Enhanced generalization of auditory conditioned fear in juvenile mice

Ito, Wataru; Pan, Bing Xing; Yang, Chao; Thakur, Siddarth; Morozov, Alexei

doi:10.1101/lm.1190809

Cited by 39 publications

(31 citation statements)

References 34 publications

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“…When the BDNF +/2 mice are 3 mo of age or above, a learning deficit in fear learning occurs. In several recent studies it has been shown that fear learning differs between adolescent and adult mice, with 4-wk-old mice expressing more conditioned freezing and showing more generalized fear than 2-mo-old animals (Hefner and Holmes 2007;Ito et al 2009). …”

Section: Discussionmentioning

confidence: 99%

Age-dependent deficits in fear learning in heterozygous BDNF knock-out mice

Endres

Leßmann

2012

Learn. Mem.

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Beyond its trophic function, the neurotrophin BDNF (brain-derived neurotrophic factor) is well known to crucially mediate synaptic plasticity and memory formation. Whereas recent studies suggested that acute BDNF/TrkB signaling regulates amygdala-dependent fear learning, no impairments of cued fear learning were reported in heterozygous BDNF knockout mice (BDNF +/2 ). Since brain BDNF levels are known to decline with aging, we hypothesized that BDNF +/2 mice might show reduced fear learning at older ages. Indeed, BDNF +/2 animals revealed an age-dependent deficit in fear learning 3 mo after birth and beyond. Since there were no alterations between the two genotypes during the conditioning training and when testing short-term memory, this learning deficit most likely reflects a deficit in memory consolidation. Importantly, there were no differences in spontaneous motor behavior and baseline anxiety in BDNF +/2 animals at any age tested. Following behavioral testing quantification of BDNF levels in the basolateral amygdala with a sensitive BDNF ELISA revealed a positive correlation between the levels of BDNF in the amygdala and the individual learning performance. However, the age-dependent decline in the efficiency of fear conditioning in BDNF +/2 mice was not accompanied by reduced BDNF expression in the amygdala. Thus, while reduced BDNF levels in general correlate with less efficient fear learning, this lack of BDNF can be compensated in young but not in older animals, suggesting that the cellular mechanisms responsible for fear learning consolidation become BDNF-dependent 3 mo after birth.

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Section: Discussionmentioning

confidence: 99%

Age-dependent deficits in fear learning in heterozygous BDNF knock-out mice

Endres

Leßmann

2012

Learn. Mem.

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“…However, it is known that overtraining protocols of fear learning also lead to a generalization of the fear response, where a defensive response is elicited even in environmental context or during exposure to cues distinct to the conditioning setting (Laxmi et al, 2003). Interestingly, enhanced generalization of fear conditioning has been observed in juvenile mice as compared with adult mice (Ito et al, 2009). This generalization, however, was significantly reduced in the presence of the explicitly unpaired cue (ie, the safety signal) in both juvenile and adult animals, suggesting that the neurobiological mechanisms required for safety learning are already functional during the adolescent period and have adaptive relevance for overcoming augmented juvenile fear generalization (Ito et al, 2009).…”

Section: Neural Correlates Of Learned Safetymentioning

confidence: 99%

“…Interestingly, enhanced generalization of fear conditioning has been observed in juvenile mice as compared with adult mice (Ito et al, 2009). This generalization, however, was significantly reduced in the presence of the explicitly unpaired cue (ie, the safety signal) in both juvenile and adult animals, suggesting that the neurobiological mechanisms required for safety learning are already functional during the adolescent period and have adaptive relevance for overcoming augmented juvenile fear generalization (Ito et al, 2009). In light of these findings, it would be tempting to explore whether, because of this heightened emotionality in adolescent animals, an Neural correlates of learned safety E Kong et al intense fear conditioning procedure could also lead to an induction of immobility in the forced-swim test.…”

Section: Neural Correlates Of Learned Safetymentioning

confidence: 99%

“…When contrasting learned safety and learned fear, several important insights about the neurobiology of learned safety can also be drawn from a host of studies in which explicitly unpaired 'control' groups had been studied. Important examples include the assessment of generalization described above (Bang et al, 2008;Ito et al, 2009;Laxmi et al, 2003), the effect on sleep (Jha et al, 2005;Madan et al, 2008), and investigations on the role of the amygdala (Choi et al, 2001;Maren, 2000;Maren et al, 2001). …”

Section: Neural Correlates Of Learned Safetymentioning

confidence: 99%

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Learning not to Fear: Neural Correlates of Learned Safety

Kong

Monje

Hirsch

et al. 2013

Neuropsychopharmacol

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The ability to recognize and properly respond to instances of protection from impending danger is critical for preventing chronic stress and anxiety-central symptoms of anxiety and affective disorders afflicting large populations of people. Learned safety encompasses learning processes, which lead to the identification of episodes of security and regulation of fear responses. On the basis of insights into the neural circuitry and molecular mechanisms involved in learned safety in mice and humans, we describe learned safety as a tool for understanding neural mechanisms involved in the pathomechanisms of specific affective disorders. This review summarizes our current knowledge on the neurobiological underpinnings of learned safety and discusses potential applications in basic and translational neurosciences.

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“…Individual components of the fear response are thought to incorporate sequentially as animals mature, eventually giving rise to what are identified as mature fear behaviors (Wiedenmayer, 2009). Indeed, several studies have revealed that distinct fear behaviors emerge at different times during early postnatal life and continue to mature during late postnatal development (Blozovski and Cudennec, 1980;Bronstein and Hirsch, 1976;Chen et al, 2006;Collier et al, 1979;Foster and Burman, 2010;Hefner and Holmes, 2007;Hubbard et al, 2004;Ito et al, 2009;Kim and Richardson, 2007;Moriceau et al, 2004;Raineki et al, 2010;Rudy, 1993;Takahashi, 1992;Wiedenmayer andBarr, 1998, 2001a,b).…”

Section: Introductionmentioning

confidence: 99%

Postnatal development of the amygdala: A stereological study in rats

Chareyron

Lavenex

2012

J of Comparative Neurology

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The amygdala is the central component of a functional brain system regulating fear and emotional behaviors. Studies of the ontogeny of fear behaviors reveal the emergence of distinct fear responses at different postnatal ages. Here, we performed a stereological analysis of the rat amygdala to characterize the cellular changes underlying its normal structural development. Distinct amygdala nuclei exhibited different patterns of postnatal development, which were largely similar to those we have previously shown in monkeys. The combined volume of the lateral, basal, and accessory basal nuclei increased by 113% from 1 to 3 weeks of age and by an additional 33% by 7 months of age. The volume of the central nucleus increased only 37% from 1 to 2 weeks of age and 38% from 2 weeks to 7 months. At 1 week of age, the medial nucleus was 77% of the 7-monthold's volume and exhibited a constant, marginal increase until 7 months. Neuron number did not differ in the amygdala from 1 week to 7 months of age. In contrast, astrocyte number decreased from 3 weeks to 2 months of age in the whole amygdala. Oligodendrocyte number increased in all amygdala nuclei from 3 weeks to 7 months of age. Our findings revealed that distinct amygdala nuclei exhibit different developmental profiles and that the rat amygdala is not fully mature for an extended period postnatally. We identified different periods of postnatal development of distinct amygdala nuclei and cellular components, which are concomitant with the ontogeny of different fear and emotional behaviors.

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Enhanced generalization of auditory conditioned fear in juvenile mice

Cited by 39 publications

References 34 publications

Age-dependent deficits in fear learning in heterozygous BDNF knock-out mice

Age-dependent deficits in fear learning in heterozygous BDNF knock-out mice

Learning not to Fear: Neural Correlates of Learned Safety

Postnatal development of the amygdala: A stereological study in rats

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