查看更多>>摘要：The nucleus tractus solitarii(NTS)is one of the morphologically and functionally defined centers that engage in the autonomic regulation of cardiovascular activ-ity.Phenotypically-characterized NTS neurons have been implicated in the differential regulation of blood pressure(BP).Here,we investigated whether phenylethanolamine N-methyltransferase(PNMT)-expressing NTS(NTSPNMT)neurons contribute to the control of BP.We demonstrate that photostimulation of NTSPNMT neurons has variable effects on BP.A depressor response was produced during optogenetic stimulation of NTSPNMT neurons projecting to the paraventricular nucleus of the hypothalamus,lateral parabrachial nucleus,and caudal ventrolateral medulla.Con-versely,photostimulation of NTSPNMT neurons projecting to the rostral ventrolateral medulla produced a robust pressor response and bradycardia.In addition,genetic ablation of both NTSPNMT neurons and those projecting to the rostral ventrolateral medulla impaired the arterial baroreflex.Over-all,we revealed the neuronal phenotype-and circuit-specific mechanisms underlying the contribution of NTSPNMT neu-rons to the regulation of BP.
查看更多>>摘要：The chronic use of morphine and other opioids is associated with opioid-induced hypersensitivity(OIH)and analgesic tolerance.Among the different forms of OIH and tolerance,the opioid receptors and cell types mediat-ing opioid-induced mechanical allodynia and anti-allo-dynic tolerance remain unresolved.Here we demonstrated that the loss of peripheral μ-opioid receptors(MORs)or MOR-expressing neurons attenuated thermal tolerance,but did not affect the expression and maintenance of morphine-induced mechanical allodynia and anti-allodynic tolerance.To confirm this result,we made dorsal root ganglia-dorsal roots-sagittal spinal cord slice preparations and recorded low-threshold Aβ-fiber stimulation-evoked inputs and out-puts in superficial dorsal horn neurons.Consistent with the behavioral results,peripheral MOR loss did not prevent the opening of Aβ mechanical allodynia pathways in the spinal dorsal horn.Therefore,the peripheral MOR signaling path-way may not be an optimal target for preventing mechanical OIH and analgesic tolerance.Future studies should focus more on central mechanisms.
查看更多>>摘要：Mechanical allodynia(MA),including punctate and dynamic forms,is a common and debilitating symptom suffered by millions of chronic pain patients.Some periph-eral injuries result in the development of bilateral MA,while most injuries usually led to unilateral MA.To date,the con-trol of such laterality remains poorly understood.Here,to study the role of microglia in the control of MA laterality,we used genetic strategies to deplete microglia and tested both dynamic and punctate forms of MA in mice.Surpris-ingly,the depletion of central microglia did not prevent the induction of bilateral dynamic and punctate MA.Moreo-ver,in dorsal root ganglion-dorsal root-sagittal spinal cord slice preparations we recorded the low-threshold Aβ-fiber stimulation-evoked inputs and outputs of superficial dorsal horn neurons.Consistent with behavioral results,microglial depletion did not prevent the opening of bilateral gates for Aβ pathways in the superficial dorsal horn.This study chal-lenges the role of microglia in the control of MA lateral-ity in mice.Future studies are needed to further understand whether the role of microglia in the control of MA laterality is etiology-or species-specific.
查看更多>>摘要：During natural viewing,we often recognize mul-tiple objects,detect their motion,and select one object as the target to track.It remains to be determined how such behavior is guided by the integration of visual form and motion perception.To address this,we studied how monkeys made a choice to track moving targets with different forms by smooth pursuit eye movements in a two-target task.We found that pursuit responses were biased toward the motion direction of a target with a hole.By computing the relative weighting,we found that the target with a hole exhibited a larger weight for vector computation.The global hole feature dominated other form properties.This dominance failed to account for changes in pursuit responses to a target with different forms moving singly.These findings suggest that the integration of visual form and motion perception can reshape the competition in sensorimotor networks to guide behavioral selection.
查看更多>>摘要：The incidence rate of anxiety and depression is significantly higher in patients with inflammatory bowel dis-eases(IBD)than in the general population.The mechanisms underlying dextran sulfate sodium(DSS)-induced depres-sive-like behaviors are still unclear.We clarified that IBD mice induced by repeated administration of DSS presented depressive-like behaviors.The paraventricular thalamic nucleus(PVT)was regarded as the activated brain region by the number of c-fos-labeled neurons.RNA-sequencing analysis showed that lipocalin 2(Lcn2)was upregulated in the PVT of mice with DSS-induced depressive behaviors.Upregulating Lcn2 from neuronal activity induced den-dritic spine loss and the secreted protein induced chemokine expression and subsequently contributed to microglial acti-vation leading to blood-brain barrier permeability.Moreo-ver,Lcn2 silencing in the PVT alleviated the DSS-induced depressive-like behaviors.The present study demonstrated that elevated Lcn2 in the PVT is a critical factor for DSS-induced depressive behaviors.
查看更多>>摘要：Evidence suggests that explicit reappraisal has limited regulatory effects on high-intensity emotions,mainly due to the depletion of cognitive resources occupied by the high-intensity emotional stimulus itself.The implicit form of reappraisal has proved to be resource-saving and therefore might be an ideal strategy to achieve the desired regulatory effect in high-intensity situations.In this study,we explored the regulatory effect of explicit and implicit reappraisal when participants encountered low-and high-intensity negative images.The subjective emotional rating indicated that both explicit and implicit reappraisal down-regulated negative experiences,irrespective of intensity.However,the amplitude of the parietal late positive potential(LPP;a neural index of experienced emotional intensity)showed that only implicit reappraisal had significant regulatory effects in the high-intensity context,though both explicit and implicit reappraisal successfully reduced the emotional neural responses elicited by low-intensity negative images.Meanwhile,implicit reappraisal led to a smaller frontal LPP amplitude(an index of cognitive cost)compared to explicit reappraisal,indicating that the implementation of implicit reappraisal consumes limited cognitive control resources.Furthermore,we found a prolonged effect of implicit emo-tion regulation introduced by training procedures.Taken together,these findings not only reveal that implicit reap-praisal is suitable to relieve high-intensity negative expe-riences as well as neural responses,but also highlight the potential benefit of trained implicit regulation in clinical populations whose frontal control resources are limited.
查看更多>>摘要：The physiological functions of endogenous amyloid-β(Aβ),which plays important role in the pathol-ogy of Alzheimer's disease(AD),have not been paid enough attention.Here,we review the multiple physiological effects of Aβ,particularly in regulating synaptic transmission,and the possible mechanisms,in order to decipher the real char-acters of Aβ under both physiological and pathological con-ditions.Some worthy studies have shown that the depriva-tion of endogenous Aβ gives rise to synaptic dysfunction and cognitive deficiency,while the moderate elevation of this peptide enhances long term potentiation and leads to neuronal hyperexcitability.In this review,we provide a new view for understanding the role of Aβ in AD pathophysiol-ogy from the perspective of physiological meaning.
查看更多>>摘要：Machine learning approaches are increasingly being applied to neuroimaging data from patients with psy-chiatric disorders to extract brain-based features for diagno-sis and prognosis.The goal of this review is to discuss recent practices for evaluating machine learning applications to obsessive-compulsive and related disorders and to advance a novel strategy of building machine learning models based on a set of core brain regions for better performance,inter-pretability,and generalizability.Specifically,we argue that a core set of co-altered brain regions(namely'core regions')comprising areas central to the underlying psychopathology enables the efficient construction of a predictive model to identify distinct symptom dimensions/clusters in individual patients.Hypothesis-driven and data-driven approaches are further introduced showing how core regions are identified from the entire brain.We demonstrate a broadly applica-ble roadmap for leveraging this core set-based strategy to accelerate the pursuit of neuroimaging-based markers for diagnosis and prognosis in a variety of psychiatric disorders.
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