H2020Индивидуална стипендия2019–2021

UNCERTHAIN · Unraveling the consequences of early cerebellothalamic dysfunction and its role in autism spectrum disorder symptoms

„Хоризонт 2020“ — Действия „Мария Склодовска-Кюри“

Период: 2019-06-01 → 2021-05-31
Финансиране от ЕС: 160 932 €
Участници: 1
Схема: MSCA-IF

Линиите свързват координатора с партньорите.

Накратко на български

Връзката между малкия мозък и таламуса се анализира, за да се разбере как нарушенията в тези пътища влияят върху развитието на мозъка. Това помага да се обяснят причините за симптомите при разстройства от аутистичния спектър.

Този кратък обзор е генериран от изкуствен интелект

Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.

Резултати накратко

Unraveling the consequences of early cerebellothalamic dysfunction and its role in autism spectrum disorder symptoms

The Action “Unraveling the consequences of early cerebellothalamic dysfunction and its role in autism spectrum disorder symptoms” aimed to decipher anatomical and functional alterations resulting from abnormal cerebello-thalamic connectivity and its relationship with symptoms present in Autism spectrum disorder (ASD). This topic is important for society because is estimated that worldwide one in 160 children has an ASD. Interestingly, early cerebellar lesions are the best known non-genetic risk factor associated to ASD. The alteration of the development and function of the cerebral cortex due to an abnormal functioning of the cerebellum could explain the cerebellar origin of the high-order deficits present in major neurodevelopmental psychiatric disorders. And the thalamus is a key intermediate structure between the cerebellum and the cortex. However, any study has tackled this issue from a neurodevelopmental perspective. The main objectives of this Marie Skłodowska-Curie Action (MSCA) have been to (a) study the formation of the cerebello-thalamic circuit; (b) develop strategies to alter this circuit and (c) investigate the anatomical and functional consequences of these alterations. Thus, we have developed different experimental approaches to target and manipulate the embryonic cerebellum in vivo. These techniques allowed us to study in detail how the cerebellothalamic circuits develop during embryogenesis. Our results have stablished for the first time the spatial and temporal window by which the cerebellum could influence the development of thalamus and its circuits. Furthermore, abnormal cerebellar inputs to thalamus let to some structural and transcriptomic alterations in this region that might explain functional and behavioral dysfunctions associated with the cerebellar origin of ASD. A parallel goal of this MSCA IF was foster the development of the individual researcher.

Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз

Цел на проекта

Cerebellar abnormalities are consistently reported in autism spectrum disorder patients, however the cerebellar contribution in the etiology of this pathophysiology remains poorly understood.It has been proposed that the cerebellum may drive the maturation and functionality of cortical high-order structures involved in the core symptoms of autism. However, the mechanisms by which the cerebellum could control these processes remain to be determined. The neural circuits linking cerebellum with the cerebral cortex via thalamic relay stations are the anatomical scaffolds underlying the cerebellar cognition. Recent data have shown that the thalamus plays a key role in the reorganization of cortical areas after early sensory deprivation. Therefore, during early development, abnormal cerebellar inputs to the thalamus may contribute to cortical dysfunctions that could lead in high-order deficits. However, despite being autism a neurodevelopmental disorder, any study has addressed the analysis of cerebello-thalamo-cortical circuits from a developmental perspective.The present project (UNCERTHAIN) offers an exceptional opportunity to shed light onto this issue as a result of the unique combination of approaches. Accordingly, we will use an experimental model that offers the possibility to embryonically alter the cerebellothalamic connectivity and thus, study the mechanisms underlying the events that influence the normal development and functioning of cortical circuits. Hence, we will adopt both multidisciplinary and innovative approaches to characterize the thalamocortical network in presence of a disrupted cerebellar input, the functional consequences and its relationship with autistic-like behaviors.The successful execution of this high-risk, high-impact research will provide insights on how the cerebellum governs the development of cortical areas essential for social and cognitive behaviors and its involvement in high-order neurodevelopmental disorders such as autism.

Оригинален текст от CORDIS (на английски).

Участници

AGENCIA ESTATAL CONSEJO SUPERIOR DE INVESTIGACIONES CIENTIFICAS · MadridКоординаторИспания