scholarly journals RGS14 modulates locomotor behavior and ERK signaling induced by environmental novelty and cocaine within discrete limbic structures

2021 ◽  
Author(s):  
Stephanie L. Foster ◽  
Daniel J. Lustberg ◽  
Nicholas H. Harbin ◽  
Sara N. Bramlett ◽  
John R. Hepler ◽  
...  

AbstractRationaleIn rodents, exposure to novel environments or psychostimulants promotes locomotor activity. Indeed, locomotor reactivity to novelty strongly predicts behavioral responses to psychostimulants in animal models of addiction. RGS14 is a plasticity restricting protein with unique functional domains that enable it to suppress ERK-dependent signaling as well as regulate G protein activity. Although recent studies show that RGS14 is expressed in multiple limbic regions implicated in psychostimulant- and novelty-induced hyperlocomotion, its function has been studied almost entirely in the context of hippocampal physiology and hippocampusdependent behaviors.ObjectiveWe sought to determine whether RGS14 modulates novelty- and psychostimulant-induced locomotion and neuronal activity.MethodsWe assessed Rgs14 knockout (RGS14 KO) mice and wild-type (WT) littermate controls using novelty-induced locomotion (NIL) and cocaine-induced locomotion (CIL) behavioral tests with subsequent quantification of c-fos and phosphorylated ERK (pERK) induction in limbic regions that express RGS14.ResultsCompared to WT controls, RGS14 KO mice exhibited attenuated locomotor responses in the NIL test, driven by avoidance of the center of the novel environment. By contrast, RGS14 KO mice demonstrated augmented peripheral locomotion in the CIL test conducted in either a familiar or novel environment. The absence of RGS14 enhanced induction of c-fos and pERK in the central amygdala and hippocampus (areas CA1 and CA2) when cocaine was administered in a novel environment.ConclusionsRGS14 regulates novelty- and psychostimulant-induced hyperlocomotion, particularly with respect to thigmotaxis. Further, our findings suggest RGS14 may reduce neuronal activity in discrete limbic subregions by inhibiting ERK-dependent signaling and transcription.

2021 ◽  
Author(s):  
Alexandra Rodriguez ◽  
Martine Hausberger ◽  
Patricia Le Quilliec ◽  
Laurence Henri ◽  
Philippe Clergeau

To understand the processes involved in biological invasions, the genetic, morphological, physiological and behavioral characteristics of invasive populations need to be understood. Many invasive species have been reported to be flying species. In birds, both invaders and migrants encounter novel situations, therefore one could expect that both groups might react similarly to novelty. Here we analyzed the behavioral responses of individuals from three populations of European starling Sturnus vulgaris: a population settled for centuries in a rural region, a population that recently colonized an urban area, and a population of winter migrant birds. We conducted a social isolation test, a novel environment test, a novel food test and a novel object test to explore their reactions towards novelty. We identified and characterized different behavioral profiles for each test. The group of migratory adults appeared to be less anxious in social isolation than the group of urban young. Urban and migrant groups entered the novel environment sooner than rural birds. Shy, bold and intermediate individuals were observed in all three groups when presented with novel food. Finally, the proportion of shy individuals which did not touch the novel object was higher than the proportion of bold individuals in the rural group. Our study emphasizes that neophilia or boldness present in migrant and invasive populations may facilitate the occupation of novel habitats. Our analysis also suggests that mixed reactions of neophobia ensure behavioral flexibility in a gregarious invasive species.


Author(s):  
Stephanie L. Foster ◽  
Daniel J. Lustberg ◽  
Nicholas H. Harbin ◽  
Sara N. Bramlett ◽  
John R. Hepler ◽  
...  

Animals ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 1383
Author(s):  
Megan Elizabeth Corgan ◽  
Temple Grandin ◽  
Sarah Matlock

It is dangerous for both riders and horses when a horse suddenly startles. Sometimes horses do this in familiar environments because familiar objects may look different when rotated. The purpose of this study was to determine whether horses that had been habituated to a complex object (children’s playset) would react to the object as novel when rotated 90 degrees. Twenty young horses were led past the playset 15 times by a handler. Next, the rotated group was led past the rotated playset 15 times. Each time the horse was led by the object was a pass. The behavioral responses observed and analyzed were ears focused on the object, nostril flares, neck raising, snort, avoid by stopping, avoid by moving feet sideways, and avoid by flight. An increasing reactivity scale was used to quantify behavioral responses. A two-sample t-test was performed on the reactivity scores comparing the first pass by the novel object to the first pass by the rotated object. The horses in the rotated group reacted to the rotated orientation similarly to the first exposure (p = 0.001, α < 0.05). Being aware of potential reactions to changes in previously familiar environments can help keep the handler safer.


2021 ◽  
pp. 014920632198979
Author(s):  
Lilia M. Cortina ◽  
M. Sandy Hershcovis ◽  
Kathryn B. H. Clancy

This article builds a broad theory to explain how people respond, both biologically and behaviorally, when targeted with incivility in organizations. Central to our theorizing is a multifaceted framework that yields four quadrants of target response: reciprocation, retreat, relationship repair, and recruitment of support. We advance the novel argument that these behaviors not only stem from biological change within the body but also stimulate such change. Behavioral responses that revolve around affiliation and produce positive social connections are most likely to bring biological benefits. However, social and cultural features of an organization can stand in the way of affiliation, especially for employees holding marginalized identities. When incivility persists over time and employees lack access to the resources needed to recover, we theorize, downstream consequences can include harms to their physical health. Like other aspects of organizational life, this biobehavioral theory of incivility response is anything but simple. But it may help explain how seemingly “small” insults can sometimes have large effects, ultimately undermining workforce well-being. It may also suggest novel sites for incivility intervention, focusing on the relational and inclusive side of work. The overarching goal of this article is to motivate new science on workplace incivility, new knowledge, and ultimately, new solutions.


2018 ◽  
Vol 50 (6) ◽  
pp. 2390-2405 ◽  
Author(s):  
Shuping Wei ◽  
Jingjing Zhang ◽  
Biao Han ◽  
Jianxun Liu ◽  
Xiaohui Xiang ◽  
...  

Background/Aims: Phenotypic switching of vascular smooth muscle cells (VSMC) plays a vital role in the development of vascular diseases. All-trans retinoic acid (ATRA) is known to regulate VSMC phenotypes. However, the underlying mechanisms remain completely unknown. Here, we have investigated the probable roles and underlying mechanisms of the novel C2H2 zinc finger transcription factor ZFP580 on ATRA-induced VSMC differentiation. Methods: VSMCs were isolated, cultured, and identified. VSMCs were infected with an adenovirus encoding ZFP580 or Ad-siRNA to silence ZFP580. The expression levels of ZFP580, SMα-actin, SM22α, SMemb, RARα, RARβ, and RARγ were assayed by Q-PCR and western blot. A rat carotid artery injury model and morphometric analysis of intimal thickening were also used in this study. Results: ATRA caused a significant reduction of VSMC proliferation and migration in a doseand time-dependent manner. Moreover, it promoted VSMC differentiation by enhancing expression of differentiation markers and reducing expression of dedifferentiation markers. This ATRA activity was accompanied by up-regulation of ZFP580, with concomitant increases in RARα expression. In contrast, silencing of the RARα gene or inhibiting RARα with its antagonist Ro41-5253 abrogated the ATRA-induced ZFP580 expression. Furthermore, ATRA binding to RARα induced ZFP580 expression via the PI3K/Akt and ERK pathways. Adenovirusmediated overexpression of ZFP580 promoted VSMC differentiation by enhancing expression of SM22α and SMα-actin and reducing expression of SMemb. In contrast, silencing ZFP580 dramatically reduced the expression of differentiation markers and increased expression of dedifferentiation markers. The classic rat carotid artery balloon injury model demonstrated that ZFP580 inhibited proliferation and intimal hyperplasia in vivo. Conclusion: The novel zinc finger transcription factor ZFP580 facilitates ATRA-induced VSMC differentiation by the RARα-mediated PI3K/Akt and ERK signaling pathways. This might represent a novel mechanism of regulation of ZFP580 by ATRA and RARα, which is critical for understanding the biological functions of retinoids during VSMC phenotypic modulation.


2021 ◽  
Vol 15 ◽  
Author(s):  
Cesar Sierra ◽  
Ilario De Toma ◽  
Lorenzo Lo Cascio ◽  
Esteban Vegas ◽  
Mara Dierssen

The use of mouse models has revolutionized the field of Down syndrome (DS), increasing our knowledge about neuropathology and helping to propose new therapies for cognitive impairment. However, concerns about the reproducibility of results in mice and their translatability to humans have become a major issue, and controlling for moderators of behavior is essential. Social and environmental factors, the experience of the researcher, and the sex and strain of the animals can all have effects on behavior, and their impact on DS mouse models has not been explored. Here we analyzed the influence of a number of social and environmental factors, usually not taken into consideration, on the behavior of male and female wild-type and trisomic mice (the Ts65Dn model) in one of the most used tests for proving drug effects on memory, the novel object recognition (NOR) test. Using principal component analysis and correlation matrices, we show that the ratio of trisomic mice in the cage, the experience of the experimenter, and the timing of the test have a differential impact on male and female and on wild-type and trisomic behavior. We conclude that although the NOR test is quite robust and less susceptible to environmental influences than expected, to obtain useful results, the phenotype expression must be contrasted against the influences of social and environmental factors.


2021 ◽  
Author(s):  
Dionnet L Bhatti ◽  
Lucian Medrihan ◽  
Michelle X Chen ◽  
Junghee Jin ◽  
Kathryn McCabe ◽  
...  

BACKGROUND: Behavioral responses to stress are, in part, mediated by the hippocampus and Parvalbumin (PV)-expressing neurons. However, whether chronic stress induces molecular and cellular adaptations in hippocampal PV neurons contribute to stress-induced behavioral outcomes remains elusive. METHOD: Using chronic social defeat stress (CSDS), we investigated the role of neuronal activity and gene expression in hippocampal PV neurons in mediating stress-resilience and -susceptibility. We first used in vivo high-density silicon probe recordings and chemogenetics to test whether the activity of PV neurons in ventral dentate gyrus (PVvDG) is associated with particular behavioral outcomes. To find critical molecular pathways associated with stress-resilience and -susceptibility, we used PV-neuron-selective translating ribosome affinity purification and RNAseq. We used immunoblotting, RNAscope, and region- or cell type-specific gene deletion to determine whether Ahnak, a molecule regulating depression-like behavior, was necessary for behavioral divergence after CSDS. RESULTS: We find CSDS modulates neuronal activity in vDG. Notably, stress-susceptibility is associated with an increase of PVvDG firing, which we find is necessary and sufficient for susceptibility. Additionally, genes involved in mitochondrial function, protein synthesis and synaptogenesis are differentially expressed in hippocampal PV neurons of stress-resilient and -susceptible mice. Interestingly, protein and mRNA levels of Ahnak, an endogenous regulator of L-type calcium channels are associated with susceptibility after CSDS. vDG- and PV cell type-specific deletions reveal that Ahnak is required for stress-susceptibility to CSDS. CONCLUSIONS: These findings indicate that CSDS-induced molecular and cellular adaptations in hippocampal PV neurons mediate behavioral consequences, proposing a mechanism underlying individual differences in stress vulnerability.


eNeuro ◽  
2021 ◽  
pp. ENEURO.0189-21.2021
Author(s):  
M Zhu ◽  
M Echeveste Sanchez ◽  
EA Douglass ◽  
JV Jahad ◽  
TD Hanback ◽  
...  

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Ji-Eun Ahn ◽  
Yan Chen ◽  
Hubert Amrein

Behavioral studies have established that Drosophila appetitive taste responses towards fatty acids are mediated by sweet sensing Gustatory Receptor Neurons (GRNs). Here we show that sweet GRN activation requires the function of the Ionotropic Receptor genes IR25a, IR76b and IR56d. The former two IR genes are expressed in several neurons per sensillum, while IR56d expression is restricted to sweet GRNs. Importantly, loss of appetitive behavioral responses to fatty acids in IR25a and IR76b mutant flies can be completely rescued by expression of respective transgenes in sweet GRNs. Interestingly, appetitive behavioral responses of wild type flies to hexanoic acid reach a plateau at ~1%, but decrease with higher concentration, a property mediated through IR25a/IR76b independent activation of bitter GRNs. With our previous report on sour taste, our studies suggest that IR-based receptors mediate different taste qualities through cell-type specific IR subunits.


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