Cortico-thalamic development and disease: From cells, to circuits, to schizophrenia

Abstract

The human brain is the most complex structure generated during development. Unveiling the ontogenesis and the intrinsic organization of specific neural networks may represent a key to understanding the physio-pathological aspects of different brain areas. The cortico-thalamic and thalamo-cortical (CT-TC) circuits process and modulate essential tasks such as wakefulness, sleep and memory, and their alterations may result in neurodevelopmental and psychiatric disorders. These pathologies are reported to affect specific neural populations but may also broadly alter physiological connections and thus dysregulate brain network generation, communication, and function. More specifically, the CT-TC system is reported to be severely affected in disorders impacting superior brain functions, such as schizophrenia (SCZ), bipolar disorder, autism spectrum disorders or epilepsy. In this review, the focus will be on CT development, and the models exploited to uncover and comprehend its molecular and cellular mechanisms. In parallel to animal models, still fundamental to unveil human neural network establishment, advanced in vitro platforms, such as brain organoids derived from human pluripotent stem cells, will be discussed. Indeed, organoids and assembloids represent unique tools to study and accelerate fundamental research in CT development and its dysfunctions. We will then discuss recent cutting-edge contributions, including in silico approaches, concerning ontogenesis, specification, and function of the CT-TC circuitry that generates connectivity maps in physiological and pathological conditions.

Sex-specific cortical, hippocampal and thalamic whole genome transcriptome data from controls and a G72 schizophrenia mouse model

“…There is also evidence of altered thalamic microstructure, e.g., in the mediodorsal nucleus, thalamo-prefrontal and thalamo-somatosensory/parietal connectivity [ 17 ]. Multiple studies have proposed an association between psychosis spectrum disorders and thalamic network dysrhythmia and/or dysconnectivity [ 18 , 19 ]. Our microarray data from these three highly relevant brain regions allow for further characterization of differentially expressed intersectional and signature genes of the individual subgroups, gene ontology and pathway analysis and biophysical studies [ 20 , 21 ] which are of relevance for future translational studies.…”

Brain organoid protocols and limitations

“…For instance, fusion between dorsal and ventral forebrain organoids is used to model interneuron migration (Bagley et al, 2017 ; Birey et al, 2017 ; Samarasinghe et al, 2021 ). Fusions of cortical organoids with other brain regions such as (1) thalamus to model thalamus dysfunction-related psychiatric disorders (Xiang et al, 2019 , 2020 ; Angulo Salavarria et al, 2023 ); (2) thalamus and retina to model the projections of visual system (Fligor et al, 2021 ); (3) striatum to model the dysfunction in neural circuits of cortico-striatal pathway as observed in autism spectrum disorder and schizophrenia (Miura et al, 2020 , 2022 ); and (4) spinal cord and muscle to model cortical control of motor contractions (Knecht et al, 2019 ; Andersen et al, 2020 ). Other brain regions, such as the hypothalamus and pituitary, can be fused as assembloids to model the hypothalamic-pituitary axis (Kasai et al, 2020 ).…”

Motor Dysfunctions in Fibromyalgia Patients: The Importance of Breathing

“…45 The thalamic somatosensory area, and in particular, the contralateral medial area of the ventroposteromedial thalamus, is stimulated via the lingual nerve, to process proprioceptive information (emotions, movement, and pain), as well as processes related to memory and cognition. [46][47][48] The hypoglossal nucleus and the trigeminal motor nucleus send afferents to the cerebellum, in order to adapt and prepare motor and emotional behavior for the respiration that will be required. 49 The insula (insular oral region) is stimulated by the tongue to receive and process somatovisceral information; the insula translates this information into empathy, pain management and self-awareness.…”