Short-term Enhancement Research Articles

Cariprazine add-on in resistant bipolar depression. Long-term effectiveness and safety data from a multicentric real-world experience

IntroductionPersistent depressive episodes and subsyndromic depressive symptoms frequently characterize mood alterations in bipolar disorder (BD) and negatively influence quality of life and suicide risk. BD patients with predominant depressive episodes generally show significantly higher treatment resistance rates. Although not specifically approved in Italy for bipolar depression, recently published observational data suggest that the cariprazine add-on may be a potential effective short-term treatment for resistant bipolar depression. Nevertheless data on long-term cariprazine treatment are lacking.ObjectivesThis study evaluated the efficacy and safety of long-term cariprazine augmentation in patients suffering from treatment-resistant bipolar depression.Methods30 resistant bipolar depressed patients, whose resistance was defined according to The CINP Guidelines on the Definition and Evidence-Based Interventions for Treatment-Resistant Bipolar Disorder, were treated with cariprazine 1,5 -3 mg flexible dose for 4 weeks, added to previous mood stabilizing and/or antidepressant treatment. Psychopathology at time 0 and at 4, 8, 12, 16, 20, 24 weeks of treatment was evaluated using the Hamilton Depression Rating Scale (HDRS), the Hamilton Anxiety Rating Scale (HARS), the Young Mania Rating Scale (YMRS) and the Bipolar Depression Rating Scale (BDRS); safety and tolerability was measured by the UKU Side Effect Rating Scale. The drop-out rate was assessed throughout the study duration.ResultsCariprazine add-on was effective in the study sample but only during the first 4 weeks of treatment. Improvement in depression scores started from the first week, reaching about 40% mean HDRS score reduction at T4; a moderate ulterior decrease (-15%) was reached at T24 but was accompanied by a significant drop-out rate; anxiety symptoms improved (mean HARS score reduction 37% at T4) mainly during the first 4 weeks. The treatment was generally well tolerated. From week 4 to 24 we observed a near 70% drop-out rate (18 total drop-outs) with maximum drop-outs between weeks 4-8 (n=7) and 18-24 (n=7). Discontinuation causes were inefficacy (5/18); clinical worsening (10/18); side effects (3/18); hypomanic shift (2/18).ConclusionsDespite the relatively small population examined and the observational design, our results suggest that cariprazine may represent an effective and safe short-term enhancement strategy in resistant bipolar depression. Long-term treatment, in this sample, did not lead to significant improvements and was burdened by a high drop-out rate, mainly due to inefficacy/clinical worsening. Further studies on larger samples are needed to confirm these preliminary findings, both in short-term and in longer observations.Disclosure of InterestNone Declared

Driving Hebbian plasticity over ventral premotor-motor projections transiently enhances motor resonance

BackgroundMaking sense of others' actions relies on the activation of an action observation network (AON), which maps visual information about observed actions onto the observer's motor system. This motor resonance process manifests in the primary motor cortex (M1) as increased corticospinal excitability finely tuned to the muscles engaged in the observed action. Motor resonance in M1 is facilitated by projections from higher-order AON regions. However, whether manipulating the strength of AON-to-M1 connectivity affects motor resonance remains unclear. MethodsWe used transcranial magnetic stimulation (TMS) in 48 healthy humans. Cortico-cortical paired associative stimulation (ccPAS) was administered over M1 and the ventral premotor cortex (PMv), a key AON node, to induce spike-timing-dependent plasticity (STDP) in the pathway connecting them. Single-pulse TMS assessed motor resonance during action observation. ResultsBefore ccPAS, action observation increased corticospinal excitability in the muscles corresponding to the observed movements, reflecting motor resonance in M1. Notably, ccPAS aimed at strengthening projections from PMv to M1 (PMv→M1) induced short-term enhancement of motor resonance. The enhancement specifically occurred with the ccPAS configuration consistent with forward PMv→M1 projections and dissipated 20 min post-stimulation; ccPAS administered in the reverse order (M1→PMv) and sham stimulation did not affect motor resonance. ConclusionsThese findings provide the first evidence that inducing STDP to strengthen PMv input to M1 neurons causally enhances muscle-specific motor resonance in M1. Our study sheds light on the plastic mechanisms that shape AON functionality and demonstrates that exogenous manipulation of AON connectivity can influence basic mirror mechanisms that underlie social perception.

The effect of Mozart's classical music on blood pressure in Wistar white rats (Rattus norvegicus)

Introduction: Classical music has beneficial effects on heart rate variability and also reduces one's stress levels due to parasympathetic dominance. Mozart's classical music was shown to provide subsequent short-term enhancement of spatial-temporal reasoning ability. This research aimed to study the effect of Mozart's classical music on blood pressure. Methods: The design of this study is true experimental with a post-test-only design with a control group. Thirty Wistar white rats were randomized by simple random sampling method into the control group and experimental group receiving Mozart’s classical music for 90 minutes, twice daily for 1, 3, and 4 weeks. SBP, DBP, and MAP were measured and analyzed using descriptive analysis, Shapiro Wilk, Mann-Whitney U, and Wilcoxon Sign Rank test. Results: DBP and MAP of the experimental group week 1 and 3 were significantly different from the control group. There were significant differences between SBP, DBP, and MAP of experimental group week 1 from week 3 (p=0.00, p=0.00, p=0.00 respectively) and week 1 from week 4 (p=0.00, p=0.00, p=0.00). Conclusion: Listening to Mozart's classical music has a direct effect on blood pressure.

Evolving Role of Ca2+ on the Long-Term Phosphate Adsorption-Regeneration Performance of Nanoconfined Hydrated Lanthanum Oxides: Short-Term Enhancement and Long-Term Inhibition

Phosphorus (P) advanced treatment by adsorption reduces the risk of eutrophication in natural waters and reservoirs. The impact of ubiquitous Ca2+ on long-term P removal is critical in assessing the regeneration efficiency of one adsorbent, which is a vital indicator for cost-effectiveness. Given the critical role of lanthanum (La)-based composite materials in P removal, in this study, we unravel the long-term evolving role of Ca2+ on phosphate removal by nanosized hydrated lanthanum oxides (HLO) confined in cross-linked polystyrene beads (HLO@201) over 20 adsorption-regeneration cycles and fixed-bed column runs, with a combination of macroscopic adsorption experiments, microscopic structural investigation, and theoretical calculations. The role of Ca2+ gradually evolves from positive (5–70% higher than Ca2+-free group) to negative (18–41% lower than the Ca2+-free group) with ongoing cyclic runs of HLO@201, which is distinctive from the bulky HLO. The presence of Ca2+ enhances P uptake by HLO@201 possibly through ≡La–P–Ca–P multiple complexation and Ca–P precipitation (i.e., hydroxyapatite, HAP) inside the polymeric host, which creates an antagonistic effect with HLO over time. The formed Ca–P precipitates may accumulate and encapsulate on the surface of HLO nanoparticles, which induce the formation of irreversible LaPO4·xH2O under nanoconfinement that deplete the active adsorptive sites. A two-step (acid wash + NaOH) regeneration method can partially recover the P removal performance of HLO@201. We envision that this study could be a cautionary tale for advanced treatment of P by adsorption, to inspire re-evaluation on the long-term performance of adsorption processes.

Time-frequency effect of crude oil and exchange rates on stock markets in BRICS countries: Evidence from wavelet quantile regression analysis

This study examines the effects of oil prices and exchange rates on stock market returns in BRICS countries (Brazil, Russia, China, India and South Africa) from a time–frequency perspective over the period 2009–2020. We use wavelet decomposition series to develop a threshold rolling window quantile regression to detect time–frequency effects at various scales. The empirical results are as follows. First, our findings confirm that the effects of both crude oil prices and exchange rates on BRICS stock returns are asymmetric. Positive shocks of crude oil have a greater impact on a bull market, whereas negative shocks have a greater impact on a bear market. Second, there is a short-term enhancement effect of crude oil and exchange rate on BRICS stock markets. In addition, volatility in the macro financial environment also exacerbates the impacts of oil prices and exchange rates on the stock market, and these fluctuations are heterogeneous. Overall, these findings provide useful insights for international investors and policy makers.

Two New Diterpenoids from Biscogniauxia sp. and Their Activities.

Two new diterpenoids, including a seco-isopimarane type (1) and an abietane type (2), were isolated from Biscogniauxia sp. (71-10-1-1). Their structures, including absolute configurations, were elucidated by NMR spectroscopic analyses, X-ray crystallography, 13C chemical shifts calculations, and ECD calculations. This is the first report of diterpenoids from Biscogniauxia sp. Furthermore, short-term memory enhancement against Alzheimer’s disease (AD), anti-inflammatory, and cytotoxic activities of 1–2 were also evaluated. The results showed that compound 1 exhibited short-term memory enhancement activity against AD.

Apical intercalated cell cluster: A distinct sensory regulator in the amygdala.

GABAergic neurons regulate different aspects of information processing in the amygdala. Among these are clusters of intercalated cells (ITCs), which have been implicated in fear-related behaviors. Although a few of the ITC clusters have been studied, the functional role of apical ITCs (apITCs) is unknown. Here, we combine monosynaptic rabies tracing with optogenetics and demonstrate that apITCs receive synaptic input from medial geniculate nucleus (MGm), posterior intralaminar nucleus (PIN), and medial dorsal nucleus of the thalamus and from a diverse range of cortical areas including temporal association, entorhinal, insular, piriform, and somatosensory cortex. Upon fear learning, PIN/MGm inputs are strengthened, indicative of their involvement in fear behaviors. 3-D reconstruction of apITCs reveals local arborization and innervation of the dorsal striatum and lateral amygdala. We further show that apITCs provide sensory feedforward inhibition to LA principal cells, a putative mechanism for controlling plasticity during fear learning.

An artifical synapse based on graphene field-effect transistor with silver gel/polarized-aptamer gate

Abstract In this work, we present an artificial synapse based on side-gate graphene-field-effect-transistor (GFET) using biocompatible silver gel/polarized-aptamer as gate dielectric. The gate functions as the presynaptic membrane, while the drain works as postsynaptic membrane. Various synaptic plasticities, including short-term enhancement (STE), short-term depression (STD), long-term potentiation (LTP), long-term depression (LTD) and the transformation from short-term plasticity to long-term plasticity have been emulated by the GFET artificial synapse. A model based on the function of a difference of two exponentials that is widely used to model the biological synapses is proposed, well fitting the behavior of the fabricated artificial synapses under different presynaptic spikes. With a fixed current of −1 μA applied to postsynaptic membrane, the excitatory-postsynaptic-potential-like spikes can be generated at postsynaptic membrane under the positive spikes applied to presynaptic membrane, suggesting the similarities between the artificial and biological synapses.

Short-term enhancement of motor neuron synaptic exocytosis during early aging extends lifespan in Caenorhabditis elegans.

The functional decline of motor activity is a common feature in almost all aging animals that leads to frailty, loss of independence, injury, and even death in the elderly population. Thus, understanding the molecular mechanism that drives the initial stage of this functional decline and developing strategies to increase human healthspan and even lifespan by targeting this process would be of great interests to the field. In this study, we found that by precisely targeting the motor neurons to potentiate its synaptic releases either genetically or pharmacologically, we can not only delay the functional aging at NMJs but also slow the rate of aging at the organismal level. Most importantly, we have demonstrated that a critical window of time, that is the early stage of NMJs functional decline, is required for the beneficial effects. A short-term treatment within this time period is sufficient to extend the animals' lifespan.

Human impact overwhelms long-term climate control of fire in the Yangtze River Basin since 3.0 ka BP

A high-resolution fire history in the Yangtze River Basin over the past 7.0 ka BP is reconstructed based on the proxy of black carbon of sediment core ECMZ on the continental shelf of the East China Sea in order to reveal the interactions among fire, climate, vegetation and human activity on a regional scale. A comparison of fire activity with climatic and vegetation proxies suggests that changes in fire activity prior to 3.0 ka BP on both millennial- and centennial-timescales were closely related to variations in temperature and precipitation, with more fire during warm and humid periods, suggesting climatic control on regional fire activities. In contrast, the significant decoupling between fire and climate on multi-timescales since ∼3.0 ka BP implies increasing anthropogenic impact on regional fire activity. There is also a distinct response of fire activity to human disturbance at different time scales. Long-term reduction in regional fire activity since ∼3.0 ka BP was caused by a general decrease in forest cover with increasing human activity while short-term (centennial-timescale) enhancement in biomass burning usually coincides with periods characterized by increasing human activity associated with population migration or technological advances.

TRPC channels regulate Ca2+-signaling and short-term plasticity of fast glutamatergic synapses

Transient receptor potential (TRP) proteins form Ca2+-permeable, nonselective cation channels, but their role in neuronal Ca2+ homeostasis is elusive. In the present paper, we show that TRPC channels potently regulate synaptic plasticity by changing the presynaptic Ca2+-homeostasis of hippocampal neurons. Specifically, loss of TRPC1/C4/C5 channels decreases basal-evoked secretion, reduces the pool size of readily releasable vesicles, and accelerates synaptic depression during high-frequency stimulation (HFS). In contrast, primary TRPC5 channel-expressing neurons, identified by a novel TRPC5–τ-green fluorescent protein (τGFP) knockin mouse line, show strong short-term enhancement (STE) of synaptic signaling during HFS, indicating a key role of TRPC5 in short-term plasticity. Lentiviral expression of either TRPC1 or TRPC5 turns classic synaptic depression of wild-type neurons into STE, demonstrating that TRPCs are instrumental in regulating synaptic plasticity. Presynaptic Ca2+ imaging shows that TRPC activity strongly boosts synaptic Ca2+ dynamics, showing that TRPC channels provide an additional presynaptic Ca2+ entry pathway, which efficiently regulates synaptic strength and plasticity.

Radio Channel Characterization of Mid-Band 5G Service Delivery for Ultra-Low Altitude Aerial Base Stations

This paper presents a study which evaluated the potential for using ultra-low altitude, unmanned aerial vehicles to deliver fifth-generation (5G) cellular connectivity, particularly into areas requiring short-term enhancement in coverage. Such short-term enhancement requirements may include large gatherings of people or during disaster scenarios where there may be service outages or a need for increased bandwidth. An evaluation of this approach was conducted with empirically generated results regarding signal quality and cellular coverage—illustrating the potential of using unmanned ultra-low altitude aerial vehicles to deliver 5G cellular mobile services. Specifically, channel gain, mean time delay of the received signals ( $\tau _{\textrm {mean}}$ ), and the root-mean-square spread of the delay ( $\tau _{\textrm {rms}}$ ) were investigated for two distinct user modes at three different drone heights for three selected environments—an open area (field), a tree-lined environment, and an enclosed area. Maximum likelihood estimates for the various drone heights, user modes, and operational environments were found to be Rician distributed for the received signal strength measurements, whereas $\tau _{\textrm {mean}}$ and $\tau _{\textrm {rms}}$ for the open and tree-lined environments were Weibull distributed with the enclosed area tests being lognormally distributed. The paper also investigates how the channel gain may be affected when operating in each of the various global bands allocated for mid-5G communications, namely, Europe, China, Japan, South Korea, and North America. These regional mid-5G band allocations were found to yield minimal variance for all the environments considered.

Investigation of Luminescence Enhancement and Decay of QD-LEDs: Interface Reactions between QDs and Atmospheres.

We investigated the current unsolved problem of short-term enhancement and long-term decay of the luminescence intensity of quantum dots (QDs)-based light-emitting diodes (LEDs) in applications for lighting and displays, and proved that the interface interaction between the QD surface and atmospheres plays a key role in the QD-LED operation process. It is suggested that the initial luminescence enhancement of QD-LEDs would be caused by the QD surface-adsorbed species, such as ligands and gas molecules, rather than QDs themselves, whereas the luminescence decay is correlated to the interface reactions between QDs and photo-generated reactive oxygen species, which leads to formations of sulfate, hydroxide, and oxide compounds after QDs are illuminated by 450 nm blue light in oxygen and water environments according to surface analysis and theoretic thermodynamic calculations. It was also found that involvement of water in the QD-LED operation can cause crystal merging of QDs possibly because of the surface sulfates in the presence of water.

Short-term enhancement of cognitive functions and music: A three-channel model

Short-term effects of music stimulus on enhancement of cognitive functions in human brain are documented, however the underlying neural mechanisms in these cognitive effects are not well investigated. In this study, we have attempted to decipher the mechanisms involved in alterations of neural networks that lead to enhanced cognitive effects post-exposure to music. We have investigated the changes in Electroencephalography (EEG) power and functional connectivity of alpha band in resting state of the brain after exposure to Indian classical music. We have quantified the changes in functional connectivity by phase coherence, phase delay, and phase slope index analyses. Spatial mapping of functional connectivity dynamics thus obtained, on brain networks revealed reduced information flow in long-distance connections between frontal and parietal cortex, and between other cortical regions underpinning intelligence. Analyses also showed increased power in the prefrontal and occipital cortex. With these findings, we have developed a stimulus-mechanism-end effect based neuro-cognitive model that explains the music induced cognitive enhancement by a three-channel framework - (1) enhanced global efficiency of brain, (2) enhanced local neural efficiency at the prefrontal lobe, and (3) increased sustained attention. Results signify that music directly affects the cognitive system and leads to improved brain efficiency through well-defined mechanisms.

Doc2-mediated superpriming supports synaptic augmentation

Various forms of synaptic plasticity underlie aspects of learning and memory. Synaptic augmentation is a form of short-term plasticity characterized by synaptic enhancement that persists for seconds following specific patterns of stimulation. The mechanisms underlying this form of plasticity are unclear but are thought to involve residual presynaptic Ca2+ Here, we report that augmentation was reduced in cultured mouse hippocampal neurons lacking the Ca2+ sensor, Doc2; other forms of short-term enhancement were unaffected. Doc2 binds Ca2+ and munc13 and translocates to the plasma membrane to drive augmentation. The underlying mechanism was not associated with changes in readily releasable pool size or Ca2+ dynamics, but rather resulted from superpriming a subset of synaptic vesicles. Hence, Doc2 forms part of the Ca2+-sensing apparatus for synaptic augmentation via a mechanism that is molecularly distinct from other forms of short-term plasticity.

Regulation of eye and jaw colouration in three-spined stickleback Gasterosteus aculeatus.

Fish can change their skin and eye colour for background matching and signalling. Males of Gasterosteus aculeatus develop ornamental blue eyes and a red jaw during the reproductive season, colours that are further enhanced during courtship. Here, the effects of different hormones on physiological colour changes in the eyes and jaws of male and female G. aculeatus were investigated in vitro. In an in vivo experiment, G. aculeatus were injected with a receptor blocker of a pivotal hormone (noradrenaline) that controls colour change. In males, noradrenaline had aggregating effects on melanophore and erythrophore pigments resulting in blue eyes and a pale jaw, whereas melanocyte-concentrating hormone (MCH) and melatonin resulted in a pale jaw only. When noradrenalin was combined with melanocyte stimulating hormone (MSH) or prolactin, the jaw became red, while the eyes remained blue. In vivo injection of yohimbine, an alpha-2 adrenoreceptor blocker, resulted in dispersion of melanophore pigment in the eyes and inhibited the blue colouration. Altogether, the data suggest that noradrenalin has a pivotal role in the short-term enhancement of the ornamental colouration of male G. aculeatus, potentially together with MSH or prolactin. This study also found a sex difference in the response to MCH, prolactin and melatonin, which may result from different appearance strategies in males, versus the more cryptic females.

An Agent-Based Model for the Role of Short-Term Memory Enhancement in the Emergence of Grammatical Agreement.

What is the influence of short-term memory enhancement on the emergence of grammatical agreement systems in multi-agent language games? Agreement systems suppose that at least two words share some features with each other, such as gender, number, or case. Previous work, within the multi-agent language-game framework, has recently proposed models stressing the hypothesis that the emergence of a grammatical agreement system arises from the minimization of semantic ambiguity. On the other hand, neurobiological evidence argues for the hypothesis that language evolution has mainly related to an increasing of short-term memory capacity, which has allowed the online manipulation of words and meanings participating particularly in grammatical agreement systems. Here, the main aim is to propose a multi-agent language game for the emergence of a grammatical agreement system, under measurable long-range relations depending on the short-term memory capacity. Computer simulations, based on a parameter that measures the amount of short-term memory capacity, suggest that agreement marker systems arise in a population of agents equipped at least with a critical short-term memory capacity.

Propranolol produces short-term facilitation of extinction in a rabbit model of post-traumatic stress disorder

Post-traumatic stress disorder (PTSD) is a learning-based anxiety disorder with significant public health challenges due to difficulties in treating the complex, multiple symptomology. We have developed an animal model of PTSD, based on Pavlovian eyeblink conditioning in rabbits, that addresses two key features: conditioned responses (CRs) to cues associated with an aversive event and a form of conditioned hyperarousal referred to as conditioning-specific reflex modification (CRM). We have found previously that unpaired extinction is ideal for reducing both CRs and CRM simultaneously and shows sensitivity to systemic serotonergic and glutamatergic manipulations. The following study aimed to extend our work to examine the role of the noradrenergic system, dysregulation of which is strongly implicated as part of the neurobiology of PTSD and which may also play a role in the balance shift from fear reconsolidation to extinction during treatment. The goal of the following two studies was to examine whether the β-adrenergic receptor antagonist propranolol combined with either a full or brief course of unpaired extinction treatment could enhance extinction of CRs and/or CRM. Results showed a within-session facilitation of propranolol on extinction of CRs, particularly during the first extinction session, and a short-term enhancement of extinction of CRM when extinction treatment was brief. However, neither benefit translated to long-term extinction retention for the majority of subjects. Findings suggest that propranolol may provide the most therapeutic benefit in situations of high arousal early in treatment, which may be more important for future patient compliance rather than long-term treatment outcomes.

Age-Dependent Pre-Vaccination Immunity Affects the Immunogenicity of Varicella Zoster Vaccination in Middle-aged Adults.

Prevention of infectious diseases is of high priority in the rapidly aging population. Unfortunately, vaccine responses in the elderly are frequently diminished. Timely vaccination of middle-aged adults might improve the immune responses to vaccines, although knowledge on pathogen-specific immune responses and factors affecting these responses, in middle-aged adults is currently limited. We thus investigated the immune responses after vaccination with Zostavax consisting of live-attenuated varicella zoster virus (VZV). Blood samples were taken pre-, 14 days, 28 days, and 1 year after a primary VZV vaccination (Zostavax) at middle age (N = 53, 50-65 years of age). VZV-specific IFNγ-producing cells were measured by ELISpot, activated T-cells by flow cytometry, antibody levels and cytokine responses by fluorescent bead-based multiplex immunoassays, and whole blood cellular kinetics by TruCOUNT analysis. Robust short-term enhancement of the VZV-specific IFNγ-producing cell numbers was observed post-vaccination in the middle-aged adults. Remarkably, long-term enhancement of VZV-specific IFNγ-producing cell numbers was induced only in participants with low numbers of VZV-specific pre-vaccination IFNγ-producing cells, who were significantly older. These participants also showed enhancement of VZV-specific activated CD4 T-cells, contrary to "exhausted" VZV-specific CD8 T-cells in participants with high numbers of VZV-specific pre-vaccination IFNγ-producing cells. Finally, a high CD4/CD8 T-cell ratio was associated with low numbers of pre-vaccination VZV-specific IFNγ-producing cells. These results suggest that adults in their early sixties, who showed a high CD4/CD8 T-cell ratio and low numbers of VZV-specific IFNγ-producing cells, benefit from VZV vaccination. This provides important knowledge on factors affecting VZV-specific immune responses in middle-aged adults as well as for strategies to strengthen immunity before reaching old age.

Effects of Social Defeat Stress on Sleep in Mice.

Stress plays a key role in the development of psychiatric disorders and has a negative impact on sleep integrity. In mice, chronic social defeat stress (CSDS) is an ethologically valid model of stress-related disorders but little is known about its effects on sleep regulation. Here, we investigated the immediate and long-term effects of 10 consecutive days of social defeat (SD) on vigilance states in C57Bl/6J male mice. Social behavior was assessed to identify susceptible mice, i.e., mice that develop long-lasting social avoidance, and unsusceptible mice. Sleep-wake stages in mice of both groups were analyzed by means of polysomnographic recordings at baseline, after the first, third, and tenth stress sessions and on the 5th recovery day (R5) following the 10-day CSDS. In susceptible mice, each SD session produced biphasic changes in sleep-wake states that were preserved all along 10-day CSDS. These sessions elicited a short-term enhancement of wake time while rapid eye-movement (REM) sleep was strongly inhibited. Concomitantly, delta power was increased during non REM (NREM) sleep. During the following dark period, an increase in total sleep time, as well as wake fragmentation, were observed after each analyzed SD session. Similar changes were observed in unsusceptible mice. At R5, elevated high-frequency EEG activity, as observed in insomniacs, emerged during NREM sleep in both susceptible and unsusceptible groups suggesting that CSDS impaired sleep quality. Furthermore, susceptible but not unsusceptible mice displayed stress-anticipatory arousal during recovery, a common feature of anxiety disorders. Altogether, our findings show that CSDS has profound impacts on vigilance states and further support that sleep is tightly regulated by exposure to stressful events. They also revealed that susceptibility to chronic psychological stress is associated with heightened arousal, a physiological feature of stress vulnerability.