The proper growth and elaboration of neural processes is essential for the establishment of a functional nervous system during development and is an integral feature of neural plasticity throughout life. Nuclear factor-kappa B(NF-κB) is classically known for its ubiquitous roles in inflammation,immune and stress-related responses and regulation of cell survival in all tissues, including the nervous system. NF-κB participation in other cellular processes remains poorly understood. Here we report a mechanism for controlling the growth of neural processes in developing peripheral and central neurons involving the transcription factor NF-κB. Inhibiting NF-κB activation with super-repressor IκB-α, BAY 11 7082(IκB-α phosphorylation inhibitor) or N-acetyl-Leu-Leu-norleucinal(proteosomal degradation inhibitor), or inhibiting NF-κB transcriptional activity with κB decoy DNA substantially reduced the size and complexity of the neurite arbors of sensory neurons cultured with brain-derived neurotrophic factor while having no effect on their survival. NF-κB exerted this effect during a restricted period of development following the phase of naturally occurring neuronal death when the processes and connections of the remaining neurons are extensively modified and refined. Inhibiting NF-κB activation or NF-κB transcriptional activity in layer 2 pyramidal neurons in postnatal somatosensory cortical slices reduced dendritic arbor size and complexity. This function of NF-κB has important implications for neural development and may provide an explanation for reported involvement of NF-κB in learning and memory.

The nuclear factor-kappa B (NF-κB) family of transcription factors has recently emerged as a major regulator of the growth and elaboration of neural processes. NF-κB signaling has been implicated in controlling axon initiation, elongation, guidance and branching and in regulating dendrite arbor size and complexity during development and dendritic spine density in the adult. NF-κB is activated by a variety of extracellular signals, and either promotes or inhibits growth depending on the phosphorylation status of the p65 NF-κB subunit. These novel roles for NF-κB, together with recent evidence implicating NF-κB in the regulation of neurogenesis in the embryo and adult, have important implications for neural development and for learning and memory in the mature nervous system.

The high avian biodiversity present in the Neotropical region offers a great opportunity to explore the ecology of host-parasite relationships. We present a survey of avian haemoparasites in a megadiverse country and explore how parasite prevalences are related to physical and ecological host characteristics. Using light microscopy, we documented the presence of haemoparasites in over 2000 individuals belonging to 246 species of wild birds, from nine localities and several ecosystems of Colombia. We analysed the prevalence of six avian haemoparasite taxa in relation to elevation and the following host traits: nest height, nest type, foraging strata, primary diet, sociality, migratory behaviour, and participation in mixed species flocks. Our analyses indicate significant associations between both mixed species flocks and nest height and Haemoproteus and Leucocytozoon prevalence. The prevalence of Leucocytozoon increased with elevation, whereas the prevalence of Trypanosoma and microfilariae decreased. Plasmodium and Haemoproteus prevalence did not vary significantly with elevation; in fact, both parasites were found up to 3300m above sea level. The distribution of parasite prevalence across the phylogeny of bird species included in this study showed little host phylogenetic signal indicating that infection rates in this system are evolutionarily labile. Vector distribution as well as the biology of transmission and the maintenance of populations of avian haemoparasites deserve more detailed study in this system.

The extracellular calcium-sensing receptor (CaSR) monitors the systemic extracellular free ionized calcium level ([Ca 2+ ] o ) in organs involved in systemic [Ca 2+ ] o homeostasis. However, the CaSR is also expressed in the nervous system where its role is unknown. Here we find high levels of the CaSR in perinatal mouse sympathetic neurons when their axons are innervating and branching extensively in their targets. Manipulating CaSR function in these neurons by varying [Ca 2+ ] o , using CaSR agonists and antagonists or expressing a dominant-negative CaSR markedly affects neurite growth in vitro Sympathetic neurons lacking the CaSR have smaller neurite arbors in vitro, and sympathetic innervation density is reduced in CaSR-deficient mice in vivo.Hippocampal pyramidal neurons, which also express the CaSR, have smaller dendrites when transfected with dominant-negative CaSR in postnatal organotypic cultures. Our findings reveal a crucial role for the CaSR in regulating the growth of neural processes in the peripheral and central nervous systems.The growth, guidance and branching of neural processes in the developing nervous system is controlled by numerous locally acting and diffusible signalling proteins that bind specific receptors on the growing tips of these processes 1,2. While changes in cytoplasmic Ca 2+ participate in transducing many of these growth and guidance signals, changes within the narrow physiological range of extracellular Ca 2+ have not been thought to play a direct role in regulating growth cone motility 3. The level of extracellular Ca 2+ is monitored by the CaSR, and in accordance with its crucial regulatory function in maintaining [Ca 2+ ] o within very narrow physiological limits 4, it is conspicuously expressed in all structures and organs involved in systemic calcium homeostasis, namely, the parathyroid glands, kidneys, bone and gut. It is also expressed in several other tissues and in multiple sites within the adult brain, including the subfornical organ, olfactory bulbs, striatum, cerebellum, basal ganglia and hippocampus, where its functions are unclear 5,6.To investigate whether CaSR has a role in neuronal development, we screened for the expression of CaSR transcripts in several experimentally tractable populations of neurons in the peripheral nervous system of fetal mice. We found significant CaSR expression in the superior cervical ganglion (SCG), a population of sympathetic neurons that is extensively

NGF plays a pivotal role in regulating sympathetic neuron survival and target field innervation during development. Here we show that a member of the TNF superfamily, GITR and its ligand GITRL are co-expressed in mouse sympathetic neurons when their axons are innervating their targets under the influence of target-derived NGF. In culture, GITRL enhances NGF-promoted neurite growth from neonatal sympathetic neurons, and preventing GITR-GITRL interaction in these neurons or GITR knockdown inhibits NGF-promoted neurite growth without affecting neuronal survival. GITR−/− neonates have reduced sympathetic innervation density in vivo compared with GITR+/+ littermates. GITR activation is required for the phosphorylation of ERK1/ERK2 by NGF that is necessary for neurite growth. Our results reveal a completely unsuspected signalling loop in developing sympathetic neurons that is crucial for NGF-dependent axon growth and target innervation.The growth and guidance of axons to their targets and the terminal arborization of axons within their targets is controlled by numerous locally acting and diffusible signalling molecules. These molecules are derived from a wide variety of cells and bind to receptors on advancing axons to influence growth rate, direction and branching1, 2. Sympathetic neurons of the developing superior cervical ganglion (SCG) are an extensively studied, experimentally tractable model for analysing the molecular basis of axonal growth and target innervation as well as other aspects of neuronal development. Several secreted factors have been implicated in promoting the growth sympathetic axons, including nerve growth factor (NGF), neurotrophin-3 (NT-3), artemin and hepatocyte growth factor (HGF)3. Of these, the most extensively studied and best understood is NGF which is needed for the innervation and terminal sprouting of sympathetic axons within many distal targets4, 5. In addition, target-derived NGF has a well-established role in promoting and regulating sympathetic neuron survival during development6.