Increased affiliative response to vasopressin in mice expressing the V1a receptor from a monogamous vole.

Arginine vasopressin influences male reproductive and social behaviours in several vertebrate taxa through its actions at the V1a receptor in the brain. The neuroanatomical distribution of vasopressin V1a receptors varies greatly between species with different forms of social organization. Here we show that centrally administered arginine vasopressin increases affiliative behaviour in the highly social, monogamous prairie vole, but not in the relatively asocial, promiscuous montane vole. Molecular analyses indicate that gene duplication and/or changes in promoter structure of the prairie vole receptor gene may contribute to the species differences in vasopressin-receptor expression. We further show that mice that are transgenic for the prairie vole receptor gene have a neuroanatomical pattern of receptor binding that is similar to that of the prairie vole, and exhibit increased affiliative behaviour after injection with arginine vasopressin. These data indicate that the pattern of V1a-receptor gene expression in the brain may be functionally associated with species-typical social behaviours in male vertebrates.     

布氏四鼠的嗅觉通讯Ⅱ──2种不同方法下气味辨别实验的重复测量方差分析

利用重复测量方差分析，研究2种不同的实验设计方法对布氏四鼠气味辨别实验的影响．结果表明：给予单个气味刺激和同时给予多个气味刺激的2种不同实验方法，所得到的数据结果没有显著性差异，都能够反映出动物对气味的辨别能力．     

Molecular cloning and expression of a rat V1a arginine vasopressin receptor.

The neurohypophyseal hormone arginine vasopressin has diverse actions, including the inhibition of diuresis, contraction of smooth muscle, stimulation of liver glycogenolysis and modulation of adrenocorticotropic hormone release from the pituitary. Arginine vasopressin receptors are G protein-coupled and have been divided into at least three types; the V1a (vascular/hepatic) and V1b (anterior pituitary) receptors which act through phosphatidylinositol hydrolysis to mobilize intracellular Ca2+, and the V2 (kidney) receptor which is coupled to adenylate cyclase. We report here the cloning of a complementary DNA encoding the hepatic V1a arginine vasopressin receptor. The liver cDNA encodes a protein with seven putative transmembrane domains, which binds arginine vasopressin and related compounds with affinities similar to the native rat V1a receptor. The messenger RNA corresponding to the cDNA is distributed in rat tissues known to contain V1a receptors.     

观察箱内成年雄性布氏田鼠间的行为和行为序

研究了不同大小观察箱内布氏田鼠（Ｍｉｃｒｏｔｕｓ ｂｒａｎｄｔｉ）陌生成年雄性个体间的行为和行为序。在大，小观察箱内，除了追逐行为，优势鼠，从属鼠的行为没有明显的差别。在观察期内，虽然一对鼠中优势鼠的非社会，社会探究，攻击行为都明显地高于从属鼠，但它们在遭遇后的第１个回合的交往中，２只鼠的社会行为没有显示的区别，社会探究，争斗行为之间相互独立，为负相关关系，而其各自内部均为正相关关系，其中社会探究     

Male mammals respond to a risk of sperm competition conveyed by odours of conspecific males

Sperm competition occurs when a female copulates with two or more males and the sperm of those males compete within the female's reproductive tract to fertilize her eggs. The frequent occurrence of sperm competition has forced males of many species to develop different strategies to overcome the sperm of competing males. A prevalent strategy is for males to increase their sperm investment (total number of sperm allocated by a male to a particular female) after detecting a risk of sperm competition. It has been shown that the proportion of sperm that one male contributes to the sperm pool of a female is correlated with the proportion of offspring sired by that male. Therefore, by increasing his sperm investment a male may bias a potential sperm competition in his favour. Here we show that male meadow voles, Microtus pennsylvanicus, increase their sperm investment when they mate in the presence of another male's odours. Such an increase in sperm investment does not occur by augmenting the frequency of ejaculations, but by increasing the amount of sperm in a similar number of ejaculations.     

野生成年棕色田鼠社会行为研究

对成年棕色田鼠 (Microtusmandarinus)的社会行为进行了实验室观察 .结果发现 ,当陌生的两只雄鼠相遇时 ,优势雄鼠和从属雄鼠间的社会行为有明显的区别 ,优势鼠接近、攻击、追赶对方的频次和持续时间明显的多于从属鼠 ,而从属鼠逃离和防御行为多于优势鼠 ;优势鼠的体重明显的大于从属鼠 ,而且攻击行为和社会探究行为的频次与体重呈正相关 ,非社会行为无明显的差别 .但当两只熟悉的雄鼠相遇时 ,则比陌生雄鼠相遇表现出较多的喜好行为和较少的攻击行为 .观察还发现 ,单独生活的异性个体相遇时表现出较少的攻击行为和较多的喜好行为 ;相反 ,和其它家庭成员生活的两个陌生异性个体相遇时表现出较多的攻击行为 .两个雌性相遇和两个雄性相遇表现出相似的行为模式 .以上结果表明 ,熟悉性、性别、个体大小、接触近况是影响棕色田鼠社会行为的重要因子 .     

Nicotine reinforcement and cognition restored by targeted expression of nicotinic receptors

Worldwide, 100 million people are expected to die this century from the consequences of nicotine addiction, but nicotine is also known to enhance cognitive performance. Identifying the molecular mechanisms involved in nicotine reinforcement and cognition is a priority and requires the development of new in vivo experimental paradigms. The ventral tegmental area (VTA) of the midbrain is thought to mediate the reinforcement properties of many drugs of abuse. Here we specifically re-expressed the beta2-subunit of the nicotinic acetylcholine receptor (nAChR) by stereotaxically injecting a lentiviral vector into the VTA of mice carrying beta2-subunit deletions. We demonstrate the efficient re-expression of electrophysiologically responsive, ligand-binding nicotinic acetylcholine receptors in dopamine-containing neurons of the VTA, together with the recovery of nicotine-elicited dopamine release and nicotine self-administration. We also quantified exploratory behaviours of the mice, and showed that beta2-subunit re-expression restored slow exploratory behaviour (a measure of cognitive function) to wild-type levels, but did not affect fast navigation behaviour. We thus demonstrate the sufficient role of the VTA in both nicotine reinforcement and endogenous cholinergic regulation of cognitive functions.     

棕色田鼠食性食量的研究

用人工室内饲养和野外实地观察的方法，对棕色田鼠的食性食量进行了初步研究．结果表明，棕色田鼠啃食多种农作物和大部分田间杂草，约有 １６ 个科近 ４０ 种．棕色田鼠日食量平均为 ３１８４ ｇ，对某种食物日食量存在着明显的季节变化．日食量与体重呈正相关，且同一年龄组（除幼体组外）的雌性鼠比雄性鼠平均日食指数高     

Cloning and characterization of a vasopressin V2 receptor and possible link to nephrogenic diabetes insipidus.

The antidiuretic effect of arginine vasopressin (AVP) is mediated by renal-type (V2) receptors linked to adenylyl cyclase. We report here the cloning of the rat kidney V2 AVP receptor complementary DNA that encodes a 370-amino-acid protein with a transmembrane topography characteristic of G protein-coupled receptors, and with similarity to the V1a (hepatic) AVP receptor in its seven membrane-spanning domains. Expression of the cloned cDNA in mammalian cells showed specific ligand binding and activity characteristic of the native V2 AVP receptor. The receptor messenger RNA is detected only in the kidney. The human V2 receptor gene has been localized to the long arm of the X chromosome close to the locus for nephrogenic diabetes insipidus, an X-linked recessive disorder characterized by renal resistance to the antidiuretic action of AVP.     

风险偏好下GRA Shapley值修正的PPP项目风险分担

引入风险偏好因素，建立由风险偏好和风险管控能力两个维度组成的PPP(public private partnership)项目风险分担评价指标体系，并结合灰色关联分析与修正后的Shapley值法，确定风险承担主体与风险共担时的分担比例。研究表明，风险偏好的引入，有利于PPP项目决策的合理化。政府部门不仅要重视社会资本对风险的管控能力，也要关注社会资本的风险偏好。对于参与者有偏好、有能力控制的风险，可将风险分配给最佳单一主体承担；对于参与者具有不合理承担意愿，但具有控制能力的风险，可采用政府与社会资本共担的模式，亦可通过风险补偿机制将其转化为单一主体承担；对于参与者既没有承担意愿，也没有控制能力的风险，可采用风险共担模式。政府部门与社会资本的共担比例可利用修正后的Shapley值求得。     

布氏田鼠的嗅觉通讯Ⅰ：非繁殖期的种内识别

通过对观察箱内处于非繁殖期的成年布氏田鼠嗅觉通讯，特别是种内识别的研究表明：布氏田鼠对带有鼠味的底物和清洁底物有分辨能力，并能够辨别自身气味和陌生个体气味，但对群体气味和不同性别的陌生个体气味在探究时间上没有表现出差异。     

Spatial synchronization of vole population dynamics by predatory birds

Northern vole populations exhibit large-scale, spatially synchronous population dynamics. Such cases of population synchrony provide excellent opportunities for distinguishing between local intrinsic and regional extrinsic mechanisms of population regulation. Analyses of large-scale survey data and theoretical modelling have indicated several plausible synchronizing mechanisms. It is difficult, however, to determine the most important one without detailed data on local demographic processes. Here we combine results from two field studies in southeastern Norway--one identifies local demographic mechanisms and landscape-level annual synchrony among 28 enclosed experimental populations and the other examines region-level multi-annual synchrony in open natural populations. Despite fences eliminating predatory mammals and vole dispersal, the growth rates of the experimental populations were synchronized and moreover, perfectly linked with vole abundance in the region. The fates of 481 radio-marked voles showed that bird predation was the synchronizing mechanism. A higher frequency of risky dispersal movements in slowly growing populations appeared to accelerate predation rate. Thus, dispersal may induce a feedback-loop between predation and population growth that enhances synchrony.     

Molecular identification of the gene responsible for congenital nephrogenic diabetes insipidus.

Antidiuretic hormone (arginine vasopressin) binds to and activates V2 receptors in renal collecting tubule cells. Subsequent stimulation of the Gs/adenylyl cyclase system promotes insertion of water pores into the luminal membrane and thereby reabsorption of fluid. In congenital nephrogenic diabetes insipidus (CNDI), an X-linked recessive disorder, the kidney fails to respond to arginine vasopressin. Here we report that an affected male of a family with CNDI has a deletion in the open reading frame of the V2 receptor gene, causing a frame shift and premature termination of translation in the third intracellular loop of the receptor protein. A normal receptor gene was found in the patient's brother. Both the normal and the mutant allele were detected in his mother. A different mutation, causing a codon change in the third transmembrane domain of the V2 receptor, was found in the open reading frame of an affected male but not in the unaffected brother belonging to another family suffering from CNDI.     

Designed divergent evolution of enzyme function

It is generally believed that proteins with promiscuous functions divergently evolved to acquire higher specificity and activity, and that this process was highly dependent on the ability of proteins to alter their functions with a small number of amino acid substitutions (plasticity). The application of this theory of divergent molecular evolution to promiscuous enzymes may allow us to design enzymes with more specificity and higher activity. Many structural and biochemical analyses have identified the active or binding site residues important for functional plasticity (plasticity residues). To understand how these residues contribute to molecular evolution, and thereby formulate a design methodology, plasticity residues were probed in the active site of the promiscuous sesquiterpene synthase gamma-humulene synthase. Identified plasticity residues were systematically recombined based on a mathematical model in order to construct novel terpene synthases, each catalysing the synthesis of one or a few very different sesquiterpenes. Here we present the construction of seven specific and active synthases that use different reaction pathways to produce the specific and very different products. Creation of these enzymes demonstrates the feasibility of exploiting the underlying evolvability of this scaffold, and provides evidence that rational approaches based on these ideas are useful for enzyme design.     

Life-history traits of voles in a fluctuating population respond to the immediate environment.

Life-history traits relating to growth and reproduction vary greatly among species and populations and among individuals within populations. In vole populations, body size and age at maturation may vary considerably among locations and among years within the same location. Individuals in increasing populations are typically larger and start reproduction earlier in the spring than those in declining populations. The cause of such life-history variation within populations has been subject of much discussion. Much of the controversy concerns whether the memory of past conditions, leading to delayed effects on life-history traits, resides in the environment (for example, predators, pathogens or food) or intrinsically within populations or individuals (age distribution, physiological state, genetic or maternal effects). Here we report from an extensive field transplant experiment in which voles were moved before the breeding season between sites that differed in average overwintering body mass. Transplanted voles did not retain the characteristics of their source population, and we demonstrate an over-riding role of the immediate environment in shaping life-history traits of small rodents.     

匈牙利田鼠视交叉上核的研究

哺乳动物下丘脑的视交叉上核控制着多种生理节奏的发生,田鼠是一种营地下生活的独特的啮齿动物,用免疫组织化学,辣根过氧化物酶法和Ｎｉｓｓｌｅ染色法做了其ＳＣＮ形态上的一些研究。     

Central target for the behavioural effects of vasopressin neuropeptides

The neurohypophysial hormone vasopressin exerts antidiuretic, vasopressor and behavioural effects (for example, facilitation of memory processes). Vasopressin may alter animal behaviour via direct effect on brain processes. Recently, however, it has been suggested that vasopressin acts mainly at peripheral receptor systems and influences behavioural mechanisms by altering visceral afferent signals. We now present data showing that (1) central administration of [Arg8]vasopressin (AVP) and more potently [pGlu, Cyt]AVP(4-8), the desglycinamide derivative of a peptide generated from AVP by brain synaptic membranes, produce the behavioural effect (promotion of passive avoidance behaviour) without the pressor effect; (2) central administration of a vasopressor antagonist blocks the behavioural but not the pressor effect of systemically administered AVP; and (3) [pGlu, Cyt]AVP(4-8) induces the behavioural effect in the absence of the pressor effect. The results indicate that AVP and related peptides affect passive avoidance behaviour by a direct central action and that the structural requirement for activation of central vasopressin receptors differs from that of the peripheral cardiovascular receptors, although both can be blocked by the same vasopressor antagonist.     

Dissociation of dopamine release in the nucleus accumbens from intracranial self-stimulation

Mesolimbic dopamine-releasing neurons appear to be important in the brain reward system. One behavioural paradigm that supports this hypothesis is intracranial self-stimulation (ICS), during which animals repeatedly press a lever to stimulate their own dopamine-releasing neurons electrically. Here we study dopamine release from dopamine terminals in the nucleus accumbens core and shell in the brain by using rapid-responding voltammetric microsensors during electrical stimulation of dopamine cell bodies in the ventral tegmental area/substantia nigra brain regions. In rats in which stimulating electrode placement failed to elicit dopamine release in the nucleus accumbens, ICS behaviour was not learned. In contrast, ICS was acquired when stimulus trains evoked extracellular dopamine in either the core or the shell of the nucleus accumbens. In animals that could learn ICS, experimenter-delivered stimulation always elicited dopamine release. In contrast, extracellular dopamine was rarely observed during ICS itself. Thus, although activation of mesolimbic dopamine-releasing neurons seems to be a necessary condition for ICS, evoked dopamine release is actually diminished during ICS. Dopamine may therefore be a neural substrate for novelty or reward expectation rather than reward itself.     

Cloning of the gene for a human dopamine D5 receptor with higher affinity for dopamine than D1.

Dopamine receptors belong to a superfamily of receptors that exert their biological effects through guanine nucleotide-binding (G) proteins. Two main dopamine receptor subtypes have been identified, D1 and D2, which differ in their pharmacological and biochemical characteristics. D1 stimulates adenylyl cyclase activity, whereas D2 inhibits it. Both receptors are primary targets for drugs used to treat many psychomotor diseases, including Parkinson's disease and schizophrenia. Whereas the dopamine D1 receptor has been cloned, biochemical and behavioural data indicate that dopamine D1-like receptors exist which either are not linked to adenylyl cyclase or display different pharmacological activities. We report here the cloning of a gene encoding a 477-amino-acid protein with strong homology to the cloned D1 receptor. The receptor, called D5, binds drugs with a pharmacological profile similar to that of the cloned D1 receptor, but displays a 10-fold higher affinity for the endogenous agonist, dopamine. As with D1, the dopamine D5 receptor stimulates adenylyl cyclase activity. Northern blot and in situ hybridization analyses reveal that the receptor is neuron-specific, localized primarily within limbic regions of the brain; no messenger RNA was detected in kidney, liver, heart or parathyroid gland. The existence of a dopamine D1-like receptor with these characteristics had not been predicted and may represent an alternative pathway for dopamine-mediated events and regulation of D2 receptor activity.     

Infection of SARS-CoV on juvenile and adult Brandt’s vole Microtus brandtii

We studied the infectious effect of SARS-CoV virus on juvenile and adult Brandt‘s Vole (Microtus brandtii) by nasal cavity spraying method (CCIDso is 10^5.7). SARS virus caused serious deaths in adults. The death adults demonstrated hemorrhage from mouth, nasal cavity and intestine, hemorrhageious interstitial pneumonia and gore in liver, spleen and kidney. The survival adults demonstrated local hemorrhagic spot in lung and emphysema, but the other organs showed no pathological abnormality. SARS virus caused no deaths in juveniles, but locomotion of infected juveniles became slower. In the early stage, there was local pneumonia in lung and SARS viruses were isolated from the pathological tissue. Only one control juvenile lived and the infected juvenile showed local pneumonia in lung. The results demonstrated that SARS-CoV infected Brandt‘s vole seriously and adults were more susceptive to SARS-CoV than juveniles. The Brandt‘s vole may be a potential animal model for SARS research.