Rapid Selection Response for Contextual Fear Conditioning in a Cross Between C57BL/6J and A/J: Behavioral, QTL and Gene Expression Analysis

Ponder, Christine A.; Huded, Chetan; Munoz, Michaelanne B.; Gulden, Forrest O.; Gilliam, T. Conrad; Palmer, Abraham A.

doi:10.1007/s10519-008-9203-6

Cited by 22 publications

(30 citation statements)

References 32 publications

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“…We confirmed a number of QTL that were previously identified using genetically diverse mouse populations derived from B6 and A/J. These include a Chromosome 1 (Chr.1) QTL (peaking at 70–80 cM) influencing open field activities (Gershenfeld and Paul, 1997), a Chr.1 QTL (peaking at ~75 cM) for body weight (Zhang and Gershenfeld, 2003), and a Chr.7 QTL (peaking at ~50 cM) co-localized with the albino ( Tyr ) locus influencing conditioned fear (Ponder et al, 2008). …”

Section: Resultsmentioning

confidence: 99%

A Systems Approach Identifies Networks and Genes Linking Sleep and Stress: Implications for Neuropsychiatric Disorders

et al. 2015

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SUMMARY Sleep dysfunction and stress susceptibility are co-morbid complex traits, which often precede and predispose patients to a variety of neuropsychiatric diseases. Here, we demonstrate multi-level organizations of genetic landscape, candidate genes, and molecular networks associated with 328 stress and sleep traits in a chronically stressed population of 338 (C57BL/6J×A/J) F2 mice. We constructed striatal gene co-expression networks, revealing functionally and cell-type specific gene co-regulations important for stress and sleep. Using a composite ranking system, we identified network modules most relevant for 15 independent phenotypic categories, highlighting a mitochondria/synaptic module that links sleep and stress. The key network regulators of this module are overrepresented with genes implicated in neuropsychiatric diseases. Our work suggests the interplay between sleep, stress, and neuropathology emerge from genetic influences on gene expression and their collective organization through complex molecular networks, providing a framework to interrogate the mechanisms underlying sleep, stress susceptibility, and related neuropsychiatric disorders.

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Section: Resultsmentioning

confidence: 99%

A Systems Approach Identifies Networks and Genes Linking Sleep and Stress: Implications for Neuropsychiatric Disorders

et al. 2015

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“…0.01 cutoff) have been identified in previous studies. These include, for example, SAMD4A, FGFR10P2, and CD99LD, which were identified during a selection response for contextual fear conditioning in rats using quantitative trait locus (QTL) and gene expression studies [Ponder et al, 2008]; KEK4, MUB and HSPB1 were identified in fruit flies selected for aggressive behavior [Dierick and Greenspan, 2006] and PEX19 and DEDD were identified proximal to a QTL hotspot on mouse chromosome 1 that modulates behavior [Mozhui et al, 2008]. Similarly, the long-term synaptic depression (LTD) pathway, one of the most overrepresented pathways revealed in our study, has been associated with predator threat.…”

Section: Discussionmentioning

confidence: 99%

Brain Transcriptomic Response of Threespine Sticklebacks to Cues of a Predator

Sanogo

Hankison²,

Band³

et al. 2011

Brain Behav Evol

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Predation pressure represents a strong selective force that influences the development and evolution of living organisms. An increasing number of studies have shown that both environmental and social factors, including exposure to predators, substantially shape the structure and function of the brain. However, our knowledge about the molecular mechanisms underlying the response of the brain to environmental stimuli is limited. In this study, we used whole-genome comparative oligonucleotide microarrays to investigate the brain transcriptomic response to cues of a predator in the threespine stickleback, Gasterosteus aculeatus. We found that repeated exposure to olfactory, visual and tactile cues of a predator (rainbow trout, Oncorrhynchus mykiss) for 6 days resulted in subtle but significant transcriptomic changes in the brain of sticklebacks. Gene functional analysis and gene ontology enrichment revealed that the majority of the transcripts differentially expressed between the fish exposed to cues of a predator and the control group were related to antigen processing and presentation involving the major histocompatibility complex, transmission of synaptic signals, brain metabolic processes, gene regulation and visual perception. The top four identified pathways were synaptic long-term depression, RAN signaling, relaxin signaling and phototransduction. Our study demonstrates that exposure of sticklebacks to cues of a predator results in the activation of a wide range of biological and molecular processes and lays the foundation for future investigations on the molecular factors that modulate the function and evolution of the brain in response to stressors.

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“…Heritable differences in fear acquisition have already been established with selective breeding experiments (Radcliffe et al 2000; Ponder et al 2007, 2008; De Castro Gomes and Landeira-Fernandez 2008), and we wished to control for this factor in assessing whether differences in extinction learning have a heritable component. Moreover, differences in initial conditioned freezing can be generated by the incidental selection of arbitrary factors unrelated to emotional learning, such as general activity level or sensitivity to the tone or shock.…”

Section: Methodsmentioning

confidence: 99%

Predictability and heritability of individual differences in fear learning

2014

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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 (h2) of extinction recall was estimated at 0.36, consistent with human estimates.Electronic supplementary materialThe online version of this article (doi:10.1007/s10071-014-0752-1) contains supplementary material, which is available to authorized users.

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Rapid Selection Response for Contextual Fear Conditioning in a Cross Between C57BL/6J and A/J: Behavioral, QTL and Gene Expression Analysis

Cited by 22 publications

References 32 publications

A Systems Approach Identifies Networks and Genes Linking Sleep and Stress: Implications for Neuropsychiatric Disorders

A Systems Approach Identifies Networks and Genes Linking Sleep and Stress: Implications for Neuropsychiatric Disorders

Brain Transcriptomic Response of Threespine Sticklebacks to Cues of a Predator

Predictability and heritability of individual differences in fear learning

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