scholarly journals Regular Music Exposure in Juvenile Rats Facilitates Conditioned Fear Extinction and Reduces Anxiety after Foot Shock in Adulthood

2019 ◽  
Vol 2019 ◽  
pp. 1-10
Author(s):  
Si Chen ◽  
Tuo Liang ◽  
Fiona H. Zhou ◽  
Ye Cao ◽  
Chao Wang ◽  
...  
Keyword(s):  
Fear Conditioning ◽  
Conditioned Fear ◽  
Conditioning Session ◽  
Fear Extinction ◽  
Extinction Training ◽  
Anterior Cingulate ◽  
Stressful Event ◽  
Sprague Dawley ◽  
Positive Role ◽  
Juvenile Rats

Music exposure is known to play a positive role in learning and memory and can be a complementary treatment for anxiety and fear. However, whether juvenile music exposure affects adult behavior is not known. Two-week-old Sprague-Dawley rats were exposed to music for 2 hours daily or to background noise (controls) for a period of 3 weeks. At 60 days of age, rats were subjected to auditory fear conditioning, fear extinction training, and anxiety-like behavior assessments or to anterior cingulate cortex (ACC) brain-derived neurotrophic factor (BDNF) assays. We found that the music-exposed rats showed significantly less freezing behaviors during fear extinction training and spent more time in the open arm of the elevated plus maze after fear conditioning when compared with the control rats. Moreover, the BDNF levels in the ACC in the music group were significantly higher than those of the controls with the fear conditioning session. This result suggests that music exposure in juvenile rats decreases anxiety-like behaviors, facilitates fear extinction, and increases BDNF levels in the ACC in adulthood after a stressful event.

scholarly journals Repeated Sevoflurane Exposures in Neonatal Rats Increased the Brain Vulnerability to Future Stress Exposure and Resulted in Fear-extinction Deficit

2021 ◽  
Author(s):  
Ben-zhen Chen ◽  
Li-hua Jiang ◽  
Ming-qiang Zhang ◽  
Ling Tan ◽  
Wen-qin Zhou ◽  
...  
Keyword(s):  
Fear Conditioning ◽  
Fear Extinction ◽  
Male Rats ◽  
Neonatal Rats ◽  
Stress Exposure ◽  
Sprague Dawley ◽  
Juvenile Rats ◽  
Acid Type ◽  
Cation Chloride Cotransporters ◽  
The Brain

Abstract Sevoflurane anesthesia during neonatal period was reported to sensitize the rodent animals to stress later in life. The authors tested the hypothesis that repeated sevoflurane exposures in neonatal rats increased the brain vulnerability to future stress exposure and resulted in fear-extinction deficit, and investigated whether the neonatal brain depolarizing γ-aminobutyric acid type A receptor (GABAAR) is involved in mediating these abnormalities. Neonatal Sprague-Dawley male rats, pretreated with vehicle or the NKCC1 inhibitor, bumetanide, received sequential exposures to 3% sevoflurane for 2 hours on postnatal days (P) 5, 6, 7 and then were exposed to electric foot shock stress in fear conditioning training at P14. Juvenile rats at different developmental brain stage receiving identical sevoflurane exposures on P25, 26, 27 were also studied. The results showed repeated sevoflurane exposures in neonatal rats increased the cation-chloride cotransporters NKCC1/KCC2 ratio in the PFC at P14. Repeated exposures to sevoflurane in neonatal rather than juvenile rats enhanced the stress response and exacerbated neuroapoptosis in the PFC after exposed to electric foot shock in fear conditioning training. Neonatal rather than juvenile sevoflurane-exposed rats exhibited deficits in fear extinction training and recall. Pretreatment of neonatal rats prior to sevoflurane exposures with bumetanide reduced the NKCC1/KCC2 ratio at P14 and ameliorated most of the subsequent adverse effects. Our study indicates that repeated sevoflurane exposures in neonatal rats might increase the brain vulnerability to future stress exposure and resulted in fear-extinction deficit, which might be associated with the neonatal enhanced brain depolarizing GABAAR activity.

Neural correlates of trait anxiety in fear extinction

2010 ◽  
Vol 41 (4) ◽  
pp. 789-798 ◽  
Author(s):  
C. Sehlmeyer ◽  
U. Dannlowski ◽  
S. Schöning ◽  
H. Kugel ◽  
M. Pyka ◽  
...  
Keyword(s):  
Fear Conditioning ◽  
Trait Anxiety ◽  
Conditioned Fear ◽  
Neural Correlates ◽  
Fear Extinction ◽  
Anterior Cingulate ◽  
Dorsal Anterior Cingulate Cortex ◽  
Neural Structure ◽  
Amygdala Activation ◽  
Conditioned Responses

BackgroundFear conditioning involves the amygdala as the main neural structure for learning fear responses whereas fear extinction mainly activates the inhibitory prefrontal cortex (PFC). In this study we investigated whether individual differences in trait anxiety affect amygdala and dorsal anterior cingulate cortex (dACC) activation during fear conditioning and extinction.MethodThirty-two healthy subjects were investigated by functional magnetic resonance imaging (fMRI) at 3 T while performing a cued fear-conditioning task. All participants completed the trait version of the State-Trait Anxiety Inventory (STAI-T). Activations of the amygdala and the dACC were examined with respect to the effects of trait anxiety.ResultsAnalysis of the fMRI data demonstrated enhanced activation in fear-related brain areas, such as the insula and the ACC, during both fear conditioning and extinction. Activation of the amygdala appeared only during the late acquisition phase whereas deactivation was observed during extinction. Regression analyses revealed that highly trait-anxious subjects exhibited sustained amygdala activation and reduced dACC involvement during the extinction of conditioned responses.ConclusionsThis study reveals that high levels of trait anxiety are associated with both increased amygdala activation and reduced dACC recruitment during the extinction of conditioned fear. This hyper-responsitivity of the amygdala and the deficient cognitive control during the extinction of conditioned fear in anxious subjects reflect an increased resistance to extinct fear responses and may thereby enhance the vulnerability to developing anxiety disorders.

scholarly journals Repeated Sevoflurane Exposures in Neonatal Rats Increased the Brain Vulnerability to Future Stress Exposure and Resulted in Fear-extinction Deficit

2021 ◽  
Author(s):  
Ben-zhen Chen ◽  
Li-hua Jiang ◽  
Ming-qiang Zhang ◽  
Wen-qin Zhou ◽  
Yu-chao Shang ◽  
...  
Keyword(s):  
Fear Conditioning ◽  
Fear Extinction ◽  
Male Rats ◽  
Neonatal Rats ◽  
Stress Exposure ◽  
Sprague Dawley ◽  
Juvenile Rats ◽  
Acid Type ◽  
Cation Chloride Cotransporters ◽  
The Brain

Abstract Sevoflurane anesthesia during neonatal period was reported to sensitize the rodent animals to stress later in life. The authors tested the hypothesis that repeated sevoflurane exposures in neonatal rats increased the brain vulnerability to future stress exposure and resulted in fear-extinction deficit, and investigated whether the neonatal brain depolarizing γ-aminobutyric acid type A receptor (GABAAR) is involved in mediating these abnormalities. Neonatal Sprague-Dawley male rats, pretreated with vehicle or the NKCC1 inhibitor, bumetanide, received sequential exposures to 3% sevoflurane for 2 hours on postnatal days (P) 5, 6, 7 and then were exposed to electric foot shock stress in fear conditioning training at P14. Juvenile rats at different developmental brain stage receiving identical sevoflurane exposures on P25, 26, 27 were also studied. The results showed repeated sevoflurane exposures in neonatal rats increased the cation-chloride cotransporters NKCC1/KCC2 ratio in the PFC at P14. Repeated exposures to sevoflurane in neonatal rather than juvenile rats enhanced the stress response and exacerbated neuroapoptosis in the PFC after exposed to electric foot shock in fear conditioning training. Neonatal rather than juvenile sevoflurane-exposed rats exhibited deficits in fear extinction training and recall. Pretreatment of neonatal rats prior to sevoflurane exposures with bumetanide reduced the NKCC1/KCC2 ratio at P14 and ameliorated most of the subsequent adverse effects. Our study indicates that repeated sevoflurane exposures in neonatal rats might increase the brain vulnerability to future stress exposure and resulted in fear-extinction deficit, which might be associated with the neonatal enhanced brain depolarizing GABAAR activity.

scholarly journals SUN-235 Deficient Fear Extinction in PRKAR1A-Defective Mice

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Margaret Keil ◽  
Enrica Paradiso ◽  
Rita S Keil ◽  
Maddalena Ugolini ◽  
Evan Harris ◽  
...  
Keyword(s):  
Gene Expression ◽  
Fear Conditioning ◽  
Conditioned Fear ◽  
Critical Role ◽  
Fear Memory ◽  
Brain Regions ◽  
Fear Extinction ◽  
Carney Complex ◽  
Bdnf Gene ◽  
Extinction Learning

Abstract Background: The role of the cAMP/PKA signaling in molecular pathways involved in fear memory is well established: PKA is required for fear memory formation and is a constraint for fear extinction. Previously we reported that a Prkar1a heterozygote (HZ) mouse that was developed in our lab to investigate Carney complex (CNC), the disease caused by PRKAR1A mutations, showed brain region-specific increased PKA activity that was associated with anxiety-like behavioral phenotype and threat bias (Keil, 2010, 2013). We hypothesized that Prkar1a+/- (HZ) mice would have deficits in fear extinction behavior. Brain derived neurotrophic factor (BDNF) has a critical role in formation of fear memory and its transcription is regulated by PKA/CREB. A mouse model with down regulation of PKA provides an opportunity for the first time to investigate the effect of altered PKA signaling on fear conditioning and extinction. Method: Fear conditioning, fear extinction learning, and fear extinction recall were tested in adult male HZ and wild-type (WT) mice as follows: fear conditioning training followed 24hr later by extinction training (new context), then 24hr later by extinction recall training. Percentage of time freezing was used to assess conditioned fear response. We measured BDNF gene expression in brain regions after completion of extinction recall training. Results: As expected, fear conditioning (learning) behavior was similar in HZ and WT mice. However, HZ mice showed a significant deficit in the early phase of fear extinction learning compared to WT. There was no difference in extinction recall between genotypes. Alterations in BDNF gene expression in the prefrontal cortex and amygdala was associated with deficit in fear extinction. Conclusion: Mice with a downregulation of Prkar1a gene demonstrate intact fear conditioning but impaired fear extinction learning, consistent with prior studies that report that PKA inhibition is necessary to facilitate extinction learning. Prkar1a+/- mice provide a valuable model to investigate impaired fear extinction to identify mechanisms for therapeutic targets for anxiety and trauma-related disorders.

scholarly journals Parametric modulators of sex-biased conditioned fear responding

2021 ◽  
Author(s):  
Julia R Mitchell ◽  
Sean G Trettel ◽  
Anna J Li ◽  
Sierra Wasielewski ◽  
Kylie A Huckleberry ◽  
...  
Keyword(s):  
Fear Conditioning ◽  
Early Recognition ◽  
Conditioned Fear ◽  
Sprague Dawley ◽  
Multiple Dimensions ◽  
Sprague Dawley Rats ◽  
Experimental Parameters ◽  
Behavioral Paradigm ◽  
Data Files ◽  
Chamber Size

Pavlovian fear conditioning is a widely used behavioral paradigm for studying associative learning in rodents. Despite early recognition that subjects may engage in a variety of behaviors that reflect the experimental parameters of a given protocol, the last several decades have seen the field narrow its focus to measure freezing as the sole indicator of conditioned fear. Additionally, unconditioned responses such as shock-related activity are rarely considered. We previously reported that female Sprague Dawley rats are more likely than males to engage in darting, an escape-like conditioned response that is associated with heightened shock reactivity, but we did not establish whether darting was sensitive to manipulations of factors such as chamber size, shock intensity, or number of trials. Our goal here was to address these questions by defining parametric and phenotypic predictors of darting in both sexes. To better capture fear-related behavioral repertoires in our animals, we developed ScaredyRat, a custom Python tool that analyzes Noldus Ethovision-generated raw data files to identify Darters and quantify both conditioned and unconditioned responses. We find that like freezing, darting probability scales with experimental alterations in multiple dimensions. In most cases, the sex bias towards females persists, but males will transition to darting in extended, or overtraining fear conditioning protocols.

scholarly journals MPP2 Interacts With SK2 Rescue The Excitability of Glutamatergic Neurons in The BLA and Facilitate The Extinction of Conditioned Fear in Mice

2021 ◽  
Author(s):  
Xiao-Han Peng ◽  
Pan-Pan Chen ◽  
Yang Zhang ◽  
Ke Wu ◽  
Ningning Ji ◽  
...  
Keyword(s):  
Fear Conditioning ◽  
Basolateral Amygdala ◽  
Conditioned Fear ◽  
Fear Memory ◽  
Fear Extinction ◽  
Definitive Evidence ◽  
Glutamatergic Neurons ◽  
Integral Role ◽  
Calcium Activated Potassium Channel ◽  
Increased Activity

Abstract Posttraumatic stress disorder (PTSD) and other anxiety disorders stem from dysregulated fear memory in which the basolateral amygdala (BLA) plays an integral role. The excitability of glutamatergic neurons in the BLA correlates with fear memory, and the afterhyperpolarization current (IAHP) mediated by small-conductance calcium-activated potassium channel subtype 2 (SK2) dominates the excitability of glutamatergic neurons. However, definitive evidence for the involvement of the SK2 channel in the BLA in fear extinction is lacking. Here, we discovered that fear conditioning decreased the levers of synaptic SK2 channels in the BLA, which were restored following fear extinction. Notably, reduced expression of synaptic SK2 channels in the BLA during fear conditioning was caused by the increased activity of protein kinase A (PKA), while increased levers of synaptic SK2 channels in the BLA during fear extinction were mediated by interactions with membrane palmitoylated protein 2 (MPP2). Collectively, our results revealed that MPP2 interacts with the SK2 channels and rescues the excitability of glutamatergic neurons by increasing the expression of synaptic SK2 channels in the BLA to promote the normalization of fear memory. These findings expand our understanding of the neurobiological mechanism of PTSD and provide a new direction for PTSD treatment.

scholarly journals Frontal Lobe Circuitry in Posttraumatic Stress Disorder

2019 ◽  
Vol 3 ◽  
pp. 247054701985016 ◽  
Author(s):  
Lynn D. Selemon ◽  
Keith A. Young ◽  
Dianne A. Cruz ◽  
Douglas E. Williamson
Keyword(s):  
Posttraumatic Stress Disorder ◽  
Posttraumatic Stress ◽  
Frontal Lobe ◽  
Stress Disorder ◽  
Conditioned Fear ◽  
Emotional Valence ◽  
Fear Extinction ◽  
Anterior Cingulate ◽  
Network Analyses ◽  
Spine Shape

Symptoms of posttraumatic stress disorder include hyperarousal, avoidance of trauma-related stimuli, re-experiencing of trauma, and mood changes. This review focuses on the frontal cortical areas that form crucial links in circuitry pertinent to posttraumatic stress disorder symptomatology: (1) the conditioned fear extinction circuit, (2) the salience circuit, and (3) the mood circuit. These frontal areas include the ventromedial prefrontal cortex (conditioned fear extinction), the dorsal anterior cingulate and insular cortices (salience), and the lateral orbitofrontal and subgenual cingulate cortices (mood). Frontal lobe structural abnormalities in posttraumatic stress disorder, including volumetric reductions in the cingulate cortices, impact all three circuits. Functional analyses of frontal cortices in posttraumatic stress disorder show abnormal activation in all three according to task demand and emotional valence. Network analyses reveal altered amygdalo-frontal connectivity and failure to suppress the default mode network during cognitive engagement. Spine shape alterations also have been detected in the medial orbitofrontal cortex in posttraumatic stress disorder postmortem brains, suggesting reduced synaptic plasticity. Importantly, frontal lobe abnormalities in posttraumatic stress disorder extend beyond emotion-related circuits to include the lateral prefrontal cortices that mediate executive functions. In conclusion, widespread frontal lobe dysfunction in posttraumatic stress disorder provides a neurobiologic basis for the core symptomatology of the disorder, as well as for executive function impairment.

scholarly journals The Laplacian eigenmaps dimensionality reduction of fMRI data for discovering stimulus-induced changes in the resting-state brain activity

2020 ◽  
Author(s):  
Nikita Pospelov ◽  
Alina Tetereva ◽  
Olga Martynova ◽  
Konstantin Anokhin
Keyword(s):  
Dimensionality Reduction ◽  
Fear Conditioning ◽  
Resting State ◽  
Brain Activity ◽  
Conditioned Fear ◽  
Fear Extinction ◽  
Laplacian Eigenmaps ◽  
Non Linear ◽  
Linear Dimensionality Reduction ◽  
Meaningful Stimuli

AbstractThe resting brain at wakefulness is active even in the absence of goal-directed behavior or salient stimuli. However, patterns of this resting-state (RS) activity can undergo alterations following exposure to meaningful stimuli. This study aimed to develop an unbiased method to detect such changes in the RS activity after exposure to emotionally meaningful stimuli. For this purpose, we used functional magnetic resonance imaging (fMRI) of RS brain activity before and after the acquisition and extinction of experimental conditioned fear. A group of healthy volunteers participated in three fMRI sessions: a RS before fear conditioning, a fear extinction session, and a RS immediately after fear extinction. The fear-conditioning paradigm consisted of three neutral visual stimuli paired with a partial reinforcement by a mild electric current. We used both linear and non-linear dimensionality reduction approaches to distinguish between the initial RS and the RS after stimuli exposure. The principal component analysis (PCA) as a linear dimensionality reduction method did not differentiate these states. Using the non-linear Laplacian eigenmaps manifold learning method, we were able to show significant differences between the two RSs at the level of individual participants. This detection was further improved by smoothing the BOLD signal with the wavelet multiresolution analysis. The developed method can improve the discrimination of functional states collected in longitudinal fMRI studies.

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