Inborn vs. acquired anxiety in cross-breeding and cross-fostering HAB/LAB mice bred for extremes in anxiety-related behavior.

Chekmareva, N. Yu.; Umriukhin, Aleksei; Landgraf, Rainer; Sotnikov, Sergey

doi:10.1037/bne0000294

Cited by 7 publications

(4 citation statements)

References 39 publications

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“…We previously reported that wildtype (Gad1 +/+ ) mice born from GAD67 haplodeficient (Gad1 GFP/+ ) mothers exhibited the vulnerability to stress at the adult age [42]. In addition, it has been reported that the anxious state in mother mice affects behavioral phenotypes in their pups at the adult age [43]. Second, we used wild-type (Gad1 +/+ ) mice as the control, but Fujihara et al [19] used Gad1 flox/+ mice as the control.…”

Section: Discussionmentioning

confidence: 99%

Global knockdown of glutamate decarboxylase 67 elicits emotional abnormality in mice

et al. 2021

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Reduced expression of glutamate decarboxylase 67 (GAD67), encoded by the Gad1 gene, is a consistent finding in postmortem brains of patients with several psychiatric disorders, including schizophrenia, bipolar disorder and major depressive disorder. The dysfunction of GAD67 in the brain is implicated in the pathophysiology of these psychiatric disorders; however, the neurobiological consequences of GAD67 dysfunction in mature brains are not fully understood because the homozygous Gad1 knockout is lethal in newborn mice. We hypothesized that the tetracycline-controlled gene expression/suppression system could be applied to develop global GAD67 knockdown mice that would survive into adulthood. In addition, GAD67 knockdown mice would provide new insights into the neurobiological impact of GAD67 dysfunction. Here, we developed Gad1tTA/STOP−tetO biallelic knock-in mice using Gad1STOP−tetO and Gad1tTA knock-in mice, and compared them with Gad1+/+ mice. The expression level of GAD67 protein in brains of Gad1tTA/STOP−tetO mice treated with doxycycline (Dox) was decreased by approximately 90%. The GABA content was also decreased in the brains of Dox-treated Gad1tTA/STOP−tetO mice. In the open-field test, Dox-treated Gad1tTA/STOP−tetO mice exhibited hyper-locomotor activity and decreased duration spent in the center region. In addition, acoustic startle responses were impaired in Dox-treated Gad1tTA/STOP−tetO mice. These results suggest that global reduction in GAD67 elicits emotional abnormalities in mice. These GAD67 knockdown mice will be useful for elucidating the neurobiological mechanisms of emotional abnormalities, such as anxiety symptoms associated with psychiatric disorders.

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Section: Discussionmentioning

confidence: 99%

Global knockdown of glutamate decarboxylase 67 elicits emotional abnormality in mice

et al. 2021

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“…To this end, several rat and mouse models based on the selective bidirectional breeding of animals according to their performance in unconditioned anxiety tests were established [7][8][9][10]. Selective breeding models have allowed the investigation of the genetic factors that contribute to the development and expression of trait anxiety.…”

Section: In Practice Our Paradigms Are Constrained By the Way The Org...mentioning

confidence: 99%

Leveraging interindividual variability in threat conditioning of inbred mice to model trait anxiety

Kovlyagina,

Wierczeiko,

Todorov

et al. 2024

PLoS Biol

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Trait anxiety is a major risk factor for stress-induced and anxiety disorders in humans. However, animal models accounting for the interindividual variability in stress vulnerability are largely lacking. Moreover, the pervasive bias of using mostly male animals in preclinical studies poorly reflects the increased prevalence of psychiatric disorders in women. Using the threat imminence continuum theory, we designed and validated an auditory aversive conditioning-based pipeline in both female and male mice. We operationalised trait anxiety by harnessing the naturally occurring variability of defensive freezing responses combined with a model-based clustering strategy. While sustained freezing during prolonged retrieval sessions was identified as an anxiety-endophenotype biomarker in both sexes, females were consistently associated with an increased freezing response. RNA-sequencing of CeA, BLA, ACC, and BNST revealed massive differences in phasic and sustained responders’ transcriptomes, correlating with transcriptomic signatures of psychiatric disorders, particularly post-traumatic stress disorder (PTSD). Moreover, we detected significant alterations in the excitation/inhibition balance of principal neurons in the lateral amygdala. These findings provide compelling evidence that trait anxiety in inbred mice can be leveraged to develop translationally relevant preclinical models to investigate mechanisms of stress susceptibility in a sex-specific manner.

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“…To this end, several rat and mouse models based on the selective bi-directional breeding of animals according to their performance in unconditioned anxiety tests were established [7][8][9][10]. Selective breeding models have allowed the investigation of the genetic factors that contribute to the development and expression of trait anxiety.…”

Section: Introductionmentioning

confidence: 99%

Freezing responses during prolonged threat memory retrieval reflect trait-like anxiety endophenotypes in female and male inbred mice

Kovlyagina,

Wierczeiko,

Todorov

et al. 2023

Preprint

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Trait anxiety is a major risk factor for stress-induced and anxiety disorders in humans. However, animal models accounting for the inter-individual variability in stress vulnerability are largely lacking. Moreover, the pervasive bias of using mostly male animals in preclinical studies poorly reflects the increased prevalence of psychiatric disorders in women. Using the threat imminence continuum theory, we designed and validated an auditory aversive conditioning-based pipeline in both female and male mice. We operationalized trait anxiety by harnessing the naturally occurring variability of defensive freezing responses combined with a model-based clustering strategy. While sustained freezing during prolonged retrieval sessions was identified as an anxiety-endophenotype biomarker in both sexes, females were consistently associated with an increased freezing response RNA-sequencing of CeA, BLA, ACC and BNST revealed massive differences in phasic and sustained responders’ transcriptomes, correlating with transcriptomic signatures of psychiatric disorders, particularly PTSD. Moreover, we detected significant alterations in the excitation/inhibition balance of principal neurons in the lateral amygdala. These findings provide compelling evidence that trait anxiety in inbred mice can be leveraged to develop translationally relevant preclinical models to investigate mechanisms of stress susceptibility in a sex-specific manner.We like to think we have constrained an organism to the task we have set. In practice, our paradigms are constrained by the way the organisms respondMcNaughton & Corr, 2004

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Inborn vs. acquired anxiety in cross-breeding and cross-fostering HAB/LAB mice bred for extremes in anxiety-related behavior.

Cited by 7 publications

References 39 publications

Global knockdown of glutamate decarboxylase 67 elicits emotional abnormality in mice

Global knockdown of glutamate decarboxylase 67 elicits emotional abnormality in mice

Leveraging interindividual variability in threat conditioning of inbred mice to model trait anxiety

Freezing responses during prolonged threat memory retrieval reflect trait-like anxiety endophenotypes in female and male inbred mice

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