Sex-specific positive and negative consequences of avoidance training during childhood on adult active avoidance learning in mice

Abstract

In humans and animals cognitive training during childhood plays an important role in shaping neural circuits and thereby determines learning capacity later in life. Using a negative feedback learning paradigm, the two-way active avoidance (TWA) learning, we aimed to investigate in mice (i) the age-dependency of TWA learning, (ii) the consequences of pretraining in childhood on adult learning capacity and (iii) the impact of sex on the learning paradigm in mice. Taken together, we show here for the first time that the beneficial or detrimental outcome of pretraining in childhood depends on the age during which TWA training is encountered, indicating that different, age-dependent long-term “memory traces” might be formed, which are recruited during adult TWA training and thereby either facilitate or impair adult TWA learning. While pretraining during infancy results in learning impairment in adulthood, pretraining in late adolescence improved avoidance learning. The experiments revealed a clear sex difference in the group of late-adolescent mice: female mice showed better avoidance learning during late adolescence compared to males, and the beneficial impact of late-adolescent pretraining on adult learning was more pronounced in females compared to males.

Imaging of Functional Brain Circuits during Acquisition and Memory Retrieval in an Aversive Feedback Learning Task: Single Photon Emission Computed Tomography of Regional Cerebral Blood Flow in Freely Behaving Rats

“…In line with results from our previous experiments with rats and mice [ 16 , 17 , 23 ] the animals displayed a continuous learning curve as reflected by a significant increase in avoidance responses over the five-day training period. While on the first training day (acquisition) exclusively escape reactions were observed, on the fifth test day (memory retrieval) reactions switched to conditioned avoidance responses.…”

Perinatal programming of emotional brain circuits: an integrative view from systems to molecules

“…In other words, once an individual learns a specific behavioral strategy during childhood it may be “stuck” with it for the rest of his/her life. In line with this view are observations in young mice using an aversive learning paradigm (Spröwitz et al, 2013 ). This study revealed that infant mice, which learned to escape from a footshock, maintain this escape strategy until adulthood, instead of switching to a more efficient avoidance strategy.…”

Functional Aging in Male C57BL/6J Mice Across the Life-Span: A Systematic Behavioral Analysis of Motor, Emotional, and Memory Function to Define an Aging Phenotype

“…In the present study, male mice were used in accordance with a tradition in scientific research. Recent evidence, however, reveals the substantial sex-based differences in mice behavior ( Jonasson, 2005 ; Spröwitz et al, 2013 ; Matsuda et al, 2015 ; Tucker et al, 2016 ). Therefore, using a balanced population of male and female mice are advocated ( Wald and Wu, 2010 ; Shansky, 2019 ).…”