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ELife Sep 2023Tastes typically evoke innate behavioral responses that can be broadly categorized as acceptance or rejection. However, research in indicates that taste responses also...
Tastes typically evoke innate behavioral responses that can be broadly categorized as acceptance or rejection. However, research in indicates that taste responses also exhibit plasticity through experience-dependent changes in mushroom body circuits. In this study, we develop a novel taste learning paradigm using closed-loop optogenetics. We find that appetitive and aversive taste memories can be formed by pairing gustatory stimuli with optogenetic activation of sensory neurons or dopaminergic neurons encoding reward or punishment. As with olfactory memories, distinct dopaminergic subpopulations drive the parallel formation of short- and long-term appetitive memories. Long-term memories are protein synthesis-dependent and have energetic requirements that are satisfied by a variety of caloric food sources or by direct stimulation of MB-MP1 dopaminergic neurons. Our paradigm affords new opportunities to probe plasticity mechanisms within the taste system and understand the extent to which taste responses depend on experience.
PubMed: 37750673
DOI: 10.7554/eLife.81535 -
The Journal of Neuroscience : the... Dec 2023Dopamine neurons (DANs) are extensively studied in the context of associative learning, in both vertebrates and invertebrates. In the acquisition of male and female...
Dopamine neurons (DANs) are extensively studied in the context of associative learning, in both vertebrates and invertebrates. In the acquisition of male and female olfactory memory, the PAM cluster of DANs provides the reward signal, and the PPL1 cluster of DANs sends the punishment signal to the Kenyon cells (KCs) of mushroom bodies, the center for memory formation. However, thermo-genetical activation of the PPL1 DANs after memory acquisition impaired aversive memory, and that of the PAM DANs impaired appetitive memory. We demonstrate that the knockdown of glutamate decarboxylase, which catalyzes glutamate conversion to GABA in PAM DANs, potentiated the appetitive memory. In addition, the knockdown of glutamate transporter in PPL1 DANs potentiated aversive memory, suggesting that GABA and glutamate co-transmitters act in an inhibitory manner in olfactory memory formation. We also found that, in γKCs, the Rdl receptor for GABA and the mGluR DmGluRA mediate the inhibition. Although multiple-spaced training is required to form long-term aversive memory, a single cycle of training was sufficient to develop long-term memory when the glutamate transporter was knocked down, in even a single subset of PPL1 DANs. Our results suggest that the mGluR signaling pathway may set a threshold for memory acquisition to allow the organisms' behaviors to adapt to changing physiological conditions and environments. In the acquisition of olfactory memory in , the PAM cluster of dopamine neurons (DANs) mediates the reward signal, while the PPL1 cluster of DANs conveys the punishment signal to the Kenyon cells of the mushroom bodies, which serve as the center for memory formation. We found that GABA co-transmitters in the PAM DANs and glutamate co-transmitters in the PPL1 DANs inhibit olfactory memory formation. Our findings demonstrate that long-term memory acquisition, which typically necessitates multiple-spaced training sessions to establish aversive memory, can be triggered with a single training cycle in cases where the glutamate co-transmission is inhibited, even within a single subset of PPL1 DANs, suggesting that the glutamate co-transmission may modulate the threshold for memory acquisition.
Topics: Animals; Female; Male; Drosophila; Smell; Dopamine; Dopaminergic Neurons; Penicillins; Glutamates; Amino Acid Transport System X-AG; gamma-Aminobutyric Acid; Mushroom Bodies; Drosophila melanogaster
PubMed: 37429719
DOI: 10.1523/JNEUROSCI.2152-22.2023 -
Mu Opioid Receptor-Positive Neurons in the Dorsal Raphe Nucleus Are Impaired by Morphine Abstinence.Biological Psychiatry Dec 2023Chronic opioid exposure leads to hedonic deficits and enhanced vulnerability to addiction, which are observed and even strengthen after a period of abstinence, but the...
BACKGROUND
Chronic opioid exposure leads to hedonic deficits and enhanced vulnerability to addiction, which are observed and even strengthen after a period of abstinence, but the underlying circuit mechanisms are poorly understood. In this study, using both molecular and behavioral approaches, we tested the hypothesis that neurons expressing mu opioid receptors (MORs) in the dorsal raphe nucleus (DRN) are involved in addiction vulnerability associated with morphine abstinence.
METHODS
MOR-Cre mice were exposed to chronic morphine and then went through spontaneous withdrawal for 4 weeks, a well-established mouse model of morphine abstinence. We studied DRN-MOR neurons of abstinent mice using 1) viral translating ribosome affinity for transcriptome profiling, 2) fiber photometry to measure neuronal activity, and 3) an opto-intracranial self-stimulation paradigm applied to DRN-MOR neurons to assess responses related to addiction vulnerability including persistence to respond, motivation to obtain the stimulation, self-stimulation despite punishment, and cue-induced reinstatement.
RESULTS
DRN-MOR neurons of abstinent animals showed a downregulation of genes involved in ion conductance and MOR-mediated signaling, as well as altered responding to acute morphine. Opto-intracranial self-stimulation data showed that abstinent animals executed more impulsive-like and persistent responses during acquisition and scored higher on addiction-like criteria.
CONCLUSIONS
Our data suggest that protracted abstinence to chronic morphine leads to reduced MOR function in DRN-MOR neurons and abnormal self-stimulation of these neurons. We propose that DRN-MOR neurons have partially lost their reward-facilitating properties, which in turn may lead to increased propensity to perform addiction-related behaviors.
Topics: Mice; Animals; Morphine; Dorsal Raphe Nucleus; Receptors, Opioid, mu; Analgesics, Opioid; Neurons
PubMed: 37393045
DOI: 10.1016/j.biopsych.2023.06.024 -
Assessment Jun 2024Existing research shows that children's responses to rewards and punishments are essential for understanding attention-deficit/hyperactivity disorder, oppositional...
Existing research shows that children's responses to rewards and punishments are essential for understanding attention-deficit/hyperactivity disorder, oppositional defiant disorder, conduct disorder, and callous-unemotional traits. The present study developed the Contingency Response Rating Scale (CRRS) to fulfill the need for a reliable and valid measure of children's contingency response style that is brief, easy to use in applied settings, and provides additional information to existing clinical measures. We examined the psychometric properties of the CRRS in a sample of 196 children (ages 5-12), most of whom were referred to evaluate attention and behavior problems in an outpatient clinic. Using principal axis factoring, we identified five factors: (a) punishment ineffectiveness, (b) reward ineffectiveness, (c) punishment dysregulation, (d) reward dysregulation, and (e) contingency insensitivity. The subscales based on these factors showed acceptable test-retest and internal consistency reliability, and scale intercorrelations varied from low to moderate. The subscales also captured significant variance not explained by child or parent demographics and were associated with measures of psychopathology and impairment. The results provide preliminary evidence that the CRRS may be a helpful tool for assessing reward and punishment sensitivity in children with attention and behavior problems.
PubMed: 38869172
DOI: 10.1177/10731911241256536 -
Scientific Reports Apr 2024In Public Goods Games (PGG), the temptation to free-ride on others' contributions poses a significant threat to the sustainability of cooperative societies. Therefore,...
In Public Goods Games (PGG), the temptation to free-ride on others' contributions poses a significant threat to the sustainability of cooperative societies. Therefore, societies strive to mitigate this through incentive systems, employing rewards and punishments to foster cooperative behavior. Thus, peer punishment, in which cooperators sanction defectors, as well as pool punishment, where a centralized punishment institution executes the punishment, is deeply analyzed in previous works. Although the literature indicates that these methods may enhance cooperation on social dilemmas under particular contexts, there are still open questions, for instance, the structural connection between graduated punishment and the monitoring of public goods games. Our investigation proposes a compulsory PGG framework under Panoptical surveillance. Inspired by Foucault's theories on disciplinary mechanisms and biopower, we present a novel mathematical model that scrutinizes the balance between the severity and scope of punishment to catalyze cooperative behavior. By integrating perspectives from evolutionary game theory and Foucault's theories of power and discipline, this research uncovers the theoretical foundations of mathematical frameworks involved in punishment and discipline structures. We show that well-calibrated punishment and discipline schemes, leveraging the panoptical effect for universal oversight, can effectively mitigate the free-rider dilemma, fostering enhanced cooperation. This interdisciplinary approach not only elucidates the dynamics of cooperation in societal constructs but also underscores the importance of integrating diverse methodologies to address the complexities of fostering cooperative evolution.
Topics: Punishment; Cooperative Behavior; Models, Theoretical; Game Theory; Peer Group
PubMed: 38570552
DOI: 10.1038/s41598-024-57842-0 -
NeuroImage Jul 2023The mesolimbic system and basal forebrain (BF) are implicated in processing rewards and punishment, but their interplay and functional properties of subregions with...
The mesolimbic system and basal forebrain (BF) are implicated in processing rewards and punishment, but their interplay and functional properties of subregions with respect to future social outcomes remain unclear. Therefore, this study investigated regional responses and interregional functional connectivity of the lateral (l), medial (m), and ventral (v) Substantia Nigra (SN), Nucleus Accumbens (NAcc), Nucleus basalis of Meynert (NBM), and Medial Septum/Diagonal Band (MS/DB) during reward and punishment anticipation in a social incentive delay task with neutral, positive, and negative feedback using high-resolution fMRI (1.5mm). Neuroimaging data (n = 36 healthy humans) of the anticipation phase was analyzed using mass-univariate, functional connectivity, and multivariate-pattern analysis. As expected, participants responded faster when anticipating positive and negative compared to neutral social feedback. At the neural level, anticipating social information engaged valence-related and valence-unrelated functional connectivity patterns involving the BF and mesolimbic areas. Precisely, valence-related connectivity between the lSN and NBM was associated with anticipating neutral social feedback, while connectivity between the vSN and NBM was associated with anticipating positive social feedback. A more complex pattern was observed for anticipating negative social feedback, including connectivity between the lSN and MS/DB, lSN and NAcc, as well as mSN and NAcc. To conclude, functional connectivity patterns of the BF and mesolimbic areas signal the anticipation of social feedback depending on their emotional valence. As such, our findings give novel insights into the underlying neural processes of social information processing.
Topics: Humans; Basal Forebrain; Feedback; Nucleus Accumbens; Substantia Nigra; Brain Mapping; Reward; Magnetic Resonance Imaging
PubMed: 37094625
DOI: 10.1016/j.neuroimage.2023.120131 -
The Journal of Neuroscience : the... Nov 2023In mouse primary visual cortex (V1), familiar stimuli evoke significantly altered responses when compared with novel stimuli. This stimulus-selective response plasticity...
In mouse primary visual cortex (V1), familiar stimuli evoke significantly altered responses when compared with novel stimuli. This stimulus-selective response plasticity (SRP) was described originally as an increase in the magnitude of visual evoked potentials (VEPs) elicited in layer 4 (L4) by familiar phase-reversing grating stimuli. SRP is dependent on NMDA receptors (NMDARs) and has been hypothesized to reflect potentiation of thalamocortical (TC) synapses in L4. However, recent evidence indicates that the synaptic modifications that manifest as SRP do not occur on L4 principal cells. To shed light on where and how SRP is induced and expressed in male and female mice, the present study had three related aims: (1) to confirm that NMDAR are required specifically in glutamatergic principal neurons of V1, (2) to investigate the consequences of deleting NMDAR specifically in L6, and (3) to use translaminar electrophysiological recordings to characterize SRP expression in different layers of V1. We find that knock-out (KO) of NMDAR in L6 principal neurons disrupts SRP. Current-source density (CSD) analysis of the VEP depth profile shows augmentation of short latency current sinks in layers 3, 4, and 6 in response to phase reversals of familiar stimuli. Multiunit recordings demonstrate that increased peak firing occurs in response to phase reversals of familiar stimuli across all layers, but that activity between phase reversals is suppressed. Together, these data reveal important aspects of the underlying phenomenology of SRP and generate new hypotheses for the expression of experience-dependent plasticity in V1. Repeated exposure to stimuli that portend neither reward nor punishment leads to behavioral habituation, enabling organisms to dedicate attention to novel or otherwise significant features of the environment. The neural basis of this process, which is so often dysregulated in neurologic and psychiatric disorders, remains poorly understood. Learning and memory of stimulus familiarity can be studied in mouse visual cortex by measuring electrophysiological responses to simple phase-reversing grating stimuli. The current study advances knowledge of this process by documenting changes in visual evoked potentials (VEPs), neuronal spiking activity, and oscillations in the local field potentials (LFPs) across all layers of mouse visual cortex. In addition, we identify a key contribution of a specific population of neurons in layer 6 (L6) of visual cortex.
Topics: Humans; Mice; Male; Female; Animals; Evoked Potentials, Visual; Learning; Neurons; Visual Cortex; Memory; Photic Stimulation
PubMed: 37714707
DOI: 10.1523/JNEUROSCI.0090-23.2023 -
Frontiers in Medicine 2023Biomedical research is intended to benefit human beings and their health. Toward that end, scientific norms involve examining and criticizing the work of others and... (Review)
Review
Biomedical research is intended to benefit human beings and their health. Toward that end, scientific norms involve examining and criticizing the work of others and prioritizing questions that should be studied. Yet, in areas of health research where industry is active, it has often utilized well-honed strategies aimed at evading scientific standards and at dominating the research agenda, largely through its financial support and lack of transparency of its research practices. These tactics have now been documented to uniformly support industry products. Commercial entities are aided in this pursuit by public policy that has significantly embedded commercial interests and agendas into federal research funding and infrastructure. Therefore, to understand the resulting landscape and its effect on priority in health research agendas, traditional definitions of individual conflicts of interest (COI) and the less well developed institutional COI must be supplemented by a new construct of structural COI, largely operating as intellectual monopolies, in support of industry. These arrangements often result in financial and reputational resources that assure dominance of commercial priorities in research agendas, crowding out any other interests and ignoring justified returns to the public from investment of its tax dollars. There is no sustained attention to mechanisms by which public interests can be heard, normative issues raised, and then balanced with commercial interests which are transparently reported. Focus on research supporting approval of commercial products ignores social and environmental determinants of health. Commercial bias can invalidate regulatory research protections through obscuring valid risk-benefit ratios considered by IRBs.
PubMed: 37809337
DOI: 10.3389/fmed.2023.1247258 -
Acta Psychologica Jul 2023Third-party punishment (TPP) effectively promotes social cooperation and maintains social norms in which equity plays a decisive role. When third-party and players are...
Third-party punishment (TPP) effectively promotes social cooperation and maintains social norms in which equity plays a decisive role. When third-party and players are affiliated with different groups, there are two distinct phenomena-in-group favoritism (IGF) and black sheep effect (BSE)-in a certain environment. Equity loses its function as a benchmark when the environment is uncertain (de Kwaadsteniet et al., 2013). Thus, we hypothesized that individuals have a stronger IGF because there is more room for interpretations of their behaviors when an uncertain environment results in ambiguous social norms. We utilized a common resource dilemma (CRD) to manipulate the environmental uncertainty by varying the range of the resource size: a certain environment is represented by a resource size of fixed tokens (i.e., 500 tokens) and an uncertain one is represented by that of 300 to 700 tokens. Additionally, group affiliation is manipulated by the alumni relation between the third-party and players. The present study revealed that the uncertain environment led to stricter costly punishment. The experiment confirms the IGF rather than the BSE. We found boundary conditions between IGF and out-group derogation (OGD). When the players' harvest was not obviously violated, the size of TPP for a control group without group affiliation manipulation anchored those of the in-group and OGD occurred. Opposite, when the harvest was obviously violated, the size of TPP for the control group anchored those of the out-group and IGF occurred. The gender of the third-party affects its decision to punish, with men anchoring the control group's punishment to the in-group and showing OGD, whereas women anchoring the control group's punishment to the out-group and showing IGF.
Topics: Humans; Female; Cooperative Behavior; Uncertainty; Punishment; Social Behavior; Social Norms
PubMed: 37329843
DOI: 10.1016/j.actpsy.2023.103957