scholarly journals Brief optogenetic inhibition of rat lateral or ventrolateral periaqueductal gray augments the acquisition of Pavlovian fear conditioning

2017 ◽  
Author(s):  
Neda Assareh ◽  
Elena E. Bagley ◽  
Pascal Carrive ◽  
Gavan P. McNally

AbstractThe midbrain periaqueductal gray (PAG) coordinates the expression and topography of defensive behaviors to threat and also plays an important role in Pavlovian fear learning itself. Whereas the role of PAG in expression of defensive behavior is well understood, the relationship between activity of PAG neurons and fear learning, the exact timing of PAG contributions to learning during the conditioning trial, and the contributions of different PAG columns to fear learning are poorly understood. We assessed the effects of optogenetic inhibition of lateral (LPAG) and ventrolateral (VLPAG) PAG neurons on fear learning. Using adenoassociated viral vectors expressing halorhodopsin (eNpHR3.0), we show that brief optogenetic inhibition of LPAG or VLPAG during delivery of the shock unconditioned stimulus (US) augments acquisition of contextual or cued fear conditioning and we also show that this inhibition augments post-encounter defensive responses to a non-noxious threat. Taken together, these results show that LPAG and VLPAG serve a key role in regulation of Pavlovian fear learning at the time of US delivery. These findings provide strong support for existing models which state that LPAG and VLPAG contribute to a fear prediction error signal determining variations in the effectiveness of the aversive US in supporting learning.

2020 ◽  
Author(s):  
Silvia Natale ◽  
Maria Esteban Masferrer ◽  
Senthilkumar Deivasigamani ◽  
Cornelius T. Gross

AbstractThe cerebral cortex is involved in the control of cognition and the processing of learned information and it appears to have a role in the adaptation of behavior in response to unpredictable circumstances. In addition, the cortex may have a role in the regulation of innate responses since rodents, cats or primates with surgical removal or accidental destruction of cortical regions show excessive irritability, aggression and rage elicited by threatening stimuli. However, it remains unclear whether cortex has an acute role in suppressing innate threat responses because the imprecision and chronic nature of these lesions leaves open the possibility that compensatory processes may underlie some of these phenotypes. In the present study we used pharmacogenetic inhibition to precisely, rapidly and reversibly suppress cortical pyramidal neuron function and examine its contribution to defensive behaviors elicited by a variety of innately aversive stimuli. Inhibition of cortex caused an increase of defensive responses elicited by an aggressive conspecific, a novel prey, and a physically stressful stimulus. These findings are consistent with a role of cortex in the acute inhibition of innate defensive behaviors.


SLEEP ◽  
2021 ◽  
Vol 44 (Supplement_2) ◽  
pp. A20-A20
Author(s):  
Anne Richards ◽  
Sabra Inslicht ◽  
J Russell Huie ◽  
Leslie Yack ◽  
Laura Straus ◽  
...  

Abstract Introduction Animal and human studies indicate that fear conditioning disrupts subsequent sleep, including REM sleep (REMS). REMS is thought to be central to fear information processing. We utilized an afternoon nap protocol to examine the effects of fear-potentiated startle (FPS), a variant of fear conditioning, on subsequent sleep integrity and REMS in trauma-exposed participants with varying levels of PTSD. We also examined the effects of changes in sleep integrity and REMS on subsequent retention and extinction of pre-sleep learning. Methods Participants (N=47) participated in 3 nap visits. The first was an adaptation nap. The second and third nap visits were counterbalanced: a stress-condition nap, during which participants underwent FPS procedures prior to a nap and assessment of retention of fear and safety signal learning and fear extinction after the nap, and a control visit during which participants had a nap opportunity without stressful procedures. Canonical correlation analysis assessed the relationship between FPS responses and change in subsequent sleep relative to a control nap, as well as the relationship between change in sleep from control to stress condition and both subsequent fear and safety learning retention, and subsequent extinction. Results Results demonstrated a relationship between fear learning and change in sleep and supported a relationship between safety signal learning and subsequent REMS, as well as differential conditioning and wake after sleep onset. Sleep did not predict measures of fear retention or extinction. PTSD symptoms did not predict fear learning or sleep measures. Conclusion These findings replicate prior work showing a relationship between safety learning and REMS, suggesting that this is a core mechanism through which stress impacts fear processing. Further research is critical to further understand this effect, and to examine how different aspects of fear learning impact different components of sleep. This study also demonstrates that nap studies can be a valuable approach for studying the stress-sleep relationship. Support (if any) VA Career Development Award to Dr. Richards (5IK2CX000871-05)


2007 ◽  
Vol 28 (1) ◽  
pp. 55-84
Author(s):  
Ruth Lusterio Rico

This article analyzes the important role of civil society groups in the enactment of a significant legislation — the Indigenous Peoples’ Rights Act (IPRA) which was passed by the Philippine Congress in 1997. It examines the legislative process, the significant role of non-government organizations (NGOs) and people’s organizations (POs) in the process, the relationship between state and non-state actors, and how this relationship affected the enactment of the law. This paper shows that in spite of the limitations faced by civil society groups, they are able to play a significant role in the making of a significant legislation. The active role of civil society groups specifically in policy formulation, the collaboration between state and civil society actors and the strong support of the administration are three important factors in the making of IPRA.


2021 ◽  
Vol ahead-of-print (ahead-of-print) ◽  
Author(s):  
Stacey Sharpe ◽  
Nicole Hanson

PurposeThis study examines the relationship between corporate social irresponsibility (CSI) and firm-level sales and estimates the potentially mitigating role of advertising.Design/methodology/approachTo test their hypotheses, the authors conduct an empirical investigation using a sample of 381 US firms engaging in socially irresponsible behavior.FindingsThe results of this investigation indicate that while sales are negatively impacted during the year of a CSI event, they generally recover in the year immediately following the event. In addition, advertising is shown to mitigate the negative impact of CSI on sales in both the event year and the year immediately following. The authors also consider whether differences exist between CSI firms with and without advertising. From this comparative analysis, it is observed that CSI firms which advertise tend to experience more severe declines in sales. Also, such firms tend to recover from the negative implications of CSI sooner.Originality/valueThis paper provides a novel and empirical approach to assessing the relationship between CSI events and firm-level sales while quantifying the mitigating effects of advertising. Furthermore, the unique contributions and practical findings of this research generate strong support for the significant role advertising can play in helping firms recover from CSI-based brand crisis events and help to establish a promising path for future research.


2020 ◽  
Vol 8 (1) ◽  
pp. 184-193 ◽  
Author(s):  
Violet Benneker ◽  
Klarita Gërxhani ◽  
Stephanie Steinmetz

Although scholars are increasingly able to explain why states (do not) comply with human rights treaties, the role of social norms in compliance has been neglected. This is remarkable because human rights often directly address social norms. Our study aims to contribute to the existing literature by providing quantitative and qualitative evidence on the relationship between citizens’ social norms and compliance with human rights treaties. The quantitative results provide strong support for such a relationship. The findings from the additional qualitative analysis suggest that bargaining over (and thus changing) social norms is an important process through which compliance with human rights can be influenced.


2021 ◽  
Author(s):  
Quentin Montardy ◽  
Zheng Zhou ◽  
Lei Li ◽  
Qingning Yang ◽  
Zhuogui Lei ◽  
...  

AbstractDopamine (DA) system is intriguing in the aspect that distinct, typically opposing physiological functions are mediated by D1 dopamine receptors (Drd1) and D2 dopamine receptors (Drd2). Both Drd1+ and Drd2+ neurons were identified in superior colliculus (SC), a visuomotor integration center known for its role in defensive behaviors to visual threats. We hypothesized that Drd1+ and Drd2+ neurons in the SC may play a role in promoting instinctive defensive responses.Optogenetic activation of Drd2+ neurons, but not Drd1+ neurons, in the SC triggered strong defensive behaviors. Chemogenetic inhibition of SC Drd2+ neurons decreased looming-induced defensive behavior, suggesting involvement of SC Drd2+ neurons in defensive responses. To further confirm this functional role of Drd2 receptors, pretreatment with the Drd2+ agonist quinpirole in the SC impaired looming-evoked defensive responses, suggesting an essential role of Drd2 receptors in the regulation of innate defensive behavior. Inputs and outputs of SC Drd2+ neurons were investigated using viral tracing: SC Drd2+ neurons mainly receive moderate inputs from the Locus Coeruleus (LC), whilst we did not find any incoming projections from other dopaminergic structures. Our results suggest a sophisticated regulatory role of DA and its receptor system in innate defensive behavior.


2021 ◽  
Author(s):  
Michael Kintscher ◽  
Olexiy Kochubey ◽  
Ralf Schneggenburger

During fear learning, defensive behaviors need to be finely balanced, to allow animals to return to normal behaviors after the termination of threat-indicating sensory cues. Nevertheless, the circuits underlying such balancing are largely unknown. Here, we investigate the role of direct (D1R+) - and indirect (Adora+) pathway neurons of the amygdala-striatal transition zone (AStria) in fear learning. In-vivo Ca2+ imaging revealed that fear learning increased the responses of D1R+ AStria neurons to an auditory CS, given that the animal moved. In Adora+ neurons, fear learning also induced a differential activity during freezing and movement, albeit with little influence of the CS. In-vivo optogenetic silencing during the training day showed that plasticity in D1R+ AStria neurons contributes to auditory-cued fear memories, whereas Adora+ neurons suppressed learned freezing when no CS was present. Circuit tracing experiments identified cortical input structures to the AStria, and recording of optogenetically-evoked EPSCs at the corresponding projection revealed different forms of long-term plasticity at synapses onto D1R+ and Adora+ AStria neurons. Taken together, direct- and indirect pathways neurons of the AStria show differential signs of in-vivo and ex-vivo plasticity after fear learning, and balance defensive behaviors in the presence and absence of aversively motivated sensory cues.


2020 ◽  
Author(s):  
Joseph Carpenter ◽  
Laura Bragdon ◽  
Suzanne L. Pineles

Objective: PTSD is often associated with heightened physiological reactivity during fear conditioning procedures, but results vary across studies. The present study examined whether anxiety sensitivity (AS), or the fear of arousal-related sensations, strengthens the relationship between PTSD symptoms and skin conductance responses (SCR) during fear conditioning and extinction. Because gonadal hormones implicated in fear learning processes fluctuate across the menstrual cycle, the stability of these relationships in women was examined in two distinct menstrual cycle phases. Method: Thirty-two trauma-exposed women with (n=16) and without PTSD (n=16) completed the Clinician-Administered PTSD Scale, Anxiety Sensitivity Inventory, and a fear conditioning and extinction paradigm during the mid-luteal (mLP) and early-follicular (eFP) menstrual cycle phases. Results: In the mLP, stronger SCR to stimuli paired with shock (CS+) during fear acquisition significantly predicted greater PTSD symptoms only when AS was high and after removing an outlier. This appeared driven by effects on Numbing and Hyperarousal symptom clusters. Other hypothesized interactions between AS and CS responses were not significant. However, in the eFP, differential SCR between the CS+ and CS- during extinction predicted significantly greater PTSD symptoms, and there was a trend for this effect being stronger as AS increased. Conclusions: Results offer preliminary evidence that high AS contributes to a stronger relationship between physiological responses during fear acquisition and PTSD symptoms, at least among women in the mLP. Further research investigating the impact of individual differences in traits such as AS on the relationship between conditioned fear responses and PTSD symptoms is warranted.


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