Stress Accelerates Defensive Responses to Looming in Mice and Involves a Locus Coeruleus-Superior Colliculus Projection
Stress Accelerates Defensive Responses to Looming in Mice and Involves a Locus Coeruleus-Superior Colliculus Projection
复制标题
压力会加速小鼠对迫在眉睫的防御反应，并涉及蓝斑-上丘投射
DOI：
10.1016/j.cub.2018.02.005
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发表时间：
2018-03-19
期刊：
影响因子：
9.2
通讯作者：
Wang, Liping
中科院分区：
文献类型：
--
作者：
Li, Lei;Feng, Xiaolong;Wang, Liping
对威胁性刺激的防御反应对物种的生存至关重要。虽然这些反应的表达被认为是本能和无条件的，但其程度可能受到环境和内部因素的影响。这种调制背后的神经回路在很大程度上仍然未知。在小鼠中，隐现诱发的防御反应是由上级丘（SC），皮层下感觉运动整合中心介导的。我们发现，反复的压力会导致小鼠出现类似焦虑的状态，并加速对迫在眉睫的防御反应。应激还诱导蓝斑（LC）酪氨酸羟化酶（TH）（+）神经元c-fos激活和SC肾上腺素能受体表达的改变，提示Th：：LC-SC投射可能参与加速防御反应。事实上，顺行和逆行神经追踪证实了解剖Th：：LC SC的投射和SC投射TH+神经元在LC被反复应激激活。光遗传刺激LC TH+神经元或Th：：LC-SC纤维也会引起焦虑样行为，并加速对迫在眉睫的防御反应。同时，LC TH+神经元的化学发生抑制和SC中肾上腺素能受体拮抗剂的输注废除了反复应激后增强的迫在眉睫的防御反应，证实了这一途径的必要性。这些发现表明Th：：LC-SC通路在由生理状态变化引起的防御行为的复杂调节中起着关键作用。
Defensive responses to threatening stimuli are crucial to the survival of species. While expression of these responses is considered to be instinctive and unconditional, their magnitude may be affected by environmental and internal factors. The neural circuits underlying this modulation are still largely unknown. In mice, looming-evoked defensive responses are mediated by the superior colliculus (SC), a subcortical sensorimotor integration center. We found that repeated stress caused an anxiety-like state in mice and accelerated defensive responses to looming. Stress also induced c-fos activation in locus coeruleus (LC) tyrosine hydroxylase (TH)(+) neurons and modified adrenergic receptor expression in SC, suggesting a possible Th::LC-SC projection that may be involved in the accelerated defensive responses. Indeed, both anterograde and retrograde neural tracing confirmed the anatomical Th:: LC-SC projection and that the SC-projecting TH+ neurons in LC were activated by repeated stress. Optogenetic stimulation of either LC TH+ neurons or the Th:: LC-SC fibers also caused anxiety-like behaviors and accelerated defensive responses to looming. Meanwhile, chemogenetic inhibition of LC TH+ neurons and the infusion of an adrenergic receptor antagonist in SC abolished the enhanced looming defensive responses after repeated stress, confirming the necessity of this pathway. These findings suggest that the Th:: LC-SC pathway plays a key role in the sophisticated adjustments of defensive behaviors induced by changes in physiological states.