Mechanisms of noradrenergic modulation of synaptic transmission and neuronal excitability in ventral horn neurons of the rat spinal cord

2019 Fiscal Year Final Research Report

• Project/Area Number: 18K16648
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 56020:Orthopedics-related
• Research Institution: Niigata University
• Principal Investigator: Shoji Hirokazu 新潟大学, 医歯学総合研究科, 客員研究員 (60783347)
• Project Period (FY): 2018-04-01 – 2020-03-31
• Keywords: 脊髄前角細胞 / モノアミン / ノルアドレナリン / 脊髄損傷 / 電気生理 / パッチクランプ

Outline of Final Research Achievements

Noradrenaline (NA) modulates the spinal motor networks for locomotion and facilitates neuroplasticity. However, neither the effects nor the mechanisms of NA on synaptic transmission and neuronal excitability in spinal ventral horn (VH) neurons are well characterized. We used a whole-cell patch-clamp approach to spinal cord slice of late neonatal rats. NA increased the frequency and amplitude of excitatory postsynaptic currents via the activation of somatic α1- and β-adrenoceptors of presynaptic neurons. Although NA also activated inhibitory synaptic transmission, we confirmed that NA enhances the excitability of VH neurons by cause of the resting membrane potentials depolarized by NA and the increased firing frequency of action potentials. Our findings provide new insights that establish NA-based pharmacological therapy as an effective method to activate neuronal networks of the spinal VH in the recovery phase of spinal cord injuries.

Free Research Field

整形外科

Academic Significance and Societal Importance of the Research Achievements

脊髄前角細胞に対しノルアドレナリンは、α1およびβ受容体を介し神経回路網を活性化することで、興奮性に作用することが明らかとなった。これら結果は脊髄損傷回復期に重要な運動神経の神経回路網の活性化において、モノアミンの１つであるノルアドレナリンを介した方策において重要な知見である。過去に筋攣縮との関連を示したα受容体作用の報告はあるもののβ受容体作用に関する報告はなく、β受容体を介した適度な神経回路網活性化の可能性を示した。