BACKGROUND: The significant role of embryonic cerebrospinal fluid (eCSF) in the initial stages of brain development has been thoroughly studied. This fluid contains crucial molecules for proper brain development such as members of the Wnt and FGF families, apolipoproteins, and retinol binding protein. Nevertheless, the source of these molecules remains uncertain since they are present before the formation of the choroid plexus, which is conventionally known as the primary producer of cerebrospinal fluid. The subcommissural organ (SCO) is a highly conserved gland located in the diencephalon and is one of the earliest differentiating brain structures. The SCO secretes molecules into the eCSF, prior to the differentiation of the choroid plexus, playing a pivotal role in the homeostasis and dynamics of this fluid. One of the key molecules secreted by the SCO is SCO-spondin, a protein involved in maintenance of the normal ventricle size, straight spinal axis, neurogenesis, and axonal guidance. Furthermore, SCO secretes transthyretin and basic fibroblast growth factor 2, while other identified molecules in the eCSF could potentially be secreted by the SCO. Additionally, various transcription factors have been identified in the SCO. However, the precise mechanisms involved in the early SCO development are not fully understood.
RESULTS: To uncover key molecular players and signaling pathways involved in the role of the SCO during brain development, we conducted a transcriptomic analysis comparing the embryonic chick SCO at HH23 and HH30 stages (4 and 7 days respectively). Additionally, a public transcriptomic data from HH30 entire chick brain was used to compare expression levels between SCO and whole brain transcriptome. These analyses revealed that, at both stages, the SCO differentially expresses several members of bone morphogenic proteins, Wnt and fibroblast growth factors families, diverse proteins involved in axonal guidance, neurogenic and differentiative molecules, cell receptors and transcription factors. The secretory pathway is particularly upregulated at stage HH30 while the proliferative pathway is increased at stage HH23.
CONCLUSIONS: The results suggest that the SCO has the capacity to secrete several morphogenic molecules to the eCSF prior to the development of other structures, such as the choroid plexus.

Mother-child interaction is highly dynamic and reciprocal. Switching roles in these back-and-forth interactions serves as a crucial feature of reciprocal behaviors while the underlying neural entrainment is still not well-studied. Here, we designed a role-controlled cooperative task with dual EEG recording to explore how differently two brains interact when mothers and children hold different roles. When children were actors and mothers were observers, mother-child interbrain synchrony emerged primarily within the theta oscillations and the frontal lobe, which highly correlated with children\'s attachment to their mothers (self-reported by mothers). When their roles were reversed, this synchrony was shifted to the alpha oscillations and the central area and associated with mothers\' perception of their relationship with their children. The results suggested an observer-actor neural alignment within the actor\'s oscillations, which was related to the actor-toward-observer emotional bonding. Our findings contribute to the understanding of how interbrain synchrony is established and dynamically changed during mother-child reciprocal interaction.

Parent-child interaction is crucial for children\'s cognitive and affective development. While bio-synchrony models propose that parenting influences interbrain synchrony during interpersonal interaction, the brain-to-brain mechanisms underlying real-time parent-child interactions remain largely understudied. Using functional near-infrared spectroscopy, we investigated interbrain synchrony in 88 parent-child dyads (Mage children = 8.07, 42.0% girls) during a collaborative task (the Etch-a-Sketch, a joint drawing task). Our findings revealed increased interbrain synchrony in the dorsolateral prefrontal cortex and temporo-parietal areas during interactive, collaborative sessions compared to non-interactive, resting sessions. Linear regression analysis demonstrated that interbrain synchrony in the left temporoparietal junction was associated with enhanced dyadic collaboration, shared positive affect, parental autonomy support, and parental emotional warmth. These associations remained significant after controlling for demographic variables including child age, child gender, and parent gender. Additionally, differences between fathers and mothers were observed. These results highlight the significant association between brain-to-brain synchrony in parent-child dyads, the quality of the parent-child relationship, and supportive parenting behaviors. Interbrain synchrony may serve as a neurobiological marker of real-time parent-child interaction, potentially underscoring the pivotal role of supportive parenting in shaping these interbrain synchrony mechanisms.

During social interactions, we constantly learn about the thoughts, feelings, and personality traits of our interaction partners. Learning in social interactions is critical for bond formation and acquiring knowledge. Importantly, this type of learning is typically bi-directional, as both partners learn about each other simultaneously. Here we review the literature on social learning and propose a new computational and neural model characterizing mutual predictions that take place within and between interactions. According to our model, each partner in the interaction attempts to minimize the prediction error of the self and the interaction partner. In most cases, these inferential models become similar over time, thus enabling mutual understanding to develop. At the neural level, this type of social learning may be supported by interbrain plasticity, defined as a change in interbrain coupling over time in neural networks associated with social learning, among them the mentalizing network, the observation-execution system, and the hippocampus. The mutual prediction model constitutes a promising means of providing empirically verifiable accounts of how relationships develop over time.

The diencephalon, an integral component of the forebrain, governs a spectrum of crucial functions, ranging from sensory processing to emotional regulation. Yet, unraveling its unique development, intricate connectivity, and its role in neurodevelopmental disorders has long been hampered by the scarcity of human brain tissue and ethical constraints. Recent advancements in stem cell technology, particularly the emergence of brain organoids, have heralded a new era in neuroscience research. Although most brain organoid methodologies have hitherto concentrated on directing stem cells toward telencephalic fates, novel techniques now permit the generation of region-specific brain organoids that faithfully replicate precise diencephalic identities. These models mirror the complexity of the human diencephalon, providing unprecedented opportunities for investigating diencephalic development, functionality, connectivity, and pathophysiology in vitro. This review summarizes the development, function, and connectivity of diencephalic structures and touches upon developmental brain disorders linked to diencephalic abnormalities. Furthermore, it presents current diencephalic organoid models and their applications in unraveling the intricacies of diencephalic development, function, and pathology in humans. Lastly, it highlights thalamocortical assembloid models, adept at capturing human-specific aspects of thalamocortical connections, along with their relevance in neurodevelopmental disorders.

The secondary general visceral sensory nucleus (SVN) receives ascending fibers from the commissural nucleus of Cajal (NCC), or the primary general visceral sensoru in the medulla oblongata of teleosts. However, the full set of fiber connections of the SVN have been studied only in the Nile tilapia. We have investigated the connections of the SVN in goldfish by tracer injection experiments to the nucleus. We paid special attention to the possible presence of spinal afferents, since the spinal cord projects to the lateral parabrachial nucleus, or the presumed homologue of SVN, in mammals. We found that the SVN indeed receives spinal projections. Spinal terminals were restricted to a region ventrolaterally adjacent to the terminal zone of NCC fibers, suggesting that the SVN can be subdivided into two subnuclei: the commissural nucleus-recipient (SVNc) and spinal-recipient (SVNsp) subnuclei. Tracer injections to the SVNc and SVNsp as well as reciprocal injections to the diencephalon revealed that both subnuclei project directly to diencephalic structures, such as the posterior thalamic nucleus and nucleus of lateral recess, although diencephalic projections of the SVNsp were rather sparse. The SVNsp appears to send fibers to more wide-spread targets in the preoptic area than the SVNc does. The SVNc projects to the telencephalon, while the SVNsp sends scarce or possibly no fibers to the telencephalon. Another notable difference was that the SVNsp gives rise to massive projections to the dorsal diencephalon (ventromedial thalamic, central posterior thalamic, and periventricular posterior tubercular nuclei). These differential connections of the subnuclei may reflect discrete functional significances of the general visceral sensory information mediated by the medulla oblongata and spinal cord.

Binocular vision requires the segregation of retinal ganglion cell (RGC) axons extending from the retina into the ipsilateral and contralateral optic tracts. RGC axon segregation occurs at the optic chiasm, which forms at the ventral diencephalon midline. Using expression analyses, retinal explants and genetically modified mice, we demonstrate that CXCL12 (SDF1) is required for axon segregation at the optic chiasm. CXCL12 is expressed by the meninges bordering the optic pathway, and CXCR4 by both ipsilaterally and contralaterally projecting RGCs. CXCL12 or ventral diencephalon meninges potently promoted axon outgrowth from both ipsilaterally and contralaterally projecting RGCs. Further, a higher proportion of axons projected ipsilaterally in mice lacking CXCL12 or its receptor CXCR4 compared with wild-type mice as a result of misrouting of presumptive contralaterally specified RGC axons. Although RGCs also expressed the alternative CXCL12 receptor ACKR3, the optic chiasm developed normally in mice lacking ACKR3. Our data support a model whereby meningeal-derived CXCL12 helps drive axon growth from CXCR4-expressing RGCs towards the diencephalon midline, enabling contralateral axon growth. These findings further our understanding of the molecular and cellular mechanisms controlling optic pathway development.

Mindfulness is considered to benefit social behavior and interpersonal communication. However, the underlying neural mechanism has not been fully examined. This study aimed to explore how mindfulness practice affected the interbrain synchrony within adolescent peer dyads when sharing emotional experience together by using the electroencephalograph hyperscanning approach. Thirty adolescent dyads were randomly assigned to a mindfulness group or a non-mindfulness group. Mindfulness group performed a 20-min mindfulness exercise. Non-mindfulness group were instructed to rest. Simultaneously, electroencephalograph was recorded when they completed a picture-processing task. Phase-locking-value in the gamma band was used to calculate adolescent dyads\' brain-to-brain synchrony. Results showed that greater interbrain synchrony in the frontal region was observed when viewing different emotional stimuli together after the mindfulness than before the mindfulness in the mindfulness group. However, there was no significant difference in the interbrain synchrony in the non-mindfulness group. Moreover, greater interbrain synchrony was observed in the mindfulness group than in the non-mindfulness group after mindfulness or rest in the frontal region. However, there was no significant difference between the mindfulness and non-mindfulness group before mindfulness or rest. The findings are discussed in light of the broader theoretical questions of how mindfulness may promote interpersonal functioning from a psychophysiological perspective.

The brain is spatially organized into subdivisions, nuclei and areas, which often correspond to functional and developmental units. A segmentation of brain regions in the form of a consensus atlas facilitates mechanistic studies and is a prerequisite for sharing information among neuroanatomists. Gene expression patterns objectively delineate boundaries between brain regions and provide information about their developmental and evolutionary histories. To generate a detailed molecular map of the larval zebrafish diencephalon, we took advantage of the Max Planck Zebrafish Brain (mapzebrain) atlas, which aligns hundreds of transcript and transgene expression patterns in a shared coordinate system. Inspection and co-visualization of close to 50 marker genes have allowed us to resolve the tripartite prosomeric scaffold of the diencephalon at unprecedented resolution. This approach clarified the genoarchitectonic partitioning of the alar diencephalon into pretectum (alar part of prosomere P1), thalamus (alar part of prosomere P2, with habenula and pineal complex), and prethalamus (alar part of prosomere P3). We further identified the region of the nucleus of the medial longitudinal fasciculus, as well as the posterior and anterior parts of the posterior tuberculum, as molecularly distinct basal parts of prosomeres 1, 2, and 3, respectively. Some of the markers examined allowed us to locate glutamatergic, GABAergic, dopaminergic, serotoninergic, and various neuropeptidergic domains in the larval zebrafish diencephalon. Our molecular neuroanatomical approach has thus (1) yielded an objective and internally consistent interpretation of the prosomere boundaries within the zebrafish forebrain; has (2) produced a list of markers, which in sparse combinations label the subdivisions of the diencephalon; and is (3) setting the stage for further functional and developmental studies in this vertebrate brain.

To understand the neural basis of episodic memory it is necessary to appreciate the significance of the fornix. This pathway creates a direct link between those temporal lobe and medial diencephalic sites responsible for anterograde amnesia. A collaboration with Andrew Mayes made it possible to recruit and scan 38 patients with colloid cysts in the third ventricle, a condition associated with variable fornix damage. Complete fornix loss was seen in three patients, who suffered chronic long-term memory problems. Volumetric analyses involving all 38 patients then revealed a highly consistent relationship between mammillary body volume and the recall of episodic memory. That relationship was not seen for working memory or tests of recognition memory. Three different methods all supported a dissociation between recollective-based recognition (impaired) and familiarity-based recognition (spared). This dissociation helped to show how the mammillary body-anterior thalamic nuclei axis, as well as the hippocampus, is vital for episodic memory yet is not required for familiarity-based recognition. These findings set the scene for a reformulation of temporal lobe and diencephalic amnesia. In this revised model, these two regions converge on overlapping cortical areas, including retrosplenial cortex. The united actions of the hippocampal formation and the anterior thalamic nuclei on these cortical areas enable episodic memory encoding and consolidation, impacting on subsequent recall.