Selective Breeding for an Infant Phenotype: Rat Pup Ultrasonic Vocalization (USV)

Abstract

To examine processes underlying generational and developmental influences on anxiety, this laboratory produced two lines of (N:NIH strain) rats, selectively bred on the basis extreme rates of ultrasonic vocalization in 2 minutes of isolation at Postnatal Day 10. The research reviewed in this article focuses on: (1) establishment of the selectively bred lines; (2) defining infant behavioral and physiological phenotypes and (3) determining whether infantile USV phenotypes endure over development. The High and Low lines have diverged widely in their USV rates from each other and from the Random control line, which has maintained N:NIH strain rates overall from generation to generation. Beginning in the 11th generation, High USV pups have shown significantly higher frequencies of defecation and urination during isolation screening than the Low USV and random control line. Both lines show altered autonomic regulation of heart rates (HR) in response to stressors as juveniles and adults. These differences in HR responses in High and Low lines appear to be mediated by changes in the balance of sympathetic versus parasympathetic mechanisms. Other behavioral characteristics of the High line are consistent with an "anxious"/ "depressive" phenotype, such as vocalizations to touch in a novel environment, and performance in the Porsolt Swim, whereas Low line shows few differences in anxiety behavior. Future work will resolve the similarities and differences in the High and Low phenotypes and provide a developmental perspective to the growing body of information about affective regulation in humans and animals provided by selectively bred animal models.

Asymmetrical stimulus generalization following differential fear conditioning

“…Genetic variations have been shown to affect the production of USVs (Brunelli;Brunelli et al, 1997;Burgdorf et al, 2005;Hahn et al, 1987;Sales & Smith, 1978), but there have been few studies of the possible influence of genetic and environmental variables in determining reactivity to these social signals (see Allen et al, 2007;Brudzynski, 2007;Endres et al, 2007). Although the stimuli used in Experiment 1 were equally neutral, as measured by unconditional freezing, they might differ in terms of salience or efficacy as cues supporting fear conditioning.…”

Behavioral evaluation of eight rat lines selected for high and low anxiety-related responses

“…The USV lines were created to produce a developmentalgenetic model system. The hypothesis is that autonomic and behavioral temperamental differences in infancy might cause behavioral or autonomic nervous system dysfunction in adulthood [33]. The results appear to be encouraging because the USV High and Low lines selected for different rates of USV in response to isolation during infancy and tested during adulthood presented reliable differences in several animal models, such as the open field, social interaction test, and elevated plus maze.…”

“…To investigate generational and developmental variables associated with anxiety, Brunelli et al [32,33] reported the creation of two lines of rats selected for different rates of USVs in response to isolation. Rat pups were screened at 10 ± 1 days of age in a 2 min isolation test.…”

Neural circuits underlying crying and cry responding in mammals

“…Various issues related to the neurochemical control of crying remain to be resolved, including the potentiation of crying when the mother is nearby (e.g., [107]). The growing availability of molecular genetic techniques applied to behavioral phenotypes opens up a huge research area for study, particularly with respect to the role of specific genes in regulating crying and cry responsivity, and the interaction of genetic and environmental factors, e.g., [14]. It is my hope that the present review will serve a useful role in focusing attention on the importance of the cry circuit in mammalian evolution, and help to stimulate a range of future studies.…”