Metamorphic remodeling of the olfactory organ of the African clawed frog,Xenopus laevis

The amphibian olfactory system undergoes massive remodeling during metamorphosis. The transition from aquatic olfaction in larvae to semiaquatic or airborne olfaction in adults requires anatomical, cellular, and molecular modifications. These changes are particularly pronounced in Pipidae, whose adults have secondarily adapted to an aquatic life style. In the fully aquatic larvae of Xenopus laevis, the main olfactory epithelium specialized for sensing water‐borne odorous substances lines the principal olfactory cavity (PC), whereas a separate olfactory epithelium lies in the vomeronasal organ (VNO). During metamorphosis, the epithelium of the PC is rearranged into the adult “air nose,” whereas a new olfactory epithelium, the adult “water nose,” forms in the emerging middle cavity (MC). Here we performed a stage‐by‐stage investigation of the anatomical changes of the Xenopus olfactory organ during metamorphosis. We quantified cell death in all olfactory epithelia and found massive cell death in the PC and the VNO, suggesting that the majority of larval sensory neurons is replaced during metamorphosis in both sensory epithelia. The moderate cell death in the MC shows that during the formation of this epithelium some cells are sorted out. Our results show that during MC formation some supporting cells, but not sensory neurons, are relocated from the PC to the MC and that they are eventually eliminated during metamorphosis. Together our findings illustrate the structural and cellular changes of the Xenopus olfactory organ during metamorphosis. J. Comp. Neurol. 524:986–998, 2016. © 2015 Wiley Periodicals, Inc.     

Somatosensory brainstem,thalamus, and cortex of the California sea lion (Zalophus californianus)

Pinnipeds (sea lions, seals, and walruses) are notable for many reasons, including their ape‐sized brains, their adaptation to a coastal niche that combines mastery of the sea with strong ties to land, and the remarkable abilities of their trigeminal whisker system. However, little is known about the central nervous system of pinnipeds. Here we report on the somatosensory areas of the nervous system of the California sea lion (Zalophus californianus). Using stains for Nissl, cytochrome oxidase, and vesicular glutamate transporters, we investigated the primary somatosensory areas in the brainstem, thalamus, and cortex in one sea lion pup and the external anatomy of the brain in a second pup. We find that the sea lion's impressive array of whiskers is matched by a large trigeminal representation in the brainstem with well‐defined parcellation that resembles the barrelettes found in rodents but scaled upward in size. The dorsal column nuclei are large and distinct. The ventral posterior nucleus of the thalamus has divisions, with a large area for the presumptive head representation. Primary somatosensory cortex is located in the neocortex just anterior to the main vertical fissure, and precisely locating it as we do here is useful for comparing the highly gyrified pinniped cortex with that of other carnivores. To our knowledge this work is the first comprehensive report on the central nervous system areas for any sensory system in a pinniped. The results may be useful both in the veterinary setting and for comparative studies related to brain evolution. J. Comp. Neurol. 524:1957–1975, 2016. © 2016 Wiley Periodicals, Inc.     

Expression dynamics of NADPH oxidases during early zebrafish development

Nicotinamide dinucleotide phosphate oxidases (NOX) control various cellular signaling cascades. In the nervous system, there is recent evidence that NOX‐derived reactive oxygen species (ROS) regulate neurite outgrowth, regeneration, and stem cell proliferation; however, a comprehensive NOX gene expression analysis is missing for all major model systems. Zebrafish embryos provide an excellent model system to study neurodevelopment and regeneration because they develop quickly and are well suited for in vivo imaging and molecular approaches. Although the sequences of five NOX genes (nox1, nox2/cybb, nox4, nox5, and duox) have been identified in the zebrafish genome, nothing is known about their expression pattern. Here, we used quantitative polymerase chain reaction combined with in situ hybridization to develop a catalog of nox1, nox2/cybb, nox5, and duox expression in zebrafish during early nervous system development from 12 to 48 hours post fertilization. We found that expression levels of nox1, nox5, and duox are dynamic during the first 2 days of development, whereas nox2/cybb levels remain remarkably stable. By sectioning in situ hybridized embryos, we found a pattern of broad and overlapping NOX isoform expression at 1 and 1.5 days post fertilization. After 2 days of development, a few brain regions displayed increased NOX expression levels. Collectively, these results represent the first comprehensive analysis of NOX gene expression in the zebrafish and will provide a basis for future studies aimed at determining the functions of NOX enzymes in neurodevelopment and regeneration. J. Comp. Neurol. 524:2130–2141, 2016. © 2015 Wiley Periodicals, Inc.     

Review: Sporadic Parkinson's disease: development and distribution of α‐synuclein pathology

The development of α‐synuclein immunoreactive aggregates in selectively vulnerable neuronal types of the human central, peripheral, and enteric nervous systems is crucial for the pathogenesis of sporadic Parkinson's disease. The presence of these lesions persists into the end phase of the disease, a process that is not subject to remission. The initial induction of α‐synuclein misfolding and subsequent aggregation probably occurs in the olfactory bulb and/or the enteric nervous system. Each of these sites is exposed to potentially hostile environmental factors. Once formed, the aggregates appear to be capable of propagating trans‐synaptically from nerve cell to nerve cell in a virtually self‐promoting pathological process. A regional distribution pattern of aggregated α‐synuclein emerges that entails the involvement of only a few types of susceptible and axonally interconnected projection neurons within the human nervous system. One major route of disease progression may originate in the enteric nervous system and retrogradely reach the dorsal motor nucleus of the vagal nerve in the lower brainstem. From there, the disease process proceeds chiefly in a caudo‐rostral direction through visceromotor and somatomotor brainstem centres to the midbrain, forebrain, and cerebral cortex. Spinal cord centres may become involved by means of descending projections from involved lower brainstem nuclei as well as by sympathetic projections connecting the enteric nervous system with postganglionic peripheral ganglia and preganglionic nuclei of the spinal cord. The development of experimental cellular and animal models is helping to explain the mechanisms of how abnormal α‐synuclein can undergo aggregation and how transmission along axonal connectivities can occur, thereby encouraging the initiation of potential disease‐modifying therapeutic strategies for sporadic Parkinson's disease.     

Review: Novel treatment strategies targeting alpha‐synuclein in multiple system atrophy as a model of synucleinopathy

Neurodegenerative disorders with alpha‐synuclein (α‐syn) accumulation (synucleinopathies) include Parkinson's disease (PD), PD dementia, dementia with Lewy bodies and multiple system atrophy (MSA). Due to the involvement of toxic α‐syn aggregates in the molecular origin of these disorders, developing effective therapies targeting α‐syn is a priority as a disease‐modifying alternative to current symptomatic treatments. Importantly, the clinical and pathological attributes of MSA make this disorder an excellent candidate as a synucleinopathy model for accelerated drug development. Recent therapeutic strategies targeting α‐syn in in vivo and in vitro models of MSA, as well as in clinical trials, have been focused on the pathological mechanisms of α‐syn synthesis, aggregation, clearance, and/or cell‐to‐cell propagation of its neurotoxic conformers. Here we summarize the most relevant approaches in this direction, with emphasis on their potential as general synucleinopathy modifiers, and enumerate research areas for potential improvement in MSA drug discovery.     

A topological approach unveils system invariances and broken symmetries in the brain

Symmetries are widespread invariances underscoring countless systems, including the brain. A symmetry break occurs when the symmetry is present at one level of observation but is hidden at another level. In such a general framework, a concept from algebraic topology, namely, the Borsuk‐Ulam theorem (BUT), comes into play and sheds new light on the general mechanisms of nervous symmetries. The BUT tells us that we can find, on an n‐dimensional sphere, a pair of opposite points that have the same encoding on an n – 1 sphere. This mapping makes it possible to describe both antipodal points with a single real‐valued vector on a lower dimensional sphere. Here we argue that this topological approach is useful for the evaluation of hidden nervous symmetries. This means that symmetries can be found when evaluating the brain in a proper dimension, although they disappear (are hidden or broken) when we evaluate the same brain only one dimension lower. In conclusion, we provide a topological methodology for the evaluation of the most general features of brain activity, i.e., the symmetries, cast in a physical/biological fashion that has the potential to be operationalized. © 2016 Wiley Periodicals, Inc.