SEX- AND DOSE-DEPENDENT MODULATION OF MOUSE BEHAVIOR BY FOXP2 IN THE MEDIODORSAL THALAMUS

FOXP2 is a transcription factor that plays a critical role in neural development. It is particularly important for the formation and functional maturation of neural circuits. Disruptions in FOXP2 function have been linked to neurodevelopmental disorders characterized by impairments in language and communication. FoxP2 is expressed in the thalamus from early embryonic stages and continues to be expressed through adulthood. During adulthood, FoxP2 contributes to the maintenance of thalamo-cortical and thalamo-striatal connectivity.
In the present study, we investigated the role of thalamic medialdorsal FoxP2 expression in mouse behavior. To this end, we used B6.Cg-Foxp2tm1.1Sfis/CfreJ mice to induce a FoxP2 cKO or overexpression in the medial dorsal thalamus. Mice were then subjected to a battery of behavioral tests, including the sucrose preference (SP), open field (OF), Y-maze (YM) and prepulse inhibition (PPI).
We observed no differences in SP or PPI across experimental groups. In the OF, all measured variables were within the normal range, however, alterations in thigmotaxis were detected, indicating increased anxiety-like behavior in male mice with thalamic FoxP2 cKO and decreased anxiety-like behavior in female mice with FoxP2 overexpression. In the YM, spontaneous alternation was altered in a graded manner, with the highest levels observed in FoxP2 cKO and the lowest in FoxP2 overexpression mice, suggesting a dose-dependent effect of FoxP2 expression on working memory. Additionally, we identified sex-specific differences in YM exploration.
Together, these results point to a sex-specific role of FoxP2 expression in the medial dorsal thalamus in regulating anxiety-like behavior, working memory, and exploration.