Macquarie Medical School, Faculty of Medicine, Health & Human Sciences, Macquarie University, Sydney, New South Wales, Australia.
Department of Physiology, University of Melbourne, Victoria, Australia.
J Physiol. 2022 Dec;600(24):5311-5332. doi: 10.1113/JP283789. Epub 2022 Dec 2.
The ability to discriminate competing external stimuli and initiate contextually appropriate behaviours is a key brain function. Neurons in the deep superior colliculus (dSC) integrate multisensory inputs and activate descending projections to premotor pathways responsible for orienting, attention and defence, behaviours which involve adjustments to respiratory and cardiovascular parameters. However, the neural pathways that subserve the physiological components of orienting are poorly understood. We report that orienting responses to optogenetic dSC stimulation are accompanied by short-latency autonomic, respiratory and electroencephalographic effects in awake rats, closely mimicking those evoked by naturalistic alerting stimuli. Physiological responses were not accompanied by detectable aversion or fear, and persisted under urethane anaesthesia, indicating independence from emotional stress. Anterograde and trans-synaptic viral tracing identified a monosynaptic pathway that links the dSC to spinally projecting neurons in the medullary gigantocellular reticular nucleus (GiA), a key hub for the coordination of orienting and locomotor behaviours. In urethane-anaesthetized animals, sympathoexcitatory and cardiovascular, but not respiratory, responses to dSC stimulation were replicated by optogenetic stimulation of the dSC-GiA terminals, suggesting a likely role for this pathway in mediating the autonomic components of dSC-mediated responses. Similarly, extracellular recordings from putative GiA sympathetic premotor neurons confirmed short-latency excitatory inputs from the dSC. This pathway represents a likely substrate for autonomic components of orienting responses that are mediated by dSC neurons and suggests a mechanism through which physiological and motor components of orienting behaviours may be integrated without the involvement of higher centres that mediate affective components of defensive responses. KEY POINTS: Neurons in the deep superior colliculus (dSC) integrate multimodal sensory signals to elicit context-dependent innate behaviours that are accompanied by stereotypical cardiovascular and respiratory activities. The pathways responsible for mediating the physiological components of colliculus-mediated orienting behaviours are unknown. We show that optogenetic dSC stimulation evokes transient orienting, respiratory and autonomic effects in awake rats which persist under urethane anaesthesia. Anterograde tracing from the dSC identified projections to spinally projecting neurons in the medullary gigantocellular reticular nucleus (GiA). Stimulation of this pathway recapitulated autonomic effects evoked by stimulation of dSC neurons. Electrophysiological recordings from putative GiA sympathetic premotor neurons confirmed short latency excitatory input from dSC neurons. This disynaptic dSC-GiA-spinal sympathoexcitatory pathway may underlie autonomic adjustments to salient environmental cues independent of input from higher centres.
辨别竞争的外部刺激并启动上下文适当的行为的能力是大脑的一项关键功能。深部上丘(dSC)中的神经元整合多感觉输入,并激活负责定向、注意力和防御的运动前通路的下行投射,这些行为涉及呼吸和心血管参数的调整。然而,调节定向生理成分的神经通路知之甚少。我们报告说,在清醒大鼠中,光遗传学刺激 dSC 会伴随着潜伏期短的自主、呼吸和脑电图效应,这些效应与自然警觉刺激引起的效应非常相似。生理反应没有伴随着可察觉的厌恶或恐惧,并且在氨基甲酸乙酯麻醉下持续存在,表明它独立于情绪压力。顺行和跨突触病毒追踪确定了一条单突触通路,该通路将 dSC 与延髓巨细胞网状核(GiA)中投射到脊髓的神经元连接起来,GiA 是协调定向和运动行为的关键枢纽。在氨基甲酸乙酯麻醉的动物中,光遗传学刺激 dSC-GiA 末端可复制 dSC 刺激引起的交感神经兴奋和心血管反应,但不能复制呼吸反应,这表明该通路可能在介导 dSC 介导的反应的自主成分中起作用。同样,来自推定的 GiA 交感运动前神经元的细胞外记录证实了来自 dSC 的潜伏期兴奋性输入。该通路代表了 dSC 神经元介导的定向反应自主成分的可能底物,并提出了一种机制,通过该机制,定向行为的生理和运动成分可以整合,而无需涉及介导防御反应情感成分的更高中心。关键点:深部上丘(dSC)中的神经元整合多模式感觉信号,引发与刻板心血管和呼吸活动相关的情境依赖性先天行为。介导上丘介导的定向行为生理成分的途径尚不清楚。我们表明,光遗传学刺激 dSC 可在清醒大鼠中诱发出短暂的定向、呼吸和自主效应,这些效应在氨基甲酸乙酯麻醉下持续存在。来自 dSC 的顺行追踪确定了投射到延髓巨细胞网状核(GiA)中投射到脊髓的神经元的投射。刺激该通路再现了刺激 dSC 神经元引起的自主效应。来自推定的 GiA 交感运动前神经元的电生理记录证实了来自 dSC 神经元的潜伏期兴奋性输入。这个不连续的 dSC-GiA-脊髓交感神经兴奋通路可能是自主调节对显著环境线索的基础,而与来自更高中心的输入无关。