Search

Metabotropic glutamate receptor 5 (mGluR5) has been implicated in stress-related psychiatric disorders, particularly major depressive disorder. Although growing evidence supports the proresilient role of mGluR5 in corticolimbic circuitry in the depressive-like behaviors following chronic stress exposure, the underlying neural mechanisms, including circuits and molecules, remain unknown.We measured the c-Fos expression and probability of neurotransmitter release in and from basolateral amygdala (BLA) neurons projecting to the medial prefrontal cortex (mPFC) and to the ventral hippocampus (vHPC) after chronic social defeat stress. The role of BLA projections in depressive-like behaviors was assessed using optogenetic manipulations, and the underlying molecular mechanisms of mGluR5 and downstream signaling were investigated by Western blotting, viral-mediated gene transfer, and pharmacological manipulations.Chronic social defeat stress disrupted neural activity and glutamatergic transmission in both BLA projections. Optogenetic activation of BLA projections reversed the detrimental effects of chronic social defeat stress on depressive-like behaviors and mGluR5 expression in the mPFC and vHPC. Conversely, inhibition of BLA projections of mice undergoing subthreshold social defeat stress induced a susceptible phenotype and mGluR5 reduction. These two BLA circuits appeared to act in an independent way. We demonstrate that mGluR5 overexpression in the mPFC or vHPC was proresilient while the mGluR5 knockdown was prosusceptible and that the proresilient effects of mGluR5 are mediated through distinctive downstream signaling pathways in the mPFC and vHPC.These findings identify mGluR5 in the mPFC and vHPC that receive BLA inputs as a critical mediator of stress resilience, highlighting circuit-specific signaling for depressive-like behaviors.

SummarySocial animals compete for limited resources, resulting in a social hierarchy. Although different neuronal subpopulations in the medial prefrontal cortex (mPFC), a hub brain region of social hierarchy, encode distinct social competition behaviors, their identities and associated molecular underpinnings have not yet been identified. In this study, we found that mPFC neurons projecting to the nucleus accumbens (mPFC-NAc) encode social winning behavior, whereas mPFC neurons projecting to the ventral tegmental area (mPFC-VTA) encode social losing behavior by monitoring and manipulating neural circuit activity. High-throughput single-cell transcriptomic analysis and projection-specific genetic manipulation revealed that the expression level of POU domain, class 3, transcription factor 1 (Pou3f1) in mPFC-VTA neurons controls social hierarchy. Optogenetic activation of mPFC-VTA neurons increasesPou3f1expression and lowers social rank. Together, these data demonstrate that discrete activity and gene expression in separate mPFC projections oppositely orchestrate social competition and hierarchy.

Social animals expend considerable energy to maintain social bonds throughout their life. Male and female mice show sexually dimorphic behaviors, yet the underlying neural mechanisms of sociability and their dysregulation during social disconnection remain unknown. Dopaminergic neurons in dorsal raphe nucleus (DRN TH ) is known to contribute to a loneliness-like state and modulate sociability. We identified that activated subpopulations in DRN TH and nucleus accumbens shell (NAc sh ) during 24 hours of social isolation underlie the increase in isolation-induced sociability in male but not in female mice. This effect was reversed by chemogenetically and optogenetically inhibiting the DRN TH -NAc sh circuit. Moreover, synaptic connectivity among the activated neuronal ensembles in this circuit was increased, primarily in D 1 receptor–expressing neurons in NAc sh . The increase in synaptic density functionally correlated with elevated dopamine release into NAc sh . Overall, specific synaptic ensembles in DRN TH -NAc sh mediate sex differences in isolation-induced sociability, indicating that sex-dependent circuit dynamics underlie the expression of sexually dimorphic behaviors.

Chronic stress causes physiological and hormonal adaptations that lead to neurobiological consequences and behavioral and cognitive impairments. In particular, chronic stress has been shown to drive reduced neurogenesis and altered synaptic plasticity in brain regions that regulate mood and motivation. The neurobiological and behavioral effects of stress resemble the pathophysiology and symptoms observed in psychiatric disorders, suggesting that there are similar underlying mechanisms. Accumulating evidence indicates that neuroimmune systems, particularly microglia, have a critical role in regulating the neurobiology of stress. Preclinical models indicate that chronic stress provokes changes in microglia phenotype and increases inflammatory cytokine signaling, which affects neuronal function and leads to synaptic plasticity deficits and impaired neurogenesis. More recent work has shown that microglia can also phagocytose neuronal elements and contribute to structural remodeling of neurons in response to chronic stress. In this review we highlight work by the Duman research group (as well as others) that has revealed how chronic stress shapes neuroimmune function and, in turn, how inflammatory mediators and microglia contribute to the neurobiological effects of chronic stress. We also provide considerations to engage the therapeutic potential of neuroimmune systems, with the goal of improving treatment for psychiatric disorders.

This study investigated attentional bias toward game-related cues in Internet gaming disorder (IGD) using electrophysiological markers of late positive potential (LPP) and identifying the sources of LPP. In addition, the association between LPP and decision-making ability was investigated. The IGD (n = 40) and healthy control (HC; n = 39) participants viewed a series of game-related and neutral pictures, while their event-related potentials (ERPs) were recorded. LPPs were calculated as the mean amplitudes between 400 and 700 ms at the centro-parietal (CP3, CP1, Cpz, CP2, and CP4) and parietal (P3, P1, Pz, P2, and P4) electrode sites. The source activations of LPP were estimated using standardized low-resolution brain electromagnetic tomography (sLORETA). In addition, decision-making ability was evaluated by the Cambridge Gambling Task. Higher LPP amplitudes were found for game-related cues in the IGD group than in the HC group. sLORETA showed that the IGD group was more active in the superior and middle temporal gyri, which are involved in social perception, than in the HC group, whereas it was less active in the frontal area. Individuals with IGD have deficits in decision-making ability. In addition, in the HC group, the lower the LPP when looking at the game-related stimuli, the better the quality of decision-making, but not in the IGD group. Enhanced LPP amplitudes are associated with emotional arousal to gaming cues and decision-making deficits in IGD. In addition, source activities suggest that patients with IGD perceive game-related cues as social stimuli. LPP can be used as a neurophysiological marker of IGD.

Often called the second brain, the gut communicates extensively with the brain and vice versa. The conversation between these two organs affects a variety of physiological mechanisms that are associated with our mental health. Over the past decade, a growing body of evidence has suggested that the gut microbiome builds a unique ecosystem inside the gastrointestinal tract to maintain the homeostasis and that compositional changes in the gut microbiome are highly correlated with several mental disorders. There are ongoing efforts to treat or prevent mental disorders by regulating the gut microbiome using probiotics. These attempts are based on the seminal findings that probiotics can control the gut microbiome and affect mental conditions. However, some issues have yet to be conclusively addressed, especially the causality between the gut microbiome and mental disorders. In this review, we focus on the mechanisms by which the gut microbiome affects mental health and diseases. Furthermore, we discuss the potential use of probiotics as therapeutic agents for psychiatric disorders.

Background Cholinergic interneurons (ChINs) in the nucleus accumbens (NAc) play critical roles in processing information related to reward. However, the contribution of ChINs to the emergence of addiction-like behaviors and its underlying molecular mechanisms remain elusive. Methods We employed cocaine self-administration to identify two mouse subpopulations: susceptible and resilient to cocaine seeking. We compared the subpopulations for physiological responses with single-unit recording of NAc ChINs, and for gene expression levels with RNA sequencing of ChINs sorted using fluorescence-activated cell sorting. To provide evidence for a causal relationship, we manipulated the expression level of dopamine D2 receptor (DRD2) in ChINs in a cell type–specific manner. Using optogenetic activation combined with a double whole-cell recording, the effect of ChIN-specific DRD2 manipulation on each synaptic input was assessed in NAc medium spiny neurons in a pathway-specific manner. Results Susceptible mice showed higher levels of nosepoke responses under a progressive ratio schedule, and impairment in extinction and punishment procedures. DRD2 was highly abundant in the NAc ChINs of susceptible mice. Elevated abundance of DRD2 in NAc ChINs was sufficient and necessary to express high cocaine motivation, putatively through reduction of ChIN activity during cocaine exposure. DRD2 overexpression in ChINs mimicked cocaine-induced effects on the dendritic spine density and the ratios of excitatory inputs between two distinct medium spiny neuron cell types, while DRD2 depletion precluded cocaine-induced synaptic plasticity. Conclusions These findings provide a molecular mechanism for dopaminergic control of NAc ChINs that can control the susceptibility to cocaine-seeking behavior.

Cholesterol homeostasis has been proposed to be implicated in the development of addiction. However, the effects of ethanol on cholesterol homeostasis within the brain are not well understood. One of the most important regulators of cholesterol homeostasis is HMG-CoA reductase (HMG-CoAR), the rate-limiting enzyme of cholesterol biosynthesis. We examined the phosphorylation of HMG-CoAR and the other key regulator of lipid synthesis, acetyl-CoA carboxylase (ACC), following acute or chronic treatment with ethanol (0.5, 1, or 2 g/kg) in the rat prefrontal cortex. The phosphorylation of AMP-activated protein kinase (AMPK), which regulates the HMG-CoAR activity, and its well-known upstream regulators, was also studied. The phosphorylation of HMG-CoAR and ACC were transiently increased by ethanol treatment only in animals previously treated chronically with ethanol. Acute administration to naive animals did not induce the phosphorylation, regardless of dosage. Similarly, the phosphorylation of AMPK and the upstream regulators, LKB1 and CaMK4, were transiently increased only in chronically ethanol-treated animals. In naive animals, a high dose (2 g/kg) of ethanol decreased phosphorylation. The phosphorylation of TAK1, another upstream kinase of AMPK, was increased only from 30 min to 24 h after the chronic treatment with ethanol. Together, these results indicate that repeated exposure is required for the activating effect of ethanol on HMG-CoAR and ACC. This effect seems to be mediated by the AMPK system, and may contribute to the long-lasting neuroadaptation involved in the development of alcohol dependence.

Study design Retrospective comparative study. Objective To investigate the radiographic and clinical effectiveness of surgical treatment using a posterior-only approach, as compared with a combined antero-posterior approach, in patients with infective spondylodiscitis. Summary of background data Spondylodiscitis is the most common infectious disease of the spine. There is currently no consensus over the surgical approach, use of bone graft, and type of instrumentation for optimal treatment of infective spondylodiscitis. Methods Seventy-nine patients who received surgical treatment for infective spondylodiscitis were divided into a combined antero-posterior (AP) group and a posterior-only (P) group. Significant differences in pre- and postoperative radiographic and clinical characteristics between the two groups were identified, and univariate and stepwise multivariate logistic regression analyses were used to determine the factors that affected the decision for treatment approach between the two groups. Results Preoperatively, initial height loss, wedge angle, and kyphotic angle were significantly higher in the AP group. However, estimated blood loss, operation time, and last visual analogue scale score for back pain were significantly lower in the P group. There was no difference in postoperative time to reach solid fusion. Postoperative corrected kyphotic angle was 12.8° in the AP group and 5.3° in the P group. The regional wedge angle was identified as a factor that influenced use of the combined antero-posterior approach, with a sensitivity of 60%, and specificity of 89.8% at the optimal cut-off value of 8.2°. Conclusion Interbody fusion with long-level pedicle screws fixation through a posterior-only approach was shown to be as effective as a combined antero-posterior approach for the surgical treatment of infective spondylodiscitis. A posterior-only approach is recommended when the regional wedge angle of the collapsed vertebra is less than 8.2°. Level of evidence 4.

Study Design: A nationwide population-based study.Purpose: Osteoporotic vertebral compression fracture (OVCF) is a major public health issue. This study examined the incidence and management trends of OVCF in South Korea. Overview of Literature: The incidence rates, management trends, and patterns of OVCF differ in different parts of the world. The age-standardized OVCF incidence rate in 2015 was higher in the United States and Asia than in Europe.Methods: A nationwide database (2012–2016) acquired from the Korean Health Insurance Review and Assessment Service was analyzed. International disease categories in the 10th revision of the International Statistical Classification of Diseases and Related Health Problems codes, medical procedure codes, and examination codes were used to identify and sort OVCF patients aged >50 years.Results: There were 644,500 OVCF cases from 2012 to 2016. OVCF was most common in patients in their seventies (45%) and the number of patients increased from 117,361 in 2012 to 139,889 in 2016 (p p p

The purpose of this study was to investigate the incidence of symptomatic venous thromboembolism (VTE) after chemoprophylaxis in patients with pelvic and lower-extremity fractures, and to identify risk factors for VTEs in this subgroup of patients. To detect VTE, multi-detector computed tomography (CT) angiography was performed. Of 363 patients assessed, the incidence of symptomatic VTE was 12.4% (45 patients), and the incidence of symptomatic PE was 5.2% (19 patients). For the risk-factor analysis, a higher Charlson comorbidity index (p = 0.037), and a history of external fixator application (p = 0.007) were associated with increased VTE risk. Among patients who had VTE, male sex (p = 0.017), and above-the-knee fractures (p = 0.035) were associated with increased pulmonary embolism (PE) risk. In conclusions, the incidence of VTE in post-traumatic patients is not low after chemoprophylaxis. Risk factors for VTE and PE are different among patients with pelvic and lower-extremity fractures.

STUDY DESIGN Population-based study. From 2008 to 2017, data from the national database of the Korean Health Insurance Review & Assessment Service were analyzed. The national insurance system and all medical expense bill data of the entire population are included in the database. OBJECTIVE The aim of this study was to elucidate the incidence and management trends of metastatic spinal tumors in South Korea. SUMMARY OF BACKGROUND DATA The spine is the most common location of bone metastases. However, population-based studies in this topic are limited. METHODS The International Classification of Disease, 10th revision, medical behavior, and examination codes were used to identify the incidence and management trends of metastatic spinal tumors. The Cochran-Armitage trend test was used in statistical analysis. RESULTS Overall, 38,007 patients (average age, 61 years) diagnosed with metastatic spinal tumors were analyzed. Metastatic tumors were most common in patients in their 60s (25.7%). The 10-year incidence of spinal metastases in South Korea was 6.68 cases per 100,000 population. The age-adjusted incidence per 100,000 population decreased from 8.16 cases in 2008 to 6.18 in 2017 (P = 0.03). Sex-adjusted incidence rates in men increased from 8.60 per 100,000 persons in 2008 to 8.70 in 2017 (P

We studied the brain mechanisms underlying action selection in a social dilemma setting in which individuals’ effortful gains are unfairly distributed among group members. A stable “worker–parasite” relationship developed when three individually operant-conditioned rats were placed together in a Skinner box equipped with response lever and food dispenser on opposite sides. Specifically, one rat, the “worker,” engaged in lever-pressing while the other two “parasitic” rats profited from the worker’s effort by crowding the feeder in anticipation of food. Anatomically, c-Fos expression in the anterior cingulate cortex (ACC) was significantly higher in worker rats than in parasite rats. Functionally, ACC inactivation suppressed the worker’s lever-press behavior drastically under social, but only mildly under individual, settings. Transcriptionally, GABA(A) receptor– and potassium channel–related messenger RNA expressions were reliably lower in the worker’s, relative to parasite’s, ACC. These findings indicate the requirement of ACC activation for the expression of exploitable, effortful behavior, which could be mediated by molecular pathways involving GABA(A) receptor/potassium channel proteins.

Brain-derived neurotrophic factor (BDNF) is widely accepted as being critical for neural and synaptic plasticity throughout the nervous system. Recent work has shown that BDNF in the mesolimbic dopamine (DA) circuit, originating in ventral tegmental area DA neurons that project to the nucleus accumbens, is crucial in the development of depressive-like behaviors following exposure to chronic social defeat stress in mice. Whereas BDNF modulates DA signaling in encoding responses to acute defeat stress, BDNF signaling alone appears to be responsible for the behavioral effects after chronic social defeat stress. Very different patterns are seen with another widely used chronic stress paradigm in mice, chronic mild stress (also known as chronic variable or unpredictable stress), where DA signaling, but not BDNF signaling, is primarily responsible for the behavioral effects observed. This review discusses the molecular, cellular, and circuit basis of this dramatic discrepancy, which appears to involve the nature of the stress, its severity and duration, and its effects on distinct cell types within the ventral tegmental area-to-nucleus accumbens mesolimbic circuit.

Animal studies using chronic social defeat stress (CSDS) in mice showed that brain-derived neurotrophic factor (BDNF) signaling in the mesolimbic dopamine (DA) circuit is important for the development of social aversion. However, the downstream molecular targets after BDNF release from ventral tegmental area (VTA) DA terminals are unknown. Here, we show that depressive-like behaviors induced by CSDS are mediated in part by Gadd45b downstream of BDNF signaling in the nucleus accumbens (NAc). We show that Gadd45b mRNA levels are increased in susceptible but not resilient mice. Intra-NAc infusion of BDNF or optical stimulation of VTA DA terminals in NAc enhanced Gadd45b expression levels in the NAc. Importantly, Gadd45b downregulation reversed social avoidance in susceptible mice. Together, these data suggest that Gadd45b in NAc contributes to susceptibility to social stress. In addition, we investigated the function of Gadd45b in demethylating CpG islands of representative gene targets, which have been associated with a depressive phenotype in humans and animal models. We found that Gadd45b downregulation changes DNA methylation levels in a phenotype-, gene-, and locus-specific fashion. Together, these results highlight the contribution of Gadd45b and changes in DNA methylation in mediating the effects of social stress in the mesolimbic DA circuit.

Behavioral sensitization, an animal model of drug addiction, persists for a prolonged period after repeated exposure to drugs of abuse. The persistence of an addiction behavioral phenotype suggests long-lasting changes in gene regulation at the epigenetic level. We measured the expression of histone deacetylases (HDACs) isoforms in the prefrontal cortex and dorsal striatum following the development of sensitization to cocaine (15 mg/kg, administered five times) and ethanol (0.5 g/kg, administered 15 times) to investigate the epigenetic changes that mediate sensitization. Animals sensitized to ethanol exhibited augmented locomotor activity in response to the cocaine challenge. Similarly, those sensitized to cocaine exhibited increased locomotor activity in response to an ethanol challenge. These findings indicate cross-sensitization between ethanol and cocaine and suggest that a common molecular mechanism underlying the cross-sensitization. In animals sensitized to cocaine or ethanol, mRNA levels of class II HDACs (HDAC4 and HDAC5) were decreased in the prefrontal cortex and dorsal striatum, whereas acute treatments with either drug had no effect on the expression of class II HDACs. By contrast, class I HDACs (HDAC1 and HDAC2) responded to the acute cocaine challenge, whereas sensitization itself did not have a consistent effect on class I HDAC levels. These findings support the hypothesis of a common epigenetic mechanism underlying persistent behavioral sensitization induced by different drugs, which may be mediated by the altered expression of class II HDACs.

This case series investigated the efficacy and optimal dose of Escherichia coli-derived bone morphogenetic protein-2 (E.BMP-2) as a bone graft substitute for additional posterolateral spinal fusion, accompanying interbody fusion procedures, for treating lumbar degenerative spinal stenosis. This study focused on the optimal dose for each segment and the efficacy of E.BMP-2 as a substitute for autogenous iliac bone graft. Ten patients were enrolled from January 2015 to December 2015, and underwent an additional posterolateral fusion procedure, with 2.5 mg of E.BMP-2 followed by decompression, transpedicular fixation, and interbody fusion. The mean follow-up period was 13.9 months, and regular radiological examinations were performed in every case. Clinical outcomes were measured with a visual analog scale for back pain (VAS-BP), and leg pain (VAS-LP) and the Korean Oswestry Disability Index (K-ODI). All parameters were assessed preoperatively and postoperatively at 12 months. All 18 segments treated with E.BMP-2 completely fused in 6 months as observed on both simple radiography and computed tomography. The mean fusion period was 4.5 months on simple radiography. At 12 months follow-up, VAS-BP, VAS-LP, and K-ODI scores (1.9 ± 1.5, 1.9 ± 1.9, 11.0 ± 6.6, respectively) had improved significantly compared to preoperative scores (5.5 ± 1.9, 6.5 ± 1.9, and 49.9 ± 11.5, respectively, P

Immunoglobulin A nephropathy (IgAN) is one of the most common primary glomerulopathies diagnosed in children and adolescents. This study aimed to evaluate the clinical features in and outcomes of pediatric IgAN over the last 30 years. Patients who were diagnosed before age of 18 at 20 centers in Korea were evaluated retrospectively. Of the 1154 patients (768 males, 386 females) with a median follow-up of 5 years, 5.6% (n = 65) progressed to stage 3&ndash, 5 chronic kidney disease (CKD). The 10- and 20-year CKD-free survival rates were 91.2% and 75.6%, respectively. Outcomes did not differ when comparing those in Korea who were diagnosed prior to versus after the year 2000. On multivariate analysis, combined asymptomatic hematuria and proteinuria as presenting symptoms and decreased renal function at the time of biopsy were associated with progression to CKD, while remission of proteinuria was negatively associated with this outcome. Patients who presented with gross hematuria or nephrotic syndrome tended toward positive outcomes, especially if they ultimately achieved remission. While remission of proteinuria might imply that the disease is inherently less aggressive, it also can be achieved by management. Therefore, more aggressive management might be required for pediatric-onset IgAN.

AIM: Although the incidence of urinary tract infection (UTI) in children with lower respiratory tract infection (LRTI) has been reported as 3.1-10.0%, the exact concomitant prevalence is questionable. Here, we evaluated the prevalence and related risk factors of UTI associated with LRTI in children under 36 months of age. METHODS: We retrospectively reviewed the medical charts of 1574 patients under 36 months of age who were hospitalised with LRTI from January 2017 to December 2019 in a single centre, Seoul, South Korea. Among them, we analysed 278 patients who showed fever and performed urine evaluation. Urine was collected by catheterisation in children under 24 months of age and by voided urine between 24 and 36 months of age. RESULTS: The prevalence of concomitant UTI and LRTI was 13.6% in children under 24 months of age. Mean age was significantly younger in the UTI versus non-UTI group (6.93 ± 7.26 months vs. 12.61 ± 11.70 months; P < 0.001). When the participants were stratified by age, the prevalence of UTI was significantly higher in children younger than 24 months of age compared to older ones (P = 0.006). UTIs were more prevalent in boys than in girls (14.6% vs. 5.8%, P = 0.018). Peak body temperature, fever duration, premature birth and detected respiratory virus type did not differ between groups. CONCLUSIONS: It is not uncommon for children with LRTI with fever to be accompanied by UTI. When evaluating for UTI in children with febrile LRTI, age and sex must be considered.

The role of somatostatin interneurons in nucleus accumbens (NAc), a key brain reward region, remains poorly understood due to the fact that these cells account for, While making up a small percentage of neurons in the nucleus accumbens, somatostatin interneurons may have important function in dopamine- and addiction-related behavior. Here, Ribeiro and colleagues show that somatostatin interneurons regulate behavioral responses to cocaine with physiological and transcriptomic changes.

Background The mesolimbic reward system plays a critical role in modulating nociception; however, its underlying molecular, cellular, and neural circuitry mechanisms remain unknown. Methods Chronic constrictive injury (CCI) of the sciatic nerve was used to model neuropathic pain. Projection-specific in vitro recordings in mouse brain slices and in vivo recordings from anesthetized animals were used to measure firing of dopaminergic neurons in the ventral tegmental area (VTA). The role of VTA−nucleus accumbens (NAc) circuitry in nociceptive regulation was assessed using optogenetic and pharmacological manipulations, and the underlying molecular mechanisms were investigated by Western blotting, enzyme-linked immunosorbent assays, and conditional knockdown techniques. Results c-Fos expression in and firing of contralateral VTA−NAc dopaminergic neurons were elevated in CCI mice, and optogenetic inhibition of these neurons reversed CCI-induced thermal hyperalgesia. CCI increased the expression of brain-derived neurotrophic factor (BDNF) protein but not messenger RNA in the contralateral NAc. This increase was reversed by pharmacological inhibition of VTA dopaminergic neuron activity, which induced an antinociceptive effect that was neutralized by injecting exogenous BDNF into the NAc. Moreover, inhibition of BDNF synthesis in the VTA with anisomycin or selective knockdown of BDNF in the VTA−NAc pathway was antinociceptive in CCI mice. Conclusions These results reveal a novel mechanism of nociceptive modulation in the mesolimbic reward circuitry and provide new insight into the neural circuits involved in the processing of nociceptive information.

The return of fear following extinction therapy is an important issue associated with the treatment of many fear-related disorders. Fear renewal is a suitable model, with which context-dependent modulation of the fear response can be examined. In this model, any context outside of an extinction context (e.g., novel or familiar contexts) could evoke relapse of the fear response. However, brain regions associated with context-dependent modulation are not fully understood. The posterior parietal cortex (PPC) is considered a center for integrating multisensory information and making decisions. To study its role in the contextual modulation of fear relapse, we reversibly inactivated the PPC in mice before they were exposed to various contexts after extinction training. When muscimol was infused into the PPC, fear renewal was impaired in a novel context, but not in a familiar context. Fear relapses were blocked during optogenetic inhibition of the PPC, only when animals were placed in a novel context. We propose that the neural activity of the PPC is necessary for the relapse of a precise response to an extinguished conditioned stimulus in a novel context.

Neuroscience research has become a national priority for the Korean government. Korean scholars have dedicated interest in the societal ramifications of neurotechnologies; neuroethics is an integral component of the Korea Brain Initiative and to the formation of its growing neuroscience community.

The cavitation bubble is essential for the ultrasonic degassing, however, the bubble could not be developed at the whole melt because of the threshold intensity for the bubble generation. The intensity of the ultrasound decreases exponentially with the propagation distance. The melt should be transferred to the effective volume that has the sufficient ultrasonic intensity to exceed the threshold for the cavitation generation. The important parameter to make melt transfer is the acoustic streaming induced by the ultrasound. This study is focused on the melt flow and the effect on the degassing level with the ultrasonic frequency to improve efficiency of ultrasonic degassing. The increase of the ultrasonic frequency and amplitude made the cavitation bubble density and the velocity of the melt flow increase, respectively. As the result, the degassing velocity could increase dramatically.

Summary Although medial prefrontal cortex (mPFC) is known to play important roles in social behaviors, how early social experiences affect the mPFC and its subcortical circuit remains unclear. We report that mice singly housed (SH) for 8 weeks after weaning show a social recognition deficit, even after 4 weeks of resocialization. In SH mice, prefrontal infralimbic (IL) neurons projecting to the shell region of nucleus accumbens (NAcSh) show decreased excitability compared with group-housed (GH) mice. NAcSh-projecting IL neurons are activated when GH mice encounter a familiar conspecific, which is not observed in SH mice. Chemogenetic inhibition of NAcSh-projecting IL neurons in normal mice impairs social recognition without affecting social preference, whereas activation of these neurons reverses social recognition deficit in SH mice. Our findings demonstrate that early social experience critically affects mPFC IL-NAcSh projection, the activation of which is required for social recognition by encoding information for social familiarity.