Anatomical Substrates of Rapid Eye Movement Sleep Rebound in a Rodent Model of Post-sevoflurane Sleep Disruption.

BACKGROUND: Previous research suggests that sevoflurane anesthesia may prevent the brain from accessing rapid eye movement (REM) sleep. If true, then patterns of neural activity observed in REM-on and REM-off neuronal populations during recovery from sevoflurane should resemble those seen after REM sleep deprivation. In this study, the authors hypothesized that, relative to controls, animals exposed to sevoflurane present with a distinct expression pattern of c-Fos, a marker of neuronal activation, in a cluster of nuclei classically associated with REM sleep, and that such expression in sevoflurane-exposed and REM sleep-deprived animals is largely similar. METHODS: Adult rats and Targeted Recombination in Active Populations mice were implanted with electroencephalographic electrodes for sleep-wake recording and randomized to sevoflurane, REM deprivation, or control conditions. Conventional c-Fos immunohistochemistry and genetically tagged c-Fos labeling were used to quantify activated neurons in a group of REM-associated nuclei in the midbrain and basal forebrain. RESULTS: REM sleep duration increased during recovery from sevoflurane anesthesia relative to controls (157.0 ± 24.8 min vs. 124.2 ± 27.8 min; P = 0.003) and temporally correlated with increased c-Fos expression in the sublaterodorsal nucleus, a region active during REM sleep (176.0 ± 36.6 cells vs. 58.8 ± 8.7; P = 0.014), and decreased c-Fos expression in the ventrolateral periaqueductal gray, a region that is inactive during REM sleep (34.8 ± 5.3 cells vs. 136.2 ± 19.6; P = 0.001). Fos changes similar to those seen in sevoflurane-exposed mice were observed in REM-deprived animals relative to controls (sublaterodorsal nucleus: 85.0 ± 15.5 cells vs. 23.0 ± 1.2, P = 0.004; ventrolateral periaqueductal gray: 652.8 ± 71.7 cells vs. 889.3 ± 66.8, P = 0.042). CONCLUSIONS: In rodents recovering from sevoflurane, REM-on and REM-off neuronal activity maps closely resemble those of REM sleep-deprived animals. These findings provide new evidence in support of the idea that sevoflurane does not substitute for endogenous REM sleep.

Diverse processing of pharmacological and natural rewards by the central amygdala.

The central amygdala (CeA) with its medial (CeM) and lateral (CeL) nuclei is the brain hub for processing stimuli with emotional context. CeL nucleus gives a strong inhibitory input to the CeM, and this local circuitry assigns values (positive or negative) to incoming stimuli, guiding appropriate behavior (approach or avoid). However, the particular involvement of CeA in processing such emotionally relevant information and adaptations of the CeA circuitry are not yet well understood. In this study, we examined synaptic plasticity in the CeA after exposure to two types of rewards, pharmacological (cocaine) and natural (sugar). We found that both rewards engage CeM, where they generate silent synapses resulting in the strengthening of the network. However, only cocaine triggers plasticity in the CeL, which leads to the weakening of its excitatory inputs. Finally, chemogenetic inhibition of CeM attenuates animal preference for sugar, while activation delays cocaine-induced increase in locomotor activity.

Whole-brain tracking of cocaine and sugar rewards processing.

Natural rewards, such as food, and sex are appetitive stimuli available for animals in their natural environment. Similarly, addictive rewards such as drugs of abuse possess strong, positive valence, but their action relies on their pharmacological properties. Nevertheless, it is believed that both of these kinds of rewards activate similar brain circuitry. The present study aimed to discover which parts of the brain process the experience of natural and addictive rewards. To holistically address this question, we used a single-cell whole-brain imaging approach to find patterns of activation for acute and prolonged sucrose and cocaine exposure. We analyzed almost 400 brain structures and created a brain-wide map of specific, c-Fos-positive neurons engaged by these rewards. Acute but not prolonged sucrose exposure triggered a massive c-Fos expression throughout the brain. Cocaine exposure on the other hand potentiated c-Fos expression with prolonged use, engaging more structures than sucrose treatment. The functional connectivity analysis unraveled an increase in brain modularity after the initial exposure to both types of rewards. This modularity was increased after repeated cocaine, but not sucrose, intake. To check whether discrepancies between the processing of both types of rewards can be found on a cellular level, we further studied the nucleus accumbens, one of the most strongly activated brain structures by both sucrose and cocaine experience. We found a high overlap between natural and addictive rewards on the level of c-Fos expression. Electrophysiological measurements of cellular correlates of synaptic plasticity revealed that natural and addictive rewards alike induce the accumulation of silent synapses. These results strengthen the hypothesis that in the nucleus accumbens drugs of abuse cause maladaptive neuronal plasticity in the circuitry that typically processes natural rewards.

Karyotype and nuclear DNA content of hexa-, octo-, and duodecaploid lines of Bromus subgen. Ceratochloa.

The subgenus Ceratochloa of the genus Bromus includes a number of closely related allopolyploid forms or species that present a difficult taxonomic problem. The present work combines data concerning chromosome length, heterochromatin distribution and nuclear genome size of different 6x, 8x and 12x accessions in this subgenus. Special attention is paid to the karyotype structure and genomic constitution of duodecaploid plants recently found in South America. Hexaploid lineages possess six almost indistinguishable genomes and a nuclear DNA content between 12.72 pg and 15.10 pg (mean 1Cx value = 2.32 pg), whereas octoploid lineages contain the same six genomes (AABBCC) plus two that are characterized by longer chromosomes and a greater DNA content (1Cx = 4.47 pg). Two duodecaploid accessions found in South America resemble each other and apparently differ from the North American duodecaploid B. arizonicus as regards chromosome size and nuclear DNA content (40.00 and 40.50 pg vs. 27.59 pg). These observations suggest that the South American duodecaploids represent a separate evolutionary lineage of the B. subgenus Ceratochloa, unrecognized heretofore.

Karyotype and nuclear DNA content of hexa-, octo-, and duodecaploid lines of Bromus subgen. Ceratochloa

The subgenus Ceratochloa of the genus Bromus includes a number of closely related allopolyploid forms or species that present a difficult taxonomic problem. The present work combines data concerning chromosome length, heterochromatin distribution and nuclear genome size of different 6x, 8x and 12x accessions in this subgenus. Special attention is paid to the karyotype structure and genomic constitution of duodecaploid plants recently found in South America. Hexaploid lineages possess six almost indistinguishable genomes and a nuclear DNA content between 12.72 pg and 15.10 pg (mean 1Cx value = 2.32 pg), whereas octoploid lineages contain the same six genomes (AABBCC) plus two that are characterized by longer chromosomes and a greater DNA content (1Cx = 4.47 pg). Two duodecaploid accessions found in South America resemble each other and apparently differ from the North American duodecaploid B. arizonicus as regards chromosome size and nuclear DNA content (40.00 and 40.50 pg vs. 27.59 pg). These observations suggest that the South American duodecaploids represent a separate evolutionary lineage of the B. subgenus Ceratochloa, unrecognized heretofore.

A global genomic transcriptional code associated with CNS-expressed genes.

Highly conserved non-coding DNA regions (HCNR) occur frequently in vertebrate genomes, but their functional roles remain unclear. Here, we provide evidence that a large portion of HCNRs are enriched for binding sites for Sox, POU and Homeodomain transcription factors, and such HCNRs can act as cis-regulatory regions active in neural stem cells. Strikingly, these HCNRs are linked to several hundreds of genes expressed in the developing CNS and they may exert locus-wide regulatory effects on multiple genes flanking their genomic location. Moreover, these data imply a unifying transcriptional logic for a large set of CNS-expressed genes in which Sox and POU proteins act as generic promoters of transcription while Homeodomain proteins control the spatial expression of genes through active repression.

Multiple dorsoventral origins of oligodendrocyte generation in the spinal cord and hindbrain.

Studies have indicated that oligodendrocytes in the spinal cord originate from a ventral progenitor domain defined by expression of the oligodendrocyte-determining bHLH proteins Olig1 and Olig2. Here, we provide evidence that progenitors in the dorsal spinal cord and hindbrain also produce oligodendrocytes and that the specification of these cells may result from a dorsal evasion of BMP signaling over time. Moreover, we show that the generation of ventral oligodendrocytes in the spinal cord depends on Nkx6.1 and Nkx6.2 function, while these homeodomain proteins in the anterior hindbrain instead suppress oligodendrocyte specification. The opposing roles for Nkx6 proteins in the spinal cord and hindbrain, in turn, appear to reflect that oligodendrocytes are produced by distinct ventral progenitor domains at these axial levels. Based on these findings, we propose that oligodendrocytes derive from several distinct positional origins and that the activation of Olig1/2 at different positions is controlled by distinct genetic programs.

Arrays of ultraconserved non-coding regions span the loci of key developmental genes in vertebrate genomes.

BACKGROUND: Evolutionarily conserved sequences within or adjoining orthologous genes often serve as critical cis-regulatory regions. Recent studies have identified long, non-coding genomic regions that are perfectly conserved between human and mouse, termed ultra-conserved regions (UCRs). Here, we focus on UCRs that cluster around genes involved in early vertebrate development; genes conserved over 450 million years of vertebrate evolution. RESULTS: Based on a high resolution detection procedure, our UCR set enables novel insights into vertebrate genome organization and regulation of developmentally important genes. We find that the genomic positions of deeply conserved UCRs are strongly associated with the locations of genes encoding key regulators of development, with particularly strong positional correlation to transcription factor-encoding genes. Of particular importance is the observation that most UCRs are clustered into arrays that span hundreds of kilobases around their presumptive target genes. Such a hallmark signature is present around several uncharacterized human genes predicted to encode developmentally important DNA-binding proteins. CONCLUSION: The genomic organization of UCRs, combined with previous findings, suggests that UCRs act as essential long-range modulators of gene expression. The exceptional sequence conservation and clustered structure suggests that UCR-mediated molecular events involve greater complexity than traditional DNA binding by transcription factors. The high-resolution UCR collection presented here provides a wealth of target sequences for future experimental studies to determine the nature of the biochemical mechanisms involved in the preservation of arrays of nearly identical non-coding sequences over the course of vertebrate evolution.

[A 25-week cervical pregnancy, complicated by extensive hemorrhage and terminated by cesarean section followed by hysterectomy and birth of a child]. / 25-tygodniowa ciaza szyjkowa, powiklana masywnym krwotokiem, zakonczona cieciem cesarskim z nastepowa histerectomia oraz urodzeniem zywego noworodka.

This is a case report of 32-year-old woman, primigravida, admitted to our department in 25th week of undiagnosed cervical pregnancy complicated by extensive, painless vaginal bleeding. The patient underwent a caesarean section followed by hysterectomy with the preservation of the ovaries, this being due to a life-threatening hemorrhage and abnormal placental location. A live female child was born. The woman was discharged after a 7 day of uneventful postoperative stay. After a 4-month treatment the baby was discharged in a good general condition, but required subsequent management of retinopathy of prematurity.