Neural Mechanisms of Absolute Tactile Localization in Monkeys

Macaca nemestrina monkeys were trained to indicate the location of suprathreshold tactile stimuli delivered to the glabrous skin of either foot. The testing paradigm involved self-initiated trials (a bar press), followed by 10-Hz stimulation at one of six locations (e.g., on the distal phalanx of the second toe on the left foot), providing the opportunity for the animal to press one of six buttons located on a facing panel. The buttons were positioned on a picture of a monkey's feet at locations corresponding to the skin loci that were stimulated on different trials. If the animal first presed the button corresponding to the position stimulated, liquid reward was delivered; responses to any other button terminated stimulation without reward, requiring initiation of another trial for the opportunity to receive reinforcement.

The localization errors for normal monkeys were reliably greater along the mediolateral dimension of the foot than they were proximodistally. For example, stimulation of the tip of toe 4 elicited responses to the button at the tip of toe 2 on 25% of the trials, as compared with only 10% errors betweeen the tip of toe 4 and the pad at the base of toe 4. Following unilateral interruption of the dorsal spinal columns at an upper thoracic level, the capacity for absolute tactile localization was unchanged over months of testing. The greater localization accuracy along the proximodistal axis of the foot remained after dorsal column transection.

In order to evaluate neural substrates of localization by monkeys, single-neuron receptive field (RF) sizes and distributions within the first somatosensory (SI) cortex were examined to determine the overlap or separation of the representations of different points on glabrous skin. The sample of neurons that provided the RF data was obtained in previous investigations of unanesthetized, neuromuscularly blocked Macaca fascicularis monkeys. Analysis of RF overlap revealed that greater than 50% of cytoarchitectural area 1 units that responded to stimulation of one digit tip also responded to another digit or to the pad at the base of a digit. These large RFs seem poorly suited to subserve a high degree of spatial localization and are compatible with the frequent localization errors by the monkeys in the behavioral experiments. However, the area 1 RF data do not explain the tendency of these animals to exhibit better localization accuracy along the proximodistal axis than along the mediolateral axis of the volar foot. We suggest that the observed asymmetry of localization accuracy may be the result of dynamic neural mechanisms that involve lateral interactions between cortical columns. Evidence from metabolic mapping experiments suggests that these lateral interactions determine the spatial distribution of cortical columns that respond to repetitive somatic stimuli (Whitsel et al, 1988).     

Prepulse Inhibition of Acoustic Startle Reflex as a Function of the Frequency Difference between Prepulse and Background Sounds in Mice

Background

Prepulse inhibition (PPI) depicts the effects of a weak sound preceding strong acoustic stimulus on acoustic startle response (ASR). Previous studies suggest that PPI is influenced by physical parameters of prepulse sound such as intensity and preceding time. The present study characterizes the impact of prepulse tone frequency on PPI.

Methods

Seven female C57BL mice were used in the present study. ASR was induced by a 100 dB SPL white noise burst. After assessing the effect of background sounds (white noise and pure tones) on ASR, PPI was tested by using prepulse pure tones with the background tone of either 10 or 18 kHz. The inhibitory effect was assessed by measuring and analyzing the changes in the first peak-to-peak magnitude, root mean square value, duration and latency of the ASR as the function of frequency difference between prepulse and background tones.

Results

Our data showed that ASR magnitude with pure tone background varied with tone frequency and was smaller than that with white noise background. Prepulse tone systematically reduced ASR as the function of the difference in frequency between prepulse and background tone. The 0.5 kHz difference appeared to be a prerequisite for inducing substantial ASR inhibition. The frequency dependence of PPI was similar under either a 10 or 18 kHz background tone.

Conclusion

PPI is sensitive to frequency information of the prepulse sound. However, the critical factor is not tone frequency itself, but the frequency difference between the prepulse and background tones.     

Caloric Restriction Engages Hepatic RNA Processing Mechanisms in Rhesus Monkeys

1. Download high-res image (305KB)
2. Download full-size image

     

实验猴麻疹预防和治疗方案初探

实验猴麻疹是造成断奶仔猴死亡的重要传染病之一,本文对该病的临床诊断、护理、预防和治疗方案进行了初步研究,并提出了行之有效的预防、护理及治疗措施。经临床实践证明,该方案对实验猴麻疹的治愈率可达90%以上,值得在国内实验猴生产及科研单位推广应用。     

Hypnotizability,Hypnosis and Prepulse Inhibition of the Startle Reflex in Healthy Women: An ERP Analysis

A working model of the neurophysiology of hypnosis suggests that highly hypnotizable individuals (HHs) have more effective frontal attentional systems implementing control, monitoring performance, and inhibiting unwanted stimuli from conscious awareness, than low hypnotizable individuals (LHs). Recent studies, using prepulse inhibition (PPI) of the auditory startle reflex (ASR), suggest that HHs, in the waking condition, may show reduced sensory gating although they may selectively attend and disattend different stimuli. Using a within subject design and a strict subject selection procedure, in waking and hypnosis conditions we tested whether HHs compared to LHs showed a significantly lower inhibition of the ASR and startle-related brain activity in both time and intracerebral source localization domains. HHs, as compared to LH participants, exhibited (a) longer latency of the eyeblink startle reflex, (b) reduced N100 responses to startle stimuli, and (c) higher PPI of eyeblink startle and of the P200 and P300 waves. Hypnosis yielded smaller N100 waves to startle stimuli and greater PPI of this component than in the waking condition. sLORETA analysis revealed that, for the N100 (107 msec) elicited during startle trials, HHs had a smaller activation in the left parietal lobe (BA2/40) than LHs. Auditory pulses of pulse-with prepulse trials in HHs yielded less activity of the P300 (280 msec) wave than LHs, in the cingulate and posterior cingulate gyrus (BA23/31). The present results, on the whole, are in the opposite direction to PPI findings on hypnotizability previously reported in the literature. These results provide support to the neuropsychophysiological model that HHs have more effective sensory integration and gating (or filtering) of irrelevant stimuli than LHs.     

黏蛋白对气道黏液高分泌的抑制及其机制研究

制造黏液是一种维持肺部健康的主要防御机制,然而黏液中主要糖蛋白成份即黏蛋白的过量产生却是哮喘、慢性阻塞性肺疾病(COPD)、囊性纤维化(CF)及肺癌的共同疾病特征.目前,以黏蛋白的过量表达与分泌作为靶标的治疗手段的研究刚刚起步.该文将讨论肺部黏蛋白基因表达及其表达产物释放到气道中的调控机制方面的最新研究进展,并提出抑制气道黏液高分泌的有效治疗策略.     

Contrasting Effect of Prepulse Signals on Performance of Toxoplasma-Infected and Toxoplasma-Free Subjects in an Acoustic Reaction Times Test

Background

About 30% of people on Earth have latent toxoplasmosis. Infected subjects do not express any clinical symptoms, however, they carry dormant stages of parasite Toxoplasma for the rest of their life. This form of toxoplasmosis is mostly considered harmless, however, recent studies showed its specific effects on physiology, behaviour and its associations with various diseases, including psychiatric disorders such as schizophrenia. Individuals who suffer from schizophrenia have about 2.7 times higher prevalence of Toxoplasma-seropositivity than controls, which suggests that some traits characteristic of schizophrenic patients, including the sex difference in schizophrenia onset, decrease of grey matter density in specific brain areas and modification of prepulse inhibition of startle reaction could in fact be caused by toxoplasmosis for those patients who are Toxoplasma-seropositive.

Methodology/Principal Findings

We measured the effect of prepulse inhibition/facilitation of the startle reaction on reaction times. The students, 170 women and 66 men, were asked to react as quickly as possible to a startling acoustic signal by pressing a computer mouse button. Some of the startling signals were without the prepulse, some were 20 msec. preceded by a short (20 msec.) prepulse signal of lower intensity. Toxoplasma-seropositive subjects had longer reaction times than the controls. Acoustic prepulse shorted the reaction times in all subjects. This effect of prepulse on reaction times was stronger in male subjects and increased with the duration of infection, suggesting that it represented a cumulative effect of latent toxoplasmosis, rather than a fading out after effect of past acute toxoplasmosis.

Conclusions

Different sensitivity of Toxoplasma-seropositive and Toxoplasma-seronegative subjects on effect of prepulses on reaction times (the toxoplasmosis-prepulse interaction) suggested, but of course did not prove, that the alternations of prepulse inhibition of startle reaction observed in schizophrenia patients probably joined the list of schizophrenia symptoms that are in fact caused by latent toxoplasmosis.     

Rosette Inhibition Test in Severely Burned Patients

The rosette inhibition test has been advocated as a test of immune reactivity in patients given transplants. We have done the test in lymphocytes from patients with severe burns, non-burnt control patients, and normal subjects. There was no correlation with the period of immunosuppression which follows a severe burn, though both groups of patients showed a wider range of minimal inhibitory concentrations (M.I.C.) than the normal group. Wide day-to-day variation of M.I.C. in burn and control patients was noted; this seemed to correlate with the ratio of sodium to potassium excreted in the urine. In-vitro experiments suggest that the M.I.C. is correlated with a plasma constituent which may be similar in action to hydrocortisone and that the rosette inhibition test is not a direct measure of immune reactivity.     

Inhibition of Adaptive Immune Responses Leads to a Fatal Clinical Outcome in SIV-Infected Pigtailed Macaques but Not Vervet African Green Monkeys

African green monkeys (AGM) and other natural hosts for simian immunodeficiency virus (SIV) do not develop an AIDS-like disease following SIV infection. To evaluate differences in the role of SIV-specific adaptive immune responses between natural and nonnatural hosts, we used SIV_agmVer90 to infect vervet AGM and pigtailed macaques (PTM). This infection results in robust viral replication in both vervet AGM and pigtailed macaques (PTM) but only induces AIDS in the latter species. We delayed the development of adaptive immune responses through combined administration of anti-CD8 and anti-CD20 lymphocyte-depleting antibodies during primary infection of PTM (n = 4) and AGM (n = 4), and compared these animals to historical controls infected with the same virus. Lymphocyte depletion resulted in a 1-log increase in primary viremia and a 4-log increase in post-acute viremia in PTM. Three of the four PTM had to be euthanized within 6 weeks of inoculation due to massive CMV reactivation and disease. In contrast, all four lymphocyte-depleted AGM remained healthy. The lymphocyte-depleted AGM showed only a trend toward a prolongation in peak viremia but the groups were indistinguishable during chronic infection. These data show that adaptive immune responses are critical for controlling disease progression in pathogenic SIV infection in PTM. However, the maintenance of a disease-free course of SIV infection in AGM likely depends on a number of mechanisms including non-adaptive immune mechanisms.     

Multiple Mechanisms for Inhibition of Excitatory Amino Acid Receptors Coupled to Phosphoinositide Hydrolysis

Excitatory amino acid (EAA) analogues activate receptors that are coupled to the increased hydrolysis of phosphoinositides (PIs). In these studies, hippocampal slices were prepared from neonatal rats (6-11 days old) to characterize the effects of EAA analogues on these receptors. The concentrations of ibotenate and trans-(+/-)-1-amino-1,3-cyclopentanedicarboxylate (trans-ACPD) required to evoke half-maximal stimulation (EC50 values) were 28 and 51 microM, respectively. Although the data for stimulation of PI hydrolysis by ibotenate and trans-ACPD were best fit to theoretical curves that had Hill slopes of 1, data for stimulation of PI hydrolysis by quisqualate were best fit to two sites. The EC50 values were 0.43 and 44 microM. The high-affinity sites were 70% of the total. A number of EAA analogues were tested for inhibition of PI metabolism. One of these, L-aspartate-beta-hydroxamate (L-A beta HA), was identified as a novel inhibitor of this response. L-A beta HA was equipotent as an inhibitor of PI metabolism stimulated by ibotenate, quisqualate, and trans-ACPD. The data for this inhibition were best fit to two sites. Between 32 and 48% of the total sites had high affinity with IC50 values in the range of 1.2-6.3 microM. The low-affinity sites had IC50 values between 610 and 2,700 microM. DL-2-Amino-3-phosphonopropionate (DL-AP3) was also equipotent as an inhibitor of PI hydrolysis stimulated by ibotenate, quisqualate, and trans-ACPD (IC50 values were 480-850 microM). In contrast to the data for L-A beta HA, the data for DL-AP3 were best fit to a single site. Both of these inhibitors reduced the maximal response caused by the agonists, consistent with noncompetitive mechanisms of action. Several experiments were designed to examine potential mechanisms for these noncompetitive effects. These studies suggest that either L-A beta HA and DL-AP3 bind to a site on the receptor and irreversibly block activation of the receptor, or that these inhibitors act via a distinct site that specifically regulates EAA receptors coupled to PI hydrolysis.     

Evaluation of Rosette Inhibition Test in Renal Transplantation

Serial rosette inhibition tests were performed on 11 renal transplant patients in an attempt to predict graft rejection. The rosette inhibition titre was higher in immunosuppressed patients than in normal subjects. The test was of predictive value in only two out of 12 rejection episodes, where a fall in titre to normal levels occurred 48 hours and 24 hours, respectively, before biochemical evidence of rejection. In two further rejection episodes the titre fell at the time of rejection. The titre changes in all tests were small and there were frequent inconsistencies in the results of individual tests. A study of the variables was undertaken, with standardization of the technique, and improvements were made in reading the test. Despite these changes the test was still not sufficiently accurate or reliable to be used as the basis of treatment of rejection episodes.     

神经调节素对大鼠脑缺血再灌注损伤后炎症反应的抑制作用和机制研究

目的：研究神经调节素及基质金属蛋白酶-9对于小鼠大脑缺血再灌注损伤后炎症反应的抑制作用和机制。方法：选取100只成年雄性大鼠,随机分成对照和治疗组。采用线栓方法由颈内到颈外进行插线处理,造成大脑中动脉处于闭塞状态的再灌注动物模型。治疗组颈动脉进行注射少量NRG-1β干预性治疗,通过氯化三苯基四氮唑（TTC）检查脑梗塞范围,细胞凋亡采用原住脱氧核糖核苷酸末端转移酶介导缺口末端进行标记,采用免疫组织化学、免疫荧光双标记法及免疫印迹法观察脑组织基质金属蛋白酶-9（MMP-9）表达。结果：脑缺血再灌注损伤后,随时间延长及缺氧,对照组大鼠大脑皮质和纹状体区脑组织细胞凋亡,并且胶质细胞MMP-9蛋白表达逐渐增加。治疗组大鼠经注射NRG-1β干预性治疗后,缺血脑组织梗死范围及其细胞凋亡数量相对呈明显下降趋势。胶质细胞MMP-9表达呈降低趋势。结论：大鼠脑缺血再灌注损伤后体内NRG-1β抑制胶质细胞MMP-9的表达,控制缺血脑组织梗死的范围并抑制正常细胞的凋亡,发挥了重要的抗炎作用,可作为对于大脑缺血再灌注损伤的研究新靶点。     

Assessing the Occurrence of Sexual Segregation in Spider Monkeys (Ateles geoffroyi yucatanensis), Its Mechanisms and Function

Sexual segregation is a recognized dimension of the socioecology of many vertebrates, but it has not been systematically examined in primates. We investigated temporal patterns of sexual segregation in spider monkeys (Ateles geoffroyi yucatanensis) using a test that distinguishes sexual segregation from aggregation and random association between the sexes. We further investigated how sexual segregation varies over time as a function of food availability, and then tested other possible factors that might be causally linked to sexual segregation in spider monkeys. We predicted that male philopatry and cooperative territorial defence leads to sexual dimorphism in behavior, which in turn creates different optimal energetic requirements for males and females as reflected in differing activity budgets and diet. We investigated sexual segregation in a group of 33–35 spider monkeys at Runaway Creek Nature Reserve in Belize over 23 mo in 2008–2009. We used the sex compositions of subgroups recorded in scan samples to test the occurrence of sexual segregation at monthly and biweekly time scales.We found that males and females were significantly segregated in 15 out of the 23 mo of the study, and that periods of nonsegregation coincided with months of low food availability. The sexes differed significantly in activity and diet; males spent more time traveling, and less time resting and feeding than females, and they had a higher proportion of ripe fruits in their diets than did females. We propose that sexual segregation in spider monkeys is primarily a form of social segregation that results from males and females pursuing optimal dietary and behavioral strategies to satisfy sex-specific energetic demands. We further suggest that sexual segregation represents an important constraint on fission–fusion dynamics that should be considered when assessing the potential for variability in subgroup composition.     

Reproducibility of a Neuraminidase Inhibition Test Employed to Measure Anti-Influenza Neuraminidase Antibody

The standard deviation was determined for 146 replications of the neuraminidase inhibition test for antineuraminidase antibody employing two ferret antisera and the recombinant viruses X-15 and X-15(HK). The standard deviation found was 0.612 log(2) and is a quantitative estimate of the reproducibility of the test.     

Microcomplement-Fixation Inhibition: a Rapid and Economical Test to Detect Non-Complement-Fixing Antibodies

Complement-fixation inhibition test was adapted to the microtiter system. When cat and monkey non-complement-fixing antibody were used, the microtest was shown to be as sensitive as the conventional tube complement-fixation inhibition test.     

Modifications of the Growth Inhibition Test and its Application to Human T-Mycoplasmas

Several factors were found to influence the growth inhibition test. Inoculum size and amount of antiserum are well known variables, but the method of applying the antiserum, the incubation temperature, and the pH of the agar medium also play significant roles. The growth inhibition test modified according to these findings was found to be specific and well suited for the classification and identification of human T-mycoplasmas.     

Peripheral Afferent Mechanisms Underlying Acupuncture Inhibition of Cocaine Behavioral Effects in Rats

Administration of cocaine increases locomotor activity by enhancing dopamine transmission. To explore the peripheral mechanisms underlying acupuncture treatment for drug addiction, we developed a novel mechanical acupuncture instrument (MAI) for objective mechanical stimulation. The aim of this study was to evaluate whether acupuncture inhibition of cocaine-induced locomotor activity is mediated through specific peripheral nerves, the afferents from superficial or deep tissues, or specific groups of nerve fibers. Mechanical stimulation of acupuncture point HT7 with MAI suppressed cocaine-induced locomotor activity in a stimulus time-dependent manner, which was blocked by severing the ulnar nerve or by local anesthesia. Suppression of cocaine-induced locomotor activity was elicited after HT7 stimulation at frequencies of either 50 (for Meissner corpuscles) or 200 (for Pacinian corpuscles) Hz and was not affected by block of C/Aδ-fibers in the ulnar nerve with resiniferatoxin, nor generated by direct stimulation of C/Aδ-fiber afferents with capsaicin. These findings suggest that HT7 inhibition of cocaine-induced locomotor activity is mediated by A-fiber activation of ulnar nerve that originates in superficial and deep tissue.