Elucidating the heterogeneous organization of locus coeruleus noradrenaline neurons

2018 Fiscal Year Final Research Report

• Project/Area Number: 16H05928
• Research Category: Grant-in-Aid for Young Scientists (A)
• Allocation Type: Single-year Grants
• Research Field: Basic / Social brain science
• Research Institution: Institute of Physical and Chemical Research
• Principal Investigator: Uematsu Akira 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 (90716242)
• Research Collaborator: Watanabe Mayumi
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 恐怖 / ノルアドレナリン / 消去 / 投射部位特異的 / 光遺伝学 / 電気生理

Outline of Final Research Achievements

I found a modular locus coeruleus (LC) organization in rats, endowed with distinct neural projection patterns and coding properties for flexible specification of opposing behavioral learning states. LC projection mapping revealed functionally distinct cell modules with specific efferent connectivity. With optogenetic manipulation, I found that an amygdala-projecting ensemble promoted aversive learning, while an independent medial prefrontal cortex-projecting ensemble extinguished aversive responses to enable flexible behavior. In line with this, activity of prefrontal projecting neuron increases during extinction. As for input, trans-synaptic retrograde tracing study shows these distinct LC populations receive inputs from various areas. Specifically, optogenetic inhibition showed distinct inputs to LC deferentially modulate fear extinction. Finally, I developed the method to collect RNAs of LC subpopulations in order to identify distinct molecular markers.

Free Research Field

神経科学

Academic Significance and Societal Importance of the Research Achievements

均一と考えられていた青斑核ノルアドレナリン神経において多様な機能があることを世界に先駆けて発見した。ノルアドレナリン神経が投射する部位により異なる役割があること、さらに入力を受ける脳部位によって異なる作用をしている可能性があることを明らかとした。これまでノルアドレナリンに作用する薬は脳に一様に作用するものであるため、特定の領域を標的にできればより効果の高い治療法に結び付けれらる可能性がある。