The rat's anticipation of diurnal and a-diurnal feeding

Rats anticipation of diurnal and a-diurnal feedin

Aversive Learning in Honeybees Revealed by the Olfactory Conditioning of the Sting Extension Reflex

Invertebrates have contributed greatly to our understanding of associative learning because they allow learning protocols to be combined with experimental access to the nervous system. The honeybee Apis mellifera constitutes a standard model for the study of appetitive learning and memory since it was shown, almost a century ago, that bees learn to associate different sensory cues with a reward of sugar solution. However, up to now, no study has explored aversive learning in bees in such a way that simultaneous access to its neural bases is granted. Using odorants paired with electric shocks, we conditioned the sting extension reflex, which is exhibited by harnessed bees when subjected to a noxious stimulation. We show that this response can be conditioned so that bees learn to extend their sting in response to the odorant previously punished. Bees also learn to extend the proboscis to one odorant paired with sugar solution and the sting to a different odorant paired with electric shock, thus showing that they can master both appetitive and aversive associations simultaneously. Responding to the appropriate odorant with the appropriate response is possible because two different biogenic amines, octopamine and dopamine subserve appetitive and aversive reinforcement, respectively. While octopamine has been previously shown to substitute for appetitive reinforcement, we demonstrate that blocking of dopaminergic, but not octopaminergic, receptors suppresses aversive learning. Therefore, aversive learning in honeybees can now be accessed both at the behavioral and neural levels, thus opening new research avenues for understanding basic mechanisms of learning and memory

Robust Food Anticipatory Activity in BMAL1-Deficient Mice

Food availability is a potent environmental cue that directs circadian locomotor activity in rodents. Even though nocturnal rodents prefer to forage at night, daytime food anticipatory activity (FAA) is observed prior to short meals presented at a scheduled time of day. Under this restricted feeding regimen, rodents exhibit two distinct bouts of activity, a nocturnal activity rhythm that is entrained to the light-dark cycle and controlled by the master clock in the suprachiasmatic nuclei (SCN) and a daytime bout of activity that is phase-locked to mealtime. FAA also occurs during food deprivation, suggesting that a food-entrainable oscillator (FEO) keeps time in the absence of scheduled feeding. Previous studies have demonstrated that the FEO is anatomically distinct from the SCN and that FAA is observed in mice lacking some circadian genes essential for timekeeping in the SCN. In the current study, we optimized the conditions for examining FAA during restricted feeding and food deprivation in mice lacking functional BMAL1, which is critical for circadian rhythm generation in the SCN. We found that BMAL1-deficient mice displayed FAA during restricted feeding in 12hr light:12hr dark (12L:12D) and 18L:6D lighting cycles, but distinct activity during food deprivation was observed only in 18L:6D. While BMAL1-deficient mice also exhibited robust FAA during restricted feeding in constant darkness, mice were hyperactive during food deprivation so it was not clear that FAA consistently occurred at the time of previously scheduled food availability. Taken together, our findings suggest that optimization of experimental conditions such as photoperiod may be necessary to visualize FAA in genetically modified mice. Furthermore, the expression of FAA may be possible without a circadian oscillator that depends on BMAL1

Bonsai Trees in Your Head: How the Pavlovian System Sculpts Goal-Directed Choices by Pruning Decision Trees

When planning a series of actions, it is usually infeasible to consider all potential future sequences; instead, one must prune the decision tree. Provably optimal pruning is, however, still computationally ruinous and the specific approximations humans employ remain unknown. We designed a new sequential reinforcement-based task and showed that human subjects adopted a simple pruning strategy: during mental evaluation of a sequence of choices, they curtailed any further evaluation of a sequence as soon as they encountered a large loss. This pruning strategy was Pavlovian: it was reflexively evoked by large losses and persisted even when overwhelmingly counterproductive. It was also evident above and beyond loss aversion. We found that the tendency towards Pavlovian pruning was selectively predicted by the degree to which subjects exhibited sub-clinical mood disturbance, in accordance with theories that ascribe Pavlovian behavioural inhibition, via serotonin, a role in mood disorders. We conclude that Pavlovian behavioural inhibition shapes highly flexible, goal-directed choices in a manner that may be important for theories of decision-making in mood disorders

Similar Neural Activity during Fear and Disgust in the Rat Basolateral Amygdala

Much research has focused on how the amygdala processes individual affects, yet little is known about how multiple types of positive and negative affects are encoded relative to one another at the single-cell level. In particular, it is unclear whether different negative affects, such as fear and disgust, are encoded more similarly than negative and positive affects, such as fear and pleasure. Here we test the hypothesis that the basolateral nucleus of the amygdala (BLA), a region known to be important for learned fear and other affects, encodes affective valence by comparing neuronal activity in the BLA during a conditioned fear stimulus (fear CS) with activity during intraoral delivery of an aversive fluid that induces a disgust response and a rewarding fluid that induces a hedonic response. Consistent with the hypothesis, neuronal activity during the fear CS and aversive fluid infusion, but not during the fear CS and rewarding fluid infusion, was more similar than expected by chance. We also found that the greater similarity in activity during the fear- and disgust-eliciting stimuli was specific to a subpopulation of cells and a limited window of time. Our results suggest that a subpopulation of BLA neurons encodes affective valence during learned fear, and furthermore, within this subpopulation, different negative affects are encoded more similarly than negative and positive affects in a time-specific manner

Neglected diseases of neglected populations: Thinking to reshape the determinants of health in Latin America and the Caribbean

BACKGROUND: People living in poverty throughout the developing world are heavily burdened with neglected communicable diseases and often marginalized by the health sector. These diseases are currently referred to as Neglected Diseases of Neglected Populations. The neglected diseases create social and financial burdens to the individual, the family, the community, and the nation. DISCUSSION: Numerous studies of successful individual interventions to manage communicable disease determinants in various types of communities have been published, but few have applied multiple interventions in an integrated, coordinated manner. We have identified a series of successful interventions and developed three hypothetical scenarios where such interventions could be applied in an integrated, multi-disease, inter-programmatic, and/or inter-sectoral approach for prevention and control of neglected diseases in three different populations: a slum, an indigenous community, and a city with a mix of populations. SUMMARY: The objective of this paper is to identify new opportunities to address neglected diseases, improve community health and promote sustainable development in neglected populations by highlighting examples of key risk and protective factors for neglected diseases which can be managed and implemented through multi-disease-based, integrated, inter-programmatic, and/or inter-sectoral approaches. Based on a literature review, analysis and development of scenarios we visualize how multiple interventions could manage multiple disease problems and propose these as possible strategies to be tested. We seek to stimulate intra- and inter-sectoral dialogue which will help in the construction of new strategies for neglected diseases (particularly for the parasitic diseases) which could benefit the poor and marginalized based on the principle of sustainability and understanding of key determinants of health, and lead to the establishment of pilot projects and activities which can contribute to the achievement of the Millennium Development Goals

Global Perspectives on Task Shifting and Task Sharing in Neurosurgery.

BACKGROUND: Neurosurgical task shifting and task sharing (TS/S), delegating clinical care to non-neurosurgeons, is ongoing in many hospital systems in which neurosurgeons are scarce. Although TS/S can increase access to treatment, it remains highly controversial. This survey investigated perceptions of neurosurgical TS/S to elucidate whether it is a permissible temporary solution to the global workforce deficit. METHODS: The survey was distributed to a convenience sample of individuals providing neurosurgical care. A digital survey link was distributed through electronic mailing lists of continental neurosurgical societies and various collectives, conference announcements, and social media platforms (July 2018-January 2019). Data were analyzed by descriptive statistics and univariate regression of Likert Scale scores. RESULTS: Survey respondents represented 105 of 194 World Health Organization member countries (54.1%; 391 respondents, 162 from high-income countries and 229 from low- and middle-income countries [LMICs]). The most agreed on statement was that task sharing is preferred to task shifting. There was broad consensus that both task shifting and task sharing should require competency-based evaluation, standardized training endorsed by governing organizations, and maintenance of certification. When perspectives were stratified by income class, LMICs were significantly more likely to agree that task shifting is professionally disruptive to traditional training, task sharing should be a priority where human resources are scarce, and to call for additional TS/S regulation, such as certification and formal consultation with a neurosurgeon (in person or electronic/telemedicine). CONCLUSIONS: Both LMIC and high-income countries agreed that task sharing should be prioritized over task shifting and that additional recommendations and regulations could enhance care. These data invite future discussions on policy and training programs

An Animal Model of Emotional Blunting in Schizophrenia

Schizophrenia is often associated with emotional blunting—the diminished ability to respond to emotionally salient stimuli—particularly those stimuli representative of negative emotional states, such as fear. This disturbance may stem from dysfunction of the amygdala, a brain region involved in fear processing. The present article describes a novel animal model of emotional blunting in schizophrenia. This model involves interfering with normal fear processing (classical conditioning) in rats by means of acute ketamine administration. We confirm, in a series of experiments comprised of cFos staining, behavioral analysis and neurochemical determinations, that ketamine interferes with the behavioral expression of fear and with normal fear processing in the amygdala and related brain regions. We further show that the atypical antipsychotic drug clozapine, but not the typical antipsychotic haloperidol nor an experimental glutamate receptor 2/3 agonist, inhibits ketamine's effects and retains normal fear processing in the amygdala at a neurochemical level, despite the observation that fear-related behavior is still inhibited due to ketamine administration. Our results suggest that the relative resistance of emotional blunting to drug treatment may be partially due to an inability of conventional therapies to target the multiple anatomical and functional brain systems involved in emotional processing. A conceptual model reconciling our findings in terms of neurochemistry and behavior is postulated and discussed

Quantifying Individual Variation in the Propensity to Attribute Incentive Salience to Reward Cues

If reward-associated cues acquire the properties of incentive stimuli they can come to powerfully control behavior, and potentially promote maladaptive behavior. Pavlovian incentive stimuli are defined as stimuli that have three fundamental properties: they are attractive, they are themselves desired, and they can spur instrumental actions. We have found, however, that there is considerable individual variation in the extent to which animals attribute Pavlovian incentive motivational properties (“incentive salience”) to reward cues. The purpose of this paper was to develop criteria for identifying and classifying individuals based on their propensity to attribute incentive salience to reward cues. To do this, we conducted a meta-analysis of a large sample of rats (N = 1,878) subjected to a classic Pavlovian conditioning procedure. We then used the propensity of animals to approach a cue predictive of reward (one index of the extent to which the cue was attributed with incentive salience), to characterize two behavioral phenotypes in this population: animals that approached the cue (“sign-trackers”) vs. others that approached the location of reward delivery (“goal-trackers”). This variation in Pavlovian approach behavior predicted other behavioral indices of the propensity to attribute incentive salience to reward cues. Thus, the procedures reported here should be useful for making comparisons across studies and for assessing individual variation in incentive salience attribution in small samples of the population, or even for classifying single animals