Effect of social odor context on the emission of isolation-induced ultrasonic vocalizations in the BTBR T+tf/J mouse model for autism.

Markus WÃ¶hr

doi:10.3389/fnins.2015.00073

Abstract

An important diagnostic criterion for social communication deficits in autism spectrum disorders (ASD) are difficulties in adjusting behavior to suit different social contexts. While the BTBR T+tf/J (BTBR) inbred strain of mice is one of the most commonly used mouse models for ASD, little is known about whether BTBR mice display deficits in detecting changes in social context and their ability to adjust to them. Here, it was tested therefore whether the emission of isolation-induced ultrasonic vocalizations (USV) in BTBR mouse pups is affected by the social odor context, in comparison to the standard control strain with high sociability, C57BL/6J (B6). It is known that the presence of odors from mothers and littermates leads to a calming of the isolated mouse pup, and hence to a reduction in isolation-induced USV emission. In accordance with their behavioral phenotypes with relevance to all diagnostic core symptoms of ASD, it was predicted that BTBR mouse pups would not display a calming response when tested under soiled bedding conditions with home cage bedding material containing maternal odors, and that similar isolation-induced USV emission rates would be seen in BTBR mice tested under clean and soiled bedding conditions. Unexpectedly, however, the present findings show that BTBR mouse pups display such a calming response and emit fewer isolation-induced USV when tested under soiled as compared to clean bedding conditions, similar to B6 mouse pups. Yet, in contrast to B6 mouse pups, which emitted isolation-induced USV with shorter call durations and lower levels of frequency modulation under soiled bedding conditions, social odor context had no effect on acoustic call features in BTBR mouse pups. This indicates that the BTBR mouse model for ASD does not display deficits in detecting changes in social context, but has a limited ability and/or reduced motivation to adjust to them.

Highlights

The BTBR T+tf/J (BTBR) inbred strain of mice is one of the most commonly used mouse models for autism spectrum disorders (ASD)
Highlighting the relevance of this calming response for behavioral phenotyping of mouse models for ASD, it was further shown that μ-opioid deficient mice do not display a reduction in isolation-induced ultrasonic vocalizations (USV) emission rates in the presence of odors from mothers and littermates (Moles et al, 2004), consistent with a variety of other social and communication deficits displayed by this ASD mouse model (Tian et al, 1997; Wöhr et al, 2011a; Cinque et al, 2012; Becker et al, 2014; Gigliucci et al, 2014; for review see: Oddi et al, 2013). In accordance with their behavioral phenotypes with relevance to all diagnostic core symptoms of ASD, it was predicted that BTBR mouse pups would not display a calming response when tested under soiled bedding conditions with home cage bedding material containing maternal odors, and that similar isolationinduced USV emission rates would be seen in BTBR mice tested under clean and soiled bedding conditions, while lower isolationinduced USV emission rates would occur in B6 mice tested under soiled bedding conditions as compared to clean bedding conditions
Effects of Social Odor Context on Isolation-Induced USV in BTBR and B6 Mouse Pups Social odor context significantly affected the emission of isolation-induced USV [main effect social odor context: F(1, 56) = 15.646, p < 0.001; Figure 1A], with emission rates significantly differing between strains [main effect strain: F(1, 56) = 124.807, p < 0.001; interaction social odor context × strain: F(1, 56) =

Summary

Introduction

The BTBR T+tf/J (BTBR) inbred strain of mice is one of the most commonly used mouse models for autism spectrum disorders (ASD). BTBR mice show high levels of restricted, repetitive behavior, such as perseverative self-grooming and marbleburying (McFarlane et al, 2008; Yang et al, 2009; Pobbe et al, 2010; Pearson et al, 2011; Amodeo et al, 2012; Jones-Davis et al, 2013; Molenhuis et al, 2014) or altered exploratory behavior in the hole board task (Moy et al, 2008) and the repetitive novel object contact task (Pearson et al, 2011) They were reported to display deficits in reversal learning in the Morris water maze (Moy et al, 2007; Yang et al, 2012a) and a set-shifting task (Molenhuis et al, 2014), yet conflicting results were obtained in T-maze reversal learning and related tasks (Moy et al, 2007; Amodeo et al, 2012; Guariglia and Chadman, 2013)

Methods

Results

Discussion

Conclusion