School of Neuroscience, Virginia Polytechnic Institute and State University (Virginia Tech), Blacksburg, VA, USA.
Translational Biology, Medicine and Health Graduate Program, Virginia Tech, Blacksburg, VA, USA.
Eur J Neurosci. 2021 Feb;53(3):814-826. doi: 10.1111/ejn.15065. Epub 2020 Dec 15.
Integrated behavioral responses to emotionally salient stimuli require the concomitant activation of descending neural circuits that integrate physiological, affective, and motor responses to stress. Our previous work interrogated descending circuits in the brainstem and spinal cord that project to motor and sympathetic targets. The hypothalamic paraventricular nucleus (PVN), a key node of this circuitry, integrates multiple motor and sympathetic responses activated by stress. The present study sought to determine whether descending projections from the PVN to targets in muscle and adrenal gland are differentially organized in rats with inborn differences in emotionality and stress responsivity. We utilized retrograde transsynaptic tract-tracing with unique pseudorabies virus (PRV) recombinants that were injected into sympathectomized gastrocnemius muscle and adrenal gland in two rat models featuring inborn differences in emotional behavior. Our tract-tracing results revealed a significant decrease in the number of PVN neurons with poly-synaptic projections to the gastrocnemius in male Wistar Kyoto [WKY] rats (versus Sprague Dawley rats) and selectively bred Low Novelty Responder [bLR] rats (versus selectively bred High Novelty Responder [bHR] rats). These neuroanatomical differences mirrored behavioral observations showing that both WKY and bLR rats display marked inhibition of emotional motor responses in a variety of settings relative to their respective controls. Our findings suggest that, in male rodents, PVN poly-synaptic projections to skeletal muscle may regulate emotional motor and coping responses to stress. More broadly, perturbations in PVN motor circuitry may play a role in mediating psychomotor disturbances observed in depression or anxiety-related disorders.
整合对情绪相关刺激的行为反应需要同时激活下行神经回路,这些神经回路整合对压力的生理、情感和运动反应。我们之前的工作研究了投射到运动和交感神经靶标的脑干和脊髓中的下行回路。下丘脑室旁核(PVN)是该回路的关键节点,整合了由压力激活的多种运动和交感神经反应。本研究旨在确定 PVN 向肌肉和肾上腺靶标投射的下行投射是否在情感性和应激反应性存在先天差异的大鼠中存在差异组织。我们利用逆行顺行追踪技术,使用独特的伪狂犬病病毒(PRV)重组体,将其注射到两种具有先天情感行为差异的大鼠模型的交感神经切断的比目鱼肌和肾上腺中。我们的追踪结果显示,PVN 神经元与多突触投射到比目鱼肌的数量在雄性 Wistar 京都(WKY)大鼠(与 Sprague Dawley 大鼠相比)和选择性繁殖的低新奇反应大鼠(与选择性繁殖的高新奇反应大鼠相比)中显著减少。这些神经解剖学差异反映了行为观察结果,表明 WKY 和 bLR 大鼠在各种环境中都表现出明显抑制情绪运动反应,相对于其各自的对照大鼠。我们的发现表明,在雄性啮齿动物中,PVN 多突触投射到骨骼肌可能调节对压力的情绪运动和应对反应。更广泛地说,PVN 运动回路的扰动可能在介导抑郁或焦虑相关障碍中观察到的精神运动障碍中发挥作用。