Understanding the regulation and function of adult neurogenesis: contribution from an insect model, the house cricket

Since the discovery of adult neurogenesis, a major issue is the role of newborn neurons and the function-dependent regulation of adult neurogenesis. We decided to use an animal model with a relatively simple brain to address these questions. In the adult cricket brain as in mammals, new neurons are produced throughout life. This neurogenesis occurs in the main integrative centers of the insect brain, the mushroom bodies (MBs), where the neuroblasts responsible for their formation persist after the imaginal molt. The rate of production of new neurons is controlled not only by internal cues such as morphogenetic hormones but also by external environmental cues. Adult crickets reared in an enriched sensory environment experienced an increase in neuroblast proliferation as compared with crickets reared in an impoverished environment. In addition, unilateral sensory deprivation led to reduced neurogenesis in the MB ipsilateral to the lesion. In search of a functional role for the new cells, we specifically ablated MB neuroblasts in young adults using brain-focused gamma ray irradiation. We developed a learning paradigm adapted to the cricket, which we call the "escape paradigm." Using this operant associative learning test, we showed that crickets lacking neurogenesis exhibited delayed learning and reduced memory retention of the task when olfactory cues were used. Our results suggest that environmental cues are able to influence adult neurogenesis and that, in turn, newly generated neurons participate in olfactory integration, optimizing learning abilities of the animal, and thus its adaptation to its environment. Nevertheless, odor learning in adult insects cannot always be attributed to newly born neurons because neurogenesis is completed earlier in development in many insect species. In addition, many of the irradiated crickets performed significantly better than chance on the operant learning task.     

Evidence that the C‐terminal domain (CtD) autoinhibits neural repression by Drosophila E(spl)M8

Analysis of the retinal defects of a CK2 phosphomimetic variant of E(spl)M8 (M8S¹⁵⁹D) and the truncated protein M8* encoded by the E(spl)D allele, suggest that the nonphosphorylated CtD “autoinhibits” repression. We have investigated this model by testing for inhibition (in “trans”) by the CtD fragment in its nonphosphorylated (M8‐CtD) and phosphomimetic (M8SD‐CtD) states. In N⁺ flies, ectopic M8‐CtD compromises lateral inhibition, i.e., elicits supernumerary bristles as with loss of N signaling. This antimorphic activity of M8‐CtD strongly rescues the reduced eye and/or bristle loss phenotypes that are elicited by ectopic M8SD or wild type M8. Additionally, the severely reduced eye of N^spl/Y; E(spl)D/+ flies is also rescued by M8‐CtD. Rescue is specific to the time and place, the morphogenetic furrow, where “founding” R8 photoreceptors are specified. In contrast, the phosphomimetic M8SD‐CtD that is predicted to be deficient for autoinhibition, exhibits significantly attenuated or negligible activity. These studies provide evidence that autoinhibition by the CtD regulates M8 activity in a phosphorylation‐dependent manner. genesis 48:44–55, 2010. © 2009 Wiley‐Liss, Inc.     

Breeding ecology of the Seychelles Black Parrot Coracopsis barklyi

Knowledge of breeding ecology is required for many conservation interventions. The Seychelles Black Parrot Coracopsis barklyi, endemic to the island of Praslin, is vulnerable to extinction. We aimed to improve understanding of C. barklyi breeding ecology to aid conservation planning. We present the results of four years of research, including nesting cavity characteristics and availability, reproductive success, breeding parameters, parental behaviour and reproductive strategy. Thirty-six breeding attempts were studied over the four seasons. Nests were mainly located in Coco de Mer palms Lodoicea maldivica. Deeper cavities with more canopy cover were preferred. There may be a shortage of high-quality nesting cavities in intensive breeding seasons. Average clutch size was 2.2 eggs, incubation period was c. 15 d and egg fertility was 71%. Rats were key nest predators, causing the failure of up to 33% of breeding attempts. The probability of nest success was 53%. At least 57% of fledglings survived their first year. This species breeds cooperatively and practices a highly unusual side-by-side copulation. We discuss the implications of the results in the context of former, ongoing and potential conservation measures for C. barklyi including translocation, invasive species management, nest box provisioning, habitat restoration and further research.     

3D reconstructions of quail–chick chimeras provide a new fate map of the avian scapula

Limbed vertebrates have functionally integrated postcranial axial and appendicular systems derived from two distinct populations of embryonic mesoderm. The axial skeletal elements arise from the paraxial somites, the appendicular skeleton and sternum arise from the somatic lateral plate mesoderm, and all of the muscles for both systems arise from the somites. Recent studies in amniotes demonstrate that the scapula has a mixed mesodermal origin. Here we determine the relative contribution of somitic and lateral plate mesoderm to the avian scapula from quail-chick chimeras. We generate 3D reconstructions of the grafted tissue in the host revealing a very different distribution of somitic cells in the scapula than previously reported. This novel 3D visualization of the cryptic border between somitic and lateral plate populations reveals the dynamics of musculoskeletal morphogenesis and demonstrates the importance of 3D visualization of chimera data. Reconstructions of chimeras make clear three significant contrasts with existing models of scapular development. First, the majority of the avian scapula is lateral plate derived and the somitic contribution to the scapular blade is significantly smaller than in previous models. Second, the segmentation of the somitic component of the blade is partially lost; and third, there are striking differences in growth rates between different tissues derived from the same somites that contribute to the structures of the cervical thoracic transition, including the scapula. These data call for the reassessment of theories on the development, homology, and evolution of the vertebrate scapula.     

Human Hippocampal Neurogenesis Persists in Aged Adults and Alzheimer’s Disease Patients

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Spinal cord regeneration: Lessons for mammals from non‐mammalian vertebrates

Unlike mammals, regenerative model organisms such as amphibians and fish are capable of spinal cord regeneration after injury. Certain key differences between regenerative and nonregenerative organisms have been suggested as involved in promoting this process, such as the capacity for neurogenesis and axonal regeneration, which appear to be facilitated by favorable astroglial, inflammatory and immune responses. These traits provide a regenerative‐permissive environment that the mammalian spinal cord appears to be lacking. Evidence for the regenerative nonpermissive environment in mammals is given by the fact that they possess neural stem/progenitor cells, which transplanted into permissive environments are able to give rise to new neurons, whereas in the nonpermissive spinal cord they are unable to do so. We discuss the traits that are favorable for regeneration, comparing what happens in mammals with each regenerative organism, aiming to describe and identify the key differences that allow regeneration. This comparison should lead us toward finding how to promote regeneration in organisms that are unable to do so. genesis 51:529–544. © 2013 Wiley Periodicals, Inc.     

Cardiac and neuroprotection regulated by α1-adrenergic receptor subtypes

Sympathetic nervous system regulation by the α₁-adrenergic receptor (AR) subtypes (α_1A, α_1B, α_1D) is complex, whereby chronic activity can be either detrimental or protective for both heart and brain function. This review will summarize the evidence that this dual regulation can be mediated through the different α₁-AR subtypes in the context of cardiac hypertrophy, heart failure, apoptosis, ischemic preconditioning, neurogenesis, locomotion, neurodegeneration, cognition, neuroplasticity, depression, anxiety, epilepsy, and mental illness.     

Formation of Postsynaptic-Like Membranes during Differentiation of Embryonic Stem Cellsin Vitro

To analyze the formation of neuromuscular junctions, mouse pluripotent embryonic stem (ES) cells were differentiated via embryoid bodies into skeletal muscle and neuronal cells. The developmentally controlled expression of skeletal muscle-specific genes coding for myf5, myogenin, myoD and myf6, α₁subunit of the L-type calcium channel, cell adhesion molecule M-cadherin, and neuron-specific genes encoding the 68-, 160-, and 200-kDa neurofilament proteins, synaptic vesicle protein synaptophysin, brain-specific proteoglycan neurocan, and microtubule-associated protein tau was demonstrated by RT-PCR analysis. In addition, genes specifically expressed at neuromuscular junctions, the γ- and ?-subunits of the nicotinic acetylcholine receptor (AChR) and the extracellular matrix protein S-laminin, were found. At the terminal differentiation stage characterized by the formation of multinucleated spontaneously contracting myotubes, the myogenic regulatory gene myf6 and the AChR ?-subunit gene, both specifically expressed in mature adult skeletal muscle, were found to be coexpressed. Only the terminally differentiated myotubes showed a clustering of nicotinic acetylcholine receptors (AChR) and a colocalization with agrin and synaptophysin. The formation of AChRs was also demonstrated on a functional level by using the patch clamp technique. Taken together, our results showed that during ES cell differentiationin vitroneuron- and muscle-specific genes are expressed in a developmentally controlled manner, resulting in the formation of postsynaptic-like membranes. Thus, the embryonic stem cell differentiation model will be helpful for studying cellular interactions at neuromuscular junctions by “loss of function” analysisin vitro.     

Verification of immunosuppression in chicks caused by Cryptosporidium baileyi infection using Brucella abortus strain 1119-3

Humoral immune response of young chicks to Brucella abortus strain 1119-3 inoculation was monitored to verify the degree of immunosuppression caused by infection with Cryptosporidium baileyi. Young chicks (2-day-old) were orally inoculated each with 2 × 10⁶ oocysts of C. baileyi, and then injected intramuscularly with 0.3 ml B. abortus strain 1119-3 containing 1 × 10⁹ living organisms on day 14 postinoculation (PI). Serum samples were tested by plate agglutination test on day 17 PI onwards at an interval of 3-6 days over a period of 36 days. Infected chicks with the coccidium showed significantly lower antibody titers than those of uninfected controls (P < 0.05). These findings document that C. baileyi infection in early life stage may predispose chicks easily to other potential poultry diseases.