Impaired Social Behavior in 5-HT3A Receptor Knockout Mice

Abstract

The 5-HT3 receptor is a ligand-gated ion channel expressed on interneurons throughout the brain. So far, analysis of the 5-HT3A knockout mouse revealed changes in nociceptive processing and a reduction in anxiety related behavior. Recently, it was shown that the 5-HT3 receptor is also expressed on Cajal-Retzius cells which play a key role in cortical development and that knockout mice lacking this receptor showed aberrant growth of the dendritic tree of cortical layer II/III pyramidal neurons. Other mouse models in which serotonergic signaling was disrupted during development showed similar morphological changes in the cortex, and in addition, also deficits in social behavior. Here, we subjected male and female 5-HT3A knockout mice and their non-transgenic littermates to several tests of social behavior. We found that 5-HT3A knockout mice display impaired social communication in the social transmission of food preference task. Interestingly, we showed that in the social interaction test only female 5-HT3A knockout mice spent less time in reciprocal social interaction starting after 5 min of testing. Moreover, we observed differences in preference for social novelty for male and female 5-HT3A knockout mice during the social approach test. However, no changes in olfaction, exploratory activity and anxiety were detected. These results indicate that the 5-HT3A knockout mouse displays impaired social behavior with specific changes in males and females, reminiscent to other mouse models in which serotonergic signaling is disturbed in the developing brain.

Altered dendritic complexity affects firing properties of cortical layer 2/3 pyramidal neurons in mice lacking the 5-HT3A receptor

“…Similarly, disturbances in serotonergic signaling have been linked to neurodevelopmental disorders (Daubert and Condron 2010; Gaspar et al 2003). In this context, it is of interest to note that 5-HT 3A receptor knockout mice display abnormalities in social behavior, reminiscent of an autistic phenotype (Smit-Rigter et al 2010). Although a direct link between the morphological and behavioral abnormalities has yet to be established, the present results may help us to understand the relation between morphology and function during (patho)physiological development and maturation of neuronal circuits.…”

The 5-HT3A receptor is essential for fear extinction

“…In the brain, the 5-HT 3A receptor is mainly expressed on interneurons in limbic regions, such as hippocampus, amygdala, and cortex (Tecott et al 1993;Morales et al 1996b;Morales and Bloom 1997), suggesting its involvement in cognitive and emotional brain functions. Indeed, previous studies have indicated that the 5-HT 3 receptor plays roles in spatial learning and memory (Stäubli and Xu 1995;Naghdi and Harooni 2005), anxiety-like behavior (Kelly et al 2003;Bhatnagar et al 2004), and social behavior (Smit-Rigter et al 2010). However, it is not known whether the 5-HT 3 receptor regulates fear memory processes.…”

Contribution of Hippocampal 5-HT3 Receptors in Hippocampal Autophagy and Extinction of Conditioned Fear Responses after a Single Prolonged Stress Exposure in Rats

“…5-HT 3A and 5-HT 3B are the two identified subunits of 5-HT 3 receptor, and previous studies have shown that 5-HT 3A subunit is essential for receptor function (Maricq et al 1991;Davies et al 1999), and is highly expressed on interneurons in limbic regions, such as hippocampus, amygdala, and cortex (Tecott et al 1993;Morales et al 1996;Morales and Bloom 1997), which are critically involved in cognitive and emotional functions. Furthermore, previous studies have indicated that the 5-HT 3 receptor are involved in social behavior (Smit-Rigter et al 2010), anxiety-like behavior (Kelley et al 2003;Bhatnagar et al 2004), and spatial learning and memory (Staubli and Xu 1995;Naghdi and Harooni 2005). Recent studies have also shown that 5-HT 3 receptor is critical for the extinction of fear memory (Kondo et al 2014).…”