A neural circuit from the dorsal CA3 to the dorsomedial hypothalamus mediates balance between risk exploration and defense

Zhong, Cheng; Wang, Lulu; Cao, Yi; Sun, Chongyang; Huang, Jianyu; Wang, Xufang; Pan, Suwan; He, Shuyu; Huang, Kang; Lu, Zhonghua; Xu, Fuqiang; Lü, Yi; Wang, Liping

doi:10.1016/j.celrep.2022.111570

Cited by 5 publications

(3 citation statements)

References 72 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Acute restraint stress also activates PeFAH Ucn-3+ 41 and AHN 44 neuronal populations, supporting the involvement of the PeFAH>LS>AHN circuit in response to anxiogenic stimuli. This circuit appears to be necessary to maintain the balance between defensive/avoidance behavior and exploratory drive, in line with the proven role of several other LS neuronal subpopulations and their circuitry in contextdependent risk assessment 16,17,37,38,42,45 .…”

Section: Discussionsupporting

confidence: 56%

A developmentally defined population of neurons in the lateral septum controls responses to aversive stimuli

García,

Tran,

Peterson

et al. 2023

Preprint

View full text Add to dashboard Cite

When interacting with their environment, animals must balance exploratory and defensive behavior to evaluate and respond to potential threats. The lateral septum (LS) is a structure in the ventral forebrain that calibrates the magnitude of behavioral responses to stress-related external stimuli, including the regulation of threat avoidance. The complex connectivity between the LS and other parts of the brain, together with its largely unexplored neuronal diversity, makes it difficult to understand how defined LS circuits control specific behaviors. Here, we describe a mouse model in which a population of neurons with a common developmental origin (Nkx2.1-lineage neurons) are absent from the LS. Using a combination of circuit tracing and behavioral analyses, we found that these neurons receive inputs from the perifornical area of the anterior hypothalamus (PeFAH) and are specifically activated in stressful contexts. Mice lacking Nkx2.1-lineage LS neurons display increased exploratory behavior even under stressful conditions. Our study extends the current knowledge about how defined neuronal populations within the LS can evaluate contextual information to select appropriate behavioral responses. This is a necessary step towards understanding the crucial role that the LS plays in neuropsychiatric conditions where defensive behavior is dysregulated, such as anxiety and aggression disorders.

show abstract

Section: Discussionsupporting

confidence: 56%

A developmentally defined population of neurons in the lateral septum controls responses to aversive stimuli

García,

Tran,

Peterson

et al. 2023

Preprint

View full text Add to dashboard Cite

show abstract

“…As such, we hypothesized that the hyperactivity could be related to an anxiolytic or exploratory behavioural outcome. LS inhibition can suppress anxiety-like behaviour (Pesold and Treit, 1996; Wang et al, 2023) and the switch to exploratory behaviour in the face of risk (Zhong et al, 2022). Therefore, we determined if MCH infusion into the LS may increase time spent investigating a food reward placed in the center of an open field.…”

Section: Discussionmentioning

confidence: 99%

Melanin-concentrating hormone promotes feeding through the lateral septum

Payant,

Shankhatheertha,

Chee

2024

Preprint

View full text Add to dashboard Cite

Feeding is necessary for survival but can be hindered by anxiety or fear, thus neural systems that can regulate anxiety states are key to elucidating the expression of food-related behaviors. Melanin-concentrating hormone (MCH) is a neuropeptide produced in the lateral hypothalamus that promotes feeding and anxiogenesis. The orexigenic actions of MCH that prolong ongoing homeostatic or hedonic feeding are context-dependent and more prominent in male than female rodents, but it is not clear where MCH acts to initiate feeding. The lateral septum (LS) promotes feeding and suppresses anxiogenesis when inhibited, and it comprises the densest projections from MCH neurons. However, it is not known whether the LS is a major contributor to MCH-mediated feeding. As MCH inhibits LS cells by MCH receptor (MCHR1) activation, MCH may promote feeding via the LS. We bilaterally infused MCH into the LS and found that MCH elicited a rapid and long-lasting increase in the consumption of standard chow and a palatable, high sugar diet in male and female mice; these MCH effects were blocked by the co-administration of a MCHR1 antagonist TC- MCH 7c. Interestingly, the orexigenic effect of MCH was abolished in a novel, anxiogenic environment even when presented with a food reward, but MCH did not induce anxiety-like behaviors. These findings indicated the LS as a novel region underlying orexigenic MCH actions, which stimulated and enhanced feeding in both sexes in a context -dependent manner that was most prominent in the homecage.

show abstract

“…相比嗅觉系统，视觉系统诱发的先天性防御反应更多是逃跑。作为视网膜接收器的上丘与视觉诱导的先天性恐惧关系最为密切［ 37 - 38 ］。目前已发现多条上丘相关神经环路参与looming刺激诱发的先天性防御反应。例如，Lin等［ 39 ］发现上丘-ZIr-丘脑连接核的三突触环路介导looming刺激诱导的逃跑反应。上丘内的小清蛋白阳性神经元向二叠体旁核投射的环路可以调节逃跑行为［ 40 ］。但又一项研究表明，上丘-二叠体旁核环路并不能介导逃跑行为，而是由二叠体旁核向上丘的反向投射发挥作用。有学者还发现危险信号在内侧上丘进行整合处理，传递到dPAG通过突触阈值启动逃跑行为［ 41 ］。上丘的Glu能神经元向腹侧被盖区的GABA能神经元投射，腹侧被盖区再将信息传递给中央杏仁核的三级投射环路介导了looming刺激诱导的逃跑行为［ 42 ］。vLGN向内侧上丘的GABA能投射环路同样可以调节逃跑反应［ 43 - 44 ］。此外，表达CCK的下丘脑PMd神经元对于逃跑是必要的，PMd CCK -dlPAG环路的激活足以诱导先天性防御反应［ 45 - 46 ］。下丘脑VMHdm/c的类固醇生成因子神经元的不同投射分别调节不同的防御行为，如激活VMHdm/c-下丘脑前核环路促进逃避防御行为，而激活VMHdm/c-dPAG环路则促进冻结行为［ 5 ， 47 - 48 ］。一项研究发现背侧海马-背外侧隔膜-下丘脑神经环路的活化减少了逃跑和抵抗等防御行为［ 49 ］。最近一项研究表明，下丘脑的外侧臂旁核中表达CCK的阳性神经元向室旁核的投射环路参与逃跑行为［ 50 ］。…”

Section: 视觉信号诱导的先天性恐惧防御行为神经环路unclassified

Advances in neural circuits of innate fear defense behavior

Zhao¹,

Song²,

Wu³

et al. 2023

J Zhejiang Univ (Med Sci)

View full text Add to dashboard Cite

恐惧是危险刺激诱发的一种负性情绪，过度恐惧会诱发精神障碍类疾病。对先天性恐惧的神经环路进行解析有助于理解相关精神疾病的病理生理机制。目前，关于先天性恐惧的研究主要基于嗅觉、视觉、听觉等不同感官信号刺激的应答反应机制，而不同类型恐惧信号输入由不同的神经环路调控。主嗅系统和副嗅系统神经回路接收并处理嗅觉刺激信息从而介导冻结等防御反应，视觉刺激信号诱发的逃跑行为主要通过上丘和下丘脑投射回路调控，而听觉刺激信息引发的逃跑等反应主要由听觉皮层投射回路介导。本文综述了视觉、听觉、嗅觉等系统危险刺激投射的神经回路变化，以期为相关精神疾病的诊治提供靶点信息。

show abstract

A neural circuit from the dorsal CA3 to the dorsomedial hypothalamus mediates balance between risk exploration and defense

Cited by 5 publications

References 72 publications

A developmentally defined population of neurons in the lateral septum controls responses to aversive stimuli

A developmentally defined population of neurons in the lateral septum controls responses to aversive stimuli

Melanin-concentrating hormone promotes feeding through the lateral septum

Advances in neural circuits of innate fear defense behavior

Contact Info

Product

Resources

About