Behavioral Expression of Contextual Fear in Male and Female Rats

Russo, Amanda S; Parsons, Ryan G.

doi:10.3389/fnbeh.2021.671017

Cited by 16 publications

(19 citation statements)

References 49 publications

(72 reference statements)

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“…Greater freezing for the Remote groups could reflect incubation of fear, or it could reflect weaker conditioning in the Recent groups. Secondly, we did not detect any sex differences in context retrieval, which is consistent with some of the literature regarding context fear [but see, e.g., Maren et al (1994) , Poulos et al (2015) , and Russo and Parsons (2021) ]. For example, Dachtler et al (2011) observed similar freezing between male and female wild-type mice when they returned to the conditioning context after a 24-h retention period.…”

Section: Discussionsupporting

confidence: 90%

“…For example, an early study found that male rats froze more than females when re-exposed to the original conditioning context (Maren et al, 1994). While this finding has been replicated (Pryce et al, 1999;Chang et al, 2009;Poulos et al, 2015;Colon et al, 2018;Russo and Parsons, 2021) there are also contradicting reports in the literature (e.g., Dachtler et al, 2011;Fenton et al, 2014).…”

Section: Introductionmentioning

confidence: 98%

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Effects of sex and retention interval on the retrieval and extinction of auditory fear conditioning

Schoenberg

Blanchard

Cheng

et al. 2022

Front. Behav. Neurosci.

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Fear memory retrieval is relevant to psychiatric disorders such as post-traumatic stress disorder (PTSD). One of the hallmark symptoms of PTSD is the repeated retrieval and re-experiencing of the initial fear memory even long after the traumatic event has occurred. Women are nearly twice as likely to develop PTSD following a trauma than men, thus sex differences in the retrieval of fear memories is highly relevant for understanding the development and maintenance of PTSD. In the current study, we aimed to examine sex differences in the retrieval and extinction of either recent or remote fear memories. To do so, we conditioned male and female rats either 1 day (recent) or 28 days (remote) prior to testing retrieval and extinction. While there was no effect of sex or retention interval on initial retrieval, we found that remotely conditioned females exhibited higher rates of freezing than remotely conditioned males in later retrieval/extinction sessions, suggesting a sex difference in the retrieval and/or extinction of remote, but not recent, fear memories. Overall, these results are the first to demonstrate a sex difference in the extinction of remote fear memory, and this may contribute to the differential expression of fear-related disorders like PTSD in men and women.

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Section: Discussionsupporting

confidence: 90%

Section: Introductionmentioning

confidence: 98%

Effects of sex and retention interval on the retrieval and extinction of auditory fear conditioning

Schoenberg

Blanchard

Cheng

et al. 2022

Front. Behav. Neurosci.

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“…We found a main effect for Time [ F (4, 32) = 46.53, P < 0.0001], but not Sex [ F (1, 8) = 0.7709, P = 0.4055] and there was not a Time X Sex interaction [ F (4, 32) = 0.6453, P = 0.6342], indicating that male and female rats performed similar during the training session. Notably, while several labs have reported conflicting results in whether a sex difference exists on this task using the same species and strain as us (Graham et al, 2009 ; Russo and Parsons, 2021 ), we have previously reported that male and female rats show similar fear to the context during the testing session when using identical training parameters (Devulapalli et al, 2021 ). In total, we found 1,261 and 476 K48 polyubiquitinated proteins in females and males, respectively, of which 378 overlapped between sexes ( Figure 1B ).…”

Section: Resultsmentioning

confidence: 71%

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

Farrell

Musaus

Navabpour

et al. 2021

Front. Mol. Neurosci.

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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.

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“…However, studies on the correlation between uremic toxin and inflammatory reactivity according to chronic kidney disease are still insufficient, and further studies are needed. In addition, the expression of contextual fear memory showed differences according to gender in the previous study results [47]. Therefore, mechanistic differences may occur for hippocampal dysfunction caused by chronic renal failure according to gender, and various memory-related behavioral tests and various effect mechanism studies are needed to investigate the relationship.…”

Section: Discussionmentioning

confidence: 71%

Cognitive Sequelae and Hippocampal Dysfunction in Chronic Kidney Disease following 5/6 Nephrectomy

Kim

et al. 2022

Brain Sciences

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Neurological disorders are prevalent in patients with chronic kidney disease (CKD). Vascular factors and uremic toxins are involved with cognitive impairment in CKD. In addition, vascular dementia-induced alterations in the structure and function of the hippocampus can lead to deficits in hippocampal synaptic plasticity and cognitive function. However, regardless of this clinical evidence, the pathophysiology of cognitive impairment in patients with CKD is not fully understood. We used male Sprague Dawley rats and performed 5/6 nephrectomy to observe the changes in behavior, field excitatory postsynaptic potential, and immunostaining of the hippocampus following CKD progression. We measured the hippocampus volume on magnetic resonance imaging scans in the controls (n = 34) and end-stage renal disease (ESRD) hemodialysis patients (n = 42). In four cognition-related behavior assays, including novel object recognition, Y-maze, Barnes maze, and classical contextual fear conditioning, we identified deficits in spatial working memory, learning and memory, and contextual memory, as well as the ability to distinguish familiar and new objects, in the rats with CKD. Immunohistochemical staining of Na+/H+ exchanger1 was increased in the hippocampus of the CKD rat models. We performed double immunofluorescent staining for aquaporin-4 and glial fibrillary acidic protein and then verified the high coexpression in the hippocampus of the CKD rat model. Furthermore, results from recoding of the field excitatory postsynaptic potential (fEPSP) in the hippocampus showed the reduced amplitude and slope of fEPSP in the CKD rats. ESRD patients with cognitive impairment showed a significant decrease in the hippocampus volume compared with ESRD patients without cognitive impairment or the controls. Our findings suggest that uremia resulting from decreased kidney function may cause the destruction of the blood–brain barrier and hippocampus-related cognitive impairment in CKD.

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Behavioral Expression of Contextual Fear in Male and Female Rats

Cited by 16 publications

References 49 publications

Effects of sex and retention interval on the retrieval and extinction of auditory fear conditioning

Effects of sex and retention interval on the retrieval and extinction of auditory fear conditioning

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

Cognitive Sequelae and Hippocampal Dysfunction in Chronic Kidney Disease following 5/6 Nephrectomy

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