Protocol for behavioral tests using chemogenetically manipulated mice

Horii-Hayashi, Noriko; Nishi, Mayumi

doi:10.1016/j.xpro.2021.100418

Cited by 3 publications

(12 citation statements)

References 21 publications

(25 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Stereotaxic surgery was performed as described previously (27, 43). Adeno-associated virus (AAV) vectors [AAV(DJ): -hSyn-DIO-hM3D(Gq)-mCherry, 1 × 10 13 copies/mL; AAV (DJ): -hSyn-DIO-mCherry, 1 × 10 13 copies/mL) (Addgene, Watertown, MA) were injected into the PeF (250 nL/side, stereotaxic coordinate: Anterior-Posterior = −0.82 mm, Mid-Lateral = ± 0.47 mm, Dorsal-Ventral = 4.5 mm from the dura matter) at a flow rate of 100 nL/min.…”

Section: Methodsmentioning

confidence: 99%

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

Self Cite

View full text Add to dashboard Cite

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.

show abstract

Section: Methodsmentioning

confidence: 99%

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

Self Cite

View full text Add to dashboard Cite

show abstract

“…Secured habitats allow animals to engage in activities essential for their survival and the preservation of species, such as feeding, mating, and rearing offspring. Animals have developed a range of defensive behaviors to protect themselves from threats, including fight/aggression, flight/escape, freezing/immobility, and risk assessment/exploration with vigilance (Blanchard and Blanchard, 2008;Blanchard et al, 2010;Insel et al, 2010;Nicholson and Sommer, 2018;Horii-Hayashi et al, 2021;Smith et al, 2022). Aggression toward intruders, often studied using the resident-intruder paradigm, is one of the defensive behaviors associated with home/territoriality (Koolhaas et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

“…Accumulating evidence supports the diverse physiological and behavioral functions of hypothalamic perifornical (PeF) neurons that express urocortin-3 (UCN3). These functions encompass energy homeostasis, defensive responses to potential threats, and infant-directed attack (Chen et al, 2010(Chen et al, , 2012Kuperman et al, 2010;Autry et al, 2019;Horii-Hayashi et al, 2021). These diverse functions are likely mediated by distinct neuronal populations in specific anatomical locations and projection targets, including the VMH and lateral septum (LS) (Lewis et al, 2001;Li et al, 2002;Kuperman et al, 2010;Autry et al, 2019;Horii-Hayashi et al, 2021).…”

Section: Introductionmentioning

confidence: 99%

“…These functions encompass energy homeostasis, defensive responses to potential threats, and infant-directed attack (Chen et al, 2010(Chen et al, , 2012Kuperman et al, 2010;Autry et al, 2019;Horii-Hayashi et al, 2021). These diverse functions are likely mediated by distinct neuronal populations in specific anatomical locations and projection targets, including the VMH and lateral septum (LS) (Lewis et al, 2001;Li et al, 2002;Kuperman et al, 2010;Autry et al, 2019;Horii-Hayashi et al, 2021). In our recent study, we focused on PeF UCN3 neurons located along the paraventricular nucleus (PVN) in mice (from −0.58 to −0.94 mm to the bregma line) and discovered their involvement in modulating defensive responses to potential threats (Horii-Hayashi et al, 2021).…”

Section: Introductionmentioning

confidence: 99%

“…These diverse functions are likely mediated by distinct neuronal populations in specific anatomical locations and projection targets, including the VMH and lateral septum (LS) (Lewis et al, 2001;Li et al, 2002;Kuperman et al, 2010;Autry et al, 2019;Horii-Hayashi et al, 2021). In our recent study, we focused on PeF UCN3 neurons located along the paraventricular nucleus (PVN) in mice (from −0.58 to −0.94 mm to the bregma line) and discovered their involvement in modulating defensive responses to potential threats (Horii-Hayashi et al, 2021). These neurons respond to novel objects/potential threats, but not to acute threats such as predator odor and intruders.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Entrance-sealing behavior in the home cage: a defensive response to potential threats linked to the serotonergic system and manifestation of repetitive/stereotypic behavior in mice

Horii-Hayashi,

Masuda,

Kato

et al. 2024

Front. Behav. Neurosci.

Self Cite

View full text Add to dashboard Cite

The security of animal habitats, such as burrows and nests, is vital for their survival and essential activities, including eating, mating, and raising offspring. Animals instinctively exhibit defensive behaviors to protect themselves from imminent and potential threats. In 1963, researchers reported wild rats sealing the entrances to their burrows from the inside using materials such as mud, sand, and vegetation. This behavior, known as “entrance sealing (ES),” involves repetitive movements of their nose/mouth and forepaws and is likely a proactive measure against potential intruders, which enhances burrow security. These observations provide important insights into the animals’ ability to anticipate potential threats that have not yet occurred and take proactive actions. However, this behavior lacks comprehensive investigation, and the neural mechanisms underpinning it remain unclear. Hypothalamic perifornical neurons expressing urocortin-3 respond to novel objects/potential threats and modulate defensive responses to the objects in mice, including risk assessment and burying. In this study, we further revealed that chemogenetic activation of these neurons elicited ES-like behavior in the home-cage. Furthermore, behavioral changes caused by activating these neurons, including manifestations of ES-like behavior, marble-burying, and risk assessment/burying of a novel object, were effectively suppressed by selective serotonin-reuptake inhibitors. The c-Fos analysis indicated that ES-like behavior was potentially mediated through GABAergic neurons in the lateral septum. These findings underscore the involvement of hypothalamic neurons in the anticipation of potential threats and proactive defense against them. The links of this security system with the manifestation of repetitive/stereotypic behaviors and the serotonergic system provide valuable insights into the mechanisms underlying the symptoms of obsessive-compulsive disorder.

show abstract

Oxytocinergic neurons, but not oxytocin, are crucial for male penile erection

Fan

Yang

et al. 2023

Neuropharmacology

View full text Add to dashboard Cite

Protocol for behavioral tests using chemogenetically manipulated mice

Cited by 3 publications

References 21 publications

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

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

Entrance-sealing behavior in the home cage: a defensive response to potential threats linked to the serotonergic system and manifestation of repetitive/stereotypic behavior in mice

Oxytocinergic neurons, but not oxytocin, are crucial for male penile erection

Contact Info

Product

Resources

About