Period determination in the food-entrainable and methamphetamine-sensitive circadian oscillator(s)

Daily rhythmic processes are coordinated by circadian clocks, which are present in numerous central and peripheral tissues. In mammals, two circadian clocks, the food-entrainable oscillator (FEO) and methamphetamine-sensitive circadian oscillator (MASCO), are "black box" mysteries because their anatomical loci are unknown and their outputs are not expressed under normal physiological conditions. In the current study, the investigation of the timekeeping mechanisms of the FEO and MASCO in mice with disruption of all three paralogs of the canonical clock gene, Period, revealed unique and convergent findings. We found that both the MASCO and FEO in Per1(-/-)/Per2(-/-)/Per3(-/-) mice are circadian oscillators with unusually short (similar to 21 h) periods. These data demonstrate that the canonical Period genes are involved in period determination in the FEO and MASCO, and computational modeling supports the hypothesis that the FEO and MASCO use the same timekeeping mechanism or are the same circadian oscillator. Finally, these studies identify Per1(-/-)/Per2(-/-)/Per3(-/-) mice as a unique tool critical to the search for the elusive anatomical location(s) of the FEO and MASCO.

Anxiolytic-like effect of oxytocin in the simulated public speaking test

Oxytocin (OT) is known to be involved in anxiety, as well as cardiovascular and hormonal regulation. The objective of this study was to assess the acute effect of intranasally administered OT on subjective states, as well as cardiovascular and endocrine parameters, in healthy volunteers (n = 14) performing a simulated public speaking test. OT or placebo was administered intranasally 50 min before the test. Assessments were made across time during the experimental session: (1) baseline (-30 min); (2) pre-test (-15 min); (3) anticipation of the speech (50 min); (4) during the speech (1:03 h), post-test time 1 (1:26 h), and post-test time 2 (1:46 h). Subjective states were evaluated by self-assessment scales. Cortisol serum and plasma adrenocorticotropic hormone (ACTH) were measured. Additionally, heart rate, blood pressure, skin conductance, and the number of spontaneous fluctuations in skin conductance were measured. Compared with placebo, OT reduced the Visual Analogue Mood Scale (VAMS) anxiety index during the pre-test phase only, while increasing sedation at the pre-test, anticipation, and speech phases. OT also lowered the skin conductance level at the pre-test, anticipation, speech, and post-test 2 phases. Other parameters evaluated were not significantly affected by OT. The present results show that OT reduces anticipatory anxiety, but does not affect public speaking fear, suggesting that this hormone has anxiolytic properties.

Availability of a rich source of sodium during the perinatal period programs the fluid balance restoration pattern in adult offspring

Osmoregulatory mechanisms can be vulnerable to electrolyte and/or endocrine environmental changes during the perinatal period, differentially programming the developing offspring and affecting them even in adulthood. The aim of this study was to evaluate whether availability of hypertonic sodium solution during the perinatal period may induce a differential programming in adult offspring osmoregulatory mechanisms. With this aim, we studied water and sodium intake after Furosemide-sodium depletion in adult offspring exposed to hypertonic sodium solution from 1 week before mating until postnatal day 28 of the offspring, used as a perinatal manipulation model [PM-Na group]. In these animals, we also identified the cell population groups in brain nuclei activated by Furosemide-sodium depletion treatment, analyzing the spatial patterns of Fos and Fos-vasopressin immunoreactivity. In sodium depleted rats, sodium and water intake were significantly lower in the PM-Na group vs. animals without access to hypertonic sodium solution [PM-Ctrol group]. Interestingly, when comparing the volumes consumed of both solutions in each PM group, our data show the expected significant differences between both solutions ingested in the PM-Ctrol group, which makes an isotonic cocktail: however, in the PM-Na group there were no significant differences in the volumes of both solutions consumed after Furosemide-sodium depletion, and therefore the sodium concentration of total fluid ingested by this group was significantly higher than that in the PM-Ctrol group. With regard to brain Fos immunoreactivity, we observed that Furosemide-sodium depletion in the PM-Na group induced a higher number of activated cells in the subfornical organ, ventral subdivision of the paraventricular nucleus and vasopressinergic neurons of the supraoptic nucleus than in the PM-Ctrol animals. Moreover, along the brainstem, we found a decreased number of sodium depletion-activated cells within the nucleus of the solitary tract of the PM-Na group. Our data indicate that early sodium availability induces a long-term effect on fluid drinking and on the cell activity of brain nuclei involved in the control of hydromineral balance. These results also suggest that availability of a rich source of sodium during the perinatal period may provoke a larger anticipatory response in the offspring, activating the vasopressinergic system and reducing thirst after water and sodium depletion, as a result of central osmosensitive mechanism alterations. (C) 2011 Elsevier Inc. All rights reserved.

Functional coupling of sensorimotor and associative areas during a catching ball task: a qEEG coherence study

Abstract Background Catching an object is a complex movement that involves not only programming but also effective motor coordination. Such behavior is related to the activation and recruitment of cortical regions that participates in the sensorimotor integration process. This study aimed to elucidate the cortical mechanisms involved in anticipatory actions when performing a task of catching an object in free fall. Methods Quantitative electroencephalography (qEEG) was recorded using a 20-channel EEG system in 20 healthy right-handed participants performed the catching ball task. We used the EEG coherence analysis to investigate subdivisions of alpha (8-12 Hz) and beta (12-30 Hz) bands, which are related to cognitive processing and sensory-motor integration. Results Notwithstanding, we found the main effects for the factor block; for alpha-1, coherence decreased from the first to sixth block, and the opposite effect occurred for alpha-2 and beta-2, with coherence increasing along the blocks. Conclusion It was concluded that to perform successfully our task, which involved anticipatory processes (i.e. feedback mechanisms), subjects exhibited a great involvement of sensory-motor and associative areas, possibly due to organization of information to process visuospatial parameters and further catch the falling object.

La governance dei rifiuti in Europa. Territori, conflitti e partecipazione

I rifiuti come oggetti impegnano tutte le istituzioni umane in una lotta di definizione del posto che occupano e quindi del valore che assumono. In tale dinamica la gestione dei rifiuti diventa un fatto sociale totale che coinvolge tutte le istituzioni umane in una lotta di definizione territorializzata. La storia del movimento ambientalista ci mostra come partendo dal disagio nei confronti dell’oggetto si è passati ad un disagio nei confronti delle idee che lo generano. Modernizzazione ecologica e modernizzazione democratica sembrano andare per un certo periodo d’accordo. Nei casi di conflittualità recente, e nello studio di caso approfondito di un piano provinciale della gestione rifiuti, il carattere anticipatore dell’attivismo ambientalista, sta rendendo sempre più costosi e incerti, investimenti e risultati strategici . Anche i principi delle politiche sono messi in discussione. La sostenibilità è da ricercare in una relativizzazione dei principi di policy e degli strumenti tecnici di valutazione (e.g. LCA) verso una maggiore partecipazione di tutti gli attori. Si propone un modello di governance che parta da un coordinamento amministrativo territoriale sulle reti logistiche, quindi un adeguamento geografico degli ATO, e un loro maggior ruolo nella gestione del processo di coordinamento e pianificazione. Azioni queste che devono a loro volta aprirsi ai flussi (ecologici ed economici) e ai loro attori di riferimento: dalle aziende multiutility agli ambientalisti. Infine è necessario un momento di controllo democratico che può avere una funzione arbitrale nei conflitti tra gli attori o di verifica. La ricerca si muove tra la storia e la filosofia, la ricerca empirica e la riflessione teorica. Sono state utilizzate anche tecniche di indagine attiva, come il focus group e l’intervista.

Pedagogia e immaginario: Fiction e giovani dell'eta' post-moderna

La ricerca prende in esame le produzioni narrative, in particolare quelle dedicate agli adolescenti e ai giovani adulti, nei cui linguaggi e nelle cui trame si insinuano modelli di vita, comportamenti, valori, stereotipie, ecc. Attraverso le fiction dell'ultimo decennio, sono offerte interpretazioni alle costanti e alle variabili che percorrono i diversi prodotti culturali e che sono metafore di caratteristiche e di dinamiche della società post-moderna. Nella ricerca si studiano le trame e i personaggi delle narrazioni e, in parallelo, si individuano le correlazioni con studi pedagogici interessati alle ultime generazioni giovanili. La comparazione ha portato ad un sistema di decifrazione per individuare il giovane dell'era post-moderna tra gli elementi di finzione. Si sono prese in esame le più importanti icone dell'immaginario che, pur attraverso innumerevoli riscritture, continuano ad imporsi come metafore per identificazione, abnegazione, catarsi. Rispetto al passato, molte icone presenti nelle ultime produzioni di fiction subiscono alterazioni leggibili come spie (i.e. Ginzburg). È in queste trasformazioni, spinte fino alla metamorfosi dell'icona, che è possibile rintracciare alcune caratteristiche proprie del mondo giovanile in rapporto con la società contemporanea. L'immaginario può dunque essere lo specchio in cui l'uomo e la società possono riconoscersi, e studiarlo apre possibilità per sviluppare prospettive di interpretazione verso nuovi orizzonti.

Momentary stress moderates procoagulant reactivity to a trauma-specific interview in patients with posttraumatic stress disorder caused by myocardial infarction

Hypercoagulability of the blood might partially explain the increased cardiovascular disease risk in posttraumatic stress disorder (PTSD) and is also triggered by anticipatory stress. We hypothesized exaggerated procoagulant reactivity in patients with PTSD in response to a trauma-specific interview that would be moderated by momentary stress levels. We examined 23 patients with interviewer-diagnosed PTSD caused by myocardial infarction (MI) and 21 post-MI patients without PTSD. A second diagnostic (i.e., trauma-specific) interview to assess posttraumatic stress severity was performed after a median follow-up of 26 months (range 12-36). Before that interview patients rated levels of momentary stress (Likert scale 0-10) and had blood collected before and after the interview. The interaction between PTSD diagnostic status at study entry and level of momentary stress before the follow-up interview predicted reactivity of fibrinogen (P=0.036) and d-dimer (P=0.002) to the PTSD interview. Among patients with high momentary stress levels, PTSD patients had greater fibrinogen (P=0.023) and d-dimer (P=0.035) reactivity than non-PTSD patients. Among patients with low momentary stress levels, PTSD patients had less d-dimer reactivity than non-PTSD patients (P=0.024); fibrinogen reactivity did not significantly differ between groups. Momentary stress levels, but not severity of posttraumatic stress, correlated with d-dimer reactivity in PTSD patients (r=0.46, P=0.029). We conclude that momentary stress levels moderated the relationship between PTSD and procoagulant reactivity to a trauma-specific interview. Procoagulant reactivity in post-MI patients with PTSD confronted with their traumatically experienced MI was observed if patients perceived high levels of momentary stress before the interview.

Brain activation during anticipation of sound sequences

Music consists of sound sequences that require integration over time. As we become familiar with music, associations between notes, melodies, and entire symphonic movements become stronger and more complex. These associations can become so tight that, for example, hearing the end of one album track can elicit a robust image of the upcoming track while anticipating it in total silence. Here, we study this predictive “anticipatory imagery” at various stages throughout learning and investigate activity changes in corresponding neural structures using functional magnetic resonance imaging. Anticipatory imagery (in silence) for highly familiar naturalistic music was accompanied by pronounced activity in rostral prefrontal cortex (PFC) and premotor areas. Examining changes in the neural bases of anticipatory imagery during two stages of learning conditional associations between simple melodies, however, demonstrates the importance of fronto-striatal connections, consistent with a role of the basal ganglia in “training” frontal cortex (Pasupathy and Miller, 2005). Another striking change in neural resources during learning was a shift between caudal PFC earlier to rostral PFC later in learning. Our findings regarding musical anticipation and sound sequence learning are highly compatible with studies of motor sequence learning, suggesting common predictive mechanisms in both domains.

The interface between morphology and action planning: a comparison of two species of New World monkeys

Recent research with several species of nonhuman primates suggests sophisticated motor-planning abilities observed in human adults may be ubiquitous among primates. However, there is considerable variability in the extent to which these abilities are expressed across primate species. In the present experiment, we explore whether the variability in the expression of anticipatory motor-planning abilities may be attributed to cognitive differences (such as tool use abilities) or whether they may be due to the consequences of morphological differences (such as being able to deploy a precision grasp). We compared two species of New World monkeys that differ in their tool use abilities and manual dexterity: squirrel monkeys, Saimiri sciureus (less dexterous with little evidence for tool use) and tufted capuchins, Sapajus apella (more dexterous and known tool users). The monkeys were presented with baited cups in an untrained food extraction task. Consistent with the morphological constraint hypothesis, squirrel monkeys frequently showed second-order motor planning by inverting their grasp when picking up an inverted cup, while capuchins frequently deployed canonical upright grasping postures. Findings suggest that the lack of ability for precision grasping may elicit more consistent second-order motor planning, as the squirrel monkeys (and other species that have shown a high rate of second-order planning) have fewer means of compensating for inefficient initial postures. Thus, the interface between morphology and motor planning likely represents an important factor for understanding both the ontogenetic and phylogenetic origins of sophisticated motor-planning abilities.

The Interface Between Morphology and Action Planning: a Comparison of Two Species of New World Monkeys

Recent research with several species of nonhuman primates suggests sophisticated motor-planning abilities observed in human adults may be ubiquitous among primates. However, there is considerable variability in the extent to which these abilities are expressed across primate species. In the present experiment, we explore whether the variability in the expression of anticipatory motor-planning abilities may be attributed to cognitive differences (such as tool use abilities) or whether they may be due to the consequences of morphological differences (such as being able to deploy a precision grasp). We compared two species of New World monkeys that differ in their tool use abilities and manual dexterity: squirrel monkeys, Saimiri sciureus (less dexterous with little evidence for tool use) and tufted capuchins, Sapajus apella (more dexterous and known tool users). The monkeys were presented with baited cups in an untrained food extraction task. Consistent with the morphological constraint hypothesis, squirrel monkeys frequently showed second-order motor planning by inverting their grasp when picking up an inverted cup, while capuchins frequently deployed canonical upright grasping postures. Findings suggest that the lack of ability for precision grasping may elicit more consistent second-order motor planning, as the squirrel monkeys (and other species that have shown a high rate of second-order planning) have fewer means of compensating for inefficient initial postures. Thus, the interface between morphology and motor planning likely represents an important factor for understanding both the ontogenetic and phylogenetic origins of sophisticated motor-planning abilities. (C) 2013 The Association for the Study of Animal Behaviour. Published by Elsevier Ltd. All rights reserved.

Assessment of Alcohol Reward in Prairie Voles (Microtus ochrogaster)

The purpose of our study was to assess whether prairie voles find alcohol rewarding. Prairie voles have recently become a species of interest for alcohol studies, which have traditionally used other rodent model species including several different strains of mice and rats. The prairie vole is one of only two known rodent species that readily administers high levels of unsweetened alcohol, implicating it as a potentially effective animal model for studying alcohol abuse. However, voluntary consumption does not necessarily imply that prairie voles find it rewarding. Therefore the purpose of our study was to investigate if alcohol has rewarding properties for prairie voles using three different approaches: place conditioning, flavor conditioning, and immunohistochemistry. Furthermore, we sought to characterize their reward profile and compare it to other commonly used rodent models ¿ C57BL/6 mice, DBA/2J mice, and Sprague-Dawley rats. Place and flavor conditioning are behavioral methods that rely on the learned association between a stimulus and the effects of a drug; the drug of interest in these studies is alcohol. To assess whether prairie voles will demonstrate a conditioned preference for alcohol-paired stimuli, seven place conditioning studies were run that investigated a range of different doses, individual conditioning session durations, and trial durations. Video analysis revealed no difference in the amount of time spent on the alcohol-paired floor, suggesting no conditioned place preference for alcohol. Two flavor conditioning tests were conducted to assess whether voles would demonstrate a preference for an alcohol-paired flavored saccharin solution. Voles demonstrated reduced consumption of the alcohol-paired flavored saccharin solution, regardless of dose or flavor, when alcohol administration occurred after conditioning sessions (p=<0.001). When alcohol was administered before conditioning sessions, no difference in consumption of the alcohol-paired and saline-paired flavored saccharin solutions was seen (p=0.545). Previous studies that have documented similar behavior have hypothesized that this is an example of an anticipatory contrast effect. This theory proposes that prairie voles reduce their intake of a hedonic solution (flavored saccharin solution) in anticipation of later drug administration (alcohol). However, conditioning-based behavioral methods of studying alcohol reward are highly sensitive to the parameters of the conditioned stimulus, thus it is possible that voles will not show preference for alcohol-related stimuli, even if they do find alcohol rewarding. Immunohistochemical analysis supplemented this behavioral data by allowing us to identify specific neural regions that were directly activated in response to the acute administration of alcohol. No difference in the number of activated c-Fos neurons in the Nucleus Accumbens (NAc) core or shell was seen (p=0.3364; p=0.6698) in animals that received an acute injection of alcohol or saline. There was a significant increase in the number of activated c-Fos neurons in the Paraventricular Nucleus of the Hypothalamus (PVN) in alcohol-treated animals compared to saline-treated animals (p=0.0034). There was no difference in the pixel count of activated c-Fos neurons or in the % area activated in the Arcuate Nucleus between alcohol and saline-treated animals (p=0.4523; p=0.3304). In conclusion, the place conditioning studies that were conducted in this thesis suggest that prairie voles do not demonstrate preference or aversion towards alcohol-paired stimuli. The flavor conditioning studies suggest that prairie voles do not demonstrate aversion but rather avoidance of the alcohol-paired flavor in anticipation of future alcohol administration. The preliminary immunohistochemical data collected is inconclusive but cannot rule out the possibility of neuronal activation patterns indicative of reward. Taken together, our data indicate that prairie voles hav

Decision-making in amnesia: do advantageous decisions require conscious knowledge of previous behavioural choices?

Previous work has reported that in the Iowa gambling task (IGT) advantageous decisions may be taken before the advantageous strategy is known [Bechara, A., Damasio, H., Tranel, D., ; Damasio, A. R. (1997). Deciding advantageously before knowing the advantageous strategy. Science, 275, 1293-1295]. In order to test whether explicit memory is essential for the acquisition of a behavioural preference for advantageous choices, we measured behavioural performance and skin conductance responses (SCRs) in five patients with dense amnesia following damage to the basal forebrain and orbitofrontal cortex, six amnesic patients with damage to the medial temporal lobe or the diencephalon, and eight control subjects performing the IGT. Across 100 trials healthy participants acquired a preference for advantageous choices and generated large SCRs to high levels of punishment. In addition, their anticipatory SCRs to disadvantageous choices were larger than to advantageous choices. However, this dissociation occurred much later than the behavioural preference for advantageous alternatives. In contrast, though exhibiting discriminatory autonomic SCRs to different levels of punishment, 9 of 11 amnesic patients performed at chance and did not show differential anticipatory SCRs to advantageous and disadvantageous choices. Further, the magnitude of anticipatory SCRs did not correlate with behavioural performance. These results suggest that the acquisition of a behavioural preference--be it for advantageous or disadvantageous choices--depends on the memory of previous reinforcements encountered in the task, a capacity requiring intact explicit memory.

The effect of natural habituation on coagulation responses to acute mental stress and recovery in men

Blood coagulation activation might be one mechanism linking acute mental stress with coronary events. We investigated the natural habituation of coagulation responses and recovery to short-term mental stress. Three times with one-week intervals, 24 men (mean age 47 +/- 7 years) underwent the same 13-min stressor (preparation, job interview, mental arithmetic). During each visit venous blood was obtained four times (baseline, immediately post-stress, 45 min of recovery, 105 min of recovery). Eight blood coagulation parameters were measured at weeks one and three. Acute stress provoked increases in von Willebrand factor antigen, fibrinogen, clotting factor FVII activity (FVII:C), FVIII:C, FXII:C (p's < or = 0.019), and D-dimer (N.S.). All coagulation parameters experienced full recovery except FVIII:C (p = 0.022). Stress did not significantly affect activated partial thromboplastin time and prothrombin time. At all time points FVIII:C and FXII:C levels were significantly higher at week one compared to week three (p's < or = 0.041). Before catheter insertion, systolic blood pressure (p = 0.001) and heart rate (p = 0.026) were relatively higher at week one. Unlike the magnitude of systolic blood pressure response to stress (p = 0.007) and of cortisol recovery from stress (p = 0.002), the magnitude of all coagulation responses to stress and the recovery from stress were similar in week one and week three. Sympathetic activation with anticipatory stress best explained increased baseline activity in FVIII and FXII at week one. An incapacity of the coagulation system to adapt to stress repeats is perhaps a consequence of evolution, but might also contribute to increased coronary risk in some individuals, particularly in those with cardiovascular diseases.

In your eyes only: deficits in executive functioning after frontal TMS reflect in eye movements

This study investigated the roles of the right and left dorsolateral prefrontal (rDLPFC, lDLPFC) and the medial frontal cortex (MFC) in executive functioning using a theta burst transcranial magnetic stimulation (TMS) approach. Healthy subjects solved two visual search tasks: a number search task with low cognitive demands, and a number and letter search task with high cognitive demands. To observe how subjects solved the tasks, we assessed their behavior with and without TMS using eye movements when subjects were confronted with specific executive demands. To observe executive functions, we were particularly interested in TMS-induced changes in visual exploration strategies found to be associated with good or bad performance in a control condition without TMS stimulation. TMS left processing time unchanged in both tasks. Inhibition of the rDLPFC resulted in a decrease in anticipatory fixations in the number search task, i.e., a decrease in a good strategy in this low demand task. This was paired with a decrease in stimulus fixations. Together, these results point to a role of the rDLPFC in planning and response selection. Inhibition of the lDLPFC and the MFC resulted in an increase in anticipatory fixations in the number and letter search task, i.e., an increase in the application of a good strategy in this task. We interpret these results as a compensatory strategy to account for TMS-induced deficits in attentional switching when faced with high switching demands. After inhibition of the lDLPFC, an increase in regressive fixations was found in the number and letter search task. In the context of high working memory demands, this strategy appears to support TMS-induced working memory deficits. Combining an experimental TMS approach with the recording of eye movements proved sensitive to discrete decrements of executive functions and allows pinpointing the functional organization of the frontal lobes.