Oxford open neuroscience最新文献

Working memory is a fundamental cognitive ability, allowing us to keep information in memory for the time needed to perform a given task. A complex neural circuit fulfills these functions, among which is the anterior cingulate cortex (CG). Functionally and anatomically connected to the medial prefrontal, retrosplenial, midcingulate and hippocampus, as well as motor cortices, CG has been implicated in retrieving appropriate information when needed to select and control appropriate behavior. The role of cingulate cortex in working memory-guided behaviors remains unclear due to the lack of studies reversibly interfering with its activity during specific epochs of working memory. We used eNpHR3.0 to silence cingulate neurons while animals perform a standard delayed non-match to trajectory task, and found that, while not causing an absolute impairment in working memory, silencing cingulate neurons during retrieval decreases the mean performance if compared to silencing during encoding. Such retrieval-associated changes are accompanied by longer delays observed when light is delivered to control animals, when compared to eNpHR3.0+ ones, consistent with an adaptive recruitment of additional cognitive resources.

PRDM16 is a dynamic transcriptional regulator of various stem cell niches, including adipocytic, hematopoietic, cardiac progenitors, and neural stem cells. PRDM16 has been suggested to contribute to 1p36 deletion syndrome, one of the most prevalent subtelomeric microdeletion syndromes. We report a patient with a de novo nonsense mutation in the PRDM16 coding sequence, accompanied by lissencephaly and microcephaly features. Human stem cells were genetically modified to mimic this mutation, generating cortical organoids that exhibited altered cell cycle dynamics. RNA sequencing of cortical organoids at day 32 unveiled changes in cell adhesion and WNT-signaling pathways. ChIP-seq of PRDM16 identified binding sites in postmortem human fetal cortex, indicating the conservation of PRDM16 binding to developmental genes in mice and humans, potentially at enhancer sites. A shared motif between PRDM16 and LHX2 was identified and further examined through comparison with LHX2 ChIP-seq data from mice. These results suggested a collaborative partnership between PRDM16 and LHX2 in regulating a common set of genes and pathways in cortical radial glia cells, possibly via their synergistic involvement in cortical development.

A child's social world is complex and rich, but has traditionally been assessed with conventional experiments where children are presented with repeated stimuli on a screen. These assessments are impoverished relative to the dynamics of social interactions in real life, and can be challenging to implement with preschoolers, who struggle to comply with strict lab rules. The current work meets the need to develop new platforms to assess preschoolers' social development, by presenting a unique virtual-reality set-up combined with wearable functional near-infrared spectroscopy (fNIRS). As a proof-of-principle, we validated this platform by measuring brain activity during self-guided social interaction in 3-to-5-year-olds, which is under-investigated, yet crucial to understand the basis of social interactions in preschoolers. 37 preschoolers chose an interaction partner from one of 4 human-like avatars of different gender and age. We recorded spontaneous brain fluctuations from the frontal and temporoparietal regions (notably engaged in social-categorization and preference) while children played a bubble-popping game with a preferred and an assigned avatar. 60% of the participants chose to play with the same-gender and same-age avatar. However, this result was driven by females (>80% vs. 50% in males). Different fronto-temporoparietal connectivity patterns when playing with the two avatars were observed, especially in females. We showed the feasibility of using a novel set-up to naturalistically assess social preference in preschoolers, which was assessed at the behavioural and functional connectivity level. This work provides a first proof-of-principle for using cutting-edge technologies and naturalistic experiments to study social development, opening new avenues of research.

Human brain development is spatially and temporally complex. Insufficient access to human brain tissue and inadequacy of animal models has limited the study of brain development and neurodegenerative diseases. Recent advancements of brain organoid technology have created novel opportunities to model human-specific neurodevelopment and brain diseases. In this review, we discuss the use of brain organoids to model the midbrain and Parkinson's disease. We critically evaluate the extent of recapitulation of PD pathology by organoids and discuss areas of future development that may lead to the model to become a next-generation, personalized therapeutic strategy for PD and beyond.

Glioblastoma (GBM) is the most aggressive adult primary brain tumor with nearly universal treatment resistance and recurrence. The mainstay of therapy remains maximal safe surgical resection followed by concurrent radiation therapy and temozolomide chemotherapy. Despite intensive investigation, alternative treatment options, such as immunotherapy or targeted molecular therapy, have yielded limited success to achieve long-term remission. This difficulty is partly due to the lack of pre-clinical models that fully recapitulate the intratumoral and intertumoral heterogeneity of GBM and the complex tumor microenvironment. Recently, GBM 3D organoids originating from resected patient tumors, genetic manipulation of induced pluripotent stem cell (iPSC)-derived brain organoids and bio-printing or fusion with non-malignant tissues have emerged as novel culture systems to portray the biology of GBM. Here, we highlight several methodologies for generating GBM organoids and discuss insights gained using such organoid models compared to classic modeling approaches using cell lines and xenografts. We also outline limitations of current GBM 3D organoids, most notably the difficulty retaining the tumor microenvironment, and discuss current efforts for improvements. Finally, we propose potential applications of organoid models for a deeper mechanistic understanding of GBM and therapeutic development.

Interpersonal brain synchronization (IBS) has been observed during social interactions and involves various factors, such as familiarity with the partner and type of social activity. A previous study has shown that face-to-face (FF) interactions in pairs of strangers increase IBS. However, it is unclear whether this can be observed when the nature of the interacting partners is different. Herein, we aimed to extend these findings to pairs of acquaintances. Neural activity in the frontal and temporal regions was recorded using functional near-infrared spectroscopy hyperscanning. Participants played an ultimatum game that required virtual economic exchange in two experimental settings: face-to-face and face-blocked conditions. Random pair analysis confirmed whether IBS was induced by social interaction. Contrary to the aforementioned study, our results did not show any cooperative behavior or task-induced IBS increase. Conversely, the random pair analysis results revealed that the pair-specific IBS was significant only in the task condition at the left and right superior frontal, middle frontal, orbital superior frontal, right superior temporal, precentral and postcentral gyri. Our results tentatively suggested that FF interaction in acquainted pairs did not increase IBS and supported the idea that IBS is affected by 'with whom we interact and how'.