scholarly journals Stress before Puberty Exerts a Sex- and Age-Related Impact on Auditory and Contextual Fear Conditioning in the Rat

2007 ◽  
Vol 2007 ◽  
pp. 1-12 ◽  
Author(s):  
Maria Toledo-Rodriguez ◽  
Carmen Sandi
Keyword(s):  
Fear Conditioning ◽  
Conditioned Fear ◽  
Early Adulthood ◽  
Contextual Fear Conditioning ◽  
Female Rats ◽  
Adult Males ◽  
Contextual Fear ◽  
Male And Female Rats ◽  
Age Related ◽  
The Impact

Adolescence is a period of major physical, hormonal, and psychological changes. It is also characterized by a significant increase in the incidence of psychopathologies and this increase is gender-specific. Stress during adolescence is associated with the development of psychiatric disorders later in life. In this study, we evaluated the impact of psychogenic stress (exposure to predator odor followed by placement on an elevated platform) experienced before puberty (days 28–30) on fear memories and hormonal response of male and female rats during adolescence and early adulthood. Stress before puberty impacted in a sex- and age-specific way on the responses to auditory and contextual fear conditioning in adolescence and adulthood: (a) increased conditioned fear to the tone in males during adolescence but not during adulthood; (b) impaired extinction to the tone in adult males; and (c) reduced freezing responses to the context in adolescent females. Stress before puberty did not influence the corticosterone levels 30 minutes after an additional stressor given in adulthood. These results indicate that stress experienced prior to puberty can exert a sex-related differential impact on fear-related behaviors displayed by individuals during late adolescence and early adulthood.

scholarly journals Advanced age attenuates the antihyperalgesic effect of morphine and decreases μ-opioid receptor expression and binding in the rat midbrain Periaqueductal Gray in male and female rats

2020 ◽  
Author(s):  
Evan F. Fullerton ◽  
Myurajan Rubaharan ◽  
Mary C. Karom ◽  
Richard I. Hanberry ◽  
Anne Z. Murphy
Keyword(s):  
Opioid Receptor ◽  
Receptor Expression ◽  
Female Rats ◽  
Advanced Age ◽  
Adult Males ◽  
Male And Female ◽  
Male And Female Rats ◽  
Age Related ◽  
Μ Opioid Receptor ◽  
The Impact

AbstractThe present study investigated the impact of advanced age on morphine modulation of persistent inflammatory pain in male and female rats. The impact of age, sex, and pain on μ-opioid receptor (MOR) expression and binding in the ventrolateral PAG (vlPAG) was also examined using immunohistochemistry and receptor autoradiography. Intraplantar administration of Complete Freund’s adjuvant induced comparable levels of edema and hyperalgesia in adult (2-3mos) and aged (16-18mos) male and female rats. Morphine potency was highest in adult males, with a two-fold decrease in morphine EC50 observed in aged versus adult males (10.22mg/kg versus 5.19mg/kg). Adult and aged female rats also exhibited significantly higher EC50 values (10.69 mg/kg and 9.00 mg/kg, respectively) compared to adult males. The upward shift in EC50 from adult to aged males was paralleled by a reduction in vlPAG MOR expression and binding. The observed age-related reductions in morphine potency and vlPAG MOR expression and binding have significant implications in pain management in the aged population.

scholarly journals Behavioral Expression of Contextual Fear in Male and Female Rats

2021 ◽  
Vol 15 ◽  
Author(s):  
Amanda S. Russo ◽  
Ryan G. Parsons
Keyword(s):  
Fear Conditioning ◽  
Freezing Behavior ◽  
Contextual Fear Conditioning ◽  
Female Rats ◽  
Post Traumatic Stress ◽  
Male And Female ◽  
Contextual Fear ◽  
Male And Female Rats ◽  
Fear Potentiated Startle ◽  
Fear And Anxiety

The study of fear conditioning has led to a better understanding of fear and anxiety-based disorders such as post-traumatic stress disorder (PTSD). Despite the fact many of these disorders are more common in women than in men, the vast majority of work investigating fear conditioning in rodents has been conducted in males. The goal of the work presented here was to better understand how biological sex affects contextual fear conditioning and expression. To this end, rats of both sexes were trained to fear a specific context and fear responses were measured upon re-exposure to the conditioning context. In the first experiment, male and female rats were given context fear conditioning and tested the next day during which freezing behavior was measured. In the second experiment, rats were trained and tested in a similar fashion while fear-potentiated startle and defecation were measured. We found that males showed more freezing behavior than females during a fear expression test. The expression of fear-potentiated startle did not differ between sexes, while males exhibited more defecation during a test in a novel context. These data suggest that the expression of defensive behavior differs between sexes and highlight the importance of using multiple measures of fear when comparing between sexes.

scholarly journals Proteomic Analysis Reveals Sex-Specific Protein Degradation Targets in the Amygdala During Fear Memory Formation

2021 ◽  
Vol 14 ◽  
Author(s):  
Kayla Farrell ◽  
Madeline Musaus ◽  
Shaghayegh Navabpour ◽  
Kiley Martin ◽  
W. Keith Ray ◽  
...  
Keyword(s):  
Protein Degradation ◽  
Fear Conditioning ◽  
Degradation Process ◽  
Fear Memory ◽  
Memory Formation ◽  
Contextual Fear Conditioning ◽  
Female Rats ◽  
Protein Targets ◽  
Male And Female Rats ◽  
Ubiquitin Proteasome

Ubiquitin-proteasome mediated protein degradation has been widely implicated in fear memory formation in the amygdala. However, to date, the protein targets of the proteasome remain largely unknown, limiting our understanding of the functional significance for protein degradation in fear memory formation. Additionally, whether similar proteins are targeted by the proteasome between sexes has yet to be explored. Here, we combined a degradation-specific K48 Tandem Ubiquitin Binding Entity (TUBE) with liquid chromatography mass spectrometry (LC/MS) to identify the target substrates of the protein degradation process in the amygdala of male and female rats following contextual fear conditioning. We found that males (43) and females (77) differed in the total number of proteins that had significant changes in K48 polyubiquitin targeting in the amygdala following fear conditioning. Many of the identified proteins (106) had significantly reduced levels in the K48-purified samples 1 h after fear conditioning, suggesting active degradation of the substrate due to learning. Interestingly, only 3 proteins overlapped between sexes, suggesting that targets of the protein degradation process may be sex-specific. In females, many proteins with altered abundance in the K48-purified samples were involved in vesicle transport or are associated with microtubules. Conversely, in males, proteins involved in the cytoskeleton, ATP synthesis and cell signaling were found to have significantly altered abundance. Only 1 protein had an opposite directional change in abundance between sexes, LENG1, which was significantly enhanced in males while lower in females. This suggests a more rapid degradation of this protein in females during fear memory formation. Interestingly, GFAP, a critical component of astrocyte structure, was a target of K48 polyubiquitination in both males and females, indicating that protein degradation is likely occurring in astrocytes following fear conditioning. Western blot assays revealed reduced levels of these target substrates following fear conditioning in both sexes, confirming that the K48 polyubiquitin was targeting these proteins for degradation. Collectively, this study provides strong evidence that sex differences exist in the protein targets of the degradation process in the amygdala following fear conditioning and critical information regarding how ubiquitin-proteasome mediated protein degradation may contribute to fear memory formation in the brain.

Contextual Conditioned Fear Blocks the Induction But Not the Maintenance of Lateral Septal LTP in Behaving Mice

1997 ◽  
Vol 78 (1) ◽  
pp. 76-81 ◽  
Author(s):  
René Garcia ◽  
Rose Marie Vouimba ◽  
Robert Jaffard
Keyword(s):  
Fear Conditioning ◽  
Conditioned Fear ◽  
Field Potential ◽  
Long Term Potentiation ◽  
Contextual Fear Conditioning ◽  
Lateral Septum ◽  
High Frequency Stimulation ◽  
Conditioning Chamber ◽  
Contextual Fear ◽  
Frequency Stimulation

Garcia, René, Rose Marie Vouimba, and Robert Jaffard. Contextual conditioned fear blocks the induction but not the maintenance of lateral septal LTP in behaving mice. J. Neurophysiol. 78: 76–81, 1997. High-frequency stimulation (HFS) of the fimbria induces long-term potentiation (LTP) in the lateral septum. This study was aimed at investigating the effect of contextual fear conditioning on septal LTP with the use of behaving C57 BL/6 mice as subjects. For the acquisition of contextual fear conditioning, animals were placed in a conditioning chamber, where they were subjected to footshocks (FSs, 0.6 mA); the following day (retention), animals were reexposed to the chamber. Animals from the first group received HFS in their home cages before being submitted to conditioning; animals from the second group were first submitted to conditioning before receiving HFS during reexposure to the conditioning chamber; animals from the third group were submitted to the same regimen as those from the second group, except that no FS was delivered in the conditioning chamber; and animals from the fourth group received FS in the conditioning chamber but were maintained in their home cages the day after for LTP induction. Before conditioning, animals from the first group, placed in a familiar context (home cage), displayed an LTP of the N3 wave of septal field potential. After conditioning, reexposure of these animals to the conditioning chamber produced a transient decrease in the amplitude of N3 but did not interfere with the duration of maintenance of LTP. Conversely, in animals from the second group, when HFS was applied during reexposure to the conditioning chamber the induction of LTP was totally blocked. However, mice from the two other groups (3rd and 4th) displayed normal levels of LTP. Taken together with previous findings, these data suggest that contextual conditioned fear may interfere with certain forms of learning via blockade of hippocampal-septal LTP.

scholarly journals Cerebellar molecular layer interneurons are dispensable for cued and contextual fear conditioning

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Katy L. H. Marshall-Phelps ◽  
Gernot Riedel ◽  
Peer Wulff ◽  
Marta Woloszynowska-Fraser
Keyword(s):  
Fear Conditioning ◽  
Purkinje Cells ◽  
Cerebellar Cortex ◽  
Conditioned Fear ◽  
Molecular Layer ◽  
Fear Memory ◽  
Memory Formation ◽  
Contextual Fear Conditioning ◽  
Contextual Fear

AbstractPurkinje cells are the only output cell of the cerebellar cortex. Their spatiotemporal activity is controlled by molecular layer interneurons (MLIs) through GABAA receptor-mediated inhibition. Recently, it has been reported that the cerebellar cortex is required for consolidation of conditioned fear responses during fear memory formation. Although the relevance of MLIs during fear memory formation is currently not known, it has been shown that synapses made between MLIs and Purkinje cells exhibit long term plasticity following fear conditioning. The present study examined the role of cerebellar MLIs in the formation of fear memory using a genetically-altered mouse line (PC-∆γ2) in which GABAA receptor-mediated signaling at MLI to Purkinje cell synapses was functionally removed. We found that neither acquisition nor recall of fear memories to tone and context were altered after removal of MLI-mediated inhibition.

scholarly journals Distinct Contributions of Median Raphe Nucleus to Contextual Fear Conditioning and Fear-Potentiated Startle

2002 ◽  
Vol 9 (4) ◽  
pp. 233-247 ◽  
Author(s):  
R. C. B. Silva ◽  
A. P. M. Cruz ◽  
V. Avanzi ◽  
J. Landeira-Fernandez ◽  
M. L. Brandão
Keyword(s):  
Fear Conditioning ◽  
Conditioned Fear ◽  
Raphe Nucleus ◽  
Contextual Fear Conditioning ◽  
Median Raphe ◽  
Median Raphe Nucleus ◽  
Contextual Fear ◽  
Electrolytic Lesions ◽  
Fear Potentiated Startle ◽  
Median Raphé

Ascending 5-HT projections from the median raphe nucleus (MRN), probably to the hippocampus, are implicated in the acquisition of contextual fear (background stimuli), as assessed by freezing behavior. Foreground cues like light, used as a conditioned stimulus (CS) in classical fear conditioning, also cause freezing through thalamic transmission to the amygdala. As the MRN projects to the hippocampus and amygdala, the role of this raphe nucleus in fear conditioning to explicit cues remains to be explained. Here we analyzed the behavior of rats with MRN electrolytic lesions in a contextual conditioning situation and in a fear-potentiated startle procedure. The animals received MRN electrolytic lesions either before or on the day after two consecutive training sessions in which they were submitted to 10 conditioning trials, each in an experimental chamber (same context) where they. received foot-shocks (0.6 mA, 1 sec) paired to a 4-sec light CS. Seven to ten days later, the animals were submitted to testing sessions for assessing conditioned fear when they were placed for five shocks, and the duration of contextual freezing was recorded. The animals were then submitted to a fear-potentiated startle in response to a 4-sec light-CS, followed by white noise (100 dB, 50 ms). Control rats (sham) tested in the same context showed more freezing than did rats with pre- or post-training MRN lesions. Startle was clearly potentiated in the presence of light CS in the sham-lesioned animals. Whereas pretraining lesions reduced both freezing and fear-potentiated startle, the post-training lesions reduced only freezing to context, without changing the fear-potentiated startle. In a second experiment, neurotoxic lesions of the MRN with local injections of N-methyl-D-aspartate or the activation of5-HT1Asomatodendritic auto-receptors of the MRN by microinjections of the5-HT1Areceptor agonist 8-hydroxy- 2-(di-n-propylamino)tetralin (8-OH-DPAT) before the training sessions also reduced the amount of freezing and the fear-potentiated startle. Freezing is a prominent response of contextual fear conditioning, but does not seem to be crucial for the enhancement of the startle reflex by explicit aversive cues. As fear-potentiated startle may be produced in posttraining lesioned rats that are unable to freeze to fear contextual stimuli, dissociable systems seem to be recruited in each condition. Thus, contextual fear and fear-potentiated startle are conveyed by distinct 5-HT-mediated circuits of the MRN.

scholarly journals Adolescent rats show estrous cycle-mediated sex-differences in extinction of conditioned fear

2020 ◽  
Author(s):  
Christina J Perry ◽  
Despina E Ganella ◽  
Ly Dao Nguyen ◽  
Xin Du ◽  
Katherine D Drummond ◽  
...  
Keyword(s):  
Anxiety Disorders ◽  
Conditioned Fear ◽  
High Plasma ◽  
Female Rats ◽  
Adolescent Male ◽  
Adult Males ◽  
Preclinical Research ◽  
Male And Female ◽  
Male And Female Rats ◽  
Estradiol Levels

AbstractAnxiety disorders are more prevalent in females than males, and frequently emerge during adolescence. Despite this, preclinical research commonly focuses on adult males. Here we use Pavlovian fear conditioning and extinction in adolescent male and female rats to understand sex- and age-dependent processes relevant to anxiety disorders. In experiment 1, 35-day-old male and female rats were exposed to 6 pairings of a conditioned stimulus (CS, a tone) with an aversive unconditioned stimulus (US, a footshock). The next day they were extinguished in a contextually distinct chamber, via 60 presentations of the CS without the US. Extinction recall was tested 24 hours later in the extinction context. Estrous phase was monitored by cytology on vaginal smears taken 1 hour after each behavioral session. In experiment 2, male and female rats were given sham surgery or gonadectomy at 21 days of age. They were then trained and tested as for experiment 1. We observed that females in proestrus or met/diestrus during extinction showed delayed extinction and impaired extinction recall the next day compared to males. Ovariectomy enhanced extinction for female rats, but orchidectomy delayed extinction for males. Plasma analyses showed that met/di/proestrus phases were associated with high estradiol levels. These findings suggest that high plasma estradiol levels impair extinction for adolescent females. While these results contradict what is observed in adult animals, they are consistent with the prevalence of anxiety disorders observed in females. Our findings have important implications for understanding and treating anxiety in adolescents, particularly where treatment involves extinction-based therapies.

scholarly journals Plasticity of GluN1 at Ventral Hippocampal Synapses in the Infralimbic Cortex

2021 ◽  
Vol 13 ◽  
Author(s):  
Yesenia Castillo-Ocampo ◽  
María Colón ◽  
Anixa Hernández ◽  
Pablo Lopez ◽  
Yamil Gerena ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Nmda Receptor ◽  
Nmda Receptors ◽  
Fear Conditioning ◽  
Contextual Fear Conditioning ◽  
Receptor Expression ◽  
Female Rats ◽  
Male Rats ◽  
Infralimbic Cortex ◽  
Male And Female Rats

Although the infralimbic cortex (IL) is not thought to play a role in fear acquisition, recent experiments found evidence that synaptic plasticity is occurring at ventral hippocampal (vHPC) synapses in IL during auditory fear acquisition as measured by changes in the N-methyl-D-aspartate (NMDA) receptor-mediated currents in male rats. These electrophysiological data suggest that fear conditioning changes the expression of NMDA receptors on vHPC-to-IL synapses. To further evaluate the plasticity of NMDA receptors at this specific synapse, we injected AAV particles expressing channelrhodopsin-EYFP into the vHPC of male and female rats to label vHPC projections with EYFP. To test for NMDA receptor changes in vHPC-to-IL synapses after fear learning, we used fluorescence-activated cell sorting (FACS) to quantify synaptosomes isolated from IL tissue punches that were positive for EYFP and the obligatory GluN1 subunit. More EYFP+/GluN1+ synaptosomes with greater average expression of GluN1 were isolated from male rats exposed to auditory fear conditioning (AFC) than those exposed to context and tones only or to contextual fear conditioning (CFC), suggesting that AFC increased NMDA receptor expression in males. In a second experiment, we found that pairing the tones and shocks was required to induce the molecular changes and that fear extinction did not reverse the changes. In contrast, females showed similar levels of EYFP+/GluN1+ synaptosomes in all behavioral groups. These findings suggest that AFC induces synaptic plasticity of NMDA receptors in the vHPC-to-IL projection in males, while female rats rely on different synaptic mechanisms.

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