CRISPR-Cas9 editing of the arginine–vasopressin V1a receptor produces paradoxical changes in social behavior in Syrian hamsters

Taylor, Jack H.; Walton, James C.; McCann, Katharine E.; Norvelle, Alisa; Liu, Qian; Velden, Jacob W Vander; Borland, Johnathan M.; Hart, Michael W.; Jin, Chengliu; Huhman, Kim L.; Cox, Daniel N.; Albers, H. Elliott

doi:10.1073/pnas.2121037119

Cited by 26 publications

(8 citation statements)

References 52 publications

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“…Furthermore, reduced V1aR binding was reported in the dLS of highly aggressive IST females ( 23 ). Accordingly, knocking out V1aRs (globally) in female hamsters strongly enhanced aggression ( 106 ). Taken together, these data imply a blunted AVP signaling in various limbic and hypothalamic regions to be associated with exacerbated aggression in virgin females.…”

Section: Neuroendocrinology Of Female Aggressionmentioning

confidence: 99%

Neuroendocrine regulation of female aggression

Oliveira

Bakker

2022

Front. Endocrinol.

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Classically the neurobiology of aggression has been studied exclusively in males. Thus, females have been considered mildly aggressive except during lactation. Interestingly, recent studies in rodents and humans have revealed that non-lactating females can show exacerbated and pathological aggression similarly to males. This review provides an overview of recent findings on the neuroendocrine mechanisms regulating aggressive behavior in females. In particular, the focus will be on novel rodent models of exaggerated aggression established in non-lactating females. Among the neuromodulatory systems influencing female aggression, special attention has been given to sex-steroids and sex-steroid-sensitive neuronal populations (i.e., the core nuclei of the neural pathway of aggression) as well as to the neuropeptides oxytocin and vasopressin which are major players in the regulation of social behaviors.

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Section: Neuroendocrinology Of Female Aggressionmentioning

confidence: 99%

Neuroendocrine regulation of female aggression

Oliveira

Bakker

2022

Front. Endocrinol.

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“…For example, prairie voles exhibit monogamous pair bonding and alloparenting behavior, so they are valuable model organisms of prosocial behaviors (Gillera et al, 2022; Stetzik et al, 2018). In contrast, both male and female Syrian hamsters are naturally antagonistic, which makes them ideal for study of social dominance and aggression (Cooper et al, 2009; Solomon et al, 2009; Taylor et al, 2022).…”

Section: Introductionmentioning

confidence: 99%

Identification of hippocampal area CA2 in hamster and vole brain

Siegler,

Shaughnessy,

Horman

et al. 2024

Preprint

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Prairie voles (Microtus ochrogaster) and Syrian, or golden, hamsters (Mesocricetus auratus) are closely related to mice (Mus musculus) and rats (Rattus norvegicus, for example) and are commonly used in studies of social behavior including social interaction, social memory, and aggression. The CA2 region of the hippocampus is known to play a key role in social memory and aggression in mice and responds to social stimuli in rats, likely owing to its high expression of oxytocin and vasopressin 1b receptors. However, CA2 has yet to be identified and characterized in hamsters or voles. In this study, we sought to determine whether CA2 could be identified molecularly in vole and hamster. To do this, we used immunofluorescence with primary antibodies raised against known molecular markers of CA2 in mice and rats to stain hippocampal sections from voles and hamsters in parallel with those from mice. Here, we report that, like in mouse and rat, staining for many CA2 proteins in vole and hamster hippocampus reveals a population of neurons that express regulator of G protein signaling 14 (RGS14), Purkinje cell protein 4 (PCP4) and striatal-enriched protein tyrosine phosphatase (STEP), which together delineate the borders with CA3 and CA1. These cells were located at the distal end of the mossy fiber projections, marked by the presence of Zinc Transporter 3 (ZnT-3) and calbindin in all three species. In addition to staining the mossy fibers, calbindin also labeled a layer of CA1 pyramidal cells in mouse and hamster but not in vole. However, Wolframin ER transmembrane glycoprotein (WFS1) immunofluorescence, which marks all CA1 neurons, was present in all three species and abutted the distal end of CA2, marked by RGS14 immunofluorescence. Staining for two stress hormone receptors, the glucocorticoid (GR) and mineralocorticoid (MR) receptors, was also similar in all three species, with GR staining found primarily in CA1 and MR staining enriched in CA2. Interestingly, although perineuronal nets (PNNs) are known to surround CA2 cells in mouse and rat, we found that staining for PNNs differed across species in that both CA2 and CA3 showed staining in voles and primarily CA3 in hamsters with only some neurons in proximal CA2 showing staining. These results demonstrate that, like in mouse, CA2 in voles and hamsters can be molecularly distinguished from neighboring CA1 and CA3 areas, but PNN staining is less useful for identifying CA2 in the latter two species. These findings reveal commonalities across species in molecular profile of CA2, which will facilitate future studies of CA2 in these species. Yet to be determined is how differences in PNNs might relate to differences in social behavior across species.

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“…Traditionally, genetic dissection has been tractable in only a handful of model species, most commonly in laboratory mice, and this has limited our ability to leverage this powerful comparative approach to help improve treatments for neurobehavioral psychiatric disorders (6). However, ongoing efforts to construct whole-genome assemblies of nontraditional model species (7), along with the recent development of efficient genome editing tools (8,9), which can be used in conjunction with versatile viral vectors (10), have made it increasingly feasible to use genetic dissection strategies in a wide range of species (11)(12)(13)(14)(15). We believe that the application of genetic dissection approaches across a range of species has great fundamental and translational value, as it will greatly enhance our ability to take advantage of nature's remarkable diversity to bolster our understanding of species-specific and general mechanisms of complex brainbehavior relationships.…”

Section: Introductionmentioning

confidence: 99%

An AAV-CRISPR/Cas9 strategy for gene editing across divergent rodent species: Targeting neural oxytocin receptors as a proof of concept

et al. 2023

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A major issue in neuroscience is the poor translatability of research results from preclinical studies in animals to clinical outcomes. Comparative neuroscience can overcome this barrier by studying multiple species to differentiate between species-specific and general mechanisms of neural circuit functioning. Targeted manipulation of neural circuits often depends on genetic dissection, and use of this technique has been restricted to only a few model species, limiting its application in comparative research. However, ongoing advances in genomics make genetic dissection attainable in a growing number of species. To demonstrate the potential of comparative gene editing approaches, we developed a viral-mediated CRISPR/Cas9 strategy that is predicted to target the oxytocin receptor ( Oxtr ) gene in >80 rodent species. This strategy specifically reduced OXTR levels in all evaluated species ( n = 6) without causing gross neuronal toxicity. Thus, we show that CRISPR/Cas9-based tools can function in multiple species simultaneously. Thereby, we hope to encourage comparative gene editing and improve the translatability of neuroscientific research.

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CRISPR-Cas9 editing of the arginine–vasopressin V1a receptor produces paradoxical changes in social behavior in Syrian hamsters

Cited by 26 publications

References 52 publications

Neuroendocrine regulation of female aggression

Neuroendocrine regulation of female aggression

Identification of hippocampal area CA2 in hamster and vole brain

An AAV-CRISPR/Cas9 strategy for gene editing across divergent rodent species: Targeting neural oxytocin receptors as a proof of concept

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