Behavioral Arousal Research Articles

0051 CIRCADIAN NEUROHORMONE EXCRETION AND OBJECTIVE SLEEP MEASURES IN TODDLERS PRENATALLY EXPOSED TO MATERNAL DEPRESSION AND ANTIDEPRESSANT MEDICATION

Serotonin reuptake inhibitors (SRIs) are prescribed for ~30% of pregnant women with depression and are reported to disrupt sleep architecture. Furthermore, prenatal maternal depression itself is associated with disrupted circadian rhythms and sleep problems in offspring. However, little is known about the effects of prenatal SRI exposure on child sleep and circadian rhythms. We examined the effects of prenatal exposure to maternal depression and SRIs on circadian neurohormone excretion and sleep in 36-month-olds. Mothers were originally enrolled during pregnancy into a larger, longitudinal study and were interviewed with standardized instruments for psychiatric diagnoses and treatment status. Mothers-child pairs (n=59) were categorized as: 1) No depression or SRI treatment during pregnancy (NoEXP, N=25); 2) Depression, no SRIs (DEP, N=15); 3) Depression with SRIs (SRI, N=19). Videosomnography and respiration recordings were collected on the children for two consecutive nights at 18 and 36-months post-birth. Recordings were manually scored by a trained rater, who was blinded to group status, for percentage of time in bed in wake, Non-REM, REM, and sleep-wake transitional states as well as sleep onset latency (SOL) and number of behavioral arousals. Overnight and daytime urine samples were obtained to determine melatonin, epinephrine, norepinephrine, and cortisol excretion. Overnight melatonin levels were significantly lower in the DEP group compared to NoEXP (Wald χ2=8.2, p<.02). The SRI group had higher cortisol levels overall compared to NoEXP and DEP groups (Wald χ2=6.6, p<.05). Higher daytime cortisol was related to shorter SOL (β=.87, p<.02) and lower amounts of NREM sleep in the early night period (β=.1.1, p<.03). Higher nighttime cortisol was related to longer SOL (β=1.3, p<.02) and more REM sleep (β=.1.1, p<.02). Higher overnight norepinephrine was related to more REM sleep (β=1.75, p<.02) across groups, while higher daytime norepinephrine was related to longer SOL (β=3.56, p<.01) in DEP and SRI groups. Prenatal exposure to maternal depression and SRIs affected sleep and neurohormone secretion of the pineal and the sympathetic nervous system in early childhood. The impact of such prenatal exposure on specific aspects of sleep might act via distinct biological pathways. NIH R01MH079033 to Amy Salisbury.

Potential hypothalamic targets of relaxin-3 innervation: a perspective.

Relaxin-3 is a recently identified neuropeptide transmitter primarily expressed by neurons of the pontine nucleus incertus, which binds/activates the G(i/o)-protein coupled receptor, RXFP3. Functional studies have demonstrated that relaxin-3 modulates behavioural arousal in rodents, and although initial anatomical mapping studies have revealed relaxin-3-positive projections within several brain regions containing neurons that control behavioural arousal, further analysis of this topography has been hampered by the unavailability of a suitable specific RXFP3 antibody. In an effort to determine some of the neuron populations that relaxin-3 signalling directly modulates, we examined the distribution of relaxin-3 immunoreactive nerve fibres/terminals within the mouse lateral hypothalamus (LH) and ventrolateral preoptic area (VLPO), relative to elements containing protein markers for arousal-related neurons. Within the LH, relaxin-3 fibres were predominately distributed more laterally than orexin immunoreactive neurons, in the so-called 'parvalbumin-immunoreactive' PV1 region; but direct contacts with these parvalbumin neurons were scarce. Within the VLPO, relaxin-3 fibres were observed in close contact with galanin-immunoreactive elements, but the soma of the galanin/GABA neurons in the area that project to and inhibit arousal-promoting neurons such as orexin/LH cells to promote sleep, were not identified under the conditions employed. Nonetheless, these preliminary studies suggest an interaction between relaxin-3 and VLPO galanin neurons that may contribute to the arousal-promoting action of relaxin-3.

Pharmacological activation of RXFP3 is not orexigenic in C57BL/6J mice.

The neuropeptide relaxin-3 and its cognate G-protein-coupled receptor, RXFP3, have been implicated in the control of feeding behaviour in rats. For example, relaxin-3-positive projections and RXFP3 are present within hypothalamic feeding circuits, and icv injection of human relaxin-3 (-0.2 to 1.0 nmol) robustly increases feeding behaviour in satiated rats. To explore whether this action is conserved in other experimental species, the present study examined feeding behaviour in C57BL/6J mice following RXFP3 modulation, as mice display near identical regional distribution patterns of relaxin-3/RXFP3, and relaxin-3/RXFP3 signalling has been shown to modulate behavioural arousal in both species. Central injection of the RXFP3 agonists R3/I5 or H3 relaxin (0.5 nmol, icv) did not alter chow consumption in satiated mice relative to vehicle controls, during the 60 min after treatment. Furthermore, relaxin-3 knockout mice displayed similar basal 24-h chow consumption and 1-h palatable food consumption to wildtype littermate controls; although further studies involving acute pharmacological antagonism of RXFP3 in WT mice are required to eliminate the likelihood of compensation in these life-long relaxin-3 deficient mice. Taken together, these findings are in contrast to the potent orexigenic effects of RXFP3 activation observed in rats, and may reflect differential RXFP3 expression within hypothalamic neuron populations in the rat and mouse, or differences in signalling upstream or downstream of relaxin-3/RXFP3 networks in these two species.

Breathing control center neurons that promote arousal in mice.

Slow, controlled breathing has been used for centuries to promote mental calming, and it is used clinically to suppress excessive arousal such as panic attacks. However, the physiological and neural basis of the relationship between breathing and higher-order brain activity is unknown. We found a neuronal subpopulation in the mouse preBötzinger complex (preBötC), the primary breathing rhythm generator, which regulates the balance between calm and arousal behaviors. Conditional, bilateral genetic ablation of the ~175 Cdh9/Dbx1 double-positive preBötC neurons in adult mice left breathing intact but increased calm behaviors and decreased time in aroused states. These neurons project to, synapse on, and positively regulate noradrenergic neurons in the locus coeruleus, a brain center implicated in attention, arousal, and panic that projects throughout the brain.

Sleep Deprivation and Caffeine Treatment Potentiate Photic Resetting of the Master Circadian Clock in a Diurnal Rodent.

Circadian rhythms in nocturnal and diurnal mammals are primarily synchronized to local time by the light/dark cycle. However, nonphotic factors, such as behavioral arousal and metabolic cues, can also phase shift the master clock in the suprachiasmatic nuclei (SCNs) and/or reduce the synchronizing effects of light in nocturnal rodents. In diurnal rodents, the role of arousal or insufficient sleep in these functions is still poorly understood. In the present study, diurnal Sudanian grass rats, Arvicanthis ansorgei, were aroused at night by sleep deprivation (gentle handling) or caffeine treatment that both prevented sleep. Phase shifts of locomotor activity were analyzed in grass rats transferred from a light/dark cycle to constant darkness and aroused in early night or late night. Early night, but not late night, sleep deprivation induced a significant phase shift. Caffeine on its own induced no phase shifts. Both sleep deprivation and caffeine treatment potentiated light-induced phase delays and phase advances in response to a 30 min light pulse, respectively. Sleep deprivation in early night, but not late night, potentiated light-induced c-Fos expression in the ventral SCN. Caffeine treatment in midnight triggered c-Fos expression in dorsal SCN. Both sleep deprivation and caffeine treatment potentiated light-induced c-Fos expression in calbindin-containing cells of the ventral SCN in early and late night. These findings indicate that, in contrast to nocturnal rodents, behavioral arousal induced either by sleep deprivation or caffeine during the sleeping period potentiates light resetting of the master circadian clock in diurnal rodents, and activation of calbindin-containing suprachiasmatic cells may be involved in this effect.SIGNIFICANCE STATEMENT Arousing stimuli have the ability to regulate circadian rhythms in mammals. Behavioral arousal in the sleeping period phase shifts the master clock in the suprachiasmatic nuclei and/or slows down the photic entrainment in nocturnal animals. How these stimuli act in diurnal species remains to be established. Our study in a diurnal rodent, the Grass rat, indicates that sleep deprivation in the early rest period induces phase delays of circadian locomotor activity rhythm. Contrary to nocturnal rodents, both sleep deprivation and caffeine-induced arousal potentiate the photic entrainment in a diurnal rodent. Such enhanced light-induced circadian responses could be relevant for developing chronotherapeutic strategies.

Dopamine in the ventral tegmental area facilitates emergence from general anesthesia.

Taylor et al . (1) showed that optogenetic activation of dopaminergic neurons in the ventral tegmental area (VTA) during continuous, steady-state isoflurane-induced general anesthesia produced electrographic arousal, and restored the righting reflex in mice. Systemic administration of the D1 receptor antagonist SCH-23390 before optical stimulation greatly attenuated electrographic and behavioral arousal. Transfection of VTA neurons with a vector carrying channelrhodopsin 2 (ChR2) allowed optical activation, and optical stimulation in control mice transfected with a vector lacking ChR2 did not induce arousal.

Ancient coexistence of norepinephrine, tyramine, and octopamine signaling in bilaterians

BackgroundNorepinephrine/noradrenaline is a neurotransmitter implicated in arousal and other aspects of vertebrate behavior and physiology. In invertebrates, adrenergic signaling is considered absent and analogous functions are performed by the biogenic amines octopamine and its precursor tyramine. These chemically similar transmitters signal by related families of G-protein-coupled receptors in vertebrates and invertebrates, suggesting that octopamine/tyramine are the invertebrate equivalents of vertebrate norepinephrine. However, the evolutionary relationships and origin of these transmitter systems remain unclear.ResultsUsing phylogenetic analysis and receptor pharmacology, here we have established that norepinephrine, octopamine, and tyramine receptors coexist in some marine invertebrates. In the protostomes Platynereis dumerilii (an annelid) and Priapulus caudatus (a priapulid), we have identified and pharmacologically characterized adrenergic α1 and α2 receptors that coexist with octopamine α, octopamine β, tyramine type 1, and tyramine type 2 receptors. These receptors represent the first examples of adrenergic receptors in protostomes. In the deuterostome Saccoglossus kowalevskii (a hemichordate), we have identified and characterized octopamine α, octopamine β, tyramine type 1, and tyramine type 2 receptors, representing the first examples of these receptors in deuterostomes. S. kowalevskii also has adrenergic α1 and α2 receptors, indicating that all three signaling systems coexist in this animal. In phylogenetic analysis, we have also identified adrenergic and tyramine receptor orthologs in xenacoelomorphs.ConclusionsOur results clarify the history of monoamine signaling in bilaterians. Given that all six receptor families (two each for octopamine, tyramine, and norepinephrine) can be found in representatives of the two major clades of Bilateria, the protostomes and the deuterostomes, all six receptors must have coexisted in the last common ancestor of the protostomes and deuterostomes. Adrenergic receptors were lost from most insects and nematodes, and tyramine and octopamine receptors were lost from most deuterostomes. This complex scenario of differential losses cautions that octopamine signaling in protostomes is not a good model for adrenergic signaling in deuterostomes, and that studies of marine animals where all three transmitter systems coexist will be needed for a better understanding of the origin and ancestral functions of these transmitters.

‘Beatlemania’ and Mass Hysteria – Still a Much Neglected Research Phenomenon

The 1964 study of crowd behavior and audience arousal was re-visited in 2014, following an inquiry from a journalist in London about the interviews the author had conducted 50 years earlier with John Lennon during the Beatles’ visit to New Zealand. The earlier project is touched upon by request, in the hope, still, of inspiring psychologists to follow suit by studying audience reactions to the music of similar vibrant musical groups. Apart from tape-recoded interviews with Lennon, the original study involved direct observation of crowd behavior and psychometric testing of target groups. It led to the elimination of clinical hysteria and delinquent proclivities as key elements causing the extraordinary social rumpus that ensued. Instead, adolescents at the immature stage of personality development were found primarily to be those who behaved fanatically and broke conventions. The study attracted widespread attention at the time, with the editors of two leading journals declaring solemnly that more studies of the kind should be conducted. However, no other researcher seems to have heeded their call. Hence regrettably the one mentioned here remains the first and only data-based study of mass-audience arousal on record.

Supplemental Material for Taxometric Analyses of Pedophilia Utilizing Self-Report, Behavioral, and Sexual Arousal Indicators

Supplemental Material for Taxometric Analyses of Pedophilia Utilizing Self-Report, Behavioral, and Sexual Arousal Indicators

The Resilient Personality Prototype

Abstract. Typologies based on Big Five questionnaire data always include the resilient prototype, which is defined by low scores on neuroticism and above-average scores on extraversion, agreeableness, and conscientiousness. When measurement of the criterion domains is based on self-reports, this type evidences superior psychological adjustment and well-being in nearly all domains. In the present study, we tested whether the personality profile constituting the resilient prototype is an artifact of self-deceptive enhancement in answering questionnaires. Therefore, we contrasted self-reports of resilients with objective data that we collected during an actual stressful event. A total of 112 pupils (15–19 years) were examined via questionnaires and asked to complete a speech task in front of a video camera. Stress reactions were measured by self-reports as well as by nonverbal behavior, achievement, and physiological responding. Results showed that resilients differed from the other personality prototypes only when self-reports (coping, affectivity) were used. By contrast, no differences between personality prototypes emerged when the three objective stress indicators (speech performance, behavior, and physiological arousal) were used. These findings call into question the superior psychological adjustment attributed to the resilient prototype and stress the necessity of multimethod assessment in personality prototype research.

An examination of the role of arousal and actual behaviour on commitment towards recycling and environmental preservation

Recycling and environmental preservation have been a topic of growing interest. However, the way individuals engage in a commitment process to the environment and its consequences are not well-known. In order to contribute to fill this gap, a model was proposed positing that self expression through environmentally proactive behaviours combined with a sense of arousal lead to an affective commitment to recycling and environmental preservation. Findings reveal the importance of energetic arousal to reinforce the self-expression in order to increase the commitment to the environmental preservation. Individuals who have an attitude of concern for the environment when making purchasing decisions tend to be more committed. Finally, committed people are more willing to sacrifice towards the cause and spread the word in favour of the cause. The study has enhanced the understanding of the determinants of recycling behaviour and has implications for schools and governmental agencies in educating and encouraging positive recycling behaviour.

An examination of the role of arousal and actual behaviour on commitment towards recycling and environmental preservation

An examination of the role of arousal and actual behaviour on commitment towards recycling and environmental preservation

Hypothalamic tuberomammillary nucleus histaminergic neurons are electrophysiologically diverse and necessary for the stability of behavioral arousal

Hypothalamic tuberomammillary nucleus histaminergic neurons are electrophysiologically diverse and necessary for the stability of behavioral arousal

Evidence of Construct Validity in the Assessment of Hebephilia.

Hebephilia refers to a persistent intense sexual interest in pubescent children. Although not as widely studied as pedophilia, studies of hebephilia have indicated convergence in self-report and sexual arousal. The present study expanded on previous work by examining convergent and divergent validity across indicators of hebephilia that included self-report, sexual behavior, and sexual arousal in a sample of 2238 men who had sexually offended. We included men who denied such interest and specifically examined the overlap between hebephilia and pedophilia and examined pedohebephilia (i.e., sexual interests in both prepubescent and pubescent children). Results indicated that there was considerable convergence across indicators of hebephilia. The results suggested poor divergent validity between hebephilia and pedophilia, as there was substantial overlap between the two constructs across analyses. Finally, a distinct pattern of sexual arousal was found in offenders with pedohebephilia. The results of the present study were discussed with a focus on implications for the assessment of sexual interest in children and the conceptualization of pedohebephilia.

Unmasking ultradian rhythms in gene expression.

Biological oscillations with an ultradian time scale of 1 to several hours include cycles in behavioral arousal, episodic glucocorticoid release, and gene expression. Ultradian rhythms are thought to have an extrinsic origin because of a perceived absence of ultradian rhythmicity in vitro and a lack of known molecular ultradian oscillators. We designed a novel, non–spectral-analysis method of separating ultradian from circadian components and applied it to a published gene expression dataset with an ultradian sampling resolution. Ultradian rhythms in mouse hepatocytes in vivo have been published, and we validated our approach using this control by confirming 175 of 323 ultradian genes identified in a prior study and found 862 additional ultradian genes. For the first time, we now report ultradian expression of >900 genes in vitro. Sixty genes exhibited ultradian transcriptional rhythmicity, both in vivo and in vitro, including 5 genes involved in the cell cycle. Within these 60 genes, we identified significant enrichment of specific DNA motifs in the 1000 bp proximal promotor, some of which associate with known transcriptional factors. These findings are in strong support of instrinsically driven ultradian rhythms and expose potential molecular mechanisms and functions underlying ultradian rhythms that remain unknown.—Van der Veen, D. R., Gerkema, M. P. Unmasking ultradian rhythms in gene expression.

Neural Correlates of Wakefulness, Sleep, and General Anesthesia: An Experimental Study in Rat.

Significant advances have been made in our understanding of subcortical processes related to anesthetic- and sleep-induced unconsciousness, but the associated changes in cortical connectivity and cortical neurochemistry have yet to be fully clarified. Male Sprague-Dawley rats were instrumented for simultaneous measurement of cortical acetylcholine and electroencephalographic indices of corticocortical connectivity-coherence and symbolic transfer entropy-before, during, and after general anesthesia (propofol, n = 11; sevoflurane, n = 13). In another group of rats (n = 7), these electroencephalographic indices were analyzed during wakefulness, slow wave sleep (SWS), and rapid eye movement (REM) sleep. Compared to wakefulness, anesthetic-induced unconsciousness was characterized by a significant decrease in cortical acetylcholine that recovered to preanesthesia levels during recovery wakefulness. Corticocortical coherence and frontal-parietal symbolic transfer entropy in high γ band (85 to 155 Hz) were decreased during anesthetic-induced unconsciousness and returned to preanesthesia levels during recovery wakefulness. Sleep-wake states showed a state-dependent change in coherence and transfer entropy in high γ bandwidth, which correlated with behavioral arousal: high during wakefulness, low during SWS, and lowest during REM sleep. By contrast, frontal-parietal θ connectivity during sleep-wake states was not correlated with behavioral arousal but showed an association with well-established changes in cortical acetylcholine: high during wakefulness and REM sleep and low during SWS. Corticocortical coherence and frontal-parietal connectivity in high γ bandwidth correlates with behavioral arousal and is not mediated by cholinergic mechanisms, while θ connectivity correlates with cortical acetylcholine levels.

Optogenetic activation of dopamine neurons in the ventral tegmental area induces reanimation from general anesthesia

Dopamine (DA) promotes wakefulness, and DA transporter inhibitors such as dextroamphetamine and methylphenidate are effective for increasing arousal and inducing reanimation, or active emergence from general anesthesia. DA neurons in the ventral tegmental area (VTA) are involved in reward processing, motivation, emotion, reinforcement, and cognition, but their role in regulating wakefulness is less clear. The current study was performed to test the hypothesis that selective optogenetic activation of VTA DA neurons is sufficient to induce arousal from an unconscious, anesthetized state. Floxed-inverse (FLEX)-Channelrhodopsin2 (ChR2) expression was targeted to VTA DA neurons in DA transporter (DAT)-cre mice (ChR2+ group; n = 6). Optical VTA stimulation in ChR2+ mice during continuous, steady-state general anesthesia (CSSGA) with isoflurane produced behavioral and EEG evidence of arousal and restored the righting reflex in 6/6 mice. Pretreatment with the D1 receptor antagonist SCH-23390 before optical VTA stimulation inhibited the arousal responses and restoration of righting in 6/6 ChR2+ mice. In control DAT-cre mice, the VTA was targeted with a viral vector lacking the ChR2 gene (ChR2- group; n = 5). VTA optical stimulation in ChR2- mice did not restore righting or produce EEG changes during isoflurane CSSGA in 5/5 mice. These results provide compelling evidence that selective stimulation of VTA DA neurons is sufficient to induce the transition from an anesthetized, unconscious state to an awake state, suggesting critical involvement in behavioral arousal.

Stimulation of the Pontine Parabrachial Nucleus Promotes Wakefulness via Extra-thalamic Forebrain Circuit Nodes

Human and animal studies have identified an especially critical role for the brainstem parabrachial (PB) complex in regulating electrocortical (electroencephalogram [EEG]) and behavioral arousal: lesions of the PB complex produce a monotonous high-voltage, slow-wave EEG and eliminate spontaneous behaviors. We report here that targeted chemogenetic activation of the PB complex produces sustained EEG and behavioral arousal in the rat. We further establish, using viral-mediated retrograde activation, that PB projections to the preoptic-basal forebrain and lateral hypothalamus, but not to the thalamus, mediate PB-driven wakefulness. We exploited this novel and noninvasive model of induced wakefulness to explore the EEG and metabolic consequences of extended wakefulness. Repeated (daily) chemogenetic activation of the PB was highly effective in extending wakefulness over 4days, although subsequent PB activation produced progressively lesser wake amounts. Curiously, no EEG or behavioral sleep rebound was observed, even after 4days of induced wakefulness. Following the last of the four daily induced wake bouts, we examined the brains and observed a chimeric pattern of c-Fos expression, with c-Fos expressed in subsets of both arousal- and sleep-promoting nuclei. From a metabolic standpoint, induced extended wakefulness significantly reduced body weight and leptin but was without significant effect on cholesterol, triglyceride, or insulin levels, suggesting that high sleep pressure or sleep debt per se does not, as previously implicated, result in a deleterious metabolic phenotype.

Alerting or Somnogenic Light: Pick Your Color.

In mammals, light exerts pervasive effects on physiology and behavior in two ways: indirectly through clock synchronization and the phase adjustment of circadian rhythms, and directly through the promotion of alertness and sleep, respectively, in diurnal and nocturnal species. A recent report by Pilorz and colleagues describes an even more complex role for the acute effects of light. In mice, blue light acutely causes behavioral arousal, whereas green wavelengths promote sleep. These opposing effects are mediated by melanopsin-based phototransduction through different neural pathways. These findings reconcile nocturnal and diurnal species through a common alerting response to blue light. One can hypothesize that the opposite responses to natural polychromatic light in night- or day-active animals may reflect higher sensitivity of nocturnal species to green, and diurnals to blue wavelengths, resulting in hypnogenic and alerting effects, respectively. Additional questions remain to be clarified. How do different light wavelengths affect other behaviors such as mood and cognition? How do those results apply to humans? How does light pose either a risk or benefit, depending on whether one needs to be asleep or alert? Indeed, in addition to timing, luminance levels, and light exposure duration, these findings stress the need to understand how best to adapt the color spectrum of light to our needs and to take this into account for the design of daily lighting concepts—a key challenge for today’s society, especially with the emergence of LED light technology.

Melanopsin Regulates Both Sleep-Promoting and Arousal-Promoting Responses to Light

Light plays a critical role in the regulation of numerous aspects of physiology and behaviour, including the entrainment of circadian rhythms and the regulation of sleep. These responses involve melanopsin (OPN4)-expressing photosensitive retinal ganglion cells (pRGCs) in addition to rods and cones. Nocturnal light exposure in rodents has been shown to result in rapid sleep induction, in which melanopsin plays a key role. However, studies have also shown that light exposure can result in elevated corticosterone, a response that is not compatible with sleep. To investigate these contradictory findings and to dissect the relative contribution of pRGCs and rods/cones, we assessed the effects of light of different wavelengths on behaviourally defined sleep. Here, we show that blue light (470 nm) causes behavioural arousal, elevating corticosterone and delaying sleep onset. By contrast, green light (530 nm) produces rapid sleep induction. Compared to wildtype mice, these responses are altered in melanopsin-deficient mice (Opn4-/-), resulting in enhanced sleep in response to blue light but delayed sleep induction in response to green or white light. We go on to show that blue light evokes higher Fos induction in the SCN compared to the sleep-promoting ventrolateral preoptic area (VLPO), whereas green light produced greater responses in the VLPO. Collectively, our data demonstrates that nocturnal light exposure can have either an arousal- or sleep-promoting effect, and that these responses are melanopsin-mediated via different neural pathways with different spectral sensitivities. These findings raise important questions relating to how artificial light may alter behaviour in both the work and domestic setting.