Molecular mechanisms of experience-dependent plasticity in visual cortex

A remarkable amount of our current knowledge of mechanisms underlying experience-dependent plasticity during cortical development comes from study of the mammalian visual cortex. Recent advances in high-resolution cellular imaging, combined with genetic manipulations in mice, novel fluorescent recombinant probes, and large-scale screens of gene expression, have revealed multiple molecular mechanisms that underlie structural and functional plasticity in visual cortex. We situate these mechanisms in the context of a new conceptual framework of feed-forward and feedback regulation for understanding how neurons of the visual cortex reorganize their connections in response to changes in sensory inputs. Such conceptual advances have important implications for understanding not only normal development but also pathological conditions that afflict the central nervous system.     

Bidirectional synaptic mechanisms of ocular dominance plasticity in visual cortex

As in other mammals with binocular vision, monocular lid suture in mice induces bidirectional plasticity: rapid weakening of responses evoked through the deprived eye followed by delayed strengthening of responses through the open eye. It has been proposed that these bidirectional changes occur through three distinct processes: first, deprived-eye responses rapidly weaken through homosynaptic long-term depression (LTD); second, as the period of deprivation progresses, the modification threshold determining the boundary between synaptic depression and synaptic potentiation becomes lower, favouring potentiation; and third, facilitated by the decreased modification threshold, open-eye responses are strengthened via homosynaptic long-term potentiation (LTP). Of these processes, deprived-eye depression has received the greatest attention, and although several alternative hypotheses are also supported by current research, evidence suggests that alpha-amino-3- hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptor endocytosis through LTD is a key mechanism. The change in modification threshold appears to occur partly through changes in N-methyl-D-aspartate (NMDA) receptor subunit composition, with decreases in the ratio of NR2A to NR2B facilitating potentiation. Although limited research has directly addressed the question of open-eye potentiation, several studies suggest that LTP could account for observed changes in vivo. This review will discuss evidence supporting this three-stage model, along with outstanding issues in the field.     

Identification of QTLs Involved in the Development of Amygdala Kindling in the Rat

Amygdala kindling is useful for modeling human epilepsy development. It has been known that genetic factors are involved in the development of amygdala kindling. The purpose of this study was to identify the loci that are responsible for the development of amygdala kindling. To achieve this, rat strains from a LEXF/FXLE recombinant inbred (RI) strain panel were used. The phenotypes of amygdala kindling-related parameters for seven RI strains and parental LE/Stm and F344/Stm strains were determined. They included the afterdischarge threshold (ADT), the afterdischarge duration (ADD), and the kindling rate, an incidence of development of kindling. Quantitative trait loci (QTL) analysis was performed to identify linkage relationships between these phenotypes and 1,033 SNP markers. Although no significant differences in pre-kindling ADT and ADD were observed, a significant difference in the kindling rate was found for the LEXF/FXLE RI strain. Two QTLs for the amygdala kindling rate (Agkr1 and Agkr2) were identified on rat chromosome 2. These findings clearly prove the existence of genetic influences that are involved in kindling development and suggest that substantial genetic components contribute to the progression of partial seizures into generalized seizures.     

Somatic embryogenesis by liquid culture of epidermal layers in sunflower: from genetic control to cell development

Embryos were obtained using liquid medium culture of sunflower hypocotyl epidermis layers according to the Pélissier etal. (1990) method. In the present work we identified genetic factors controlling somatic embryogenesis and we evidenced the role of ionic channels in embryogenic tissues. Two traits, the number of embryogenic explants (EE) and the number of embryos (EM) were scored in 74 recombinant inbred lines (RILs) from a cross between lines PAC-2 and RHA-266. Analysis of variance indicated the existence of highly significant differences among the parental genotypes and their RILs. Heritability for the somatic embryogenesis traits studied were high (0.64 for EE and 0.77 for EM). Four quantitative trait loci (QTLs) for EE and seven for EM were detected using composite interval mapping. The QTLs for EE explained 48% of the phenotypic variation while the QTLs for EM explained about 89% of the variation, thus revealing several genomic regions related to somatic embryogenesis control in sunflower. In order to study the distribution of ion channels in somatic embryos as compared to zygotic ones, we used a fluorescent-labelled phenylalkylamine, DM-Bodipy PAA, as a probe. Fluorescence labelling was determined by confocal microscopy. The probe intensively labelled the protoderm and epidermis cells in both zygotic and somatic embryos. Callus exhibited labelling on sites where somatic embryos developed. Considering that the location of phenylalkylamine (PAA) binding sites is related to the distribution of ion channels, the high intensity in the protoderm and epidermis of embryos, point to similar properties and functions and their key role in embryo development.     

Quantitative trait locus analysis of lateral branch– related traits in cucumber (Cucumis sativus L.) using recombinant inbred lines

A group of 224 recombinant inbred lines (RILs) was derived from a narrow cross between 2 cucumber (Cucumis sativus L.) lines, namely, S94 (Northern China type with weak lateral branch growth potential and early lateral branch sprouting time) and S06 (Northern European type with strong lateral branch growth potential and late lateral branch sprouting time). These lines were then used for investigating lateral branch-related traits. A total of 36 quantitative trait loci (QTLs) were detected for the following 4 lateral branch-related traits: lateral branch average length (LBAL), lateral branch total length (LBTL), lateral branch number (LBN), and first lateral branch node (FLBN). Further, each QTL explained 3.1% (lbtl2.1, spring) to 32.3% (lbn2.3, spring) of the observed phenotypic variance. Eleven QTLs (lbal1.1, lbtl1.1, lbn1.2, flbn1.2, etc.) for different traits were found to be clustered on the e23m18d-ME23EM6c section (7.4 cM) of linkage group (LG) 1; further, 15 QTLs (lbal2.1, lbtl2.1, lbn2.1, flbn2.1, etc.) were found to be clustered on the S94A1-ME4SA4a section (13.9 cM) of LG2. Twenty-one QTLs explained more than 10% of the phenotypic variance. Moreover, lbtl1.3 (autumn, 26.2%, logarithm of odds (LOD) = 17.4; spring, 26.9%, LOD = 17.9) had stable position and contribution in both seasons. Several se-quence-anchor markers (CMBR40, F, CS30, S94A1, CSWTA11B, etc.) were closely linked with some QTLs for LBAL, LBTL, LBN, and FLBN, which can be used for the marker-assisted selection to improve the plant architecture in cucumber breeding.     

GW3-1和IND109标记对普通小麦粒重的QTL定位分析

应用一个由115个系组成的W7984/Opata85的重组自交系(RIL)群体,建立了一个由394个(292个RFLP、94个SSR和8个特殊的基因杂交探针)DNA分子标记组成的遗传连锁图,对小麦千粒重进行了单个标记的回归分析和复合区间作图的QTL定位,在单个标记的回归分析中检测到11个千粒重的QTLs(P<0.01);复合区间作图分析结果表明,其中4个标记bcd348a、GW3-1、IND109和Rz2的遗传效应较大,其贡献率分别为9.1%、19.0%、8.07%和8.14%,分别位于小麦的2BS、4AL、5BL和7DS上,特别是在水稻第3条染色体上控制籽粒大小的GW3-1和IND109分别位于小麦4A和5B染色体的长臂端.研究结果对小麦应用分子标记辅助选择或分子克隆基因有重要的参考价值.     

Quantitative trait loci segregating in crosses between New Hampshire and White Leghorn chicken lines: I. egg production traits

A genome scan was performed to detect chromosomal regions that affect egg production traits in reciprocal crosses between two genetically and phenotypically extreme chicken lines: the partially inbred line New Hampshire (NHI) and the inbred line White Leghorn (WL77). The NHI line had been selected for high growth and WL77 for low egg weight before inbreeding. The result showed a highly significant region on chromosome 4 with multiple QTL for egg production traits between 19.2 and 82.1 Mb. This QTL region explained 4.3 and 16.1% of the phenotypic variance for number of eggs and egg weight in the F₂ population, respectively. The egg weight QTL effects are dependent on the direction of the cross. In addition, genome‐wide suggestive QTL for egg weight were found on chromosomes 1, 5, and 9, and for number of eggs on chromosomes 5 and 7. A genome‐wide significant QTL affecting age at first egg was mapped on chromosome 1. The difference between the parental lines and the highly significant QTL effects on chromosome 4 will further support fine mapping and candidate gene identification for egg production traits in chicken.     

Identification of heterotic metabolite QTL in Arabidopsis thaliana RIL and IL populations

Two mapping populations of a cross between the Arabidopsis thaliana accessions Col-0 and C24 were cultivated and analyzed with respect to the levels of 181 metabolites to elucidate the biological phenomenon of heterosis at the metabolic level. The relative mid-parent heterosis in the F₁ hybrids was <20% for most metabolic traits. The first mapping population consisting of 369 recombinant inbred lines (RILs) and their test cross progeny with both parents allowed us to determine the position and effect of 147 quantitative trait loci (QTL) for metabolite absolute mid-parent heterosis (aMPH). Furthermore, we identified 153 and 83 QTL for augmented additive (Z₁) and dominance effects (Z₂), respectively. We identified putative candidate genes for these QTL using the aracyc database ( http://www.arabidopsis.org/biocyc ), and calculated the average degree of dominance, which was within the dominance and over-dominance range for most metabolites. Analyzing a second population of 41 introgression lines (ILs) and their test crosses with the recurrent parent, we identified 634 significant differences in metabolite levels. Nine per cent of these effects were classified as over-dominant, according to the mode of inheritance. A comparison of both approaches suggested epistasis as a major contributor to metabolite heterosis in Arabidopsis. A linear combination of metabolite levels was shown to significantly correlate with biomass heterosis ( r  = 0.62).     

MATING SYSTEM,HALDANE'S SIEVE,AND THE DOMESTICATION PROCESS

Mating systems are expected to have a strong influence on both the dynamic of adaptation and the genetic architecture of adaptive traits. In particular, the bias toward the fixation of dominant or partially dominant beneficial mutations predicted under outcrossing (Haldane's sieve) is expected to be reduced under self‐fertilization. To test this prediction in plants, we considered domestication as an example of adaptation. We compiled data from studies reporting the degree of dominance of quantitative trait loci (QTL) involved in the domestication syndrome. We found that adaptation to cultivation mostly proceeded through the selection of recessive and partially recessive genes in predominantly selfing species whereas a much larger fraction of domestication‐related QTL were dominant or partially dominant in outcrossers, as expected under Haldane's sieve. Our study also showed that levels of dominance in mixed mating crop species resemble those observed in selfers, suggesting that recessive alleles can contribute to adaptation even under moderate selfing rates. Although these results rely on a particular example of adaptation, they constitute one of the first attempts to test theoretical expectations on the level of dominance of genes involved in plant adaptation.     

Use of recombinant inbred strains to map genes of aging

Recombinant inbred strains have been used in a number of organisms for segregation and linkage analysis of quantitative traits. One major advantage of the recombinant inbred (RI) methodology is that the genetic identity of individuals within a strain permits replicate measures of the same recombinant genotype. Such replicability is important for traits such as aging inDrosophila, where phenotypic expression is highly influenced by different environmental conditions. RI strain methodology has an added advantage for DNA marker-based linkage analysis of traits measured over the lifespan of the organism. The DNA can be extracted from individuals of the same genotype as those measured in a longevity study. In this paper an argument is presented for the use of a set of recombinant inbred strains to map the quantitative trait loci involved in the aging process inDrosophila. A unique use of a set of stable, transposable moleular markers to trace the quantitative trait loci involved is suggested.     

Genetic architecture of the mouse hippocampus: identification of gene loci with selective regional effects

We recently mapped two quantitative trait loci that have widespread effects on hippocampal architecture in mouse: Hipp1a and Hipp5a. We also noted remarkable strain differences in the relative sizes of different hippocampal regions. Estimated heritable variation for these differences was 42% in hippocampus proper, 40% in dentate gyrus, 31% in granule cell layer and 18% in pyramidal cell layer. Region size varied at least 50% from largest to smallest measurement. Here we have utilized these differences to identify loci with effects on the dentate gyrus, granule cell layer, hippocampus proper and pyramidal cell layer. Our sample consists of C57BL/6J and DBA/2J and 32 BXD recombinant inbred strains. Volumetric data were corrected for shrinkage and for differences in brain weight. We identified significant loci on chromosomes (Chr) 6, 13 and 15, and a significant interaction locus on proximal Chr 11. A suggestive distal Chr 1 locus overlaps with Hipp1a. HipV13a (Chr 13, 42-78Mb) has an additive effect of 0.56 mm3 (12.1%) on dentate gyrus volume, while GrV6a (Chr 6, 29-65 Mb) has additive effects of 0.14 mm3 (16.0%) on the volume of the granule cell layer. HipV13a also interacts with DGVi11a, a locus on proximal Chr 11 that operates exclusively through its epistatic effect on HipV13a and has no independent main effect HipV15a (Chr 15, 0-51 Mb) has an additive effect of 1.76 mm3 (9.0%) on the volume of the hippocampus proper. We used WebOTL, a recently described web-based tool, to examine genetic correlation of gene expression with hippocampal volume. We identified a number of genes that map within the OTL intervals and have highly correlated expression patterns. Using WebQTL's extensive database of published BXD phenotypes, we also detected a strong and potentially biologically meaningful correlation between hippocampal volume and the acoustic startle response.     

Mapping quantitative trait loci associated with aluminum toxin tolerance in NJRIKY recombinant inbred line population of soybean (Glycine max)

To investigate the genetic mechanism of AI-tolerance in soybean,a recombinant inbred line population (RIL) with 184 F2:7:11 lines derived from the cross of Kefeng No.1 x Nannong 1138-2 (AI-tolerant x AI-sensitive) were tested in pot experimentwith sand culture medium in net room in Nanjing.Four traits,i.e.plant height,number of leaves,shoot dry weight and root dry weight at seedling stage,were evaluated and used to calculate the average membership index (FAi) as the indicator of AI-tolerance.The composite interval mapping (ClM) under WinQTL Cartographer v.2.5 detected five QTLs (i.e.qFAiol,qFAi-2,qFAi-3,qFAi-4 and qFAi-5),explaining 5.20%-9.07% of the total phenotypic variation individually.While with the multiple interval mapping (MIM) of the same software,five QTLs (qFAi-1,qFAi-5,qFAi-6,qFAi-7,and qFAi-8) explaining 5.7%-24.60% of the total phenotypic variation individually were mapped.Here qFAi-1 and qFAi-5 were detected by both CIM and MIM with the locations in a same flanking marker region,GMKF046-GMKF080 on B1 and satt278-sat_95 on L,respectively.While qFAi-2 under CIM and qFAi-6 under MIM both on D1b2 were located in neighboring regions with their confidence intervals overlapped and might be the same locus.Segregation analysis under major gene plus polygene inheritance model showed that Al-tolerance was controlled by two major genes (h2mg =33.05%) plus polygenes (h2pg=52.73%).Both QTL mapping and segregation analysis confirmed two QTLs responsible for Al-tolerance with relatively low heritability,and there might be a third QTL,confounded with the polygenes in segregation analysis.     

Genetic markers linked to quantitative traits in poultry

This study utilized DNA fingerprints and crosses of two genetically distinct lines of layer-type chickens to identify genetic markers linked to quantitative trait loci (QTL). In phase I, back-cross (BC¹) hens were separately ranked for each of eight traits and then blood pools were produced in groups along each phenotypic distribution. The DNA was isolated from the blood pools and used in a gradient analysis to screen for DNA fingerprint bands that exhibited intensity gradients associated with the phenotypic traits. To identify linkage of bands with QTL and to estimate band effects, F₂ progeny were produced in phase II from the phase I BC, population. A single-trait animal model was used for analysis of associations of all individual DNA fingerprint bands of sires and their progeny phenotypic performance. Twenty fingerprint bands, only two of which had shown trait-associated gradients in phase I, were identified by the animal model analysis of the progeny test as QTL linked (P≤005) to specific traits of growth, reproduction and egg quality. These 20 bands warrant further study as potentially valuable molecular markers for QTL.     

小麦萌发期抗旱和耐盐性状的QTL分析

该研究以‘山农0431×鲁麦21’RIL群体及其父母本为材料,用20%PEG-6000溶液和100 mmol·L-1 NaCl溶液分别模拟干旱和盐环境,对12个小麦萌发期抗旱耐盐相关性状进行测定,结合已构建的分子标记遗传图谱对小麦萌发期抗旱、耐盐的相关性状进行QTL分析,为小麦抗旱、耐盐基因的克隆和分子标记辅助选择提供参考。结果表明:(1)正常、干旱和盐胁迫3种处理下共检测到143个QTL。检测到相对高频QTL(RHF-QTL)29个,平均贡献率范围为4.39%~13.28%,贡献率在10%以上的主效RHF-QTL有10个。(2)检测到胁迫下特异表达的RHF-QTL共17个,正常处理下特异表达的RHF-QTL为8个,稳定表达的RHF-QTL为4个。(3)QTL分析结果表明,7个RHF-QTL形成了3个QTL簇,且分布在2D、4D和5B等3条染色体上,其中:QC1位于2D染色体的wPt-6847~D-1172783区间,包括3个QTL(QRl-2D.2、QSdw-2D.3、QTdw-2D);QC2位于4D染色体短臂的D-2245724~D-1108531区间,包括2个QTL(QSl-4D、QShl-4D);QC3位于5B染色体的D-982263~S-1083095区间,包括2个QTL(QSl-5B.2、QTdw-5B.1)。     

Genetic mapping of quantitative trait loci for aseasonal reproduction in sheep

The productivity and economic prosperity of sheep farming could benefit greatly from more effective methods of selection for year-round lambing. Identification of QTL for aseasonal reproduction in sheep could lead to more accurate selection and faster genetic improvement. One hundred and twenty microsatellite markers were genotyped on 159 backcross ewes from a Dorset × East Friesian crossbred pedigree. Interval mapping was undertaken to map the QTL underlying several traits describing aseasonal reproduction including the number of oestrous cycles, maximum level of progesterone prior to breeding, pregnancy status determined by progesterone level, pregnancy status determined by ultrasound, lambing status and number of lambs born. Seven chromosomes (1, 3, 12, 17, 19, 20 and 24) were identified to harbour putative QTL for one or more component traits used to describe aseasonal reproduction. Ovine chromosomes 12, 17, 19 and 24 harbour QTL significant at the 5% chromosome-wide level, chromosomes 3 and 20 harbour QTL that exceeded the threshold at the 1% chromosome-wide level, while the QTL identified on chromosome 1 exceeded the 1% experiment-wide significance level. These results are a first step towards understanding the genetic mechanism of this complex trait and show that variation in aseasonal reproduction is associated with multiple chromosomal regions.     

7个烤烟产量相关性状的QTL定位分析

以烤烟Y3和K326为亲本,采用单粒传法(SSD)获得一个包含262个F6株系的重组自交系群体(RILs)。基于该群体构建了一张含有24个连锁群、626个SSR标记,总长为1 120.45cM的遗传图谱。通过两年一点3次重复的随机区组田间试验,测定了株高、节距、叶数、茎围、茎叶角度、腰叶长和腰叶宽7个与产量相关农艺性状,采用混合线性模型的严格复合区间作图法(rMQM)在烟草全基因组范围内进行QTL扫描分析。结果显示:(1)烤烟7个目标性状在RILs群体内各株系间存在较大范围的连续变异,具有显著的双向超亲分离,且各性状的平均值很接近中亲值;7个农艺性状的平均广义遗传率为73.33%,其中株高和节距的广义遗传率在80%以上,而茎围和茎叶角度的广义遗传率则低于60%,表明7个与烤烟产量相关的农艺性状是既受微效多基因控制又受环境条件影响的数量性状。(2)共检测到30个QTLs分布在9条连锁群上,其中与株高、节距、叶数、腰叶长和腰叶宽相关的5个主效QTLs在连续两年中均可检测到,且具有较大的效应值,可解释大于10%的表型变异。(3)7个目标性状之间存在一定程度的相关性,与之对应在基因组中也存在一些较小区域,每个区域包含2个或2个以上紧密连锁的不同性状的QTLs。烟草产量相关农艺性状的QTL分析和主效QTLs的获得,为进一步利用分子标记辅助选择培育烟草高产新品种奠定了理论基础。     

Improving QTL Mapping Resolution Based on Genotypic Sampling—a Case Using a RIL Population

The QTL mapping results were compared with the genotypically selected and random samples of the same size on the base of a RIL population. The results demonstrated that there were no obvious differences in the trait distribution and marker segregation distortion between the genotypically selected and random samples with the same population size. However, a significant increase in QTL detection power, sensitivity, specificity, and QTL resolution in the genotypically selected samples were observed. Moreover, the highly significant effect was detected in small size of genotypically selected samples. In QTL mapping, phenotyping is a more sensitive limiting factor than genotyping so that the selection of samples could be an attractive strategy for increasing genome-wide QTL mapping resolution. The efficient selection of samples should be more helpful for QTL maker assistant selection, fine mapping, and QTL cloning.     

基于基因型选择提高QTL作图的精度——以一个RIL群体为例

以PCR为基础的分子标记以及其他检测技术的发展,使得大规模的标记分析成为现实。这也为通过大群体标记分析,然后基于基因型选择挑选合适的小群体,从而提高QTL定位准确性和精度提供了可能。以一个包含294个家系的重组自交系（RIL）群体为例,通过基因型选择和随机选择的办法产生了一系列大小不等的亚群体,比较了两类群体QTL定位的结果。分析表明：相同大小的基因型选择群体与随机群体相比性状的表型分布都符合正态分布;标记的偏分离情况也没有明显的差别,都随着群体大小的增大,偏分离的比例也逐渐增大。但同等大小的基因型选择群体比随机群体的交换富集率（CE）要大,且随着选择强度的增大不断增大,如群体大小为270时,CE=1．04,群体大小为30时,CE=1．45。总体上,随着群体大小的增加,不管是随机群体还是选择群体,其QTL检测能力、灵敏性和特异性也随之增加,但选择群体的检测能力、灵敏性和特异性总体上要好于随机群体。当群体大于或等于240时,其QTL检测能力基本没有差别;群体大小大于或等于210时,其QTL检测的灵敏性和特异性也没有什么差别。这也说明：选择强度越大,效果越明显。以QTLI—LOD区间作为衡量QTL精度的一个指标,结果显示所有基因型选择群体都比相同大小随机群体的QTL定位精度高。目前QTL定位研究中,基因型数据较表型数据而言更容易准确获得,因此通过基因型选择可以更好的优化群体结构,减少田间实验的工作量,提高全基因组水平QTL作图的精度,为随后的QTL辅助选择和精细定位以及克隆提供帮助。     

大白菜部分形态性状的QTL定位与分析

应用352个标记位点的大白菜AFLP和RAPD图谱和一套栽培品种间杂交获得的重组自交系群体,采用复合区间作图的方法对大白菜9个形态性状进行QTL定位及遗传效应研究。在14个连锁群上检测到50个QTL:其中控制株型的QTL有5个;控制株高的QTL有6个;控制开展度的QTL有5个;控制最大叶长的QTL有7个;控制最大叶宽的QTL有4个;控制叶形指数的QTL有6个;控制中肋长的QTL有7个;控制中肋宽的QTL有4个;控制抽苔的QTL有6个。另外,估算了单个QTL的遗传贡献率和加性效应。这将为大白菜品种改良中形态性状的分子标记辅助选择提供理论依据。     

How the mechanisms of long-term synaptic potentiation and depression serve experience-dependent plasticity in primary visual cortex

Donald Hebb chose visual learning in primary visual cortex (V1) of the rodent to exemplify his theories of how the brain stores information through long-lasting homosynaptic plasticity. Here, we revisit V1 to consider roles for bidirectional ‘Hebbian’ plasticity in the modification of vision through experience. First, we discuss the consequences of monocular deprivation (MD) in the mouse, which have been studied by many laboratories over many years, and the evidence that synaptic depression of excitatory input from the thalamus is a primary contributor to the loss of visual cortical responsiveness to stimuli viewed through the deprived eye. Second, we describe a less studied, but no less interesting form of plasticity in the visual cortex known as stimulus-selective response potentiation (SRP). SRP results in increases in the response of V1 to a visual stimulus through repeated viewing and bears all the hallmarks of perceptual learning. We describe evidence implicating an important role for potentiation of thalamo-cortical synapses in SRP. In addition, we present new data indicating that there are some features of this form of plasticity that cannot be fully accounted for by such feed-forward Hebbian plasticity, suggesting contributions from intra-cortical circuit components.