Unexpected Rewards Research Articles

Evaluating sex and line differences in successive negative contrast and ethanol consumption using alcohol preferring and high alcohol drinking rats.

The loss of a job or relationship are a couple of examples of unexpected reward loss. Life events, such as these can induce negative emotional reactions (e.g., anxiety and stress), which have been associated with increased alcohol consumption and in turn, an increased risk of developing an alcohol use disorder (AUD). The present study analyzed consummatory successive negative contrast (SNC) for the first time in alcohol preferring (P) and high alcohol drinking (HAD) rats that have been selectively bred to consume high amounts of ethanol. Following reward loss, animals were given free access to ethanol to determine whether consumption would increase as a possible indication of any negative emotional reaction. Male and female P and HAD rats were split into shifted and unshifted groups receiving either 32% or 4% sucrose for 5 min across 10 preshift days. Subsequently, all animals received 4% sucrose for four postshift days, across which, animals were given access to 20% ethanol for 30 min after access to 4% sucrose. Male and female P rats demonstrated a longer contrast effect than HAD rats, indicated by a longer recovery time following the downshift in reward. Conversely, HAD males did not demonstrate a contrast effect following this downshift in reward unlike their female counterparts. Surprisingly, P rats who experienced a loss of reward consumed significantly less ethanol than animals who did not. Lastly, individual measure of contrast size, or shift ratio, was significantly associated with greater ethanol consumption in HAD males only, who did not display a contrast effect. These data indicate different reactivity to SNC between these two lines and sexes, suggesting different genetic and sex-related mechanisms underlying sensitivity to an unexpected loss of reward and ethanol consumption following this loss.

Reward-driven cerebellar climbing fiber activity influences both neural and behavioral learning.

The cerebellum plays a key role in motor coordination and learning. In contrast with classical supervised learning models, recent work has revealed that CFs can signal reward-predictive information in some behaviors. This raises the question of whether CFs may also operate according to principles similar to those described by reinforcement learning models. To test how CFs operate during reward-guided behavior, and evaluate the role of reward-related CF activity in learning, we have measured CF responses in Purkinje cells of the lateral cerebellum during a Pavlovian task using 2-photon calcium imaging. Specifically, we have performed multi-stimulus experiments to determine whether CF activity meets the requirements of a reward prediction error (rPE) signal for transfer from an unexpected reward to a reward-predictive cue. We find that once CF activity is transferred to a conditioned stimulus, and there is no longer a response to reward, CFs cannot generate learned responses to a second conditioned stimulus that carries the same reward prediction. In addition, by expressing the inhibitory opsin GtACR2 in neurons of the inferior olive, and optically inhibiting these neurons across behavioral training at the time of unexpected reward, we find that the transfer of CF signals to the conditioned stimulus is impaired. Moreover, this optogenetic inhibition also impairs learning, resulting in a deficit in anticipatory lick timing. Together, these results indicate that CF signals can exhibit several characteristics in common with rPEs during reinforcement learning, and that the cerebellum can harness these learning signals to generate accurately timed motor behavior.

Frustrative nonreward: Detailed c-Fos expression patterns in the amygdala after consummatory successive negative contrast

The amygdala has been implicated in frustrative nonreward induced by unexpected reward downshifts, using paradigms like consummatory successive negative contrast (cSNC). However, existing evidence comes from experiments involving the central and basolateral nuclei on a broad level. Moreover, whether the amygdala’s involvement in reward downshift requires a cSNC effect (i.e., greater suppression in downshifted animals than in unshifted controls) or just consummatory suppression without a cSNC effect, remains unclear. Three groups were exposed to (1) a large reward disparity leading to a cSNC effect (32-to-2% sucrose), (2) a small reward disparity involving consummatory suppression in the absence of a cSNC effect (8-to-2% sucrose), and (3) an unshifted control (2% sucrose). Brains obtained after the first reward downshift session were processed for c-Fos expression, a protein often used as a marker for neural activation. c-Fos-positive cells were counted in the anterior, medial, and posterior portions (A/P axis) of ten regions of the rat basolateral, central, and medial amygdala. c-Fos expression was higher in 32-to-2% sucrose downshift animals than in the other two groups in four regions: the anterior and the medial lateral basal amygdala, the medial capsular central amygdala, and the anterior anterio-ventral medial amygdala. None of the areas exhibited differential c-Fos expression between the 8-to-2% sucrose downshift and the unshifted conditions. Thus, amygdala activation requires exposure to a substantial reward disparity. This approach has identified, for the first time, specific amygdala areas relevant to understand the cSNC effect, suggesting follow-up experiments aimed at testing the function of these regions in reward downshift.

Predictions about reward outcomes in rhesus monkeys.

Human infants and nonhuman animals respond to surprising events by looking longer at unexpected than expected situations. These looking responses provide core cognitive evidence that nonverbal minds make predictions about possible outcomes and detect when these predictions fail to match reality. We propose that this phenomenon has crucial parallels with the processes of reward prediction error, indexing the difference between expected and actual reward outcomes. Most work on reward prediction errors to date involves neurobiological techniques that cannot be implemented in many relevant populations, so we developed a novel behavioral task to assess monkeys' predictions about reward outcomes using looking time responses. In Study 1, we tested how semi-free-ranging monkeys (n = 210) responded to positive error (more rewards than expected), negative error (less rewards than expected), and a number control. We found that monkeys looked longer at a given reward when it was unexpectedly large or small, compared to when the same quantity was expected. In Study 2, we compared responses in the positive error condition in monkeys ranging from infancy to old age (n = 363), to assess lifespan changes in sensitivity to reward predictions. We found that adolescent monkeys showed heightened responses to unexpected rewards, similar to patterns seen in humans, but showed no changes during aging. These results suggest that monkeys' looking responses can be used to track their predictions about rewards, and that monkeys share some developmental signatures of reward sensitivity with humans, providing a new approach to access cognitive processes underlying reward-based decision making. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Standardized patients’ experiences of portraying characters in difficult communication scenarios: Narrative inquiry

Background There are limited studies that explored the preparation and challenges faced by standardized patients (SPs) in portraying characters in difficult communication scenarios, and the strategies used to overcome these challenges. The purpose of this study was to understand the experience of SPs in interpreting difficult communication situations and the learning needs of performing similar scenarios. And it allows the researchers to explore the meaning, beliefs, values, and aspiration associated with their role as SPs. The findings could shade light on the significance of their experiences and provide valuable insights for the development of future SP training programs. Methods The design of this study is framed by a narrative inquiry, using semi-structured guidelines to conduct in-depth interviews with 11 SPs who have participated in the performances of difficult communication situations. Research data were analyzed by Polkinghorne narrative analysis, and Riessman’s four criteria were used to establish rigor. Results Analysis revealed the following five themes: scenarios to real life connections, process of preparing for a performance, methods to detach from character, obtaining unexpected rewards, and needs for performance training. There are two to three subthemes that are subsumed under each theme. Conclusions To strengthen training in difficult communication for healthcare professionals, the use of SPs to interpret challenging difficult communication scenarios will continue to increase. Educators need to ensure that SPs are fully prepared physically and emotionally before, during and after their performance. Offering of continuing education and training in feedback techniques are crucial to extend the tenure of SPs, reduce their frustration, prevent attrition, and ultimately, reduce training costs. In the future, SP training should also include detachment and feedback techniques to alleviate SPs’ stress.

Open field activity is linked to, but is not affected by, the rate of recovery from reward downshift in female Wistar rats

Frustration is an aversive emotion triggered by unexpected reward downshifts. Using the consummatory successive negative contrast (cSNC) task, a 32-to-2% sucrose downshift was shown to initially suppress consummatory behavior. Such suppression was followed by behavioral recovery over subsequent sessions. Individual differences often emerge in the rate of recovery after the initial consummatory suppression. These experiments were designed to determine whether a stable trait of sensation/novelty seeking (SNS) is related to such individual differences in recovery from reward downshift. In Experiment 1, open field (OF) activity in the central area served as a measure of SNS. A week later, animals received training in the cSNC task involving ten 5-min sessions of access to 32% sucrose followed by four sessions of access to 2% sucrose. Higher OF activity predicted greater consummatory suppression after downshift, but a steeper recovery rate across downshifted sessions. Controls not exposed to the OF showed cSNC, but downshifted animals performed at equivalent levels whether they had OF exposure or not. In Experiment 2, after a 32-to-2% sucrose downshift, fast vs. slow recovery animals displayed similar levels of central activity in the OF. In Experiment 3, animals exhibited similar levels of central activity whether after a 32-to-2% or an 8-to-2% sucrose downshift. In both experiments, activity levels were similar whether immediately after session 12 (onset of recovery) or after session 15 (fully recovered). These results suggest that individual variations in recovery from reward downshift are correlated with levels of SNS as a stable trait.

Ketamine retards recovery from reward downshift and supports conditioned taste aversion

Ketamine is a noncompetitive N-methyl-d-aspartate (NMDA) receptor antagonist with antidepressant, anxiolytic, and memory effects in clinical and preclinical studies. The present studies investigated the behavioral effects of ketamine in animals exposed to a consummatory successive negative contrast (cSNC) task involving unexpected reward downshift, negative emotion (frustration), and aversive memory. Food-restricted male rats had 5-min access to 32 % sucrose in each of 10 preshift sessions followed by 4 % sucrose in 4 postshift sessions. Unshifted controls had access to 4 % sucrose during all 14 sessions. Ketamine (10 mg/kg, ip) was injected 30 min before sessions 11 and 12 (Experiment 1) or immediately after session 11 (Experiment 3). The results showed that both pre- and postdownshift session injection of ketamine increased consummatory suppression, as Group 32-4/Ket exhibited lower sucrose intake than Groups 32-4/Sal, 4-4/Ket, and 4-4/Sal. These effects extended beyond the day(s) of injection. Experiments 2 and 4 showed that the same dose, route of administration, and time of injection induced significant conditioned taste aversion to 4 % sucrose, in the absence of reward downshift. These data suggest that ketamine induces an aversive state that may summate with frustration induced by reward downshift in the cSNC task and also support a conditioned taste aversion to 4 % sucrose in the absence of reward downshift. Implications for these and other experiments involving pre- and postsession administration of ketamine are discussed.

Striatal Dopamine Signals and Reward Learning.

We are constantly bombarded by sensory information and constantly making decisions on how to act. In order to optimally adapt behavior, we must judge which sequences of sensory inputs and actions lead to successful outcomes in specific circumstances. Neuronal circuits of the basal ganglia have been strongly implicated in action selection, as well as the learning and execution of goal-directed behaviors, with accumulating evidence supporting the hypothesis that midbrain dopamine neurons might encode a reward signal useful for learning. Here, we review evidence suggesting that midbrain dopaminergic neurons signal reward prediction error, driving synaptic plasticity in the striatum underlying learning. We focus on phasic increases in action potential firing of midbrain dopamine neurons in response to unexpected rewards. These dopamine neurons prominently innervate the dorsal and ventral striatum. In the striatum, the released dopamine binds to dopamine receptors, where it regulates the plasticity of glutamatergic synapses. The increase of striatal dopamine accompanying an unexpected reward activates dopamine type 1 receptors (D1Rs) initiating a signaling cascade that promotes long-term potentiation of recently active glutamatergic input onto striatonigral neurons. Sensorimotor-evoked glutamatergic input, which is active immediately before reward delivery will thus be strengthened onto neurons in the striatum expressing D1Rs. In turn, these neurons cause disinhibition of brainstem motor centers and disinhibition of the motor thalamus, thus promoting motor output to reinforce rewarded stimulus-action outcomes. Although many details of the hypothesis need further investigation, altogether, it seems likely that dopamine signals in the striatum might underlie important aspects of goal-directed reward-based learning.

Cholinergic Reinforcement Signaling Is Impaired by Amyloidosis Prior to Its Synaptic Loss.

Alzheimer's disease (AD) is associated with amyloidosis and dysfunction of the cholinergic system, which is crucial for learning and memory. However, the nature of acetylcholine signaling within regions of cholinergic-dependent plasticity and how it changes with experience is poorly understood, much less the impact of amyloidosis on this signaling. Therefore, we optically measure the release profile of acetylcholine to unexpected, predicted, and predictive events in visual cortex (VC)-a site of known cholinergic-dependent plasticity-in a preclinical mouse model of AD that develops amyloidosis. We find that acetylcholine exhibits reinforcement signaling qualities, reporting behaviorally relevant outcomes and displaying release profiles to predictive and predicted events that change as a consequence of experience. We identify three stages of amyloidosis occurring before the degeneration of cholinergic synapses within VC and observe that cholinergic responses in amyloid-bearing mice become impaired over these stages, diverging progressively from age- and sex-matched littermate controls. In particular, amyloidosis degrades the signaling of unexpected rewards and punishments, and attenuates the experience-dependent (1) increase of cholinergic responses to outcome predictive visual cues, and (2) decrease of cholinergic responses to predicted outcomes. Hyperactive spontaneous acetylcholine release occurring transiently at the onset of impaired cholinergic signaling is also observed, further implicating disrupted cholinergic activity as an early functional biomarker in AD. Our findings suggest that acetylcholine acts as a reinforcement signal that is impaired by amyloidosis before pathologic degeneration of the cholinergic system, providing a deeper understanding of the effects of amyloidosis on acetylcholine signaling and informing future interventions for AD.SIGNIFICANCE STATEMENT The cholinergic system is especially vulnerable to the neurotoxic effects of amyloidosis, a hallmark of Alzheimer's disease (AD). Though amyloid-induced cholinergic synaptic loss is thought in part to account for learning and memory impairments in AD, little is known regarding how amyloid impacts signaling of the cholinergic system before its anatomic degeneration. Optical measurement of acetylcholine (ACh) release in a mouse model of AD that develops amyloidosis reveals that ACh signals reinforcement and outcome prediction that is disrupted by amyloidosis before cholinergic degeneration. These observations have important scientific and clinical implications: they implicate ACh signaling as an early functional biomarker, provide a deeper understanding of the action of acetylcholine, and inform on when and how intervention may best ameliorate cognitive decline in AD.

Unique functional responses differentially map onto genetic subtypes of dopamine neurons

Dopamine neurons are characterized by their response to unexpected rewards, but they also fire during movement and aversive stimuli. Dopamine neuron diversity has been observed based on molecular expression profiles; however, whether different functions map onto such genetic subtypes remains unclear. In this study, we established that three genetic dopamine neuron subtypes within the substantia nigra pars compacta, characterized by the expression of Slc17a6 (Vglut2), Calb1 and Anxa1, each have a unique set of responses to rewards, aversive stimuli and accelerations and decelerations, and these signaling patterns are highly correlated between somas and axons within subtypes. Remarkably, reward responses were almost entirely absent in the Anxa1+ subtype, which instead displayed acceleration-correlated signaling. Our findings establish a connection between functional and genetic dopamine neuron subtypes and demonstrate that molecular expression patterns can serve as a common framework to dissect dopaminergic functions.

Dopamine in the dorsal bed nucleus of stria terminalis signals Pavlovian sign-tracking and reward violations.

Midbrain and striatal dopamine signals have been extremely well characterized over the past several decades, yet novel dopamine signals and functions in reward learning and motivation continue to emerge. A similar characterization of real-time sub-second dopamine signals in areas outside of the striatum has been limited. Recent advances in fluorescent sensor technology and fiber photometry permit the measurement of dopamine binding correlates, which can divulge basic functions of dopamine signaling in non-striatal dopamine terminal regions, like the dorsal bed nucleus of the stria terminalis (dBNST). Here, we record GRABDA signals in the dBNST during a Pavlovian lever autoshaping task. We observe greater Pavlovian cue-evoked dBNST GRABDA signals in sign-tracking (ST) compared to goal-tracking/intermediate (GT/INT) rats and the magnitude of cue-evoked dBNST GRABDA signals decreases immediately following reinforcer-specific satiety. When we deliver unexpected rewards or omit expected rewards, we find that dBNST dopamine signals encode bidirectional reward prediction errors in GT/INT rats, but only positive prediction errors in ST rats. Since sign- and goal-tracking approach strategies are associated with distinct drug relapse vulnerabilities, we examined the effects of experimenter-administered fentanyl on dBNST dopamine associative encoding. Systemic fentanyl injections do not disrupt cue discrimination but generally potentiate dBNST dopamine signals. These results reveal multiple dBNST dopamine correlates of learning and motivation that depend on the Pavlovian approach strategy employed.

Dopamine error signal to actively cope with lack of expected reward

To obtain more of a particular uncertain reward, animals must learn to actively overcome the lack of reward and adjust behavior to obtain it again. The neural mechanisms underlying such coping with reward omission remain unclear. Here, we developed a task in rats to monitor active behavioral switch toward the next reward after no reward. We found that some dopamine neurons in the ventral tegmental area exhibited increased responses to unexpected reward omission and decreased responses to unexpected reward, following the opposite responses of the well-known dopamine neurons that signal reward prediction error (RPE). The dopamine increase reflected in the nucleus accumbens correlated with behavioral adjustment to actively overcome unexpected no reward. We propose that these responses signal error to actively cope with lack of expected reward. The dopamine error signal thus cooperates with the RPE signal, enabling adaptive and robust pursuit of uncertain reward to ultimately obtain more reward.

Slow-rising and fast-falling dopaminergic dynamics jointly adjust negative prediction error in the ventral striatum.

The greater the reward expectations are, the more different the brain's physiological response will be. Although it is well-documented that better-than-expected outcomes are encoded quantitatively via midbrain dopaminergic (DA) activity, it has been less addressed experimentally whether worse-than-expected outcomes are expressed quantitatively as well. We show that larger reward expectations upon unexpected reward omissions are associated with the preceding slower rise and following larger decrease (DA dip) in the DA concentration at the ventral striatum of mice. We set up a lever press task on a fixed ratio (FR) schedule requiring five lever presses as an effort for a food reward (FR5). The mice occasionally checked the food magazine without a reward before completing the task. The percentage of this premature magazine entry (PME) increased as the number of lever presses approached five, showing rising expectations with increasing proximity to task completion, and hence greater reward expectations. Fibre photometry of extracellular DA dynamics in the ventral striatum using a fluorescent protein (genetically encoded GPCR activation-based DA sensor: GRABDA2m ) revealed that the slow increase and fast decrease in DA levels around PMEs were correlated with the PME percentage, demonstrating a monotonic relationship between the DA dip amplitude and degree of expectations. Computational modelling of the lever press task implementing temporal difference errors and state transitions replicated the observed correlation between the PME frequency and DA dip amplitude in the FR5 task. Taken together, these findings indicate that the DA dip amplitude represents the degree of reward expectations monotonically, which may guide behavioural adjustment.

Choice-selective sequences dominate in cortical relative to thalamic inputs to NAc to support reinforcement learning.

SUMMARYHow are actions linked with subsequent outcomes to guide choices? The nucleus accumbens, which is implicated in this process, receives glutamatergic inputs from the prelimbic cortex and midline regions of the thalamus. However, little is known about whether and how representations differ across these input pathways. By comparing these inputs during a reinforcement learning task in mice, we discovered that prelimbic cortical inputs preferentially represent actions and choices, whereas midline thalamic inputs preferentially represent cues. Choice-selective activity in the prelimbic cortical inputs is organized in sequences that persist beyond the outcome. Through computational modeling, we demonstrate that these sequences can support the neural implementation of reinforcement-learning algorithms, in both a circuit model based on synaptic plasticity and one based on neural dynamics. Finally, we test and confirm a prediction of our circuit models by direct manipulation of nucleus accumbens input neurons.

Effects of theta transcranial alternating current stimulation (tACS) on exploration and exploitation during uncertain decision-making

Exploring ones surroundings may yield unexpected rewards, but is associated with uncertainty and risk. Alternatively, exploitation of certain outcomes is related to low risk, yet potentially better outcomes remain unexamined. As such, risk-taking behavior depends on perceived uncertainty and a trade-off between exploration-exploitation. Previously, it has been suggested that risk-taking may relate to theta activity in the prefrontal cortex. Furthermore, previous studies hinted at a relationship between a right-hemispheric bias in frontal theta asymmetry and risky behavior. In the present double-blind sham-controlled within-subject study, we applied bifrontal transcranial alternating current stimulation (tACS) at the theta frequency (5 Hz) on eighteen healthy volunteers during a gambling task. Two tACS montages with either left-right or posterior-anterior current flow were employed at an intensity of 1 mA. Results showed that, compared to sham, theta tACS increased perceived uncertainty irrespective of current flow direction. Despite this observation, no direct effect of tACS on exploration behavior and general risk-taking was observed. Furthermore, frontal theta asymmetry was more right-hemispherically biased after posterior-anterior tACS, compared to sham. Finally, we used electric field simulation to identify which regions were targeted by the tACS montages as an overlap in regions may explain why the two montages resulted in comparable outcomes. Our findings provide a first step towards understanding the relationship between frontal theta oscillations and different features of risk-taking.

Incentive disengagement and the adaptive significance of frustrative nonreward.

Mammals respond to an unexpected reward omission or reduction with a variety of behavioral and physiological responses consistent with an aversive emotion traditionally called frustrative nonreward. This review focuses on two aspects of frustrative nonreward, namely (1) the evidence for an aversive emotional state activated by the surprising omission or reduction of a rewarding outcome, and (2) the adaptive value of frustration. Frustrative nonreward has been mainly studied in terms of its mechanisms, across development in rats and across vertebrate species in comparative research. However, its adaptive function remains obscure. Following Domjan's approach to animal learning, this article explores a specific adaptive function hypothesis of frustrative nonreward called the incentive disengagement hypothesis. According to this hypothesis, the adaptive function of frustrative nonreward is to break an attachment to a site, situation, or stimulus that no longer yields appetitive resources (especially food and fluids) to promote the search for rewards in alternative locations. This function is of particular relevance given that mammals are especially vulnerable to reward loss due to their high metabolic rate and the energy demands of their relatively large brain.

The effect of unexpected rewards on decision making in cuttlefish

Despite numerous studies demonstrating the cognitive ability of cephalopods, there is currently no study showing an emotion-like behavior in this group of animals. To examine whether cuttlefish have different internal states, we developed a behavioral paradigm to assess if prior surprised events are able to alter the choice made by cuttlefish. By presenting unexpected food rewards to cuttlefish before the test, we investigated whether the reaction time of choosing between two shrimps, an intuitive response toward the prey without previous learning, at three different levels of discriminative tests (easy, difficult, and ambiguous), are different compared to the one without an unexpected reward. This behavioral paradigm serves to demonstrate whether cuttlefish are aware of ambiguous situations, and their choice outcome and reaction time are dependent of their internal states. The results show that the response latency was significantly shortened in the difficult and ambiguous tests when choosing from two shrimps that are either moderately different in size or similar sizes, respectively, when cuttlefish have received unexpected rewards before the test. These results were compared with tests during which the cuttlefish did not receive any reward in advance. Furthermore, this shortening of latency did not result in a difference in choice outcome during the difficult and ambiguous tests. Interestingly, even when cuttlefish have obtained the expected food rewards or simply made tentacular strike without prey capture each time before test, these prior experiences were sufficient to shorten the response latency in the difficult and ambiguous tests. However, different from the result of unexpected rewards, food consumption alone or prey capture failure did affect the choice outcome during the simple and difficult tests. Taken together, our findings suggest that pre-test treatments of unexpected and expected rewards or simply unsuccessful visual attack seem to induce cuttlefish to adopt different foraging behaviors. This context dependent decision making suggests that cuttlefish’s foraging strategies are influenced by the previously surprised event and their internal states. It also shows a speed-accuracy tradeoff in difficult and ambiguous situations when foraging for prey. This observation may lead to a future investigation of the presence of emotional state in cephalopods.

All-fiber-transmission photometry for simultaneous optogenetic stimulation and multi-color neuronal activity recording

Manipulating and real-time monitoring of neuronal activities with cell-type specificity and precise spatiotemporal resolution during animal behavior are fundamental technologies for exploring the functional connectivity, information transmission, and physiological functions of neural circuits<italic>in vivo</italic>. However, current techniques for optogenetic stimulation and neuronal activity recording mostly operate independently. Here, we report an all-fiber-transmission photometry system for simultaneous optogenetic manipulation and multi-color recording of neuronal activities and the neurotransmitter release in a freely moving animal. We have designed and manufactured a wavelength-independent multi-branch fiber bundle to enable simultaneous optogenetic manipulation and multi-color recording at different wavelengths. Further, we combine a laser of narrow linewidth with the lock-in amplification method to suppress the optogenetic stimulation-induced artifacts and channel crosstalk. We show that the collection efficiency of our system outperforms a traditional epi-fluorescence system. Further, we demonstrate successful recording of dynamic dopamine (DA) responses to unexpected rewards in the nucleus accumbens (NAc) in a freely moving mouse. We also show simultaneous dual-color recording of neuronal Ca²⁺ signals and DA dynamics in the NAc upon delivering an unexpected reward and the simultaneous optogenetic activating at dopaminergic terminals in the same location. Thus, our multi-function fiber photometry system provides a compatible, efficient, and flexible solution for neuroscientists to study neural circuits and neurological diseases.

The critical balance between dopamine D2 receptor and RGS for the sensitive detection of a transient decay in dopamine signal.

In behavioral learning, reward-related events are encoded into phasic dopamine (DA) signals in the brain. In particular, unexpected reward omission leads to a phasic decrease in DA (DA dip) in the striatum, which triggers long-term potentiation (LTP) in DA D2 receptor (D2R)-expressing spiny-projection neurons (D2 SPNs). While this LTP is required for reward discrimination, it is unclear how such a short DA-dip signal (0.5–2 s) is transferred through intracellular signaling to the coincidence detector, adenylate cyclase (AC). In the present study, we built a computational model of D2 signaling to determine conditions for the DA-dip detection. The DA dip can be detected only if the basal DA signal sufficiently inhibits AC, and the DA-dip signal sufficiently disinhibits AC. We found that those two requirements were simultaneously satisfied only if two key molecules, D2R and regulators of G protein signaling (RGS) were balanced within a certain range; this balance has indeed been observed in experimental studies. We also found that high level of RGS was required for the detection of a 0.5-s short DA dip, and the analytical solutions for these requirements confirmed their universality. The imbalance between D2R and RGS is associated with schizophrenia and DYT1 dystonia, both of which are accompanied by abnormal striatal LTP. Our simulations suggest that D2 SPNs in patients with schizophrenia and DYT1 dystonia cannot detect short DA dips. We finally discussed that such psychiatric and movement disorders can be understood in terms of the imbalance between D2R and RGS.

Subjective well-being among street mothers community

The goal of this research was to understand the subjective well-being of mothers who work in the streets. This qualitative phenomenological study collected data using a semi-structured interview. Data were collected from six street mothers aged 18-40 years living in the dense residence of Kali Code, Karanganyar, Brontokusuman, Mergangsan, and Yogyakarta, Indonesia. The content analysis was used in this research, and the results showed that street mothers were satisfied with their current lives. Some of the reasons for their satisfaction include having a place to stay, gathering with their family every day, having a job, having independent earning, supporting children's education, and meeting their family's needs. This study also found that life satisfaction was associated with feeling satisfied with the self, family life, health, job, and community environment. Furthermore, participants expressed positive affect in the form of happiness when their job and earnings were good when gathering with the family or neighbors when the family is in harmony. The children are obedient when they can meet the needs of the children when they receive unexpected rewards. In contrast, the participants experienced negative affect in the form of guilt when they were unable to make the family happy, and disappointed when daily earnings were small. They were sad when children were not obedient, angry, and disappointed about living conditions and worried, anxious, and afraid about the workplace conditions.