Individual Differences in Learning Rate and Fear Response Predict Fear Memory and Recovery in Mice and Human Subjects.
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ABSTRACT:
SUBMITTER: Gao Y
PROVIDER: S-EPMC7340707 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Our objective was to characterize individual differences in fear conditioning and extinction in an outbred rat strain, to test behavioral predictors of these individual differences, and to assess their heritability. We fear-conditioned 100 Long-Evans rats, attempted to extinguish fear the next day, and tested extinction recall on the third day. The distribution of freezing scores after fear conditioning was skewed, with most rats showing substantial freezing; after fear extinction, the distribution was bimodal with most rats showing minimal freezing, but a substantial portion showing maximal freezing. Longer rearing episodes measured prior to conditioning predicted less freezing at the beginning of extinction, but differences in extinction learning were not predicted by any baseline exploratory behaviors. We tested the heritability of extinction differences by breeding rats from the top and bottom 20% of freezing scores during extinction recall. We then ran the offspring through the same conditioning/extinction procedure, with the addition of recording ultrasonic vocalizations throughout training and testing. Only a minority of rats emitted distress vocalizations during fear acquisition, but the incidence was less frequent in the offspring of good extinguishers than in poor extinguishers or randomly bred controls. The occurrence of distress vocalizations during acquisition predicted higher levels of freezing during fear recall regardless of breeding line, but the relationship between vocalization and freezing was no longer evident following extinction training, at which point freezing levels were influenced only by breeding and not by vocalization. The heritability (h(2)) of extinction recall was estimated at 0.36, consistent with human estimates.
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Project description:Memory formation is key for brain functioning. Uncovering the memory mechanisms is helping us to better understand neural processes in health and disease. Moreover, more specific treatments for fear-related disorders such as posttraumatic stress disorder and phobias may help to decrease their negative impact on mental health. In this line, the Tachykinin 2 (Tac2) pathway in the central amygdala (CeA) has been shown to be sufficient and necessary for the modulation of fear memory consolidation. CeA-Tac2 antagonism and its pharmacogenetic temporal inhibition impair fear memory in male mice. Surprisingly, we demonstrate here the opposite effect of Tac2 blockade on enhancing fear memory consolidation in females. Furthermore, we show that CeA-testosterone in males, CeA-estradiol in females and Akt/GSK3β/β-Catenin signaling both mediate the opposite-sex differential Tac2 pathway regulation of fear memory.
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Project description:Individuals are consistently better at recognizing own-race faces compared to other-race faces (other-race effect, ORE). One popular hypothesis is that this recognition memory ORE is caused by differential own- and other-race holistic processing, the simultaneous integration of part and configural face information into a coherent whole. Holistic processing may create a more rich, detailed memory representation of own-race faces compared to other-race faces. Despite several studies showing that own-race faces are processed more holistically than other-race faces, studies have yet to link the holistic processing ORE and the recognition memory ORE. In the current study, we sought to use a more valid method of analyzing individual differences in holistic processing by using regression to statistically remove the influence of the control condition (part trials in the part-whole task) from the condition of interest (whole trials in the part-whole task). We also employed regression to separately examine the two components of the ORE: own-race advantage (regressing other-race from own-race performance) and other-race decrement (regressing own-race from other-race performance). First, we demonstrated that own-race faces were processed more holistically than other-race faces, particularly the eye region. Notably, using regression, we showed a significant association between the own-race advantage in recognition memory and the own-race advantage in holistic processing and that these associations were weaker when examining the other-race decrement. We also demonstrated that performance on own- and other-race faces across all of our tasks was highly correlated, suggesting that the differences we found between own- and other-race faces are quantitative rather than qualitative. Together, this suggests that own- and other-race faces recruit largely similar mechanisms, that own-race faces more thoroughly engage holistic processing, and that this greater engagement of holistic processing is significantly associated with the own-race advantage in recognition memory.
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Project description:It remains unexplored in the field of fear memory whether functional neuronal connectivity between two brain areas is necessary for one sex but not the other. Here, we show that chemogenetic silencing of centromedial (CeM)-Tac2 fibers in the lateral posterior BNST (BNSTpl) decreased fear memory consolidation in male mice but not females. Optogenetic excitation of CeM-Tac2 fibers in the BNSTpl exhibited enhanced inhibitory postsynaptic currents in males compared to females. In vivo calcium imaging analysis revealed a sex-dimorphic fear memory engram in the BNSTpl. Furthermore, in humans, the single-nucleotide polymorphism (SNP) in the Tac2 receptor (rs2765) (TAC3R) decreased CeM-BNST connectivity in a fear task, impaired fear memory consolidation, and increased the expression of the TAC3R mRNA in AA-carrier men but not in women. These sex differences in critical neuronal circuits underlying fear memory formation may be relevant to human neuropsychiatric disorders with fear memory alterations such as posttraumatic stress disorder.
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