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The epithalamus is present in all vertebrates where it is a central part of the dorsal diencephalic conduction system whose functions are critical for survival. The epithalamus consists of both nuclei and tracts. Studies on the development of the epithalamus in amniotes (reptiles, birds, and mammals) based on cytoarchitecture have commonly been part of a larger report on the embryogenesis of the diencephalon. Of these, observations on the epithalamus of reptiles are few with limited descriptions and figures. The present analysis fills this gap in knowledge by examining the development of the epithalamus in one group of reptiles, Alligator mississippiensis, using stains for cells and fibers. The time of origin and subsequent development of the nuclei and the tracts that course through the epithalamus were determined. These data provide a basis for future studies and for comparisons with other amniotes.

Organization and development of the forebrain in crocodilians are reviewed. In juvenile Caiman crocodilus, the following features were examined: identification and classification of dorsal thalamic nuclei and their respective connections with the telencephalon, presence of local circuit neurons in the dorsal thalamic nuclei, telencephalic projections to the dorsal thalamus, and organization of the thalamic reticular nucleus. These results document many similarities between crocodilians and other reptiles and birds. While crocodilians, as well as other sauropsids, demonstrate several features of neural circuitry in common with mammals, certain striking differences in organization of the forebrain are present. These differences are the result of evolution. To explore a basis for these differences, embryos of Alligator misissippiensis were examined to address the following. First, very early development of the brain in Alligator is similar to that of other amniotes. Second, the developmental program for individual vesicles of the brain differs between the secondary prosencephalon, diencephalon, midbrain, and hindbrain in Alligator. This is likely to be the case for other amniotes. Third, initial development of the diencephalon in Alligator is similar to that in other amniotes. In Alligator, alar and basal parts likely follow a different developmental scheme.

BackgroundIntracranial aneurysms at the posterior communicating artery (PCOM) are known to have high rupture rates compared to other locations. We developed and internally validated a statistical model discriminating between ruptured and unruptured PCOM aneurysms based on hemodynamic and geometric parameters, angio-architectures, and patient age with the objective of its future use for aneurysm risk assessment.MethodsA total of 289 PCOM aneurysms in 272 patients modeled with image-based computational fluid dynamics (CFD) were used to construct statistical models using logistic group lasso regression. These models were evaluated with respect to discrimination power and goodness of fit using tenfold nested cross-validation and a split-sample approach to mimic external validation.ResultsThe final model retained maximum and minimum wall shear stress (WSS), mean parent artery WSS, maximum and minimum oscillatory shear index, shear concentration index, and aneurysm peak flow velocity, along with aneurysm height and width, bulge location, non-sphericity index, mean Gaussian curvature, angio-architecture type, and patient age. The corresponding area under the curve (AUC) was 0.8359. When omitting data from each of the three largest contributing hospitals in turn, and applying the corresponding model on the left-out data, the AUCs were 0.7507, 0.7081, and 0.5842, respectively.ConclusionsStatistical models based on a combination of patient age, angio-architecture, hemodynamics, and geometric characteristics can discriminate between ruptured and unruptured PCOM aneurysms with an AUC of 84%. It is important to include data from different hospitals to create models of aneurysm rupture that are valid across hospital populations.

Optogenetics provide a potential alternative approach to the treatment of chronic pain, in which complex pathology often hampers efficacy of standard pharmacological approaches. Technological advancements in the development of thin, wireless, and mechanically flexible optoelectronic implants offer new routes to control the activity of subsets of neurons and nerve fibers . This study reports a novel and advanced design of battery-free, flexible, and lightweight devices equipped with one or two miniaturized LEDs, which can be individually controlled in real time. Two proof-of-concept experiments in mice demonstrate the feasibility of these devices. First, we show that blue-light devices implanted on top of the lumbar spinal cord can excite channelrhodopsin expressing nociceptors to induce place aversion. Second, we show that nocifensive withdrawal responses can be suppressed by green-light optogenetic (Archaerhodopsin-mediated) inhibition of action potential propagation along the sciatic nerve. One salient feature of these devices is that they can be operated via modern tablets and smartphones without bulky and complex lab instrumentation. In addition to the optical stimulation, the design enables the simultaneously wireless recording of the temperature in proximity of the stimulation area. As such, these devices are primed for translation to human patients with implications in the treatment of neurological and psychiatric conditions far beyond chronic pain syndromes.

Diencephalon development was investigated in a reptilian embryo, Alligator mississipiensis, beginning at a single compartment stage and continuing until internal subdivisions were present within major units. A variety of morphological techniques were used: immunocytochemistry, histochemistry, and cresyl violet staining. The diencephalon begins as a single unit. In the transverse domain, the diencephalon subsequently divides into two: the parencephalon and the synencephalon. The parencephalon then splits into the parencephalon anterior and parencephalon posterior. Still later, the synencephalon undergoes parcellation into the synencephalon anterior and synencephalon posterior. Subsequently, internal subdivisions occur in each of these four compartments. When the diencephalon has become subdivided into two compartments and continuing until internal subdivisions are present in each unit, a longitudinal border separating a dorsal, presumed alar plate, from a ventral, presumed basal plate, was seen. No clear cut subunits were reliably identified in the telencephalon or secondary prosencephalon during this period of early development in Alligator. Early diencephalon development in birds (chick) and mammals (humans) follows a similar pattern. Specifically, a single diencephalic compartment divides into two zones: the par-encephalon and synencephalon. Subsequently, the parencephalon becomes subdivided into an anterior and posterior unit. Some studies, including the present one, have noted further parcellation of the synencephalon into an anterior and posterior component, whereas others have not. Notwithstanding differences as to whether the synencephalon is a single unit or not, these detailed analyses in reptiles (Alligator), birds (chick), and mammals (humans), suggest that the initial pattern of early diencephalon development in amniotes is similar.

We present a neuro-symbolic visual question answering (VQA) pipeline for CLEVR, which is a well-known dataset that consists of pictures showing scenes with objects and questions related to them. Our pipeline covers (i) training neural networks for object classification and bounding-box prediction of the CLEVR scenes, (ii) statistical analysis on the distribution of prediction values of the neural networks to determine a threshold for high-confidence predictions, and (iii) a translation of CLEVR questions and network predictions that pass confidence thresholds into logic programmes so that we can compute the answers using an answer-set programming solver. By exploiting choice rules, we consider deterministic and non-deterministic scene encodings. Our experiments show that the non-deterministic scene encoding achieves good results even if the neural networks are trained rather poorly in comparison with the deterministic approach. This is important for building robust VQA systems if network predictions are less-than perfect. Furthermore, we show that restricting non-determinism to reasonable choices allows for more efficient implementations in comparison with related neuro-symbolic approaches without losing much accuracy.

Comparisons of characters in both adult and developing vertebrate central nervous systems require an understanding of the concept of homology. This article begins with a definition of homology in adult animals and then discusses criteria and methodology used to make appropriate comparisons of characters at a variety of hierarchical levels. Crucial to such an analysis is the methodology employed by neurocladistics to ensure meaningful comparisons. Then, a similar approach is used to address these identical problems in embryos. Concerns unique to comparisons of developing central nervous systems are enumerated. In addition, a number of special features of central nervous system formation and organization in both adults and embryos are discussed within the framework of homology and neurocladistics. Lastly, the concept of field homology as applied to vertebrate central nervous system characters is addressed.

Cell proliferation, as determined by immunoreactivity to proliferating cell nuclear antigen (PCNA) was investigated during early hindbrain development in Alligator. At the earliest stage examined, stage 3, when five rhombomeres are present, PCNA immunoreactivity is more robust laterally towards the pial margin and interrhombomeric boundaries are clearly seen. Subsequently, PCNA immunoreactivity fills each respective rhombomere and increases in intensity but respects the boundaries between segments until stage 7. At this time, borders between rhombomeres become less distinct. At stage 8, when the full compliment of rhombomeres is present, two longitudinal columns of PCNA immunoreactivity are seen rostrally which coalesce into a single column caudally. Interrhombomeric borders are indistinct. Later, at stage 9/10, two longitudinal columns span the entire length of the hindbrain and interrhombomeric boundaries remain less clear. The more lateral column fades whereas the medial stripe persists through stage 12. Thereafter, immunoreactivity fades. These observations confirm the findings in other species that rhombomeres are centers of cell proliferation. This feature is most likely common to hindbrain development in all gnathostomes. It is hypothesized that these two longitudinal columns of cell proliferation might be important for future patterning of the hindbrain.

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Nucleus rotundus is a prominent nucleus in the dorsal thalamus of nonmammalian amniotes. In one group of reptiles, Caiman crocodilus, previous studies have identified three parts of this neuronal aggregate. The central portion, the rotundal core, which receives visual input from the midbrain and projects to a restricted portion of the telencephalon, contains relay cells only. Previous examinations using Nissl morphology indicated that neurons of the rotundal core were not a homogeneous population of cells. The present investigation utilized another methodology to examine cell populations within the rotundal core, immunoreactivity to the calcium binding proteins, calbindin/calretinin and parvalbumin. Light microscopic observations revealed the following features. First, calbindin/calretinin immunoreactive neurons and parvalbumin immunoreactive neurons were present in the rotundal core. Of these two antibodies, immunoreactivity to calbindin/calretinin was much more robust and calbindin/calretinin immunoreactive neurons were more numerous than parvalbumin cells. Second, neurons immunoreactive to either calbindin/calretinin or parvalbumin were not homogeneous but comprised several populations based on perikaryal shape and size and neuronal process morphology. These results are compared with similar data in other amniotes.