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Especificación de las neuronas y circuitos claustroamigdalares y paleocorticales

Navjot Kaur¹, Rothem Kovner¹, Forrest O Gulden¹

¹Department of Neuroscience, Yale School of Medicine, New Haven, CT, USA.

|January 15, 2025

Resumen

Los factores clave de transcripción SOX4, SOX11 y TFAP2D son cruciales para el desarrollo de las neuronas excitatorias palial ventrolateral (VLp) y sus conexiones con la corteza prefrontal (PFC). Su dosificación afecta el desarrollo cerebral y los comportamientos relevantes para los trastornos neuropsiquiátricos.

Área de la Ciencia:

La neurociencia
Biología del desarrollo
La genética

Sus antecedentes:

Las neuronas excitatorias palial ventrolateral (VLp) en el complejo claustroamigdalino y la corteza piriforme (PIR) se conectan con la corteza prefrontal (PFC), integrando información sensorial y cognitiva para comportamientos adaptativos.
Las interrupciones en estos circuitos VLp-PFC durante la vida temprana están asociadas con trastornos neuropsiquiátricos, enfatizando la necesidad de comprender sus mecanismos de desarrollo.

Objetivo del estudio:

Investigar el papel de los factores de transcripción SOX4, SOX11 y TFAP2D en el desarrollo, la identidad y la conectividad PFC de las neuronas excitatorias VLp.
Aclarar la red reguladora de genes conservados que gobiernan la formación y función de estas poblaciones neuronales críticas en todas las especies, incluidos los humanos.

Principales métodos:

Investigó los efectos de la ausencia de SOX4 y SOX11 en las neuronas excitatorias postmitóticas en el desarrollo del complejo de la amígdala basolateral (BLC), el claustro (CLA) y el PIR.
Analizó la relación reguladora entre la expresión de SOX4/SOX11 y Tfap2d en la formación de BLC.
Se han realizado análisis entre especies para identificar patrones de expresión de Tfap2d conservados.
Se examinaron las consecuencias conductuales y neuroanatómicas de las diferentes dosis de Tfap2d (pérdida y insuficiencia haploide).

Principales resultados:

La ausencia de SOX4 y SOX11 redujo significativamente el tamaño de BLC, CLA y PIR, lo que indica su papel crítico en el desarrollo.
SOX4 y SOX11 regulan directamente la expresión de Tfap2d, controlando la formación de BLC.
Se encontró una expresión conservada de Tfap2d en el desarrollo de neuronas excitatorias del BLC, CLA, PIR y áreas corticales asociadas en todas las especies.
La dosis alterada de Tfap2d condujo a cambios en los comportamientos aprendidos de respuesta a la amenaza, el tamaño del BLC y la conectividad BLC-PFC, imitando los síntomas de los trastornos neuropsiquiátricos.

Conclusiones:

SOX4, SOX11 y TFAP2D son componentes esenciales de una red reguladora de genes conservada que rige el desarrollo de la neurona excitatoria VLp y la conectividad PFC.
La dosificación de TFAP2D es crítica para orquestar los cambios en el desarrollo de la conectividad BLC-PFC y los comportamientos asociados.
Estos hallazgos proporcionan información sobre la evolución de estos circuitos neuronales y ofrecen objetivos potenciales para comprender y tratar los trastornos neuropsiquiátricos.

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