Sequential Photoperiodic Programing of Serotonin Neurons, Signaling and Behaviors During Prenatal and Postnatal Development

Early life stimuli during critical developmental time frames have been linked to increased risk for neurodevelopmental disorders later in life. The serotonergic system of the brain is implicated in mood disorders and is impacted by the duration of daylight, or photoperiod. Here we sought to investigate sensitive periods of prenatal and postnatal development for photoperiodic programming of DRN serotonin neurons, midbrain serotonin and metabolite levels along with affective behaviors in adolescence (P30) or adulthood (P50). To address these questions we restricted the interval of exposure to prenatal development (E0-P0) for Long summer-like photoperiods (LD 16:8), or Short winter-like photoperiods (LD 8:16) with postnatal development and maturation then occurring under the opposing photoperiod. Prenatal exposure alone to Long photoperiods was sufficient to fully program increased excitability of DRN serotonin neurons into adolescence and adulthood, similar to maintained exposure to Long photoperiods throughout development. Interestingly, Long photoperiod exposure can elevate serotonin and its’ corresponding metabolite levels along with reducing affective behavior, which appear to have both pre and postnatal origins. Thus, exposure to Long photoperiods prenatally programs increased DRN serotonin neuronal excitability, but this step is insufficient to program serotonin signaling and affective behavior. Continuing influence of Long photoperiods during postnatal development then modulates serotonergic content and has protective effects for depressive-like behavior. Photoperiodic programing of serotonin function in mice appears to be a sequential process with programing of neuronal excitability as a first step occurring prenatally, while programing of circuit level serotonin signaling and behavior extends into the postnatal period

Photoperiodic Programming of the SCN and Its Role in Photoperiodic Output

Though the seasonal response of organisms to changing day lengths is a phenomenon that has been scientifically reported for nearly a century, significant questions remain about how photoperiod is encoded and effected neurobiologically. In mammals, early work identified the master circadian clock, the suprachiasmatic nuclei (SCN), as a tentative encoder of photoperiodic information. Here, we provide an overview of research on the SCN as a coordinator of photoperiodic responses, the intercellular coupling changes that accompany that coordination, as well as the SCN’s role in a putative brain network controlling photoperiodic input and output. Lastly, we discuss the importance of photoperiodic research in the context of tangible benefits to human health that have been realized through this research as well as challenges that remain

The core clock gene Per1 phases molecular and electrical circadian rhythms in SCN neurons

ABSTRACT The brain's biological clock, the suprachiasmatic nucleus (SCN), exhibits endogenous 24-hour rhythms in gene expression and spontaneous firing rate; however, the functional relationship between these neuronal rhythms is not fully understood. Here, we used a Per1::GFP transgenic mouse line that allows for the simultaneous quantification of molecular clock state and firing rate in SCN neurons to examine the relationship between these key components of the circadian clock. We find that there is a stable, phased relationship between E-box-driven clock gene expression and spontaneous firing rate in SCN neurons and that these relationships are independent of light input onto the system or of GABA A receptor-mediated synaptic activity. Importantly, the concordant phasing of gene and neural rhythms is disrupted in the absence of the homologous clock gene Per1, but persists in the absence of the core clock gene Per2. These results suggest that Per1 plays a unique, non-redundant role in phasing gene expression and firing rate rhythms in SCN neurons to increase the robustness of cellular timekeeping

The Infrared Properties of Submillimeter Galaxies: Clues From Ultra-Deep 70 Micron Imaging

We present 70 micron properties of submillimeter galaxies (SMGs) in the Great Observatories Origins Deep Survey (GOODS) North field. Out of thirty submillimeter galaxies (S_850 > 2 mJy) in the central GOODS-N region, we find two with secure 70 micron detections. These are the first 70 micron detections of SMGs. One of the matched SMGs is at z ~ 0.5 and has S_70/S_850 and S_70/S_24 ratios consistent with a cool galaxy. The second SMG (z = 1.2) has infrared-submm colors which indicate it is more actively forming stars. We examine the average 70 micron properties of the SMGs by performing a stacking analysis, which also allows us to estimate that S_850 > 2 mJy SMGs contribute 9 +- 3% of the 70 micron background light. The S_850/S_70 colors of the SMG population as a whole is best fit by cool galaxies, and because of the redshifting effects these constraints are mainly on the lower z sub-sample. We fit Spectral Energy Distributions (SEDs) to the far-infrared data points of the two detected SMGs and the average low redshift SMG (z_{median}= 1.4). We find that the average low-z SMG has a cooler dust temperature than local ultraluminous infrared galaxies (ULIRGs) of similar luminosity and an SED which is best fit by scaled up versions of normal spiral galaxies. The average low-z SMG is found to have a typical dust temperature T = 21 -- 33 K and infrared luminosity L_{8-1000 micron} = 8.0 \times 10^11 L_sun. We estimate the AGN contribution to the total infrared luminosity of low-z SMGs is less than 23%.Comment: Accepted by ApJ. 14 pages, 6 figures. Minor revisions 20th Dec 200

Targeting retinal dopaminergic neurons in tyrosine hydroxylase-driven green fluorescent protein transgenic zebrafish

Purpose: Dopamine plays key roles in a variety of basic functions in the central nervous system. To study developmental and functional roles of dopaminergic cells in zebrafish, we have generated a transgenic line of zebrafish expressing green fluorescent protein (GFP) under the control of the tyrosine hydroxylase (th1) promoter. Methods: A 12 kb gene fragment that contains the th1 promoter was isolated and ligated to the MmGFP coding sequence, linearized, microinjected into 1−2 cell stage embryos and the founders crossed with wild−type fish to screen for transgenic lines. Tg(−12th:MmGFP) embryos were visualized under fluorescence microscopy for GFP expression during development. Confocal microscopy was used to visualize GFP−labeled cells in the living whole mount retina and immunostained vertical sections of adult zebrafish retina. Single−cell reverse transcription polymerase chain reaction (RT−PCR) was performed on individual GFP+ cells collected from dispersed retinal cell cultures for th1 and dopamine transporter (dat). Loose−patch recordings of spike activity of GFP+ neurons were made in isolated whole mount retinas. Results: th1 promoter−driven GFP exhibited robust expression in the brain and retina during zebrafish development. In juvenile and adult fish retinas, GFP was expressed in cells located in the inner nuclear layer. Immunocytochemistry with antibodies for GFP and TH showed that 29±2% of GFP−labeled cells also expressed TH. Two subpopulations of GFP−labeled cells were identified by fluorescent microscopy: bright GFP−expressing cells and dim GFP−expressing cells. Seminested single−cell RT−PCR showed that 71% of dim GFP−expressing cells expressed both th and dat mRNA. Loose−patch voltage−clamp recording from dim GFP−labeled cells in retinal whole mounts revealed that many of these dopaminergic neurons are spontaneously active in darkness. Conclusions: Although this Tg(−12th:MmGFP) line is not a completely specific reporter for dopaminergic neurons, using relative GFP intensity we are able to enrich for the selection of retinal dopaminergic cells in vitro and in situ in molecular and electrophysiological experiments. This transgenic line provides a useful tool for studying retinal dopaminergic cells in the zebrafish

Intraretinal signaling by ganglion cell photoreceptors to dopaminergic amacrine neurons

Retinal dopaminergic amacrine neurons (DA neurons) play a central role in reconfiguring retinal function according to prevailing illumination conditions, yet the mechanisms by which light regulates their activity are poorly understood. We investigated the means by which sustained light responses are evoked in DA neurons. Sustained light responses were driven by cationic currents and persisted in vitro and in vivo in the presence of L-AP4, a blocker of retinal ON-bipolar cells. Several characteristics of these L-AP4-resistant light responses suggested that they were driven by melanopsin-expressing intrinsically photosensitive retinal ganglion cells (ipRGCs), including long latencies, marked poststimulus persistence, and a peak spectral sensitivity of 478 nm. Furthermore, sustained DA neuron light responses, but not transient DA neuron responses, persisted in rod/cone degenerate retinas, in which ipRGCs account for virtually all remaining retinal phototransduction. Thus, ganglion-cell photoreceptors provide excitatory drive to DA neurons, most likely by way of the coramification of their dendrites and the processes of DA neurons in the inner plexiform layer. This unprecedented centrifugal outflow of ganglion-cell signals within the retina provides a novel basis for the restructuring of retinal circuits by light

A conditional form of Bruton's tyrosine kinase is sufficient to activate multiple downstream signaling pathways via PLC Gamma 2 in B cells

BACKGROUND: Bruton's tyrosine kinase (Btk) is essential for B cell development and function. Mutations of Btk elicit X-linked agammaglobulinemia in humans and X-linked immunodeficiency in the mouse. Btk has been proposed to participate in B cell antigen receptor-induced signaling events leading to activation of phospholipase C-γ2 (PLCγ2) and calcium mobilization. However it is unclear whether Btk activation is alone sufficient for these signaling events, and whether Btk can activate additional pathways that do not involve PLCγ2. To address such issues we have generated Btk:ER, a conditionally active form of the kinase, and expressed it in the PLCγ2-deficient DT40 B cell line. RESULTS: Activation of Btk:ER was sufficient to induce multiple B cell signaling pathways in PLCγ2-sufficient DT40 cells. These included tyrosine phosphorylation of PLCγ2, mobilization of intracellular calcium, activation of extracellular signal-regulated kinase (ERK) and c-Jun NH(2)-terminal kinase (JNK) mitogen-activated protein kinase (MAPK) pathways, and apoptosis. In DT40 B cells deficient for PLCγ2, Btk:ER activation failed to induce the signaling events described above with the consequence that the cells failed to undergo apoptosis. CONCLUSIONS: These data suggest that Btk:ER regulates downstream signaling pathways primarily via PLCγ2 in B cells. While it is not known whether activated Btk:ER precisely mimics activated Btk, this conditional system will likely facilitate the dissection of the role of Btk and its family members in a variety of biological processes in many different cell types

Neonicotinoids Disrupt Circadian Rhythms and Sleep in Honey Bees

Honey bees are critical pollinators in ecosystems and agriculture, but their numbers have significantly declined. Declines in pollinator populations are thought to be due to multiple factors including habitat loss, climate change, increased vulnerability to disease and parasites, and pesticide use. Neonicotinoid pesticides are agonists of insect nicotinic cholinergic receptors, and sub-lethal exposures are linked to reduced honey bee hive survival. Honey bees are highly dependent on circadian clocks to regulate critical behaviors, such as foraging orientation and navigation, time-memory for food sources, sleep, and learning/memory processes. Because circadian clock neurons in insects receive light input through cholinergic signaling we tested for effects of neonicotinoids on honey bee circadian rhythms and sleep. Neonicotinoid ingestion by feeding over several days results in neonicotinoid accumulation in the bee brain, disrupts circadian rhythmicity in many individual bees, shifts the timing of behavioral circadian rhythms in bees that remain rhythmic, and impairs sleep. Neonicotinoids and light input act synergistically to disrupt bee circadian behavior, and neonicotinoids directly stimulate wake-promoting clock neurons in the fruit fly brain. Neonicotinoids disrupt honey bee circadian rhythms and sleep, likely by aberrant stimulation of clock neurons, to potentially impair honey bee navigation, time-memory, and social communication

Ionic high-pressure form of elemental boron

Boron is an element of fascinating chemical complexity. Controversies have shrouded this element since its discovery was announced in 1808: the new 'element' turned out to be a compound containing less than 60-70 percent of boron, and it was not until 1909 that 99-percent pure boron was obtained. And although we now know of at least 16 polymorphs, the stable phase of boron is not yet experimentally established even at ambient conditions. Boron's complexities arise from frustration: situated between metals and insulators in the periodic table, boron has only three valence electrons, which would favour metallicity, but they are sufficiently localized that insulating states emerge. However, this subtle balance between metallic and insulating states is easily shifted by pressure, temperature and impurities. Here we report the results of high-pressure experiments and ab initio evolutionary crystal structure predictions that explore the structural stability of boron under pressure and, strikingly, reveal a partially ionic high-pressure boron phase. This new phase is stable between 19 and 89 GPa, can be quenched to ambient conditions, and has a hitherto unknown structure (space group Pnnm, 28 atoms in the unit cell) consisting of icosahedral B12 clusters and B2 pairs in a NaCl-type arrangement. We find that the ionicity of the phase affects its electronic bandgap, infrared adsorption and dielectric constants, and that it arises from the different electronic properties of the B2 pairs and B12 clusters and the resultant charge transfer between them.Comment: Published in Nature 453, 863-867 (2009

The Allen Telescope Array Pi GHz Sky Survey I. Survey Description and Static Catalog Results for the Bootes Field

The Pi GHz Sky Survey (PiGSS) is a key project of the Allen Telescope Array. PiGSS is a 3.1 GHz survey of radio continuum emission in the extragalactic sky with an emphasis on synoptic observations that measure the static and time-variable properties of the sky. During the 2.5-year campaign, PiGSS will twice observe ~250,000 radio sources in the 10,000 deg^2 region of the sky with b > 30 deg to an rms sensitivity of ~1 mJy. Additionally, sub-regions of the sky will be observed multiple times to characterize variability on time scales of days to years. We present here observations of a 10 deg^2 region in the Bootes constellation overlapping the NOAO Deep Wide Field Survey field. The PiGSS image was constructed from 75 daily observations distributed over a 4-month period and has an rms flux density between 200 and 250 microJy. This represents a deeper image by a factor of 4 to 8 than we will achieve over the entire 10,000 deg^2. We provide flux densities, source sizes, and spectral indices for the 425 sources detected in the image. We identify ~100$ new flat spectrum radio sources; we project that when completed PiGSS will identify 10^4 flat spectrum sources. We identify one source that is a possible transient radio source. This survey provides new limits on faint radio transients and variables with characteristic durations of months.Comment: Accepted for publication in ApJ; revision submitted with extraneous figure remove