Glutamatergic lateral hypothalamus promotes defensive behaviors

Chen, Li; Cai, Ping; Wang, Renfei; Lu, Yiping; Chen, Huiyun; Guo, Yu-Rou; Huang, Shengnan; Hu, Lihuan; Chen, Jian; Zheng, Ze-Hong; He, Peng; Zhang, Bingfeng; Liu, Jiyuan; Wang, Wenxiang; Li, Huangyuan; Yu, Chang‐Xi

doi:10.1016/j.neuropharm.2020.108239

Cited by 17 publications

(19 citation statements)

References 39 publications

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“…In addition to receiving direct inputs from cortical and subcortical regions that transmit information about motor commands or outcomes, we found that the CART + EW also received projections from multifunctional regions involved in responses to pain or threat, including the somatosensory cortex (Iwamoto et al, 2021), lateral hypothalamus (Chen et al, 2020;Siemian et al, 2021), zona incerta (Chou et al, 2018;Zhou et al, 2018), and periaqueductal gray (George et al, 2019;Lefler et al, 2020) (Figure 6B).…”

Section: The Cart + Ew Is Functionally Peptidergicmentioning

confidence: 75%

Peptidergic modulation of fear responses by the Edinger-Westphal nucleus

Priest

Freda

Badong

et al. 2021

Preprint

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Many neuronal populations that release fast-acting excitatory and inhibitory neurotransmitters in the brain also contain slower acting neuropeptides. These facultative peptidergic cell types are common, but it remains uncertain whether obligate peptidergic neurons exist. Our fluorescence in situ hybridization, genetically-targeted electron microscopy, and electrophysiological characterization data strongly suggest that neurons of the non-cholinergic, centrally-projecting Edinger-Westphal nucleus in mice are fundamentally obligately peptidergic. We further show, using fiber photometry, monosynaptic retrograde tracing, anterograde projection mapping, and a battery of behavioral assays, that this peptidergic population both promotes fear responses and analgesia and activates in response to loss of motor control and pain. Together, these findings elucidate an integrative, ethologically relevant function for the Edinger-Westphal nucleus and functionally align the nucleus with the periaqueductal gray, where it resides. This work advances our understanding of the peptidergic modulation of fear and provides a framework for future investigations of putative obligate peptidergic systems.

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Section: The Cart + Ew Is Functionally Peptidergicmentioning

confidence: 75%

Peptidergic modulation of fear responses by the Edinger-Westphal nucleus

Priest

Freda

Badong

et al. 2021

Preprint

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“…When encountering a predator, animals will hide in nearby nest or shelter if one is available. To test whether activation of VTA glutamatergic neurons can induce hiding, we adapted another apparatus to test mice’s hiding behavior according to previous studies ( Wang et al, 2015 ; Chen et al, 2020 ). The hiding apparatus consisted of an open area at the center, a hiding box and a feeding area located in a diagonal corner ( Figure 3C ).…”

Section: Resultsmentioning

confidence: 99%

“…We adapted a hiding apparatus developed in previous studies to examine animals’ hiding behavior ( Wang et al, 2015 ; Chen et al, 2020 ). The hiding apparatus was a plexiglass cuboid with an open area, hiding box, and feeding area.…”

Section: Methodsmentioning

confidence: 99%

Control of Behavioral Arousal and Defense by a Glutamatergic Midbrain-Amygdala Pathway in Mice

Chen

Yao

et al. 2022

Front. Neurosci.

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In response to external threatening signals, animals evolve a series of defensive behaviors that depend on heightened arousal. It is believed that arousal and defensive behaviors are coordinately regulated by specific neurocircuits in the central nervous system. The ventral tegmental area (VTA) is a key structure located in the ventral midbrain of mice. The activity of VTA glutamatergic neurons has recently been shown to be closely related to sleep–wake behavior. However, the specific role of VTA glutamatergic neurons in sleep–wake regulation, associated physiological functions, and underlying neural circuits remain unclear. In the current study, using an optogenetic approach and synchronous polysomnographic recording, we demonstrated that selective activation of VTA glutamatergic neurons induced immediate transition from sleep to wakefulness and obviously increased the amount of wakefulness in mice. Furthermore, optogenetic activation of VTA glutamatergic neurons induced multiple defensive behaviors, including burrowing, fleeing, avoidance and hiding. Finally, viral-mediated anterograde activation revealed that projections from the VTA to the central nucleus of the amygdala (CeA) mediated the wake- and defense-promoting effects of VTA glutamatergic neurons. Collectively, our results illustrate that the glutamatergic VTA is a key neural substrate regulating wakefulness and defensive behaviors that controls these behaviors through its projection into the CeA. We further discuss the possibility that the glutamatergic VTA-CeA pathway may be involved in psychiatric diseases featuring with excessive defense.

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“…Previous research reported that vPAG-projecting LH glutamatergic neurons encode prediction in danger and evasion [11]. Recent studies elucidated different functions of the LH glutamatergic neurons including promotion of defensive behaviors [40] and inhibition of food intake [32,41]. These findings seem somewhat contradictory to the finding here that activating the LH CaMKIIα + neurons, partly glutamatergic neurons, induces feeding, approaching, and hunting behavior; this may be due to the existing highly heterogeneous LH glutamatergic neurons: our results showed that 96.71% vGluT2 + neurons are CaMKIIα + but only 63.87% CaMKIIα + neurons are vGluT2 + ; remaining 36.13% CaMKIIα + neurons may be an important part.…”

Section: Discussionmentioning

confidence: 99%

Lateral Hypothalamus Calcium/Calmodulin-Dependent Protein Kinase II α Neurons Encode Novelty-Seeking Signals to Promote Predatory Eating

Tan

Shi

et al. 2022

Research

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Predatory hunting is an innate appetite-driven and evolutionarily conserved behavior essential for animal survival, integrating sequential behaviors including searching, pursuit, attack, retrieval, and ultimately consumption. Nevertheless, neural circuits underlying hunting behavior with different features remain largely unexplored. Here, we deciphered a novel function of lateral hypothalamus (LH) calcium/calmodulin-dependent protein kinase II α (CaMKIIα+) neurons in hunting behavior and uncovered upstream/downstream circuit basis. LH CaMKIIα+ neurons bidirectionally modulate novelty-seeking behavior, predatory attack, and eating in hunting behavior. LH CaMKIIα+ neurons integrate hunting-related novelty-seeking information from the medial preoptic area (MPOA) and project to the ventral periaqueductal gray (vPAG) to promote predatory eating. Our results demonstrate that LH CaMKIIα+ neurons are the key hub that integrate MPOA-conveyed novelty-seeking signals and encode predatory eating in hunting behavior, which enriched the neuronal substrate of hunting behavior.

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Glutamatergic lateral hypothalamus promotes defensive behaviors

Cited by 17 publications

References 39 publications

Peptidergic modulation of fear responses by the Edinger-Westphal nucleus

Peptidergic modulation of fear responses by the Edinger-Westphal nucleus

Control of Behavioral Arousal and Defense by a Glutamatergic Midbrain-Amygdala Pathway in Mice

Lateral Hypothalamus Calcium/Calmodulin-Dependent Protein Kinase II α Neurons Encode Novelty-Seeking Signals to Promote Predatory Eating

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