Bombesin-like peptide recruits disinhibitory cortical circuits and enhances fear memories

1. Download : Download high-res image (200KB)
2. Download : Download full-size image

     

Early life environment determines the development of adult phobic‐like fear responses in BALB/cAnN mice

Environmental factors may unleash genetically determined susceptibility to psychopathology. Great effort has been spent in identifying both the genetic basis and environmental sources of exaggerated fear in animal models of anxiety disorders. Here, we show that the origin of inbred mice, probably via subtle differences in breeding and rearing conditions, may have large consequences specifically on acquisition and retention of fear memories, while leaving anxiety‐related behaviours unaffected. These effects could be seen in BALB/cAnN (BALB), but not in C57BL/6N (C57BL/6) mice, thus suggesting their dependency on the genetic background. Increased susceptibility for developing exaggerated fear responses was accompanied by decreased long‐term depression and increased surface trafficking of the AMPA receptor GluR1 subunit at the level of the basolateral amygdala complex. Together, these data raise a novel caveat in the debate about the origins of variation in behavioural studies with experimental animals. Considering that there are currently no animal models which explicitly consider conceptual analogy to the specific gene–environment interactions observed in the aetiology of phobias, our study might suggest a novel approach and direction for further preclinical studies focusing on such aspects of phobic‐like fears.     

Amygdala Reward Neurons Form and Store Fear Extinction Memory

Download : Download video (97MB)     

Enhanced hippocampus‐dependent memory and reduced anxiety in mice over‐expressing human catalase in mitochondria

Oxidative stress (OS) and reactive oxygen species (ROS) play a modulatory role in synaptic plasticity and signaling pathways. Mitochondria (MT), a major source of ROS because of their involvement in energy metabolism, are important for brain function. MT‐generated ROS are proposed to be responsible for a significant proportion of OS and are associated with developmental abnormalities and aspects of cellular aging. The role of ROS and MT function in cognition of healthy individuals is relatively understudied. In this study, we characterized behavioral and cognitive performance of 5‐ to 6‐month‐old mice over‐expressing mitochondrial catalase (MCAT). MCAT mice showed enhancements in hippocampus‐dependent spatial learning and memory in the water maze and contextual fear conditioning, and reduced measures of anxiety in the elevated zero maze. Catalase activity was elevated in MCAT mice in all brain regions examined. Measures of oxidative stress (glutathione, protein carbonyl content, lipid peroxidation, and 8‐hydroxyguanine) did not significantly differ between the groups. The lack of differences in these markers of oxidative stress suggests that the differences observed in this study may be due to altered redox signaling. Catalase over‐expression might be sufficient to enhance cognition and reduce measures of anxiety even in the absence of alteration in levels of OS.     

Dog training as a violence prevention tool for at-risk adolescents

Abstract

Humane education programs often target at-risk children and seek to teach empathy and gentleness with animals, but few of these have been assessed. This prospective, longitudinal study examined the effects of “Teaching Love and Compassion” (TLC), a humane education program employing educational group discussions and dog training for seventh-grade, inner city youth in Los Angeles, California. The TLC program is offered to groups of 10 to 12 students during their three-week vacation at the year-round school. Students for the experimental and control groups were selected from the pool of those scoring below the 25th percentile in reading and mathematics. The study, conducted over a two-year period, assessed four successive sessions, comprising an experimental group of 41 children and a control group of 42 children. In morning sessions, the experimental group had discussions focusing on interpersonal issues and conflict management. In the afternoons they were taught the proper care and obedience training of shelter dogs. Pre-, post-, and follow-up tests, specially developed to accommodate the children's reading ability and scheduling constraints, were given to both the experimental and control groups to assess their knowledge of animal care, conflict management skills, attitudes toward self and others, and fear of dogs. Members of the experimental group increased their understanding of pet care and the needs of animals and retained this information more than did the control group for all four TLC sessions, both at post-testing (F=58.4, p=0.0001) and follow-up testing (F=18.9, p=0.0001). At post-testing, the experimental group showed a trend toward a decreased fear of dogs (F=3.6, p=0.062), that was significant at follow-up testing (F=4.2, p=0.019). For these children who are exposed to daily violence and aggression to people and animals, these modest changes were associated with the three-week intervention.     

The brain‐derived neurotrophic factor VAL68MET polymorphism modulates how developmental ethanol exposure impacts the hippocampus

Prenatal exposure to alcohol causes a wide range of deficits known as fetal alcohol spectrum disorders (FASDs). Many factors determine vulnerability to developmental alcohol exposure including timing and pattern of exposure, nutrition and genetics. Here, we characterized how a prevalent single nucleotide polymorphism in the human brain‐derived neurotrophic factor (BDNF) gene (val66met) modulates FASDs severity. This polymorphism disrupts BDNF's intracellular trafficking and activity‐dependent secretion, and has been linked to increased incidence of neuropsychiatric disorders such as depression and anxiety. We hypothesized that developmental ethanol (EtOH) exposure more severely affects mice carrying this polymorphism. We used transgenic mice homozygous for either valine (BDNF^val/val) or methionine (BDNF^met/met) in residue 68, equivalent to residue 66 in humans. To model EtOH exposure during the second and third trimesters of human pregnancy, we exposed mice to EtOH in vapor chambers during gestational days 12 to 19 and postnatal days 2 to 9. We found that EtOH exposure reduces cell layer volume in the dentate gyrus and the CA1 hippocampal regions of BDNF^met/met but not BDNF^val/val mice during the juvenile period (postnatal day 15). During adulthood, EtOH exposure reduced anxiety‐like behavior and disrupted trace fear conditioning in BDNF^met/met mice, with most effects observed in males. EtOH exposure reduced adult neurogenesis only in the ventral hippocampus of BDNF^val/val male mice. These studies show that the BDNF val66met polymorphism modulates, in a complex manner, the effects of developmental EtOH exposure, and identify a novel genetic risk factor that may regulate FASDs severity in humans.