 脳神経科学研究センター, 研究員 (80756784)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: Fear learning and memory / Noradrenaline / Optogenetics / Consolidation / Amygdala

Outline of Final Research Achievements

Noradrenaline in the lateral amygdala (LA) modulates Hebbian plasticity mechanisms via beta-adrenergic (b-AR) receptors to facilitate formation
of auditory fear memories. We have showed that LC activity and activation of LC terminals in LA specifically during aversive experience is required for and facilitates fear memory formation. We have also found that NA release from the LC terminals in LA regulates fear conditioning through actions on CRTC1. Fear learning produced a significant increase in CRTC1 nuclear accumulation in LA neurons and expression of dominant negative form of CRTC1 reduced long term fear memory formation, implicating CRTC1 as a potential mechanism for transducing noradrenergic signaling in LA neurons into long term fear memories.

Free Research Field

Neuroscience

Academic Significance and Societal Importance of the Research Achievements

We have examined both the circuit and molecular mechanism behind aversive memory formation and potentially identified a therapeutic strategy for excessive fear memories and anxiety disorders.