Hypothalamic perifornical Urocortin-3 neurons modulate defensive responses to a potential threat stimulus

Horii-Hayashi, Noriko; Nomoto, Kensaku; Endo, Nozomi; Yamanaka, Akihiro; Kikusui, Takefumi; Nishi, Mayumi

doi:10.1016/j.isci.2020.101908

Cited by 8 publications

(30 citation statements)

References 56 publications

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“…Although this protocol uses adult male Ucn3-Cre mice, it can be applied to females and/or younger animals. However, expected outcomes indicated below are observed in adult male Ucn3-Cre mice ( Horii-Hayashi et al., 2021 ). Females and/or younger animals have not been investigated.…”

Section: Materials and Equipmentmentioning

confidence: 81%

“…Both open field and novel object tests can be used for evaluating animal anxiety ( Belzung and Le Pape, 1994 ; Calhoon and Tye, 2015 ). These tests can be sequentially performed on the same day ( Anthony et al., 2014 ; Dietrich et al., 2015 ; Horii-Hayashi et al., 2021 ), which can save time and evaluate behavioral responses to novel environment and novel objects.…”

Section: Step-by-step Methods Detailsmentioning

confidence: 99%

“…Ethologically, burying and risk assessment in rodents are categorized into defensive behavior ( Blanchard et al., 1991 ; De Boer and Koolhaas, 2003 ; Horii-Hayashi et al., 2021 ; Koolhaas et al., 1999 ). Activation of hypothalamic Ucn3 neurons increases both behaviors ( Horii-Hayashi et al., 2021 ). This test directly measures burying action and concurrently enables the evaluation of investigatory behaviors, including risk assessment and sniffing.…”

Section: Step-by-step Methods Detailsmentioning

confidence: 99%

“…A series of these tests are useful in evaluating animal anxiety and their defensive response patterns to potential threats. For complete details on the use and execution of this protocol, please refer to Horii-Hayashi et al. (2021) .…”

mentioning

confidence: 99%

“…For complete details on the use and execution of this protocol, please refer to Horii-Hayashi et al. (2021) .…”

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confidence: 99%

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Protocol for behavioral tests using chemogenetically manipulated mice

Horii-Hayashi

Nishi

2021

STAR Protocols

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Summary Behavioral analyses using mice chemogenetically manipulated by designer receptors exclusively activated by designer drugs (DREADDs) are powerful tools to elucidate neural functions. Here, we describe the detailed protocols for stereotaxic surgery, adeno-associated virus (AAV)-mediated introduction to Gq-DREADDs in mice, and for behavioral testing and analyses related to anxiety, risk assessment, and burying behaviors. A series of these tests are useful in evaluating animal anxiety and their defensive response patterns to potential threats. For complete details on the use and execution of this protocol, please refer to Horii-Hayashi et al. (2021) .

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Section: Materials and Equipmentmentioning

confidence: 81%

Section: Step-by-step Methods Detailsmentioning

confidence: 99%

Section: Step-by-step Methods Detailsmentioning

confidence: 99%

mentioning

confidence: 99%

“…For complete details on the use and execution of this protocol, please refer to Horii-Hayashi et al. (2021) .…”

mentioning

confidence: 99%

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Protocol for behavioral tests using chemogenetically manipulated mice

Horii-Hayashi

Nishi

2021

STAR Protocols

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A Checking Model of Obsessive-Compulsive Disorder Based on the Hypothalamic Defensive System Against a Potential Threat

Horii-Hayashi

Masuda

Kato

et al. 2022

Preprint

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BACKGROUND: Obsessive-compulsive disorder (OCD) is a psychiatric disorder characterized by obsessive thoughts and compulsive behavior. While some theories imply that OCD patients have cognitive biases and dysfunctional motivation regarding a potential threat, these views are not adequately supported by neurological evidence. Hypothalamic perifornical (PeF) urocortin-3 (UCN3) neurons are involved in defensive responses to a potential threat, and the activation of these neurons in mice induces repetitive and excessive checking and burying of novel objects. In this study, we evaluated the hypothesis that mice in which PeF UCN3 neurons are activated can serve as an OCD model. METHODS: PeF UCN3 neurons were chemogenetically activated with clozapine-N oxide (CNO) in Ucn3-Cre mice. Marble-burying activity, repetitive/stereotypic behaviors in the homecage, and excessive responses to a novel object were measured as OCD-like behaviors. The effects of clinically used drugs for treating OCD on these behaviors were evaluated. The effect of CNO on neural activity in the cortico-striato-thalamo-cortical loop (which is regarded as an OCD circuit) was assessed with c-Fos immunolabeling. RESULTS: CNO increased marble-burying activity, evoked homecage-specific repetitive/stereotypic behaviors that probably aimed to seal entrances, and induced repetitive and excessive checking and burying of novel objects. These behaviors were suppressed by selective serotonin-reuptake inhibitors but not by diazepam. CNO increased neural activity in the cortico-striato-thalamo-cortical loop. CONCLUSIONS: These results indicated that mice whose PeF UCN3 neurons are activated can serve as a model of OCD, particularly as a checking model. This supports theories concerning the role of potential threats in the pathophysiology of OCD.

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

García,

Tran,

Peterson

et al. 2023

Preprint

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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.

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Hypothalamic perifornical Urocortin-3 neurons modulate defensive responses to a potential threat stimulus

Cited by 8 publications

References 56 publications

Protocol for behavioral tests using chemogenetically manipulated mice

Protocol for behavioral tests using chemogenetically manipulated mice

A Checking Model of Obsessive-Compulsive Disorder Based on the Hypothalamic Defensive System Against a Potential Threat

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

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