Abstract
Mice socially isolated during adolescence exhibit behaviors of anxiety, depression and impaired social interaction. Although these behaviors are well documented, very little is known about the associated neurobiological changes that accompany these behaviors. It has been hypothesized that social isolation during adolescence alters the development of the prefrontal cortex, based on similar behavioral abnormalities observed in isolated mice and those with disruption of this structure. To establish relationships between behavior and underlying neurobiological changes in the prefrontal cortex, Thy-1-GFP mice were isolated from weaning until adulthood and compared to group-housed littermates regarding behavior, electrophysiological activity and dendritic morphology. Results indicate an immaturity of dendritic spines in single housed animals, with dendritic spines appearing smaller and thinner. Single housed mice additionally show impaired plasticity through measures of long-term potentiation. Together these findings suggest an altered development and impairment of the prefrontal cortex of these animals underlying their behavioral characteristics.
Highlights
IntroductionIsolated mice have been used as a model for several psychiatric phenotypes, including depressive-like behavior (Koike et al, 2009; Amiri et al, 2015b), social deficits (Koike et al, 2009; Okada et al, 2015) and anxiety behaviors (Ago et al, 2007; Amiri et al, 2015b)
These effects have been demonstrated in more complex circuits, such as the basolateral amygdalaprefrontal cortex bidirectional pathway (Castillo-Gómez et al, 2017; Ueno et al, 2017), which are areas that are correspondingly underdeveloped in humans with socio-emotional deprivation (Eluvathingal et al, 2006)
Confocal imaging demonstrated a lack of maturity among dendritic spines in this region, which may contribute to the lack of stable Long Term Potentiation (LTP) responses
Summary
Isolated mice have been used as a model for several psychiatric phenotypes, including depressive-like behavior (Koike et al, 2009; Amiri et al, 2015b), social deficits (Koike et al, 2009; Okada et al, 2015) and anxiety behaviors (Ago et al, 2007; Amiri et al, 2015b). In addition to these abnormal behaviors, these animals exhibit alterations in neurotransmission (Haj-Mirzaian et al, 2015; Okada et al, 2015), and demonstrate abnormal pharmacological responses (Ago et al, 2007; Koike et al, 2009; Amiri et al, 2015a) These behaviors among socially isolated mice have been shown to be improved with treatment of methylphenidate, a common treatment for Attention Deficit Hyperactivity Disorder (ADHD), and with fluoxetine, a selective serotonin reuptake inhibitor, leading some to suggest socially isolated mice as a potential model for studying the pathophysiology of psychiatric disorders of ADHD and depression. These effects have been demonstrated in more complex circuits, such as the basolateral amygdalaprefrontal cortex bidirectional pathway (Castillo-Gómez et al, 2017; Ueno et al, 2017), which are areas that are correspondingly underdeveloped in humans with socio-emotional deprivation (Eluvathingal et al, 2006)
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