The amygdala modulates prepulse inhibition of the auditory startle reflex through excitatory inputs to the caudal pontine reticular nucleus.
The amygdala modulates prepulse inhibition of the auditory startle reflex through excitatory inputs to the caudal pontine reticular nucleus.
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DOI：
10.1186/s12915-021-01050-z
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发表时间：
2021-06-03
期刊：
影响因子：
5.4
通讯作者：
Fénelon K
中科院分区：
文献类型：
--
作者：
Cano JC;Huang W;Fénelon K
感觉运动门控是一种基本的前注意过程，被定义为感觉事件对运动反应的抑制。感觉运动门控，通常使用听觉惊吓反射任务的前脉冲抑制（PPI）来测量，在患有各种神经和精神疾病的患者中受损。PPI缺陷是精神分裂症的标志，通常与注意力和其他认知障碍有关。尽管PPI缺陷的逆转在动物模型中被广泛用于抗精神病药物筛选的临床前研究，但PPI的神经递质系统和突触机制仍然没有得到解决，即使在生理条件下。最近的证据排除了长期存在的假设，即PPI介导的中脑胆碱能输入到脑桥尾侧网状核（PnC）。相反，在PnC水平，谷氨酸能、甘氨酸能和GABA能抑制机制对PPI至关重要。由于杏仁核功能障碍改变PPI和常见的病理显示感觉运动门控缺陷，本研究的目的是测试，直接投射到PnC起源于杏仁核有助于PPI。使用野生型和转基因小鼠表达eGFP的控制下的甘氨酸转运蛋白2型启动子（GlyT 2-eGFP小鼠），我们首先采用跟踪，形态重建，和免疫组化分析，以证明中央核杏仁核（CeA）发送animatergic输入lateroventrally PnC神经元，包括GlyT 2+细胞。然后，我们显示了CeA-PnC兴奋性突触在体内对PPI的贡献，通过证明这种连接的光遗传学抑制降低PPI，并且光遗传学激活诱导部分PPI。最后，在GlyT 2-Cre小鼠中，GlyT 2 + PnC神经元在体外的全细胞记录与CeA纤维的光遗传学刺激配对，以及GlyT 2 + PnC神经元在体内的光抑制，使我们能够将GlyT 2+神经元牵连到PPI通路中。我们的研究结果揭示了脑干惊吓回路中的前馈抑制机制，通过该机制，杏仁核神经元和GlyT 2 + PnC神经元有助于PPI。我们正在为PPI的临床相关理论构建提供新的见解，PPI在各种神经精神和神经系统疾病中被破坏。在线版本包含补充材料，可通过10.1186/s12915-021-01050-z获得。
Sensorimotor gating is a fundamental pre-attentive process that is defined as the inhibition of a motor response by a sensory event. Sensorimotor gating, commonly measured using the prepulse inhibition (PPI) of the auditory startle reflex task, is impaired in patients suffering from various neurological and psychiatric disorders. PPI deficits are a hallmark of schizophrenia, and they are often associated with attention and other cognitive impairments. Although the reversal of PPI deficits in animal models is widely used in pre-clinical research for antipsychotic drug screening, the neurotransmitter systems and synaptic mechanisms underlying PPI are still not resolved, even under physiological conditions. Recent evidence ruled out the longstanding hypothesis that PPI is mediated by midbrain cholinergic inputs to the caudal pontine reticular nucleus (PnC). Instead, glutamatergic, glycinergic, and GABAergic inhibitory mechanisms are now suggested to be crucial for PPI, at the PnC level. Since amygdalar dysfunctions alter PPI and are common to pathologies displaying sensorimotor gating deficits, the present study was designed to test that direct projections to the PnC originating from the amygdala contribute to PPI. Using wild type and transgenic mice expressing eGFP under the control of the glycine transporter type 2 promoter (GlyT2-eGFP mice), we first employed tract-tracing, morphological reconstructions, and immunohistochemical analyses to demonstrate that the central nucleus of the amygdala (CeA) sends glutamatergic inputs lateroventrally to PnC neurons, including GlyT2+ cells. Then, we showed the contribution of the CeA-PnC excitatory synapses to PPI in vivo by demonstrating that optogenetic inhibition of this connection decreases PPI, and optogenetic activation induces partial PPI. Finally, in GlyT2-Cre mice, whole-cell recordings of GlyT2+ PnC neurons in vitro paired with optogenetic stimulation of CeA fibers, as well as photo-inhibition of GlyT2+ PnC neurons in vivo, allowed us to implicate GlyT2+ neurons in the PPI pathway. Our results uncover a feedforward inhibitory mechanism within the brainstem startle circuit by which amygdalar glutamatergic inputs and GlyT2+ PnC neurons contribute to PPI. We are providing new insights to the clinically relevant theoretical construct of PPI, which is disrupted in various neuropsychiatric and neurological diseases. The online version contains supplementary material available at 10.1186/s12915-021-01050-z.
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影响因子：
4.2
作者：
Fung, Simon J.;Xi, MingChu;Zhang, JianHua;Torterolo, Pablo;Sampogna, Sharon;Morales, Francisco R.;Chase, Michael H.
通讯作者：
Chase, Michael H.
影响因子：
25
作者：
Giber K;Diana MA;Plattner V;Dugué GP;Bokor H;Rousseau CV;Maglóczky Z;Havas L;Hangya B;Wildner H;Zeilhofer HU;Dieudonné S;Acsády L
通讯作者：
Acsády L
影响因子：
3.3
作者：
Bosch, D.;Schmid, S.
通讯作者：
Schmid, S.
影响因子：
3.3
作者：
Fendt, M;Schwienbacher, I;Koch, M
通讯作者：
Koch, M
影响因子：
3.7
作者：
GRAHAM, FK
通讯作者：
GRAHAM, FK