Comparative analysis of Foxp2 expression in the thalamus of mice, rats, and macaques: implications for the evolution of language circuits

Foxp2 is a transcription factor essential for the development and function of neural circuits involved in language. Although its expression has been extensively characterized in the cortex and basal ganglia, its organization within the adult thalamus remains poorly understood. In this study, we present a comparative analysis of Foxp2 protein expression across thalamic nuclei in mice, rats, and macaques, with a focus on nuclei associated with higher-order cognitive functions and language-related circuits in humans. We found that Foxp2 is expressed in most thalamic nuclei across species, with a consistent absence in the reticular nucleus and zona incerta. Expression was highest in midline and intralaminar nuclei, whereas the anterior group showed low and variable expression among species. Macaques exhibited broader and, in some nuclei, more intense FoxP2 expression, particularly in associative regions such as the pulvinar and parts of the ventral group, consistent with differences in thalamocortical organization across species. This distribution suggests a conserved role for Foxp2 in shaping thalamic circuits supporting sensorimotor integration, attention, memory, and linguistic processing. Phylogenetic comparisons suggest that enhanced Foxp2 expression in associative thalamic territories in primates may be related to the increased complexity of thalamocortical circuits. These findings provide molecular and anatomical insights into the organization of thalamocortical networks and may offer a framework for understanding their involvement in higher-order cognitive functions and neuropsychiatric disorders.