A core component of the avian pallial cognitive network is the multimodal nidopallium caudolaterale (NCL) that is considered to be analogous to the mammalian prefrontal cortex (PFC). The NCL plays a key role in a multitude of executive tasks such as working memory, decision-making during navigation, and extinction learning in complex learning environments. Like the PFC, the NCL is positioned at the transition from ascending sensory to descending motor systems. For the latter, it sends descending premotor projections to the intermediate arcopallium (AI) and the medial striatum (MSt). To gain detailed insight into the organization of these projections, we conducted several retrograde and anterograde tracing experiments. First, we tested whether NCL neurons projecting to AI (NCLarco neurons) and MSt (NCLMSt neurons) are constituted by a single neuronal population with bifurcating neurons, or whether they form two distinct populations. Here, we found two distinct projection patterns to both target areas that were associated with different morphologies. Second, we revealed a weak topographic projection toward the medial and lateral striatum and a strong topographic projection toward AI with clearly distinguishable sensory termination fields. Third, we investigated the relationship between the descending NCL pathways to the arcopallium with those from the hyperpallium apicale, which harbors a second major descending pathway of the avian pallium. We embed our findings within a system of parallel pallio-motor loops that carry information from separate sensory modalities to different subpallial systems. Our results also provide insights into the evolution of the avian motor system from which, possibly, the song system has emerged.

Cellular-level anatomical data from early fetal brain are sparse yet critical to the understanding of neurodevelopmental disorders. We characterize the organization of the human cerebral cortex between 13 and 15 gestational weeks using high-resolution whole-brain histological data sets complimented with multimodal imaging. We observed the heretofore underrecognized, reproducible presence of infolds on the mesial surface of the cerebral hemispheres. Of note at this stage, when most of the cerebrum is occupied by lateral ventricles and the corpus callosum is incompletely developed, we postulate that these mesial infolds represent the primordial stage of cingulate, callosal, and calcarine sulci, features of mesial cortical development. Our observations are based on the multimodal approach and further include histological three-dimensional reconstruction that highlights the importance of the plane of sectioning. We describe the laminar organization of the developing cortical mantle, including these infolds from the marginal to ventricular zone, with Nissl, hematoxylin and eosin, and glial fibrillary acidic protein (GFAP) immunohistochemistry. Despite the absence of major sulci on the dorsal surface, the boundaries among the orbital, frontal, parietal, and occipital cortex were very well demarcated, primarily by the cytoarchitecture differences in the organization of the subplate (SP) and intermediate zone (IZ) in these locations. The parietal region has the thickest cortical plate (CP), SP, and IZ, whereas the orbital region shows the thinnest CP and reveals an extra cell-sparse layer above the bilaminar SP. The subcortical structures show intensely GFAP-immunolabeled soma, absent in the cerebral mantle. Our findings establish a normative neurodevelopment baseline at the early stage.

The mammalian cerebrum has changed substantially during evolution, characterized by increases in neurons and glial cells and by the expansion and folding of the cerebrum. While these evolutionary alterations are thought to be crucial for acquiring higher cognitive functions, the molecular mechanisms underlying the development and evolution of the mammalian cerebrum remain only partially understood. This is, in part, because of the difficulty in analyzing these mechanisms using mice only. To overcome this limitation, genetic manipulation techniques for the cerebrum of gyrencephalic carnivore ferrets have been developed. Furthermore, successful gene knockout in the ferret cerebrum has been accomplished through the application of the CRISPR/Cas9 system. This review mainly highlights recent research conducted using gyrencephalic carnivore ferrets to investigate the mechanisms underlying the development and evolution of cortical folds.

Many predatory animals, such as the praying mantis, use vision for prey detection and capture. Mantises are known in particular for their capability to estimate distances to prey by stereoscopic vision. While the initial visual processing centers have been extensively documented, we lack knowledge on the architecture of central brain regions, pivotal for sensory motor transformation and higher brain functions. To close this gap, we provide a three-dimensional (3D) reconstruction of the central brain of the Asian mantis, Hierodula membranacea. The atlas facilitates in-depth analysis of neuron ramification regions and aides in elucidating potential neuronal pathways. We integrated seven 3D-reconstructed visual interneurons into the atlas. In total, 42 distinct neuropils of the cerebrum were reconstructed based on synapsin-immunolabeled whole-mount brains. Backfills from the antenna and maxillary palps, as well as immunolabeling of γ-aminobutyric acid (GABA) and tyrosine hydroxylase (TH), further substantiate the identification and boundaries of brain areas. The composition and internal organization of the neuropils were compared to the anatomical organization of the brain of the fruit fly (Drosophila melanogaster) and the two available brain atlases of Polyneoptera-the desert locust (Schistocerca gregaria) and the Madeira cockroach (Rhyparobia maderae). This study paves the way for detailed analyses of neuronal circuitry and promotes cross-species brain comparisons. We discuss differences in brain organization between holometabolous and polyneopteran insects. Identification of ramification sites of the visual neurons integrated into the atlas supports previous claims about homologous structures in the optic lobes of flies and mantises.

Cortical wall of human fetal cerebral cortex (early second trimester immunostained for a synaptic marker [red]) revealing the extent of the subplate, which is considerably wider than the cortical plate at this developmental stage.

The trigeminal nerve is the sensory afferent of the orofacial regions and divided into three major branches. Cell bodies of the trigeminal nerve lie in the trigeminal ganglion and are surrounded by satellite cells. There is a close interaction between ganglion cells via satellite cells, but the function is not fully understood. In the present study, we clarified the ganglion cells' three-dimensional (3D) localization, which is essential to understand the functions of cell-cell interactions in the trigeminal ganglion. Fast blue was injected into 12 sites of the rat orofacial regions, and ganglion cells were retrogradely labeled. The labeled trigeminal ganglia were cleared by modified 3DISCO, imaged with confocal laser-scanning microscopy, and reconstructed in 3D. Histograms of the major axes of the fast blue-positive somata revealed that the peak major axes of the cells innervating the skin/mucosa were smaller than those of cells innervating the deep structures. Ganglion cells innervating the ophthalmic, maxillary, and mandibular divisions were distributed in the anterodorsal, central, and posterolateral portions of the trigeminal ganglion, respectively, with considerable overlap in the border region. The intermingling in the distribution of ganglion cells within each division was also high, in particular, within the mandibular division. Specifically, intermingling was observed in combinations of tongue and masseter/temporal muscles, maxillary/mandibular molars and masseter/temporal muscles, and tongue and mandibular molars. Double retrograde labeling confirmed that some ganglion cells innervating these combinations were closely apposed. Our data provide essential information for understanding the function of ganglion cell-cell interactions via satellite cells.

The intricate development of the human amygdala involves a complex interplay of diverse processes, varying in speed and duration. In humans, transient cytoarchitectural structures deliquesce, leading to the formation of functionally distinct nuclei as a result of multiple interdependent developmental events. This study compares the amygdala's cytoarchitectural development in conjunction with specific antibody reactivity for neuronal, glial, neuropil, and radial glial fibers, synaptic, extracellular matrix, and myelin components in 39 fetal human brains. We recognized that the early fetal period, as a continuation of the embryonic period,is still dominated by relatively uniform histogenetic processes. The typical appearance of ovoid cell clusters in the lateral nucleus during midfetal period is most likely associated with the cell migration and axonal growth processes in the developing human brain. Notably, synaptic markers are firstly detected in the corticomedial group of nuclei, while immunoreactivity for the panaxonal neurofilament marker SMI 312 is found dorsally. The late fetal period is characterized by a protracted migration process evidenced by the presence of doublecortin and SOX-2 immunoreactivity ventrally, in the prospective paralaminar nucleus, reinforced by vimentin immunoreactivity in the last remaining radial glial fibers. Nearing the term period, SMI 99 immunoreactivity indicates that perinatal myelination becomes prominent primarily along major axonal pathways, laying the foundation for more pronounced functional maturation. This study comprehensively elucidates the rate and sequence of maturational events in the amygdala, highlighting the key role of prenatal development in its behavioral, autonomic, and endocrine regulation, with subsequent implications for both normal functioning and psychiatric disorders.

Retinoic acid-induced 1 (RAI1) encodes a transcriptional regulator critical for brain development and function. RAI1 haploinsufficiency in humans causes a syndromic autism spectrum disorder known as Smith-Magenis syndrome (SMS). The neuroanatomical distribution of RAI1 has not been quantitatively analyzed during the development of the prefrontal cortex, a brain region critical for cognitive function and social behaviors and commonly implicated in autism spectrum disorders, including SMS. Here, we performed comparative analyses to uncover the evolutionarily convergent and divergent expression profiles of RAI1 in major cell types during prefrontal cortex maturation in common marmoset monkeys (Callithrix jacchus) and mice (Mus musculus). We found that while RAI1 in both species is enriched in neurons, the percentage of excitatory neurons that express RAI1 is higher in newborn mice than in newborn marmosets. By contrast, RAI1 shows similar neural distribution in adult marmosets and adult mice. In marmosets, RAI1 is expressed in several primate-specific cell types, including intralaminar astrocytes and MEIS2-expressing prefrontal GABAergic neurons. At the molecular level, we discovered that RAI1 forms a protein complex with transcription factor 20 (TCF20), PHD finger protein 14 (PHF14), and high mobility group 20A (HMG20A) in the marmoset brain. In vitro assays in human cells revealed that TCF20 regulates RAI1 protein abundance. This work demonstrates that RAI1 expression and protein interactions are largely conserved but with some unique expression in primate-specific cells. The results also suggest that altered RAI1 abundance could contribute to disease features in disorders caused by TCF20 dosage imbalance.