Serotonin Modulates Olfactory Processing in the Antennal Lobe of Drosophila

Sensory systems must be able to extract features of environmental cues within the context of the different physiological states of the organism and often temper their activity in a state-dependent manner via the process of neuromodulation. We examined the effects of the neuromodulator serotonin on a well-characterized sensory circuit, the antennal lobe of Drosophila melanogaster, using two-photon microscopy and the genetically expressed calcium indicator, G-CaMP. Serotonin enhances sensitivity of the antennal lobe output projection neurons in an odor-specific manner. For odorants that sparsely activate the antennal lobe, serotonin enhances projection neuron responses and causes an offset of the projection neuron tuning curve, most likely by increasing projection neuron sensitivity. However, for an odorant that evokes a broad activation pattern, serotonin enhances projection neuron responses in some, but not all, glomeruli. Further, serotonin enhances the responses of inhibitory local interneurons, resulting in a reduction of neurotransmitter release from the olfactory sensory neurons via GABA_B receptor-dependent presynaptic inhibition, which may be a mechanism underlying the odorant-specific modulation of projection neuron responses. Our data suggest that the complexity of serotonin modulation in the antennal lobe accommodates coding stability in a glomerular pattern and flexible projection neuron sensitivity under different physiological conditions.     

Activation of Dopamine D2 Receptor Alleviates Neuroinflammation in a Mouse Model of Allergic Rhinitis With Olfactory Dysfunction

PurposeAllergic rhinitis (AR) is a common otolaryngology disease and one of the clinical causes of olfactory dysfunction (OD). The olfactory bulb serves as a transfer station for olfactory information transmission, and alleviating its neuroinflammation may be expected to improve AR-induced OD. Recent studies have suggested that the dopamine D2 receptor acts as a key target in regulating immune functions and neuroinflammatory reaction. However, the effect of dopamine D2 receptor on AR-induced neuroinflammation is still unknown.MethodsAn AR mouse model with OD induced by ovalbumin were constructed. The buried food pellet test was to evaluate the olfactory function of the mice. Immunofluorescence staining, hematoxylin and eosin staining, enzyme-linked immunosorbent assay and western blotting were also used to investigate the molecular mechanisms underlying the anti-inflammatory effects of the dopamine D2 receptor in AR-induced OD.ResultsWe found that AR-induced OD has a relationship with inflammatory responses in the olfactory bulb. Nasal administration of quinpirole (Quin, a dopamine D2 receptor agonist, 3 mg/kg) improved olfactory function in mice, inhibited the expression of toll-like receptor 4 (TLR4)/nuclear factor-κB (NF-κB) signalings and the levels of tumor necrosis factor-α, interleukin (IL)-1β and IL-6 in the olfactory bulb. In vitro, Quin (20 μmol/L) inhibited the release of TLR4/NF-κB signalings-dependent inflammatory cytokines in cultured microglia.ConclusionsActivation of the dopamine D2 receptor inhibits the release of inflammatory cytokines through TLR4/NF-κB signaling in the olfactory bulb microglia, and protects olfactory function.     

Model for olfactory discrimination and learning in Limax procerebrum incorporating oscillatory dynamics and wave propagation

We extend our model of the procerebral (PC) lobe of Limax, which is comprised of a layer of coupled oscillators and a layer of memory neurons, each layer 4 rows by 20 columns, corresponding to the cell body layer (burster cells) and neuropil layer (nonburster cells) of the PC lobe. A gradient of connections in the layer of model burster cells induces periodic wave propagation, as measured in the PC lobe. We study odor representations in the biological PC lobe using the technique of Kimura and coworkers. Lucifer yellow injection into intact Limax after appetitive or aversive odor learning results in a band or patch of labeled cells in the PC lobe with the band long axis normal to the axis of wave propagation. Learning two odors yields two parallel bands of labeled PC cells. We introduce olfactory input to our model PC lobe such that each odor maximally activates a unique row of four cells which produces a short-term memory trace of odor stimulation. A winner-take-all synaptic competition enabled by collapse of the phase gradient during odor presentation produces a single short-term memory band for each odor. The short-term memory is converted to long-term memory if odor stimulation is followed by activation of an input pathway for the unconditioned stimulus (US) which presumably results in release of one or more neuromodulatory amines or peptides in the PC lobe.     

嗅觉神经系统识别机制模型研究进展

相对人体其他的感觉系统,嗅觉神经系统是目前人们了解得较少的感觉神经系统.近来的科学研究表明,对复杂的嗅觉系统的研究有助于人们了解人体整个感觉系统的工作原理.本文以嗅觉神经系统的时空编码和解码机制研究为重点,介绍了近年来国际上广泛研究的、基于嗅觉生理解剖基础之上的嗅觉神经系统识别机制模型的研究工作.最后,结合我们目前的研究工作对嗅觉系统识别模型研究的发展进行了展望.     

生物嗅觉神经系统模型的模拟与分析

研究生物嗅觉神经系统模型,有助于更好地了解嗅觉机理和嗅神经的放电模式.本研究分析了K系列嗅觉神经系统模型的拓扑结构、数学基础的发展和应用,对该系列模型中的KⅢ模型进行了数值模拟及时域,频域和时频域分析;概述了K系列模型的发展和应用.由结果看出,KⅢ网络模型可以很好地模拟嗅觉神经系统的电活动.     

Leukocyte Infiltration Triggers Seizure Recurrence in a Rat Model of Temporal Lobe Epilepsy

Epilepsy, which affects about 1 % of the population worldwide, leads to poor prognosis and increased morbidity. However, effective drugs providing satisfactory control on seizure relapse were rare, which encouraged more etiological studies. Whether inflammation is one of key events underlying seizure is in debate. In order to explore the role of inflammatory in the pathogenesis and development of epilepsy, we conducted intra-caudal vein injection of leukocytes to aggravated brain inflammatory process in kainic acid-induced seizure model in this study. The results showed that intravenous administration of activated leukocytes increased the frequency and reduced the latent phase of seizure recurrences in rat models of epileptic seizure, during which leukocyte inflammation, brain–blood barrier damage, and neuron injury were also significantly aggravated, indicating that leukocyte infiltration might facilitate seizure recurrence through aggravating brain inflammation, brain–blood barrier damage, and neuron injury.     

Predictive Capability of Anorectal Physiologic Tests for Unfavorable Outcomes Following Biofeedback Therapy in Dyssynergic Defecation

The purpose of this study is to evaluate the predictive capability of anorectal physiologic tests for unfavorable outcomes prior to the initiation of biofeedback therapy in patients with dyssynergic defecation. We analyzed a total of 80 consecutive patients who received biofeedback therapy for chronic idiopathic functional constipation with dyssynergic defecation. After classifying the patients into two groups (responders and non-responders), univariate and multivariate analyses were performed to determine the predictors associated with the responsiveness to biofeedback therapy. Of the 80 patients, 63 (78.7%) responded to biofeedback therapy and 17 (21.3%) did not. On univariate analysis, the inability to evacuate an intrarectal balloon (P=0.028), higher rectal volume for first, urgent, and maximal sensation (P=0.023, P=0.008, P=0.007, respectively), and increased anorectal angle during squeeze (P=0.020) were associated with poor outcomes. On multivariate analysis, the inability to evacuate an intrarectal balloon (P=0.018) and increased anorectal angle during squeeze (P=0.029) were both found to be independently associated with a lack of response to biofeedback therapy. Our data show that the two anorectal physiologic test factors are associated with poor response to biofeedback therapy for patients with dyssynergic defecation. These findings may assist physicians in predicting the responsiveness to therapy for this patient population.     

FDG-PET and NeuN-GFAP Immunohistochemistry of Hippocampus at Different Phases of the Pilocarpine Model of Temporal Lobe Epilepsy

Purpose: Hippocampal glucose hypometabolism has been implicated in the pathogenesis of temporal lobe epilepsy (TLE). However, the underlying pathophysiological basis for this hypometabolism remains elusive. The aim of this study was to investigate the relationship between hippocampal hypometabolism and the histological changes seen in rats after systemic pilocarpine treatment.Methods: ¹⁸F-fluorodeoxyglucose (FDG) small-animal positron emission tomography (microPET) was performed on day zero (untreated), day seven (latent) and day sixty (chronic phase) after the initial status epilepticus. The microPET imaging data were correlated with the immunoreactivity of neuron-specific nuclear protein (NeuN) and glial fibrillary acidic protein (GFAP) in the hippocampus at each time point.Results: ¹⁸F-FDG-microPET images showed the hippocampus presented with persistent hypometabolism during epileptogenesis and partly recovered in the chronic phase. Hippocampal glucose uptake defects correlate with NeuN immunoreactivity in the latent phase and GFAP immunoreactivity in the chronic phase.Conclusions: Severe glucose hypometabolism in the hippocampus during the latent phase correlates with neuronal cell loss. The partial recovery of hippocampal glucose uptake in the chronic phase may be due to astrogliosis.     

Efficacy of the Star Excursion Balance Tests in Detecting Reach Deficits in Subjects With Chronic Ankle Instability

OBJECTIVE: Chronic instability after lateral ankle sprain has been shown to cause balance deficits during quiet standing. Although static balance assessment in those with ankle instability has been thoroughly examined in the literature, few researchers have studied performance on more dynamic tasks. Our purpose was to determine if the Star Excursion Balance Tests (SEBTs), lower extremity reach tests, can detect deficits in subjects with chronic ankle instability. DESIGN AND SETTING: We performed all testing in a university athletic training facility. We tested lower extremity reach using the SEBTs, which incorporates single-leg stance with maximal reach of the contralateral leg. SUBJECTS: Twenty subjects with unilateral, chronic ankle instability (age = 19.8 +/- 1.4 years, height = 176.8 +/- 4.5 cm, mass = 82.9 +/- 21.2 kg) and 20 uninjured subjects matched by sex, sport, and position (age = 20.2 +/- 1.4 years, height = 178.7 +/- 4.1 cm, mass = 82.7 +/- 19.9 kg). MEASUREMENTS: We measured the reach distances in centimeters (cm) and averaged 3 reaches in each of the 8 directions while the subjects stood on each leg for data analysis. RESULTS: The group with chronic ankle instability demonstrated significantly decreased reach while standing on the injured limb compared with the matched limb of the uninjured group (78.6 cm versus 82.8 cm). Additionally, subjects with chronic ankle instability reached significantly less when standing on their injured limbs as compared with their uninjured limbs (78.6 cm versus 81.2 cm). CONCLUSIONS: The SEBTs appear to be an effective means for determining reach deficits both between and within subjects with unilateral chronic ankle instability.     

最小模型参数的估计对胰岛素敏感性指数的影响

Bergman最小模型是研究葡萄糖和胰岛素代谢最具代表性的模型。通过随机变动Bergman模型中部分参数值,数值计算得到各时间点胰岛素和葡萄糖的浓度值。利用这些数据拟合模型参数并估计出SG值和ISI值,使用统计学方法分析Bergman最小模型法估计值的SG值和ISI值随模型参数变化的情况。分析结果表明,P1在临床指标内取值,最小模型计算得到的估计值数据分布为正态;胰岛素动力学方程的参数与SG和ISI的估计值存在着强线性相关关系;而P1和P3的取值对SG和ISI的估计值有着直接的影响;SG和ISI的估计值存在着低估现象,但误差的范围小于2.5%。