The grooming invitation dance is a striking behavior in honey bee colonies that has not been extensively studied. The objectives of this study were (1) to describe the dance through video analysis, ...(2) to test the functional hypothesis that it is a grooming solicitation signal, and (3) to analyze the stimuli that cause its production. A worker bee producing the grooming invitation dance stands stationary and vibrates her whole body from side‐to‐side at a frequency of 4.2 ± 0.2 Hz for 9.3 ± 1.0 s. Sometimes the bee mixes bouts of body vibration with brief bouts of self‐grooming (average duration = 1.4 s). Bees that perform the grooming invitation dance have a far higher probability of being quickly groomed by a nest mate than do bees that do not perform the dance. Bees that had chalk dust puffed onto the bases of their wings produced significantly more grooming invitation dances than did control bees that received only puffs of air. This shows that it may be the accumulation of small particles at the bases of the wings that normally triggers the dance. We suggest that the evolutionary origin of this signal is self‐grooming behavior.
The fitness of a social insect colony depends greatly on the quality (i.e., mating ability, fecundity, and offspring viability) of its queen(s). In honeybees, there is marked variation in the quality ...of young queens that compete in a series of lethal duels to replace a colony’s previous queen. Workers interact with queens during these duels and could increase their inclusive fitness by biasing the outcomes of the duels in favor of high-quality queens. We predicted that workers will have more antagonistic interactions (chasing, grabbing, clamping) and fewer beneficent interactions (feeding, grooming) with low-quality than high-quality queens. To test this prediction, we reared queens from 0-day-old, 2-day-old, and 3-day-old worker larvae in observation colonies undergoing queen replacement, thus producing high-quality, low-quality, and very low-quality queens, respectively. Immediately after each queen emerged, we observed her for 1 h to record her interactions with the workers. Subsequent morphological measurement of the queens confirmed that initial larval age had a significant effect on queen quality. However, there was no consistent effect of queen quality on the rates of worker–queen interactions, thus falsifying our hypothesis. The mean power of our tests was high (0.599), therefore the probability of a type II error (a false negative) is low. We conclude that if workers actively select high-quality queens, then they do so prior to queen duels, during queen development. We suggest that each worker–queen interaction has a distinct adaptive significance rather than forming a suite of behavior that favors particular queens (e.g., chasing repels any queen that approaches a queen cell, thus protecting all queen cells from destruction).
The dynorphin/κ-opioid receptor (KOR) system has been previously implicated in the regulation of cognition, but the neural circuitry and molecular mechanisms underlying KOR-mediated cognitive ...disruption are unknown. Here, we used an operational test of cognition involving timing and behavioral inhibition and found that systemic KOR activation impairs performance of male and female C57BL/6 mice in the differential reinforcement of low response rate (DRL) task. Systemic KOR antagonism also blocked stress-induced disruptions of DRL performance. KOR activation increased 'bursts' of incorrect responses in the DRL task and increased marble burying, suggesting that the observed disruptions in DRL performance may be attributed to KOR-induced increases in compulsive behavior. Local inactivation of KOR by injection of the long-acting antagonist nor-BNI in the ventral tegmental area (VTA), but not the infralimbic prefrontal cortex (PFC) or dorsal raphe nucleus (DRN), prevented disruption of DRL performance caused by systemic KOR activation. Cre-dependent genetic excision of KOR from dopaminergic, but not serotonergic neurons, also blocked KOR-mediated disruption of DRL performance. At the molecular level, we found that these disruptive effects did not require arrestin-dependent signaling, because neither global deletion of G-protein receptor kinase 3 (GRK3) nor cell-specific deletion of GRK3/arrestin-dependent p38α MAPK from dopamine neurons blocked KOR-mediated DRL disruptions. We then showed that nalfurafine, a clinically available G-biased KOR agonist, could also produce DRL disruptions. Together, these studies demonstrate that KOR activation in VTA dopamine neurons disrupts behavioral inhibition in a GRK3/arrestin-independent manner and suggests that KOR antagonists could be beneficial for decreasing stress-induced compulsive behaviors.
Stress-induced release of dynorphins (Dyn) activates kappa opioid receptors (KOR) in serotonergic neurons to produce dysphoria and potentiate drug reward; however, the circuit mechanisms responsible ...for this effect are not known. In male mice, we found that conditional deletion of KOR from Slc6a4 (SERT)-expressing neurons blocked stress-induced potentiation of cocaine conditioned place preference (CPP). Within the dorsal raphe nucleus (DRN), two overlapping populations of KOR-expressing neurons: Slc17a8 (VGluT3) and SERT, were distinguished functionally and anatomically. Optogenetic inhibition of these SERT
neurons potentiated subsequent cocaine CPP, whereas optical inhibition of the VGluT3
neurons blocked subsequent cocaine CPP. SERT
/VGluT3
expressing neurons were concentrated in the lateral aspect of the DRN. SERT projections from the DRN were observed in the medial nucleus accumbens (mNAc), but VGluT3 projections were not. Optical inhibition of SERT
neurons produced place aversion, whereas optical stimulation of SERT
terminals in the mNAc attenuated stress-induced increases in forced swim immobility and subsequent cocaine CPP. KOR neurons projecting to mNAc were confined to the lateral aspect of the DRN, and the principal source of dynorphinergic (Pdyn) afferents in the mNAc was from local neurons. Excision of Pdyn from the mNAc blocked stress-potentiation of cocaine CPP. Prior studies suggested that stress-induced dynorphin release within the mNAc activates KOR to potentiate cocaine preference by a reduction in 5-HT tone. Consistent with this hypothesis, a transient pharmacological blockade of mNAc 5-HT
receptors potentiated subsequent cocaine CPP. 5-HT
is known to be expressed on 5-HT terminals in NAc, and 5-HT
transcript was also detected in Pdyn
, Adora2a
and ChAT
(markers for direct pathway, indirect pathway, and cholinergic interneurons, respectively). Following stress exposure, 5-HT
transcript was selectively elevated in Pdyn
cells of the mNAc. These findings suggest that Dyn/KOR regulates serotonin activation of 5HT
receptors within the mNAc and dynamically controls stress response, affect, and drug reward.
Ketamine produces rapid and sustained antidepressant actions in depressed patients, but the precise cellular mechanisms underlying these effects have not been identified. Here we determined if ...modulation of neuronal activity in the infralimbic prefrontal cortex (IL-PFC) underlies the antidepressant and anxiolytic actions of ketamine. We found that neuronal inactivation of the IL-PFC completely blocked the antidepressant and anxiolytic effects of systemic ketamine in rodent models and that ketamine microinfusion into IL-PFC reproduced these behavioral actions of systemic ketamine. We also found that optogenetic stimulation of the IL-PFC produced rapid and long-lasting antidepressant and anxiolytic effects and that these effects are associated with increased number and function of spine synapses of layer V pyramidal neurons. The results demonstrate that ketamine infusions or optogenetic stimulation of IL-PFC are sufficient to produce long-lasting antidepressant behavioral and synaptic responses similar to the effects of systemic ketamine administration.
Significance Clinical studies report that a single, low dose of ketamine produces a rapid antidepressant response in treatment-resistant depressed patients. Although rodent studies have begun to elucidate the molecular mechanisms underlying the behavioral actions of ketamine, the brain regions and cellular mechanisms have not been defined. Using a combination of pharmacological silencing and optogenetic stimulation approaches, the results of the current study demonstrate that ketamine infusion or optogenetic stimulation of the infalimbic prefrontal cortex produces antidepressant behavioral and synaptic responses similar to the actions of systemic ketamine. These findings further elucidate the mechanisms underlying the therapeutic actions of ketamine and will enhance the development of safer rapid-acting and efficacious agents.
The influence of micronutrients on dopamine systems is not well defined. Using mice, we show a potential role for reduced dietary vitamin D3 (cholecalciferol) in promoting diet-induced obesity (DIO), ...food intake, and drug consumption while on a high fat diet. To complement these deficiency studies, treatments with exogenous fully active vitamin D3 (calcitriol, 10 µg/kg, i.p.) were performed. Nondeficient mice that were made leptin resistant with a high fat diet displayed reduced food intake and body weight after an acute treatment with exogenous calcitriol. Dopamine neurons in the midbrain and their target neurons in the striatum were found to express vitamin D3 receptor protein. Acute calcitriol treatment led to transcriptional changes of dopamine-related genes in these regions in naive mice, enhanced amphetamine-induced dopamine release in both naive mice and rats, and increased locomotor activity after acute amphetamine treatment (2.5 mg/kg, i.p.). Alternatively, mice that were chronically fed either the reduced D3 high fat or chow diets displayed less activity after acute amphetamine treatment compared with their respective controls. Finally, high fat deficient mice that were trained to orally consume liquid amphetamine (90 mg/L) displayed increased consumption, while nondeficient mice treated with calcitriol showed reduced consumption. Our findings suggest that reduced dietary D3 may be a contributing environmental factor enhancing DIO as well as drug intake while eating a high fat diet. Moreover, these data demonstrate that dopamine circuits are modulated by D3 signaling, and may serve as direct or indirect targets for exogenous calcitriol.
Maladaptive responses to stress adversely affect human behavior, yet the signaling mechanisms underlying stress-responsive behaviors remain poorly understood. Using a conditional gene knockout ...approach, the α isoform of p38 mitogen-activated protein kinase (MAPK) was selectively inactivated by AAV1-Cre-recombinase infection in specific brain regions or by promoter-driven excision of p38α MAPK in serotonergic neurons (bySlc6a4-CreorePet1-Cre)or astrocytes (byGfap-CreERT2).Social defeat stress produced social avoidance (a model of depression-like behaviors) and reinstatement of cocaine preference (a measure of addiction risk) in wild-type mice, but not in mice having p38α MAPK selectively deleted in serotonin-producing neurons of the dorsal raphe nucleus. Stress-induced activation of p38α MAPK translocated the serotonin transporter to the plasma membrane and increased the rate of transmitter uptake at serotonergic nerve terminals. These findings suggest that stress initiates a cascade of molecular and cellular events in which p38α MAPK induces a hyposerotonergic state underlying depression-like and drug-seeking behaviors.
Although stress has profound effects on motivated behavior, the underlying mechanisms responsible are incompletely understood.In this study we elucidate a functional pathway in mouse brain that ...encodes the aversive effects of stress and mediates stress-inducedreinstatement of cocaine place preference (CPP). Activation of the dynorphin/kappa opioid receptor (KOR) system by eitherrepeated stress or agonist produces conditioned place aversion (CPA). Because KOR inhibition of dopamine release in the mesolimbicpathway has been proposed to mediate the dysphoria underlying this response, we tested dopamine-deficient mice in this studyand found that KOR agonist in these mice still produced CPA. However, inactivation of serotonergic KORs by injection of theKOR antagonist norBNI into the dorsal raphe nucleus (DRN), blocked aversive responses to the KOR agonist U50,488 and blockedstress-induced reinstatement of CPP. KOR knockout (KO) mice did not develop CPA to U50,488; however, lentiviral re-expressionof KOR in the DRN of KOR KO mice restored place aversion. In contrast, lentiviral expression in DRN of a mutated form of KORthat fails to activate p38 MAPK required for KOR-dependent aversion, did not restore place aversion. DRN serotonergic neuronsproject broadly throughout the brain, but the inactivation of KOR in the nucleus accumbens (NAc) coupled with viral re-expressionin the DRN of KOR KO mice demonstrated that aversion was encoded by a DRN to NAc projection. These results suggest that theadverse effects of stress may converge on the serotonergic system and offers an approach to controlling stress-induced dysphoriaand relapse.
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