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Children of ages 3 to 4.5 years (N = 107; 45 boys, 62 girls) were studied twice, 6 months apart, to examine whether the cortisol rise in child care at Time 1 (T1) was associated with (a) changes in anxious, vigilant behavior from T1 to Time 2 (T2) and (b) higher internalizing symptoms at T2. Controlling for measures of home environment and child care quality at T1, as well as for cortisol activity at T2, we obtained results indicating that behavioral inhibition moderated the associations between the rise in cortisol at T1 and child outcomes at T2 (i.e., anxious, vigilant behavior and internalizing symptoms). For both outcomes, the rise in cortisol at T1 became more positively predictive at increasing levels of behavioral inhibition. Specifically, at higher levels of behavioral inhibition, children with larger T1 cortisol increases expressed more internalizing symptoms than did children at lower levels of behavioral inhibition; in contrast, for those with low cortisol activity at T1, children with higher levels of inhibition expressed fewer internalizing symptoms than did children at lower levels of inhibition. In addition, children with higher levels of behavioral inhibition and lower cortisol activity at T1 exhibited reductions in anxious, vigilant behavior from T1 to T2, whereas at lower levels of behavioral inhibition, variations in the T1 cortisol rise bore no relation to changes in this behavior. These results suggest that the rise in cortisol at child care may have differential predictive value as a function of behaviorally inhibited temperament. (Contains 4 tables and 2 figures.)

Quality of mothering relies on the integrity of multiple physiological and behavioral systems and on two maternal factors, one proximal and one distal, that have a great impact on how a mother mothers: postpartum depression and early experiences. To mother appropriately requires the action of systems that regulate sensation, perception, affect, reward, executive function, motor output and learning. When a mother is at risk to engage in less than optimal mothering, such as when she is depressed or has experienced adversity in childhood, the function of many or all of maternal and related systems may be affected. In this paper, we will review what is currently known about the biological basis of mothering, with attention to literature on hormones but with a particular focus on recent advances in the fields of functional neuroimaging. Instead of discussing strictly "maternal" brain imaging studies, we instead use a systems approach to survey important findings relevant to brain systems integral to and/or strongly related to the mothering experience: (a) social behavior; (b) reward and affect; (c) executive function; and (d) maternal behavior. We find that there are many commonalities in terms of the brain regions identified across these systems and, as we would expect, all are sensitive to the influence of, or function differently in the context of, depression and adverse early experience. It is likely that the similarity and cross-talk between maternal, affect and stress systems, observed behaviorally, hormonally and in the context of brain function, allows for mood disturbance and early adverse experiences to have a significant impact on the quality of mothering and the motivation to mother.

Objective: Prenatal exposure to inappropriate levels of glucocorticoids (GCs) and maternal stress are putative mechanisms for the fetal programming of later health outcomes. The current investigation examined the influence of prenatal maternal cortisol and maternal psychosocial stress on infant physiological and behavioral responses to stress. Methods: The study sample comprised 116 women and their full term infants. Maternal plasma cortisol and report of stress, anxiety and depression were assessed at 15, 19, 25, 31 and 36 + weeks' gestational age. Infant cortisol and behavioral responses to the painful stress of a heel-stick blood draw were evaluated at 24 hours after birth. The association between prenatal maternal measures and infant cortisol and behavioral stress responses was examined using hierarchical linear growth curve modeling. Results: A larger infant cortisol response to the heel-stick procedure was associated with exposure to elevated concentrations of maternal cortisol during the late second and third trimesters. Additionally, a slower rate of behavioral recovery from the painful stress of a heel-stick blood draw was predicted by elevated levels of maternal cortisol early in pregnancy as well as prenatal maternal psychosocial stress throughout gestation. These associations could not be explained by mode of delivery, prenatal medical history, socioeconomic status or child race, sex or birth order. Conclusions: These data suggest that exposure to maternal cortisol and psychosocial stress exerts programming influences on the developing fetus with consequences for infant stress regulation.

This practical paper describes a novel fluorescence imaging experiment to study the three processes of photochemistry, fluorescence and thermal energy dissipation, which compete during the dissipation of excitation energy in photosynthesis. The technique represents a non-invasive tool for revealing and understanding the spatial heterogeneity in leaf performance caused by internal and external factors, such as development and abiotic stress. Fluorescence yield (F), effective PSII quantum yield (Y(II)) and non-photochemical quenching (NPQ) were analysed by fluorescence imaging in leaves of "Avena sativa" L. and two species of "Brassica" ("B. fruticulosa" and "B. oleracea") plants during the first stages of plant development and under high illumination. In young leaves, F was 0.1 or less, Y(II) between 0.7 and 0.8 and NPQ less than 0.3, indicating that photochemical efficiency was high (70-80%) and that fluorescence emission (less than 10%) and heat dissipation (less than 30%) were low. As leaf age increased, differences were observed between species, indicating different development and senescence patterns in each. "Avena sativa" and "B. fruticulosa" (a wild species adapted to high light intensity in its natural habitat) showed greater tolerance to high illumination than "B. oleracea" (an agricultural species), which experienced photoinhibition caused by excessive light. This practical paper is intended for advanced students of plant biochemistry and plant physiology. (Contains 2 figures and 1 table.)

Introduction: Performance of health care professionals depends on both medical knowledge and the certainty with which they possess it. Conventional continuing medical education interventions assess the correctness of learners' responses but do not determine the degree of confidence with which they hold incorrect information. This study describes the use of confidence-based learning (CBL) in an activity designed to enhance learners' knowledge, confidence in their knowledge, and clinical competence with regard to constipation-predominant IBS (IBS-C), a frequently underdiagnosed and misdiagnosed condition. Methods: The online CBL activity included multiple-choice questions in 2 modules: Burden of Care (BOC; 28 questions) and Patient Scenarios (PS; 9 case-based questions). After formative assessment, targeted feedback was provided, and the learner focused on material with demonstrated knowledge and/or confidence gaps. The process was repeated until 85% of questions were answered correctly and confidently (ie, mastery was attained). Results: Of 275 participants (24% internal medicine, 13% gastroenterology, 32% family medicine, and 31% other), 249 and 167 completed the BOC and PS modules, respectively. Among all participants, 61.8% and 98.2% achieved mastery in the BOC and PS modules, respectively. Baseline mastery levels between specialties were significantly different in the BOC module (p = 0.002); no significant differences were evident between specialties in final mastery levels. Approximately one-third of learners were confident and wrong in topics of epidemiology, defining IBS and constipation, and treatments in the first iteration. No significant difference was observed between specialties for the PS module in either the first or last iterations. Discussion: Learners achieved mastery in topics pertaining to IBS-C regardless of baseline knowledge or specialty. These data indicate that CME activities employing CBL can be used to address knowledge and confidence gaps. (Contains 7 figures and 3 tables.)

Both limb and cranial motor functions are adversely impacted by Parkinson's disease (PD). While current pharmacological and surgical interventions are effective in alleviating general limb motor symptoms of PD, they have failed to provide significant benefit for cranial motor functions. This suggests that the neuropathologies mediating limb and cranial motor impairments in PD may differ. Animal models provide a mechanism by which the potential neural dysfunctions underlying these different motor impairments may be characterized. Central goals to our laboratory have been to (a) determine the differential responses of cranial motor and limb motor function to striatal dopamine depletion and (b) determine the differential effects of striatal dopamine depletion on the integrity of cranial motor and limb motor neural circuits. This paper details the use of a comprehensive battery of limb and cranial motor behavioral tasks and the application of intracortical microstimulation to assess corticospinal and corticobulbar circuits in a rodent model of PD. Our work suggests that striatal dopamine depletion does differentially affect cranial and limb motor function and corticospinal and corticobulbar circuits. Further, we propose that cranial motor impairments in PD may be mediated by pathology both within and outside nigrostriatal dopamine system. Learning outcomes: Readers will be able to (a) describe a set of motor tests used to assess limb motor and cranial motor function in an animal model of Parkinson's disease, (b) understand the application of intracortical microstimulation to assess corticospinal and corticobulbar circuits, (c) describe the differential effects of dopamine depletion on limb motor and cranial motor function in a rodent model of PD, and (d) understand the potential role of dysfunction outside the nigrostriatal system mediating cranial motor impairments in Parkinson's disease. (Contains 6 figures.)

Morehouse School of Medicine chose to restructure its first year medical curriculum in 2005. The anatomy faculty had prior experience in integrating courses, stemming from the successful integration of individual anatomical sciences courses into a single course called Human Morphology. The integration process was expanded to include the other first year basic science courses (Biochemistry, Physiology, and Neurobiology) as we progressed toward an integrated curriculum. A team, consisting of the course directors, a curriculum coordinator, and the Associate Dean for Educational and Faculty Affairs, was assembled to build the new curriculum. For the initial phase, the original course titles were retained but the lecture order was reorganized around the Human Morphology topic sequence. The material from all four courses was organized into four sequential units. Other curricular changes included placing laboratories and lectures more consistently in the daily routine, reducing lecture time from 120 to 90 minute blocks, eliminating unnecessary duplication of content, and increasing the amount of independent study time. Examinations were constructed to include questions from all courses on a single test, reducing the number of examination days in each block from three to one. The entire restructuring process took two years to complete, and the revised curriculum was implemented for the students entering in 2007. The outcomes of the restructured curriculum include a reduction in the number of contact hours by 28%, higher or equivalent subject examination average scores, enhanced student satisfaction, and a first year curriculum team better prepared to move forward with future integration. (Contains 6 tables and 3 figures.)

Developmental psychologists have long been concerned with the ways that early adversity influences children's long-term outcomes. In the current study, activity of the hypothalamic-pituitary-adrenal axis of medically at-risk (e.g., preterm) infants was measured as a result of maternal participation in a novel cognitively based home visitation program (versus a Healthy Start home visitation program). Maternal participation in the cognitive intervention predicted lower basal cortisol levels among infants--with reduced levels of maternal avoidance/withdrawal serving as a mediator of this relation. Lower cortisol levels in infancy, in turn, predicted higher verbal short-term memory (STM) at age 3. STM represents a cognitive ability that has importance for children's later educational outcomes. Findings provide experimental evidence concerning the pathway by which an early intervention may produce hormonal changes that can, in turn, influence children's learning outcomes.

The relation of stress hormones and activity in stress response systems to the development of aspects of cognition and behavior important for educational achievement and attainment is examined from the perspective of the developmental psychobiological model. It is proposed that research in neuroendocrinology supports three general conclusions, namely (1) that there is a neuroscientifically definable optimal level of stress arousal in children against which various curricula and teaching and learning activities can be examined; (2) that consideration of the time course of stress arousal indicates that optimal levels of stress arousal are temporally limited and can be matched to specific instructional activities; and (3) that alterations to stress response systems through processes of allostasis and allostatic load, particularly for children facing early psychosocial disadvantage, can impair the flexible regulation of stress response systems needed for effective learning in school.

Estrogen has been shown to have a strong modulatory influence on several types of cognition in both women and female rodents. Latent inhibition is a task in which pre-exposure to a neutral stimulus, such as a tone, later impedes the association of that stimulus with a particular consequence, such as a shock. Previous work from our lab demonstrates that high levels of estradiol (E2) administered to ovariectomized (OVX) female rats abolishes latent inhibition when compared to female rats with low levels of E2 or male rats. To determine if this E2-induced impairment also occurs with the natural variations of ovarian hormones during the estrous cycle, this behavior was investigated in cycling female rats. In addition, pre-pubertal male and female rats were also tested in this paradigm to determine if the previously described sex differences are activational or organizational in nature. In a latent inhibition paradigm using a tone and a shock, adult rats were conditioned during different points of the estrous cycle. Rats conditioned during proestrus, a period of high E2 levels, exhibited attenuated latent inhibition when compared to rats conditioned during estrus or metestrus, periods associated with low levels of E2. Moreover, this effect is not seen until puberty indicating it is dependent on the surge of hormones at puberty. This study confirms recent findings that high E2 interferes with latent inhibition and is the first to show this is based in the activational actions of hormones. (Contains 2 figures.)

This review briefly summarizes recent empirical research on touch. The research includes the role of touch in early development, touch deprivation, touch aversion, emotions that can be conveyed by touch, the importance of touch for interpersonal relationships and how friendly touch affects compliance in different situations. MRI data are reviewed showing activation of the orbitofrontal cortex and the caudate cortex during affective touch. Physiological and biochemical effects of touch are also reviewed including decreased heart rate, blood pressure and cortisol and increased oxytocin. Similar changes noted following moderate pressure massage appear to be mediated by the stimulation of pressure receptors and increased vagal activity. Increased serotonin and decreased substance P may explain its pain-alleviating effects. Positive shifts in frontal EEG also accompany moderate pressure massage along with increased attentiveness, decreased depression and enhanced immune function including increased natural killer cells, making massage therapy one of the most effective forms of touch.

In the present study, we investigated the effect of a long-term mountain expedition on glucose tolerance and insulin action. Twelve registered mountaineers ages 31 years (SD = 1.1) participated in a 25-day expedition at a 2,200-3,800-m altitude with an average duration of 8 hr per day. Arterial oxygen saturation (SaO[subscript 2]) was substantially reduced during hiking. Glucose tolerance and insulin responses were measured prior to and twice during the expedition period. Maximal oxygen consumption increased from 43.0 [plus or minus] 2.7 to 49.1 [plus or minus] 2.2 mL/kg/min. Percentage of body fat decreased from 19.4 [plus or minus] 6.8% to 16.9 [plus or minus] 5.9%. The area under the curves for insulin and glucose during the oral glucose tolerance test were also reduced in Days 3 and 25. The present study demonstrated that altitude hiking activity is an effective lifestyle intervention to improve insulin action. (Contains 4 tables and 2 figures.)

The nucleus accumbens (NAc) plays a role in hedonic reactivity to taste stimuli. Learning can alter the hedonic valence of a given stimulus, and it remains unclear how the NAc encodes this shift. The present study examined whether the population response of NAc neurons to a taste stimulus is plastic using a conditioned taste aversion (CTA) paradigm. Electrophysiological and electromyographic (EMG) responses to intraoral infusions of a sucrose (0.3 M) solution were made in naive rats (Day 1). Immediately following the session, half of the rats (n = 6; Paired) received an injection of lithium chloride (0.15 M; i.p.) to induce malaise and establish a CTA while the other half (n = 6; Unpaired) received a saline injection. Days later (Day 5), NAc recordings during infusions of sucrose were again made. Electrophysiological and EMG responses to sucrose did not differ between groups on Day 1. For both groups, the majority of sucrose responsive neurons exhibited a decrease in firing rate (77% and 71% for Paired and Unpaired, respectively). Following conditioning, in Paired rats, EMG responses were indicative of aversion. Moreover, the majority of responsive NAc neurons now exhibited an increase in firing rate (69%). Responses in Unpaired rats were unchanged by the experience. Thus, the NAc differentially encodes the hedonic value of the same stimulus based on learned associations.

In independent studies delirium was associated with higher levels of cortisol, interleukin(IL)s, and S100B. The aim of this study was to simultaneously compare cortisol, IL-6, IL-8, and S100B levels in patients aged 65 years and older admitted for hip fracture surgery with and without delirium. Cortisol, IL-6, IL-8, and S100B were assayed in repeated blood samples. 120 patients (mean age 84 years, 62 patients with delirium) were included. Highest levels of IL-8 (27.1, 95% Confidence Interval (CI): 13.6-53.1 pg/ml) and cortisol (666, 95% CI: 475-859 nmol/L) were before delirium, but of IL-6 (84.3, 95% CI: 46.5-151.4 pg/mL) and S100B (0.18, 95% CI: 0.12-0.24 microgram/L) during delirium. In multivariable analysis cortisol, LogIL-6, and LogS100B were significantly associated with delirium, but adjusted for pre-existing cognitive impairment, only LogS100B remained significantly associated. Cortisol, IL-6 and S100B may have a role in the pathogenesis of delirium, but S100B is the strongest independent marker. (Contains 3 tables and 1 figure.)

Spatial abilities vary during the menstrual cycle. The effects of a similar rhythm in men are unknown. Mental rotation and spatial visualization of young healthy volunteers (29 females and 31 males) were tested during the menstrual and periovulatory phase of the menstrual cycle in women, and during the low-testosterone and high-testosterone phases of the circatrigintan rhythm in men in random order. Men outperformed women in both tests. In women, higher scores were achieved during the periovulatory phase, in men during the low-testosterone phase. The correlation between actual salivary testosterone levels and spatial abilities were positive in women and negative in men. According to our knowledge, this is the first study showing effects of a male infradian rhythm on cognitive abilities. (Contains 3 figures.)

It is now well established that cannabinoid agonists such as [delta][superscript 9]-tetrahydrocannabinol (THC), anandamide, and WIN 55,212-2 (WIN-2) produce potent and specific deficits in working memory (WM)/short-term memory (STM) tasks in rodents. Although mediated through activation of CB1 receptors located in memory-related brain regions such as the hippocampus and prefrontal cortex, these may, in part, be due to a reduction in acetylcholine release (i.e., cholinergic hypofunction). To determine the interaction between cannabinoid and cholinergic systems, we exposed rats treated with WIN-2 or cholinergic drugs to a hippocampal-dependent delayed nonmatch to sample (DNMS) task to study STM, and recorded hippocampal single-unit activity in vivo. WIN-2 induced significant deficits in DNMS performance and reduced the average firing and bursting rates of hippocampal principal cells through a CB1 receptor-mediated mechanism. Rivastigmine, an acetylcholinesterase inhibitor, reversed these STM deficits and normalized hippocampal discharge rates. Effects were specific to 1 mg/kg WIN-2 as rivastigmine failed to reverse the behavioral and physiological deficits that were observed in the presence of MK-801, an NMDA receptor antagonist. This supports the notion that cannabinoid-modulated cholinergic activity is a mechanism underlying the performance deficits in DNMS. Whether deficits are due to reduced nicotinic or muscarinic receptor activation, or both, awaits further analysis.

The popularity of sport psychology, both as an academic discipline and an applied practice, has grown substantially over the past two decades. Few within the realm of competitive athletics would argue with the importance of being mentally prepared prior to an athletic competition as well as the need to maintain that particular mindset during a competitive contest. Nevertheless, recent research has shown that many athletes, coaches, and sporting administrators are still quite reluctant to seek out the services of a qualified sport psychologist, even if they believe it could help. One of the primary reasons for this hesitation appears to be a lack of understanding about the process and the mechanisms by which these mental skills affect performance. Unlike the "harder sciences" of sport physiology and biochemistry where athletes can see the tangible results in themselves or other athletes (e.g., he or she lifted weights, developed larger muscles, and is now stronger/faster as a result), the unfamiliar and often esoteric nature of sport psychology appears to be impeding a large number of athletes from soliciting these important services. As such, the purpose of this article is to provide the reader with a simple framework depicting how mental skills training translates into improved within-competition performance. This framework is intended to help bridge the general "understanding gap" that is currently being reported by a large number of athletes and coaches, while also helping sport psychology practitioners sell their valuable services to individual athletes and teams. (Contains 6 figures.)

This research examined whether variations in salivary measures of the hypothalamic-pituitary-adrenal axis (cortisol) and autonomic nervous system (alpha amylase [sAA]) contribute to individual differences in the association between peer victimization and aggression. Children (N = 132; M age = 9.46 years, SD = 0.33) completed a measure of peer victimization, teachers rated children's aggression, and children's saliva was collected prior to, and following, participation in a laboratory-based peer-oriented social challenge task. Children rated their level of frustration at the end of the task. Results revealed that victimization interacted with cortisol and sAA measured in anticipation of the task to predict aggression; the victimization x cortisol contribution to aggression was partly mediated by children's self-reported frustration level. Victimization also was associated with heightened frustration in girls with high task-related sAA reactivity. Task-related sAA reactivity was associated with heightened aggression, but only for girls. These findings suggest that associations between peer victimization and aggression are moderated by variation in the activity of the major components of the psychobiology of stress; results are discussed in relation to theoretical models of individual differences in biological sensitivity to context.

The role of hypovitaminosis D as a possible risk factor for multiple sclerosis is reviewed. First, it is emphasized that hypovitaminosis D could be only one of the risk factors for multiple sclerosis and that numerous other environmental and genetic risk factors appear to interact and combine to trigger the disease. Secondly, the classical physiological notions about vitamin D have recently been challenged and the main new findings are summarized. This vitamin could have an important immunological role involving a number of organs and pathologies, including autoimmune diseases and multiple sclerosis. Furthermore, human requirements for this vitamin are much higher than previously thought, and in medium- or high-latitude countries, they might not be met in the majority of the general population due to a lack of sunshine and an increasingly urbanized lifestyle. Thereafter, the different types of studies that have helped to implicate hypovitaminosis D as a risk factor for multiple sclerosis are reviewed. In experimental autoimmune encephalomyelitis, vitamin D has been shown to play a significant immunological role. Diverse epidemiological studies suggest that a direct chain of causality exists in the general population between latitude, exposure to the sun, vitamin D status and the risk of multiple sclerosis. New epidemiological analyses from France support the existence of this chain of links. Recently reported immunological findings in patients with multiple sclerosis have consistently shown that vitamin D significantly influences regulatory T lymphocyte cells, whose role is well known in the pathogenesis of the disease. Lastly, in a number of studies on serum levels of vitamin D in multiple sclerosis, an insufficiency was observed in the great majority of patients, including at the earliest stages of the disease. The questionable specificity and significance of such results is detailed here. Based on a final global analysis of the cumulative significance of these different types of findings, it would appear likely that hypovitaminosis D is one of the risk factors for multiple sclerosis.

Nutrient digestion and absorption is necessary for the survival of living organisms and has evolved into the complex and specific task of the gastrointestinal (GI) system. While most people simply assume that their GI tract will work properly to use nutrients, provide energy, and release wastes, few nonscientists know the details about how various nutrients are digested and how the breakdown products traverse the cells lining the small intestine to reach the blood stream and to be used by the other cells of the body. There have been several recent discoveries of new transporters that likely contribute to the absorption of oligopeptides and fatty acids. In addition, details are being clarified about how transporters work and in what forms nutrients can be absorbed. The enzymes that digest basic carbohydrates, proteins, and fats have been identified in various segments of the GI tract, and details are becoming clearer about what types of bonds they hydrolyze. Usually, detailed information about the digestion of basic nutrients is presented and learned in biochemistry courses and detailed information about absorption via transepithelial transport of the breakdown products of digestion is studied in physiology courses. The goal of this Staying Current article is to combine the details of the biochemistry of digestion with the updated information about the physiology of nutrient absorption into one source for teachers of physiology. Insights are included about some of the diseases and conditions that can bring about malabsorption of food in the GI tract and their consequences.

There is increasing focus on the neurophysiological underpinnings of brain activations, giving birth to an emerging branch of neuroscience--neuroenergetics. However, no common definition of "brain activation" exists thus far. In this article, we define brain activation as the information-driven reorganization of energy flows in a population of neuroglial units that leads to an overall increase in energy utilization in this population. On the basis of this definition, the key aspects of modern biochemical and biophysical approaches to neuroenergetics are considered from the perspective of the links between these approaches within the context of the free energy minimization principle and the neurophysiological conception of deviance detection. In this light, we consider brain basal activity as subserving internal representations of the environment (predictive coding), and brain activation as reflecting the level of deviance from predictive coding. (Contains 3 figures.)

The neurobiology of borderline personality disorder (BPD) remains unclear. Dysfunctions of several neurobiological systems, including serotoninergic, dopaminergic, and other neurotransmitter systems, have been discussed. Here we present a theory that alterations in the sensitivity of opioid receptors or the availability of endogenous opioids constitute part of the underlying pathophysiology of BPD. The alarming symptoms and self-destructive behaviors of the affected patients may be explained by uncontrollable and unconscious attempts to stimulate their endogenous opioid system (EOS) and the dopaminergic reward system, regardless of the possible harmful consequences. Neurobiological findings that support this hypothesis are reviewed: Frantic efforts to avoid abandonment, frequent and risky sexual contacts, and attention-seeking behavior may be explained by attempts to make use of the rewarding effects of human attachment mediated by the EOS. Anhedonia and feelings of emptiness may be an expression of reduced activity of the EOS. Patients with BPD tend to abuse substances that target [mu]-opioid receptors. Self-injury, food restriction, aggressive behavior, and sensation seeking may be interpreted as desperate attempts to artificially set the body to survival mode in order to mobilize the last reserves of the EOS. BPD-associated symptoms, such as substance abuse, anorexia, self-injury, depersonalization, and sexual overstimulation, can be treated successfully with opioid receptor antagonists. An understanding of the neurobiology of BPD may help in developing new treatments for patients with this severe disorder. (Contains 1 table and 1 figure.)

Metabolism is a dynamic, simultaneous, and integrative science that cuts across nutrition, biochemistry, and physiology. Teaching this science can be a challenge. The use of a scenario-based, visually appealing, interactive, computer-animated CD may overcome the limitations of learning "one pathway at a time" and engage two- and four-year college students in a deep understanding of integrative metabolism. (Contains 11 figures and 2 tables.)

Background: Previous studies indicate that children may experience disrupted cortisol secretion in child care. The extent to which this is a transient or long-term disruption is not known, as most studies have relied on cross-sectional designs, and age-heterogeneous small sample sizes. This study aims to (a) compare cortisol secretion measured at home and in child care at 2 and 3 years of age, (b) investigate cortisol changes from 2 to 3 years of age, (c) examine whether age at initiation of child care is associated with cortisol secretion, and (d) investigate whether cortisol secretion in child care is linked to behavioural problems. Methods: Saliva samples were collected in a cohort of children recruited at 2 years of age from a larger population sample composed of women seen for the first time during pregnancy. Saliva was sampled twice a day (morning and afternoon) over two consecutive days at home and in child care at 2 (n = 155) and 3 years of age (n = 116). Interviews regarding the familial socioeconomic background and child care history were conducted with the mothers. Results: At 2 years of age, children showed a flat diurnal cortisol pattern in child care and a decreasing pattern at home. At age 3 years, children showed decreasing patterns both at home and in child care. Also at 3 years, children with less child care experience (i.e., entry after 16 months) had higher cortisol levels in child care and lower levels at home. In contrast, those with more experience (i.e., entry prior to 8 months) had lower cortisol in child care and higher cortisol at home. Conclusion: The different patterns of diurnal secretion observed in child care as compared to home is transient for most children, diminishing as they get older, whereas home and child care overall levels later on may be influenced by the cumulated experience with child care.

Different physiological and behavioral events activate transcription of "Arc/Arg3.1" in neurons in vivo, but the signal transduction pathways that mediate induction in particular situations remain to be defined. Here, we explore the relationships between induction of "Arc/Arg3.1" transcription in dentate granule cells in vivo and activation of mitogen-activated protein (MAP) kinase as measured by extracellular-regulated kinase 1/2 (ERK1/2) phosphorylation. We show that ERK1/2 phosphorylation is strongly induced in dentate granule cells within minutes after induction of perforant path long-term potentiation (LTP). Phospho-ERK staining appears in nuclei within minutes after stimulation commences, and ERK phosphorylation returns to control levels within 60 min. Electroconvulsive seizures, which strongly induce prolonged "Arc/Arg3.1" transcription in dentate granule cells, induced ERK1/2 phosphorylation in granule cells that returned to control levels within 30 min. Following 30, 60, and 120 min of exploration in a novel complex environment, "Arc/Arg3.1" transcription was activated in many more granule cells than stained positively for p-ERK at all time points. Although "Arc/Arg3.1" transcription was induced in most pyramidal neurons in CA1 following exploration, very few pyramidal neurons exhibited nuclear p-ERK1/2 staining. Local delivery of U0126 during the induction of perforant path LTP blocked transcriptional activation of "Arc/Arg3.1" in a small region near the injection site and blocked Arc/Arg3.1 protein expression over a wider region. Our results indicate that activation of "Arc/Arg3.1" transcription in dentate granule cells in vivo is mediated in part by MAP kinase activation, but other signaling pathways also contribute, especially in the case of "Arc/Arg3.1" induction in response to experience.

Developmental differences in hypothalamic-pituitary-adrenal (HPA) axis responsiveness to stressors and ongoing development of glucocorticoid-sensitive brain regions in adolescence suggest that similar to the neonatal period of ontogeny, adolescence may also be a sensitive period for programming effects of stressors on the central nervous system. Although research on this period of life is scarce compared to early life and adulthood, the available research indicates that effects of stress exposure during adolescence differ from, and may be longer-lasting than, effects of the same stress exposure in adulthood. Research progress in animal models in this field is reviewed including HPA function and the enduring effects of stress exposures in adolescence on sensitivity to drugs of abuse, learning and memory, and emotional behaviour in adulthood. The effects of adolescent stress depend on a number of factors, including the age, gender, the duration of stress exposure, the type of stressor, and the time between stress exposure and testing. (Contains 7 tables.)

Objective: To determine if sensory overresponsivity (SOR) is a moderating condition impacting the activity of the Hypothalamic Pituitary Adrenal (HPA) Axis in children with ADHD. Method: Participants were children with (n = 24) and without ADHD (n = 24). Children in the ADHD group were divided into SOR (ADHDs) and non-SOR (ADHDt) groups using the Sensory Over-Responsivity Inventory. All children participated in the Sensory Challenge Protocol. Salivary cortisol was used as a measure of HPA activity. Two prechallenge and seven postchallenge samples of saliva were taken. Cortisol patterns between groups were examined using a mixed-effects ANOVA. Results: There was a borderline significant difference found between the ADHDt and ADHDs group (p = 0.056) and a significant difference between ADHDt and the typical group (p = 0.014). Conclusion: Preliminary results support the premise that SOR may be a moderating variable used to create subgroups in diagnostic populations such as ADHD. (Contains 5 tables and 2 figures.)

The central question in this study is whether individual variability in children's cortisol levels and wellbeing at childcare can be explained by indices of quality of care and child characteristics. Participants were 71 children from childcare homes and 45 children from childcare centers in the age range of 20-40 months. In both types of settings equivalent measures and procedures were used. In home-based childcare, children experienced higher caregiver sensitivity, lower noise levels, and showed higher wellbeing compared to children in childcare centers. Caregiver sensitivity in home-based childcare--but not in center care--was positively associated with children's wellbeing. Additionally, children displayed higher cortisol levels at childcare than at home, irrespective of type of care. In home-based childcare, lower caregiver sensitivity was associated with higher total production of salivary cortisol during the day. In center-based childcare, lower global quality of care was associated with a rise in cortisol between 11 AM and 3 PM during the day. Quality of care is an important factor in young children's wellbeing and HPA stress reactivity. (Contains 6 tables and 2 figures.)

The consequences of prenatal maternal stress for development were examined in 125 full-term infants at 3, 6, and 12 months of age. Maternal cortisol and psychological state were evaluated 5 times during pregnancy. Exposure to elevated concentrations of cortisol early in gestation was associated with a slower rate of development over the 1st year and lower mental development scores at 12 months. Elevated levels of maternal cortisol late in gestation, however, were associated with accelerated cognitive development and higher scores at 12 months. Elevated levels of maternal pregnancy-specific anxiety early in pregnancy were independently associated with lower 12-month mental development scores. These data suggest that maternal cortisol and pregnancy-specific anxiety have programming influences on the developing fetus. (Contains 5 tables and 2 figures.)

This study examined relations among family environment, cortisol response, and behavior in the context of a randomized controlled trial with 92 children (M = 48 months) at risk for antisocial behavior. Previously, researchers reported an intervention effect on cortisol response in anticipation of a social challenge. The current study examined whether changes in cortisol response were related to later child aggression. Among lower warmth families, the intervention effect on aggression was largely mediated by the intervention effect on cortisol response. Although the intervention also resulted in significant benefits on child engaging behavior, cortisol response did not mediate this effect. These findings demonstrate meaningful associations between cortisol response and aggression among children at familial risk for antisocial behavior. (Contains 3 tables and 2 figures.)

Iron deficiency (ID) causes negative outcomes on psychomotor and behavioral development of infants and young children. Children with autistic spectrum disorders (ASD) are under risk for ID and this condition may increase the severity of psychomotor and behavioral problems, some of which already inherently exist in these children. In the present study, the frequency of ID and the association between ID and autistic symptoms, developmental level, and behavioral problems in preschool children attending a clinic for ASD (N = 31) were evaluated. No association was observed between ID and the severity of autistic symptoms, developmental level and behavioral problems. ID was detected in 32.3% (N = 10) of the children based on serum ferritin level. In this study, the negative impact of low serum ferritin in ASD has not been confirmed. On the other hand, the rate of ID was considerably high in this sample of children with ASD compared to normative data of preschool children. Further studies with larger samples are needed to clarify the relationship between ID and clinical variables associated with ASD. (Contains 2 tables.)

The understanding of complex physiological processes requires information from many different areas of knowledge. To meet this interdisciplinary scenario, the ability of integrating and articulating information is demanded. The difficulty of such approach arises because, more often than not, information is fragmented through under graduation education in Health Sciences. Shifting from a fragmentary and deep view of many topics to joining them horizontally in a global view is not a trivial task for teachers to implement. To attain that objective we proposed a course herein described--Biochemistry of the envenomation response--aimed at integrating previous contents of Health Sciences courses, following international recommendations of interdisciplinary model. The contents were organized by modules with increasing topic complexity. The full understanding of the envenoming pathophysiology of each module would be attained by the integration of knowledge from different disciplines. Active-learning strategy was employed focusing concept map drawing. Evaluation was obtained by a 30-item Likert-type survey answered by ninety students; 84% of the students considered that the number of relations that they were able to establish as seen by concept maps increased throughout the course. Similarly, 98% considered that both the theme and the strategy adopted in the course contributed to develop an interdisciplinary view. (Contains 2 tables and 1 box.)

Since the topic of the role of the kidneys in the regulation of acid base balance was last reviewed from a teaching perspective (Koeppen BM. Renal regulation of acid-base balance. Adv Physiol Educ 20: 132-141, 1998), our understanding of the specific membrane transporters involved in H+, HCO , and NH transport, and especially how these transporters are regulated in response to systemic acid-base disorders, has advanced considerably. In this review, these new aspects of renal function are presented, as are the broader and more general concepts related to the role of the kidneys in maintaining the acid-base balance. It is intended that this review will assist those who teach this aspect of human physiology to first-year health profession students.

Background: The importance of understanding which environmental and biological factors are involved in determining individual differences in physiological response to stress is widely recognized, given the impact that stress has on physical and mental health. Methods: The child-mother attachment relationship and some genetic polymorphisms (5-HTTLPR, COMT and GABRA6) were tested as predictors of salivary cortisol and alpha amylase concentrations, two biomarkers of hypothalamic-pituitary-adrenocortical (HPA) axis and sympathetic adrenomedullary (SAM) system activity, during the Strange Situation (SS) procedure in a sample of more than 100 healthy infants, aged 12 to 18 months. Results: Individual differences in alpha amylase response to separation were predicted by security of attachment in interaction with 5-HTTLPR and GABRA6 genetic polymorphisms, whereas alpha amylase basal levels were predicted by COMT x attachment interaction. No significant effect of attachment, genetics and their interaction on cortisol activity emerged. Conclusions: These results help to disentangle the role played by both genetic and environmental factors in determining individual differences in stress response in infancy. The results also shed light on the suggestion that HPA and SAM systems are likely to have different characteristic responses to stress.

Focal lacunar infarctions due to cerebral small vessel atherosclerosis or single/multiple large cortical infarcts lead to vascular dementia, and different genes and environmental factors have been implicated in causation or aggravation of the disease. Previous reports suggest that some of the risk factors may be common to both vascular as well as degenerative dementia. Among genetic factors, role of angiotensin converting enzyme (ACE) and methylene-tetrahydrofolate reductase (MTHFR) genes as putative risk factors has been examined but the outcome of these studies remain inconclusive. Present study attempted to see the importance of ACE alu insertion/deletion and MTHFR C677T polymorphisms as genetic predisposers to dementia. The study comprised of 80 vascular dementia patients, 90 degenerative dementia patients and 170 age matched controls. All were genotyped for ACE, MTHFR and APOE polymorphisms using PCR-RFLP method. Frequency of ACE D allele was seemingly high in dementia cases (26.7%) when compared to controls (11.2%). However, after adjusting for age and APOE E4*, none of the ACE alleles showed good correlation. MTHFR genotypes or alleles also did not show any correlation. Our study suggests no true correlation of ACE or MTHR genes with dementia in elderly. (Contains 4 tables.)

Catechol-O-methyltransferase (COMT) is a methylation enzyme that catalyzes the degradation pathway and inactivation of dopamine. It is accepted widely as being involved in the modulation of dopaminergic physiology and prefrontal cortex (PFC) function. The COMT Val158Met polymorphism is associated with variation in COMT activity. COMT 158Met allele may be advantageous for PFC-related cognitive abilities; however, it is also associated with increased anxiety, depression, and emotional vulnerability in response to stress or educational adversity. We hypothesized that the COMT polymorphism might be associated with academic performance. In this study, 779 Taiwanese tenth-grade volunteers were recruited. Scores from the Basic Competency Test (BCT), an annual national competitive entrance examination, were used to evaluate academic performance. The results indicated that students bearing homozygous for the Met allele tended to perform more poorly in all BCT subtests as compared to the other groups. In particular, the former performed significantly more poorly in the science and social science subtests. These findings provide evidence that affective factors might overwhelm cognitive abilities in high-stake tests like the BCT. (Contains 3 tables and 1 figure.)

Background: This paper examined children's fearful, sad, and angry reactivity to interparental conflict as mediators of associations between their exposure to interparental aggression and physiological functioning. Methods: Participants included 200 toddlers and their mothers. Assessments of interparental aggression and children's emotional reactivity were derived from maternal surveys and a semi-structured interview. Cortisol levels and cardiac indices of sympathetic nervous system (SNS) and parasympathetic nervous system (PNS) activity were used to assess toddler physiological functioning. Results: Results indicated that toddler exposure to interparental aggression was associated with greater cortisol levels and PNS activity and diminished SNS activity. Toddler angry emotional reactivity mediated associations between interparental aggression and cortisol and PNS functioning. Fearful emotional reactivity was a mediator of the link between interparental aggression and SNS functioning. Conclusions: The results are interpreted within conceptualizations of how exposure and reactivity to family risk organize individual differences in physiological functioning.

Models of stress and health suggest that emotions mediate the effects of stress on health; yet meta-analytic reviews have not confirmed these relationships. Categorizations of emotions along broad dimensions such as valence (e.g., positive and negative affect) may obscure important information about the effects of specific emotions on physiology. Within the context of the integrated specificity model, we present a novel theoretical framework that posits that specific emotional responses associated with specific types of environmental demands influence cortisol and immune outcomes in a manner that would have likely promoted the survival of our ancestors. We analyzed experiments from 66 journal articles that directly manipulated social stress or emotions and measured subsequent cortisol or immune responses. Judges rated experiments for the extent to which participants would experience theoretically relevant cognition and affect clustered around five categories: (a) cognitive appraisals, (b) basic emotions, (c) rumination and worry, (d) social threat, and (e) global mood states. As expected, global mood states were unassociated with the effect sizes, whereas exemplars from the other categories were generally associated with effect sizes in the expected manner. The present research suggests that coping strategies that alter appraisals and emotional responses may improve long-term health outcomes. This might be especially relevant for stressors that are acute or imminent, threaten one's social status, or require extended effort. (Contains 9 figures, 6 tables and 6 footnotes.)

Cumulative exposure to glucocorticoid hormones (GC) over the lifespan has been associated with cognitive impairment and may contribute to physical and cognitive degeneration in aging. The objective of the present study was to examine whether the pattern of cognitive deficits in patients with Cushing's syndrome (CS), a disorder characterized by chronic exposure to elevated levels of glucocorticoids (GC), is similar to that observed in older individuals. Ten subjects with CS were compared to sex-, age-, and education-matched healthy controls and older subjects (age of CS subjects + 15 yr). All participants were administered tests to assess attention, visuospatial processing, learning and memory, reasoning, concept formation and verbal fluency. MANCOVAs with depression scores as covariate and polynomial contrasts revealed that the age-matched control group performed better than the CS and older subject groups in visual target detection, trail making test, stroop task, digit symbol substitution, block design, object assembly, visual reproduction, spatial memory and similarities. The CS and older subjects performed similarly on these tasks. Further, a principal component analysis revealed two significant factors, representing general cognitive function and verbal memory explaining 39.9% and 10.0% of the variance, respectively. Additional MANCOVAs with depression as a covariate revealed that CS and older control subjects showed impaired performance on general cognitive function compared to age-matched controls. These results suggest that hypersecretion of GCs has "aging-like" effects on cognitive performance in individuals with CS. (Contains 7 tables.)

The purpose of this research is to explore the dynamics of cortisol regulation in the context of center-based child care by examining the impact of social context (large classroom vs. small group) and relationship quality with caregivers (conflict with mothers and teachers). We extend the research on children's physiologic stress system functioning in center-based child care by focusing on morning cortisol levels among young children living in poverty. While in high-quality center-based child care, children's cortisol levels decreased over the course of the morning--a result that contrasts with findings in previous research with middle-class children, for whom cortisol typically increased over the course of the day while attending center-based child care. Cortisol levels were further reduced when children were moved from a large classroom environment to a small group context. Relationship conflict with mothers and teachers moderated these effects. Children who had high conflict with their mother exhibited cortisol levels that remained higher (decreased less) over the course of the morning, and children who had high conflict with their teacher exhibited cortisol levels that remained higher (decreased less) in response to the small group context. These results indicate that high-quality child care has the potential to support reduced stress among children living in poverty, at least as indicated by adrenocortical activity.

This teaching article uses the report by Kwan et al., "Effects of methacholine, thapsigargin, and La[superscript 3+] on plasmalemmal and intracellular Ca[superscript 2+] transport in lacrimal acinar cells," where the effects of Ca[superscript 2+]-mobilizing agents in regulating Ca[superscript 2+] fluxes were examined under various conditions. Upper-level undergraduate and new graduate students in physiology are the target audience. Teaching and learning points are put forth in this article to illustrate 1) the characteristics of methacholine- and thapsigargin-induced Ca[superscript 2+] responses, 2) the different endoplasmic reticulum Ca[superscript 2+] stores accessible to methacholine and thapsigargin, 3) the inhibitory effects of La[superscript 3+] on Ca[superscript 2+] extrusion and Ca[superscript 2+] influx, and 4) the facilitatory role of La[superscript 3+] on endoplasmic reticulum Ca[superscript 2+] recycling. Each of the above concepts is first explained with references to the figures adapted from the original article. A list of student learning questions then follows, where the answers are found in the teaching notes for the instructors. It is the objective of this article to make both teaching and learning Ca[superscript 2+] regulation a rewarding experience for all. (Contains 5 figures.)

Stimulus-secretion coupling (SSC) in endocrine cells remains underappreciated as a subject for the study/teaching of general physiology. In the present article, we review key new electrophysiological, electrochemical, and fluorescence optical techniques for the study of exocytosis in single cells that have made this a fertile area for recent research. Based on findings using these techniques, we developed a model of SSC for adrenal chromaffin cells that blends features of Ca[superscript 2+] entry-dependent SSC (characteristic of neurons) with G protein receptor-coupled, Ca[superscript 2+] release-dependent, and second messenger-dependent SSC (characteristic of epithelial exocrine cells and nucleated blood cells). This model requires two distinct pools of secretory granules with differing Ca[superscript 2+] sensitivities. We extended this model to account for SSC in a wide variety of peripheral and hypothalamic/pituitary-based endocrine cells. These include osmosensitive magnocellular neurosecretory cells releasing antidiuretic hormone, stretch-sensitive atrial myocytes secreting atrial natriuretic peptide, K[superscript +]-sensitive adrenal glomerulosa cells secreting aldosterone, Ca[superscript 2+]-sensitive parathyroid chief cells secreting parathyroid hormone, and glucose-sensitive beta- and alpha-cells of pancreatic islets secreting insulin and glucagon, respectively. We conclude this article with implications of this approach for pathophysiology and therapeutics, including defects in chief cell Ca[superscript 2+] sensitivity, resulting in the hyperparathyroidism of renal disease, and defects in biphasic insulin secretion, resulting in diabetes mellitus. (Contains 8 figures and 1 footnote.)

The course "Management of Fluid and Electrolyte Disorders" is an applied physiology course taught using lectures and paper-based cases. The course approaches fluid therapy from both basic science and clinical perspectives. While paper cases provide a basis for application of basic science concepts, they lack key components of genuine clinical cases that, by nature, are diverse, change over time, and respond in unique ways to therapeutic interventions. We developed a dynamic model using STELLA software that simulates normal and abnormal fluid and electrolyte balance in the dog. Students interact, not with the underlying model, but with a user interface that provides sufficient data (skin turgor, chemistry panel, etc.) for the clinical assessment of patients and an opportunity for treatment. Students administer fluids and supplements, and the model responds in "real time," requiring regular reassessment and, potentially, adaptation of the treatment strategy. The level of success is determined by clinical outcome, including improvement, deterioration, or death. We expected that the simulated cases could be used to teach both the clinical and basic science of fluid therapy. The simulation provides exposure to a realistic clinical environment, and students tend to focus on this aspect of the simulation while, for the most part, ignoring an exploration of the underlying physiological basis for patient responses. We discuss how the instructor's expertise can provide sufficient support, feedback, and scaffolding so that students can extract maximum understanding of the basic science in the context of assessing and treating at the clinical level. (Contains 3 tables and 3 figures.)

Purpose: Ion-driven transepithelial water fluxes participate in maintaining superficial vocal fold hydration, which is necessary for normal voice production. The authors hypothesized that Cl[superscript -] channels are present in vocal fold epithelial cells and that transepithelial Cl[superscript -] fluxes can be manipulated pharmacologically. Method: Immunohistochemical assays were used to identify cystic fibrosis transmembrane regulator Cl[superscript -] channels in ovine vocal fold mucosae (n = 2). Electrophysiological responses of vocal fold mucosae (n = 80) to Cl[superscript -] channel inhibitors and secretagogues were evaluated in an ovine model using a randomized controlled experimental design. Results: Cystic fibrosis transmembrane regulator channels were localized to the plasma membranes of epithelial cells. The Cl[superscript -] transport inhibitor, diphenylamine-2-carboxylate, elicited a 30% decrease in mean short-circuit current (I[subscript sc]; n = 10). The secretagogue, isobutylmethylxanthine, yielded a 31.7% increase in mean I[subscript sc] (n = 10). Another secretagogue, uridine triphosphate, elicited a 48.8% immediate and 17.3% sustained increase in mean I[subscript sc] (n = 10). No sustained increases occurred following application of secretagogues to mucosae bathed in a low Cl[superscript -] environment (n = 10), suggesting that responses were Cl[superscript -] dependent. Conclusions: The authors provide structural and functional evidence for the presence of a transepithelial pathway for Cl[superscript -] fluxes. Pharmacological manipulation of this pathway may offer a mechanism for maintaining superficial vocal fold hydration.

Background: Prevalence of pre-menstrual syndrome (PMS) may be higher in women with Down syndrome due to syndrome specific characteristics in biochemistry, psychopathology and lifestyle. Recognition of PMS may be difficult for women with intellectual disabilities and their carers. Method: A daily diary, used to diagnose PMS with typical women, was adapted. Following its validation, the diary was completed by 33 women with Down syndrome, then adapted, and completed by a further 32 women with Down syndrome/carers. Results: PMS was diagnosed in 18-20% although a higher proportion (54%) of mothers thought their daughter had PMS. Conclusions: The hypotheses that PMS would be higher or go unrecognized in women with Down syndrome was not supported. The diary was well received by both carers and women with Down syndrome and could be an educative, clinical and research tool for use with any woman with intellectual disability.

The objective of this study was to investigate loss and the experience of emotional distress through a series of three studies. In Study 1, results indicated that when controlling for the total number of traumas experienced, children with loss traumas did not differ significantly from children with other types of traumas in terms of the level of PTSD symptoms reported and diurnal cortisol levels. In Study 2, results indicated that youth with loss traumas had significantly higher parent-reported internalizing and externalizing symptoms than control participants. In Study 3, we replicated and extended findings from Study 1 using an independent sample of non-clinic-referred youth. Findings are discussed in terms of how loss events may constitute a traumatic stressor in youth. (Contains 5 tables.)

Associations between multiple risks, emotion regulation skill, and basal cortisol levels were examined in a community sample of 69 African American youth (mean age = 11.30 years; 49% male) living in an urban setting. Multiple risks were assessed at Time 1 and consisted of 10 demographic and psychosocial risk factors including parent, child, and observer reports. Parents rated the child's emotion regulation skill at Time 2, 6 months later. Three saliva samples were collected one morning in the week following the Time 2 interview and assayed for cortisol, a stress hormone. Regression results indicated that multiple risks at Time 1 were associated with depressed cortisol levels at Time 2, but that patterns of association differed across levels of emotion regulation skill and sex. Youth with good emotion regulation skills showed no differences in cortisol across low and high levels of risk. In contrast, females with poor emotion regulation skill showed strong negative associations between multiple risks and basal cortisol levels. Hypocortisolism is a response of some youth to multiple risks, but protective factors can attenuate this association. (Contains 2 tables and 1 figure.)

The introduction of dwarfing traits into crops was a major factor in increased grain yields during the "Green Revolution." In most cases those traits were the consequence of altered synthesis or response to the gibberellin (GA) plant hormones. Our current understanding of GA synthesis and physiology has been facilitated by the characterization of mutants. To introduce concepts about GA hormone physiology and plant transformation in an undergraduate laboratory course we have used "ga5", a semi-dwarf "Arabidopsis" mutant with reduced activity of GA 20-oxidase. In this laboratory exercise, "Arabidopsis ga5" mutant plants are transformed by the floral-dip method using "Agrobacterium tumefaciens" carrying plasmid constructs conferring kanamycin resistance and containing the "GA5" gene. Within 4 weeks, seeds of transformed plants can be easily screened by antibiotic resistance on plates. After transfer to soil the dwarf mutant plants transformed with a wild-type version of the gene show normal size. In addition to offering a visual understanding of the effect of GA on stem elongation, students learn additional techniques in this experiment, including PCR and agarose gel electrophoresis. This experiment is cost effective and can be completed within a 4-month term. (Contains 6 figures.)

Recent studies have shown that nitric oxide (NO) signaling plays a crucial role in memory consolidation of Pavlovian fear conditioning and in synaptic plasticity in the lateral amygdala (LA). In the present experiments, we examined the role of the cGMP-dependent protein kinase (PKG), a downstream effector of NO, in fear memory consolidation and long-term potentiation (LTP) at thalamic and cortical input pathways to the LA. In behavioral experiments, rats given intra-LA infusions of either the PKG inhibitor Rp-8-Br-PET-cGMPS or the PKG activator 8-Br-cGMP exhibited dose-dependent impairments or enhancements of fear memory consolidation, respectively. In slice electrophysiology experiments, bath application of Rp-8-Br-PET-cGMPS or the guanylyl cyclase inhibitor LY83583 impaired LTP at thalamic, but not cortical inputs to the LA, while bath application of 8-Br-cGMP or the guanylyl cyclase activator YC-1 resulted in enhanced LTP at thalamic inputs to the LA. Interestingly, YC-1-induced enhancement of LTP in the LA was reversed by concurrent application of the MEK inhibitor U0126, suggesting that the NO-cGMP-PKG signaling pathway may promote synaptic plasticity and fear memory formation in the LA, in part by activating the ERK/MAPK signaling cascade. As a test of this hypothesis, we next showed that rats given intra-LA infusion of the PKG inhibitor Rp-8-Br-PET-cGMPS or the PKG activator 8-Br-cGMP exhibit impaired or enhanced activation, respectively, of ERK/MAPK in the LA after fear conditioning. Collectively, our findings suggest that an NO-cGMP-PKG-dependent form of synaptic plasticity at thalamic input synapses to the LA may underlie memory consolidation of Pavlovian fear conditioning, in part, via activation of the ERK/MAPK signaling cascade. (Contains 7 figures.)