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In autism spectrum disorder (ASD), disrupted functional and structural connectivity in the social brain has been suggested as the core biological mechanism underlying the social recognition deficits of this neurodevelopmental disorder. In this study, we aimed to identify genetic and neurostructural abnormalities at birth in a non-human primate model of ASD, the common marmoset with maternal exposure to valproic acid (VPA), which has been reported to display social recognition deficit in adulthood. Using a comprehensive gene expression analysis, we found that 20 genes were significantly downregulated in VPA-exposed neonates. Of these, Frizzled3 (FZD3) and PIK3CA were identified in an axon guidance signaling pathway. FZD3 is essential for the normal development of the anterior commissure (AC) and corpus callosum (CC); hence, we performed diffusion tensor magnetic resonance imaging with a 7-Tesla scanner to measure the midsagittal sizes of these structures. We found that the AC size in VPA-exposed neonates was significantly smaller than that in age-matched controls, while the CC size did not differ. These results suggest that downregulation of the genes related to axon guidance and decreased AC size in neonatal primates may be linked to social brain dysfunctions that can happen later in life. •Common marmosets were exposed to VPA in utero as a model of ASD.•FZD3 and PIK3CA were downregulated in the social brain cortex of VPA-exposed neonates.•Midsagittal AC size in VPA-exposed neonates was smaller than that in controls.•Our findings may provide novel genetic and neurostructural signatures at birth and potential targets for early intervention.

Linx is a member of the leucine-rich repeat and immunoglobulin family of membrane proteins which has critical roles in the development of the peripheral nervous system and forebrain connectivity. A previous study showed that Linx is expressed in projection neurons in the cortex and in cells that comprise the passage to the prethalamus that form the internal capsule, indicating the involvement of Linx in axon guidance and cell-cell communication. In this study, we found that Linx-deficient mice develop severe hydrocephalus and die perinatally by unknown mechanisms. Importantly, mice heterozygous for the linx gene exhibited defects in the development of the anterior commissure in addition to hydrocephalus, indicating haploinsufficiency of the linx gene in forebrain development. In N1E-115 neuroblastoma cells and primary cultured hippocampal neurons, Linx depletion led to impaired neurite extension and an increase in cell body size. Consistent with this, but of unknown significance, we found that Linx interacts with and upregulates the activity of Rho-kinase, a modulator of many cellular processes including cytoskeletal organization. These data suggest a role for Linx in the regulation of complex forebrain connectivity, and future identification of its extracellular ligand(s) will help clarify this function.

The genetic control of anterior brain development is highly conserved throughout animals. For instance, a conserved anterior gene regulatory network specifies the ancestral neuroendocrine center of animals and the apical organ of marine organisms. However, its contribution to the brain in non-marine animals has remained elusive. Here, we study the function of the Tc-foxQ2 forkhead transcription factor, a key regulator of the anterior gene regulatory network of insects. We characterized four distinct types of Tc-foxQ2 positive neural progenitor cells based on differential co-expression with Tc-six3/optix, Tc-six4, Tc-chx/vsx, Tc-nkx2.1/scro, Tc-ey, Tc-rx and Tc-fez1. An enhancer trap line built by genome editing marked Tc-foxQ2 positive neurons, which projected through the primary brain commissure and later through a subset of commissural fascicles. Eventually, they contributed to the central complex. Strikingly, in Tc-foxQ2 RNAi knock-down embryos the primary brain commissure did not split and subsequent development of midline brain structures stalled. Our work establishes foxQ2 as a key regulator of brain midline structures, which distinguish the protocerebrum from segmental ganglia. Unexpectedly, our data suggest that the central complex evolved by integrating neural cells from an ancestral anterior neuroendocrine center.

PurposeThe objective of this review is to provide a structured approach to the main white matter commissures, their anatomic and radiological definition and disease implications.MethodsThe Pubmed database and The JAMA Network were used for the literature review and the following terms were searched using Sort by: Best Match and Sort by: Most Recent: telencephalic commissure, forebrain commissure anatomy, fornix anatomy, commissure of fornix, posterior commissure, corpus callosum, commissural agenesis, Probst bundle, corpus callosum disorders review, corpus callosum diseases review, Marchiafava–Bignami, Alzheimer’s disease and Forel commissure; 36 papers were selected, one excluded due to the language barrier.ResultsThe interhemispheric communication in the brain is achieved via the brain commissures, bundles of white matter linking the two cerebral hemispheres. Anterior white commissure (AWC)—related with olfactory and non-visual communication, hippocampal commissure—main efferent pathway of the hippocampus, connecting the hippocampal formation to structures beyond the temporal lobe, crucial in declarative memory formation and consolidation—and the corpus callosum (CC)—from the anterior commissure to the hippocampal commissure—are the main telencephalic commissures. Supramammilary commissure, posterior commissure, supraoptic commissure and habenular commissure are diencephalic commissures—unknown function, probably related to involuntary eye movements. Commissural agenesis (AWC is absent or impossible to recognize), Alzheimer’s Disease (hippocampal commissure may contribute for disease dissemination) and agenesis of corpus callosum are some of the disturbances that involve the telenchephalic commissures.ConclusionsA comprehensive understanding of the clinic–anatomic correlation is pivotal to understand the pathology and therefore improve our diagnostic accuracy and treatment options, in the background of all patient management.

Background The annelid anterior central nervous system is often described to consist of a dorsal prostomial brain, consisting of several commissures and connected to the ventral ganglionic nerve cord via circumesophageal connectives. In the light of current molecular phylogenies, our assumptions on the primary design of the nervous system in Annelida has to be reconsidered. For that purpose we provide a detailed investigation of the adult nervous system of Magelonidae – a putatively basally branching annelid family - and studied early stages of the development of the latter. Results Our comparative investigation using an integrative morphological approach shows that the nervous system of Magelonidae is located inside the epidermis. The brain is composed of an anterior compact neuropil and posteriorly encircles the prostomial coelomic cavities. From the brain two lateral medullary cords branch off which fuse caudally. Prominent brain structures such as nuchal organs, ganglia or mushroom bodies are absent and the entire nervous system is medullary. Our investigations also contradict previous investigations and present an updated view on established assumptions and descriptions. Conclusion The comprehensive dataset presented herein enables a detailed investigation of the magelonid anterior central nervous system for the first time. The data reveal that early in annelid evolution complexity of brains and anterior sensory structures rises. Polymorphic neurons in clusters and distinct brain parts, as well as lateral organs - all of which are not present in outgroup taxa and in the putative magelonid sister group Oweniidae - already evolved in Magelonidae. Commissures inside the brain, ganglia and nuchal organs, however, most likely evolved in the stem lineage of Amphinomidae + Sipuncula and Pleistoannelida (Errantia+ Sedentaria). The investigation demonstrates the necessity to continuously question established descriptions and interpretations of earlier publications and the need for transparent datasets. Our results also hint towards a stronger inclusion of larval morphology and developmental investigations in order to understand adult morphological features, not only in Annelida.

Dibothriocephalus ditremus and Dibothriocephalus latus are diphyllobothriidean tapeworms autochthonous to Europe. Their larval stages (plerocercoids) may seriously alter health of their intermediate fish hosts (D. ditremus) or cause intestinal diphyllobothriosis of the final human host (D. latus). Despite numerous data on the internal structure of broad tapeworms, many aspects of the morphology and physiology related to host–parasite co-existence remain unclear for these 2 species. The main objective of this work was to elucidate functional morphology of the frontal part (scolex) of plerocercoids, which is crucial for their establishment in fish tissues and for an early attachment in final hosts. The whole-mount specimens were labelled with different antibodies and examined by confocal microscope to capture their complex 3-dimensional microanatomy. Both species exhibited similar general pattern of immunofluorescent signal, although some differences were observed. In the nervous system, FMRF amide-like immunoreactivity (IR) occurred in the bi-lobed brain, 2 main nerve cords and surrounding nerve plexuses. Differences between the species were found in the structure of the brain commissures and the size of the sensilla. Synapsin IR examined in D. ditremus occurred mainly around FMRF amide-like IR brain lobes and main cords. The unexpected finding was an occurrence of FMRF amide-like IR in terminal reservoirs of secretory gland ducts and excretory canals, which has not been observed previously in any tapeworm species. This may indicate that secretory/excretory products, which play a key role in host–parasite relationships, are likely to contain FMRF amide-related peptide/s.

The corpus callosum (CC) is the largest interhemispheric commissure in the eutherian brain, enabling inter-hemispheric sensory integration and higher-order cognitive functions. Historically viewed through a neuron- and axon-centric lens, extensive research has established that glial cells (astrocytes, oligodendrocytes, and microglia) are essential regulators of CC ontogenesis. Astrocytic guidepost cells sculpt midline architecture and secrete axonal guidance cues; oligodendrocytes drive callosal axonal maturation and myelination; and microglia regulate their fasciculation and pruning, myelination patterns, and synaptic refinement. In addition to these cell-specific roles, coordinated bidirectional signaling between neurons and glia ensures that axon targeting, maturation, and interhemispheric integration proceed in a precisely orchestrated manner. Disruptions to these glial functions are implicated in congenital and developmental brain pathologies, including malformations and CC agenesis. This review integrates molecular, developmental, and translational insights to provide a comprehensive, mechanistic understanding of glial contributions to CC development and how their dysfunction shapes pathology.

The corpus callosum (CC), the largest brain commissure and the primary white matter pathway for interhemispheric cortical connectivity, was traditionally viewed as a predominantly homotopic structure, connecting mirror areas of the cortex. However, new studies verified that most callosal commissural fibers are heterotopic. Recently, we reported that ~75% of the callosal connections in the brains of mice, marmosets, and humans are heterotopic, having an essential role in determining the global properties of brain networks. In the present study, we leveraged high-resolution diffusion-weighted imaging and graph network modeling to investigate the relationship between heterotopic and homotopic callosal fibers in human subjects and in a spontaneous mouse model of Corpus Callosum Dysgenesis (CCD), a congenital developmental CC malformation that leads to widespread whole-brain reorganization. Our results show that the CCD brain is more heterotopic than the normotypical brain, with both mouse and human CCD subjects displaying highly variable heterotopicity maps. CCD mice have a clear heterotopicity cluster in the anterior CC, while hypoplasic humans have strongly variable patterns. Graph network-based connectivity profile showed a direct impact of heterotopic connections on CCD brains altering several network-based statistics. Our collective results show that CCD directly alters heterotopic connections and brain connectivity.

Background Recent phylogenomic analyses congruently reveal a basal clade which consists of Oweniidae and Mageloniidae as sister group to the remaining Annelida. These results indicate that the last common ancestor of Annelida was a tube-dwelling organism. They also challenge traditional evolutionary hypotheses of different organ systems, among them the nervous system. In textbooks the central nervous system is described as consisting of a ganglionic ventral nervous system and a dorsally located brain with different tracts that connect certain parts of the brain to each other. Only limited information on the fine structure, however, is available for Oweniidae, which constitute the sister group (possibly together with Magelonidae) to all remaining annelids. Results The brain of Oweniidae is ring- shaped and basiepidermal. Ganglia, higher brain centers or complex sensory organs do not exist; instead the central nervous system is medullary. Posterior to the brain the ventral medullary cord arises directly from the ventral region of the brain in Myriowenia sp. while in Owenia fusiformis two medullary cords arise perpendicular to the brain ring, extend caudally and fuse posterior. The central nervous system is composed of a central neuropil and surrounding somata of the neurons. According to ultrastructural and histological data only one type of neuron is present in the central nervous system. Conclusion The central nervous system of Oweniidae is the simplest in terms of enlargement of the dorsal part of the brain and neuron distribution found among Annelida. Our investigation suggests that neither ganglia nor commissures inside the brain neuropil or clusters of polymorphic neurons were present in the annelid stem species. These structures evolved later within Annelida, most likely in the stem lineage of Amphinomidae, Sipuncula and Pleistoannelida. Palps were supposedly present in the last common ancestor of annelids and innervated by two nerves originating in the dorsal part of the brain. A broader comparison with species of each major spiralian clade shows the medullary nervous system to be a common feature and thus possibly representing the ancestral state of the spiralian nervous system. Moreover, ganglia and clusters of polymorphic neurons seemingly evolved independently in the compared taxa of Spiralia and Annelida.

The muscle system and the FMRFamide immunopositive components of the nervous system of flatworms Acrolichanus auriculatus (Digenea, Allocreadiidae), an intestine parasite of acipenserid fishes, were studied for the first time by immunocytochemical, histochemical methods and confocal laser scanning microscopy. Scanning electron microscopy in A. auriculatus revealed a consistent pattern in the number and arrangement of ciliated and unciliated sensory papillae along the digenean body. Morphological data demonstrated the presence of the circular, longitudinal and diagonal muscles in different body regions of A. auriculatus . The musculature of the oral and ventral suckers, the digestive system, as well as the muscles extending radially from the genital pore are described. The study revealed the presence of the FMRFamide immunopositive staining in the central and peripheral nervous systems of A. auriculatus : in the neurons and neurites of the brain, brain commissure, in three pairs of the longitudinal nerve cords and commissures. FMRFamide immunopositive nerve elements innervate the attachment organs and the compartments of the digestive, reproductive and excretory systems.