[Analysis on survival time and influencing factors among reported HIV/AIDS in Yunnan Province, 1989-2021].

Objective: To analyze the survival time of reported HIV/AIDS and influencing factors of Yunnan Province from 1989 to 2021. Methods: The data were extracted from the Chinese HIV/AIDS comprehensive response information management system. The retrospective cohort study was conducted. The life table method was applied to calculate the survival probability. Kaplan-Meier was used to draw survival curves in different situations. Furthermore, the Cox proportion hazard regression model was constructed to identify the factors related to survival time. Results: Of the 174 510 HIV/AIDS, the all-cause mortality density was 4.23 per 100 person-years, the median survival time was 20.00 (95%CI:19.52-20.48) years, and the cumulative survival rates in 1, 10, 20, and 30 years were 90.75%, 67.50%, 47.93% and 30.85%. Multivariate Cox proportional risk regression model results showed that the risk of death among 0-14 and 15-49 years old groups were 0.44 (95%CI: 0.34-0.56) times and 0.51 (95%CI:0.50-0.52) times of ≥50 years old groups. The risk for death among the first CD4+T lymphocytes counts (CD4) counts levels of 200-349 cells/µl, 350-500 cells/µl and ≥501 cells/µl groups were 0.52 (95%CI: 0.50-0.53) times, 0.41 (95%CI: 0.40-0.42) times and 0.35 (95%CI: 0.34-0.36) times of 0-199 cells/µl groups. The risk of death among the cases that have not received antiretroviral therapy (ART) was 11.56 (95%CI: 11.26-11.87) times. The risk for death among the cases losing to ART, stopping to ART, both losing and stopping ART was 1.66 (95%CI:1.61-1.72) times, 2.49 (95%CI:2.39-2.60) times, and 1.65 (95%CI:1.53-1.78) times of the cases on ART. Conclusions: The influencing factors for the survival time of HIV/AIDS cases were age at diagnosis in Yunnan province from 1989 to 2021. The first CD4 counts levels, antiretroviral therapy, and ART compliance. Early diagnosis, early antiretroviral therapy, and increasing ART compliance could extend the survival time of HIV/AIDS cases.

[Analysis on the proportion of men who have sex with men and related factors among male over 15 years old in Kunming].

Objectives: To investigate the proportion of MSM among males over 15 years old and analyze its related factors to provide a reference for estimation of MSM size. Methods: Using cross-sectional survey design, multi-stage sampling method, and street interception survey method, a survey was conducted on males over 15 years old in Kunming from October to December 2019, with an estimated sample size of 9 908. Results: Totally, 10 707 males were recruited from 30 sites in 5 counties, and 10 283 were effectively surveyed with a response rate of 96.0%. Respondents aged 16 to 40 accounted for 75.3% (7 748), senior high school or above 71.1% (7 312), and unmarried 49.8% (5 121). The proportion of homosexual behavior in the past half-year was 1.06% (95%CI: 0.86%-1.26%), and the age-adjusted rate was 0.97% (95%CI: 0.78%-1.16%). And multivariate logistic regression showed the associated factors for homosexual behavior as following: proportion of main urban area was 2.217 times (95%CI:1.004-4.895) that of the outer suburbs, registered residence outside Kunming was 0.421 times (95%CI:0.260-0.682) that of in Kunming, having been in Kunming ≤6 months was 2.282 times (95%CI:1.262-4.126) that of >6 months, senior middle school or above was 0.336 times (95%CI:0.228-0.495) that of junior middle school and below, and being married was 0.462 times (95%CI:0.303-0.705) that of unmarried. Conclusions: The proportion of over 15-year-old males who have recently practiced male-male behavior was close to 1.00% in Kunming. The relevant factors included survey areas with a permanent residency of Kumming, short-time residency, education level, and marital status. This study obtained the data and related factors, which provided a reference for estimating MSM size in Yunnan province.

[Knowledge, related behavior and on AIDS/HIV infection among rural adults with Derung minority, in Yunnan province, 2016].

Objective: To understand the related risk behaviors, knowledge and status of HIV/AIDS infection among rural adults of Derung minority, to provide relevant messages for the development of HIV/AIDS intervention strategy in this minority group. Methods: We used system sampling method to conduct a cross-sectional survey in 6 administration villages of Derung Township, Gongshan Derung and Nu Autonomous County in Nujiang Lisu Autonomous Prefecture of Yunnan Province, with a sample size estimated as 383. Adult residents with Derung minority in six villages of Gongshan County were involved, with relevant information collected through door-to-door visit. HIV antibody was tested and SPSS 17.0 was used for statistical analysis. Results: Information on 394 valid respondents was collected, with age as between 18 and 65 (34.39±9.74), 80.7% (318/394) as married, 54.0% (213/394) having had primary school education, 13.2% (52/394) as migrant workers. In this population, the overall HIV infection rate appeared as 0.5% (2/400), mainly through sexually transmission. The rate of awareness on HIV/AIDS was 69.8% (275/394), mainly through free publicized materials 50.0% (197/394). Rates on premarital sexual behavior on multiple sexual partners in the past year, on temporary sexual partners in the past year, having commercial sexual experiences in the past year and ever used condoms when engaging in casual sex, were 6.4% (60/366), 18.0%(66/366), 5.7%(21/366), 1.9%(7/366) and 8.0%(25/311), respectively. Conclusions: Few numbers of HIV infections were identified among the migrating workers with Derung minority, with sexual transmission as the major route, along with the increased number of rural migrant workers and the low rates both on AIDS knowledge and condom use, accompanied by the high risk sexual behavior appeared in this rural adult residents of Derung minority. Relative strategies on HIV/AIDS intervention and control should be developed.

[Characteristics of HIV seropositive cases and related high risk behaviors in a community in Yunnan province, 2012-2015].

Objective: To understand the characteristics of newly detected HIV infection cases and related high risk behaviors in the areas with high HIIV infection prevalence in Yunnan province. Methods: A questionnaire survey was conducted with census method during January to March 2016 among newly detected HIV infected persons in Dehong, Honghe, Lincang and Dali prefectures in Yunnan during 2012-2015. Results: Among 451 HIV seropositive cases, the major transmission route of HIV was heterosexual contact, accounting for 92.5% (417/451). The total awareness rate of AIDS related knowledge was 73.0% (329/451). The rates of condom use at sex with regular sexual partners, occasional sexual partners, commercial sexual partners and men who have sex with men within 1 year before knowing their infection status were 48.7% (167/343), 4.2% (7/165), 9.9% (15/151) and 0.0% (0/3), respectively. The risk factors for using no condom at sex with regular sexual partners included living at Dali, being farmer, unmarried, cohabitation, divorced and widowed, monthly income under 1 000 yuan (RMB), living in urban area before infection, knowing no AIDS related knowledge etc. The risk factors for using no condom at sex with occasional sexual partners included living in Dehong, Honghe and Lincang, aged ≤30 years and being farmer. The injecting drug users accounted for 8.2% (37/450) and 75.5% of these cases had received AIDS related intervention (340/450). Conclusion: High prevalence of heterosexual transmission of HIV, poor AIDS related knowledge on awareness, high risk behavior and poor condom use and poor intervention service utilization were found among newly detected HIV infected persons in areas with high HIV infection prevalence in Yunnan.

[A large scale cohort study on AIDS in communities in Dali, Yunnan province, 2014-2015].

Objective: To understand HIV incidence in community residents and epidemiological characteristics of newly detected HIV infection cases in Dali, Yunnan province. Methods: A cohort study was conducted among 146 720 community residents who were tested to be HIV negative during 2010-2011, they were followed-up from June 1, 2014 to May 31, 2015. Results: A total of 136 356 community residents received follow up (92.9%). The follow-up time was 0.23-5.40 years (medium: 3.43 years), cumulatively 459 675 person years, and 78 people were found to be HIV positive. The incidence rate of HIV infection was 0.170/1 000 person years. The incidence rate was 0.037/1 000 person years in age group 15-29 years, 0.288/1 000 person years in age group 30-44 years, 0.210/1 000 person years in age group 45-59 years, 0.204/1 000 person years in age ≥60 years; 0.213/1 000 person years in males, 0.130/1 000 person years in females; 0.248/1 000 person years in Han ethnic group, 0.149/1 000 person years in Minorities; 0.194/1 000 in people with education level ≤ junior middle school, 0.046/1 000 person years in people with education level > junior middle school; 0.070/1 000 person years in the unmarried, 0.194/1 000 person years in the married and 0.425/1 000 person years in the divorced/widowed. Cox proportional hazards regression analysis showed that being male (HR=1.731), aged 30-44 years (HR=13.158), aged 45-59 years (HR=10.329), aged ≥60 years (HR=8.291), unmarried (HR=3.162) and divorced/widowed (HR=2.689) were the risk factors for HIV infection, while the education level > junior middle school (HR=0.132) was the protective factor for HIV infection. Conclusions: By medium 3.43 years follow up, the cohort study showed that incidence rate HIV infection was 0.170/1 000 person years in the community residents in Dali. Male, middle aged and old people, people with low education level, the unmarried and the divorced/widowed had relatively higher risk to be infected with HIV, Close attention should be paid to the prevention and control of AIDS in these populations.

[HIV prevalence and risk factors among left-behind women in high HIV epidemic rural areas of Yunnan province].

OBJECTIVE: To understand the status of HIV infection and risk factors among those left-behind women (LBW) in high HIV epidemic rural areas. METHODS: A cross-sectional investigation was conducted between March and May, 2015 in Dehong and Lincang prefectures, Yunnan province, where HIV appeared highly epidemic. Probability Proportion to Size (PPS) sampling method was used, and 500 cases were involved and tested for HIV antibody. RESULTS: The total rate of HIV infection among LBW was 8.2% (41/500). The rate of HIV infection among LBWs whose husbands were on medication was 22.7% (30/132). Data from Multi-factor logistic regression analysis showed that the risk factors of HIV infection were: being minorities, education background lower than junior high school, widowed, living in Lincang prefecture, husband infected with HIV but did not consistently use condoms,etc. The rate of HIV infection among other LBWs was 2.8% (10/363). Data from Multi-factor logistic regression analysis showed that the risk factors of HIV infection would include: aged between 30-40 years, being minorities, education background lower than junior high school, divorced, living in Dehong prefecture, having had multiple-sex partners, husband coming home less than once a year,etc. The rate of HIV infection among drug users whose husbands did not take HIV medication was 20.0% (1/5). CONCLUSION: HIV prevalence among LBWs in highly HIV epidemic areas was high, and the major risk factors related to their husbands were: being drug users or with HIV infected. Further effort should be made on consistently use of anti-HIV drugs and prevention of inter-marital sexual transmission. Comprehensive intervention should be carried out for LBWs who were having lower education background, being minority and having multiple-sex partners.

[Relationship between shift work and overweight/obesity in male steel workers].

Objective: To investigate the relationship between shift work and overweight/obesity in male steel workers. Methods: A questionnaire survey was conducted among the male steel workers selected during health examination in Tangshan Steel Company from March 2015 to March 2016. The relationship between shift work and overweight/obesity in the male steel workers were analyzed by using logistic regression model and restricted cubic splinemodel. Results: A total of 7 262 male steel workers were surveyed, the overall prevalence of overweight/obesitywas 64.5% (4 686/7 262), the overweight rate was 34.3% and the obesity rate was 30.2%, respectively. After adjusting for age, educational level and average family income level per month by multivariable logistic regression analysis, shift work was associated with overweight/obesity and obesity in the male steel workers. The OR was 1.19(95% CI: 1.05-1.35) and 1.15(95% CI: 1.00-1.32). Restricted cubic spline model analysis showed that the relationship between shift work years and overweight/obesity in the male steel workers was a nonlinear dose response one (nonlinear test χ2=7.43, P<0.05). Restricted cubic spline model analysis showed that the relationship between shift work years and obesity in the male steel workers was a nonlinear dose response one (nonlinear test χ2=10.48, P<0.05). Conclusion: Shift work was associated with overweight and obesity in the male steel workers, and shift work years and overweight/obesity had a nonlinear relationship.

Adult nasolacrimal sac mucocele.

Adult nasolacrimal sac mucocele is an uncommon mass arising in the medial canthal region of the orbit. Twenty-one cases with lacrimal sac mucocele were reviewed retrospectively. We gathered information about the clinical characteristics, natural history, mechanism for mucocele formation and optimal management of this disorder. The results show that the medial canthal mass was confirmed to be dacryo-cystocele-associated with distal nasolacrimal duct obstruction and proximal obstruction at the junction of the common canaliculus and sac. The interventional procedure of polyurethane stent placement is a practicable and simplified treatment for lacrimal sac mucocele.

Comparing fluctuations of synaptic responses mediated via AMPA and NMDA receptor channels--implications for synaptic plasticity.

Glutamate-releasing synapses are essential in fast neuronal signalling. Plasticity at these synapses is important for learning and memory as well as for the activity-dependent control of neuronal development. We have evaluated the trial-to-trial fluctuations of excitatory postsynaptic currents mediated by glutamate receptors of the AMPA and NMDA types in CA1 pyramidal cells. By using the whole cell patch clamp technique in brain slices from young rats, we have demonstrated that the relative variability of AMPA and NMDA receptor mediated responses, expressed as the coefficient of variation, is similar for these two types of responses [Brain Res. 800 (1998) 253-259]. The present paper summarizes and discusses these results in relation to current theories on hippocampal synaptic plasticity, especially with regard to the ideas of glutamate spillover and silent synapses. Our finding of a correspondence between AMPA and NMDA responses with respect to fluctuations is compatible with our previous finding of equal relative changes of the two during activity induced synaptic plasticity. However, the results argue against the glutamate spillover model according to which the effect of glutamate--and hence the induction of plasticity--may spread unspecifically between synapses. But how can silent synapses become functional if no spread of glutamate occurs and no initial signal is present to trigger the functionalization? Is it necessary that NMDA responses are present at these synapses, which are then silent merely with respect to AMPA receptors, or do other alternatives exist? Our discussion aims to elucidate these questions.

Metabotropic glutamate receptor activation causes a rapid redistribution of AMPA receptors.

Electrophysiology, immunostaining and time lapse imaging techniques were employed to study the mechanism of long-term depression (LTD) induced by DHPG, a specific group I metabotropic glutamate receptor (mGluR) agonist. Experiments were performed in primary hippocampal culture or in the CA1 area of acute rat hippocampal slices. In agreement with previous results by others, we show that DHPG (200 microM, 10 min) can induce LTD (DHPG-LTD) in acute slices, in the presence or absence of synaptic inhibition. In addition, in voltage clamp whole cell experiments we find that accompanying the reduction in the evoked excitatory postsynaptic current (EPSC), miniature EPSC amplitude and frequency are reduced. Similar results were obtained in cultured neurons. Immunostaining and time lapse imaging showed a long-lasting loss of AMPA receptors from the membrane surface of cultured neurons after DHPG treatment, which appears to occur in only a subset of the puncta. Further electrophysiological recordings on slices showed that blocking postsynaptic endocytosis by introducing a blocking peptide named D15 in recording pipettes abolished the DHPG-LTD. In conclusion, these data suggest that LTD induced by mGluR activation is due to a rapid removal of AMPA receptors from the postsynaptic membrane.

[Clinical application of a new nasolacrimal stent].

Seventy-two patients(ninety-one eyes) with epiphore due to obstruction of the nasolacrimal duct underwent nasolacrimal stent of our own disign. The period postoperative follow-up was 6 to 20(mean 14.5) months. Seventy-six eyes demonstrated obvious resolution of epiphore, twelve eyes had partial resolution, and three eyes had no resolution. The success rate were 96.7%. The common complications included occluded stent and a slightly blood-stanied nasal discharge. The placement of the nasolacrimal stent is a safe simple and effective method for treatment of epiphore due to obstruction of the nasolacrimal duct.

[Significance of preoperative digital subtraction dacryocystography for nasolacrimal stent].

Digital subtraction dacryocystography were performed prior to placement of a nasolacrimal stent. Among the 107 eyes, the sites of obstruction were in the common canaliculus in 9 eyes, above the neck of the lacrimal sac in 12 eyes and under the neck of the lacrimal sac in 86 eyes. The placement of a nasolacrimal stent may become the treatment of choice for epiphora due to obstruction of the nasolacrimal duct at the saccular or subsaccular level. After operation, these nasolacrimal ducts after stenting were patent and epiphora was resolved completely or partially. The results suggest that the preoperative digital subtraction dacryocystography is helpful in selective indication of placement of a nasolacrimal stent and prognostic assessment of the postoperative outcome.

Potentiation and depression following stimulus interruption in young rat hippocampi.

We examined the effect of stimulus interruption on dual component field EPSPs in the hippocampal CA1 region. Resuming test stimulation at 0.1 Hz after 10-60 min silent periods led to an increase of the response followed by a decline, involving AMPA and NMDA components to a similar extent. Similar changes were seen when stimulation was initially applied to a naive pathway or the stimulus strength was increased during an experiment. The potentiation of the AMPA response was largely blocked by prior application of the NMDA antagonist AP5 while application of this drug immediately after the initial potentiation prevented the following decline. The results demonstrate that NMDA-dependent potentiation and depression, possibly equivalent to LTP and LTD, can both be induced by the same, very low, test stimulus frequency. Furthermore, the depression appeared to have a longer time window for its induction than the potentiation.

Variability of AMPA and NMDA receptor mediated responses in CA1 pyramidal cells of young rats.

The relative variability of excitatory postsynaptic currents (EPSCs) was studied using whole cell recording in CA1 pyramidal cells of hippocampal slices from 2 to 3-week-old rats. EPSCs were evoked by stimulating the Schaffer collateral-commissural pathway and recorded at holding potentials of -75, -30 or +40 mV. The recordings were either isolated alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) or N-methyl-D-aspartate (NMDA) receptor mediated EPSCs, or composite ones. EPSC variability was quantified by coefficient of variation (CV). The inverse variability expressed as 1/CV2 was employed in comparisons. Using early (5-15 ms) and late (40-100 ms) measurements to estimate the AMPA and NMDA components of composite EPSCs showed no difference in the variability of the two components. Comparing isolated AMPA EPSCs at -75 mV with NMDA EPSCs at -30 mV also failed to reveal a difference. However, in accord with previous studies by others, NMDA EPSCs recorded at +40 mV were less variable than AMPA EPSCs at -75 mV, the ratio of 1/CV2 for NMDA vs. AMPA being around 1.7. A comparison between isolated AMPA EPSCs revealed a similar pattern of dependency of CV on membrane potential, the EPSCs at +40 mV being less variable than those at -30 or -75 mV (1/CV2 ratios of 1.5-1.6). In conclusion, our results did not demonstrate any inherent difference in CV between AMPA and NMDA receptor mediated EPSCs and the observed differences in CV could be accounted for by a dependency on membrane potential, the mechanism of which remains to be resolved. The present results have implications for the interpretation of CV changes as observed, for instance, during synaptic plasticity.

Comparing long-term depression with pharmacologically induced synaptic attenuations in young rat hippocampi.

Field excitatory postsynaptic potentials (EPSPs) were recorded in the CA1 region of hippocampal slices from 12-18-day-old rats. The isolated N-methyl-D-aspartate (NMDA) receptor mediated field EPSP as well as the composite field EPSP of both NMDA and alpha-amino-3-hydroxy-5-methylisoxazolepropionic acid (AMPA) receptor mediated components were obtained in low Mg2+ solutions with 10 microM or 1 microM of the AMPA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), respectively. The isolated AMPA receptor mediated field EPSP was obtained either in normal Mg2+ solution or in a low Mg2+ solution in the presence of the NMDA receptor antagonist D-2-amino-5-phosphonopentanoic acid. The waveforms of the field EPSPs were studied and the effect of long-term depression (LTD) on these waveforms was compared with the effects of several pharmacological agents that attenuate the synaptic efficacy. It was shown that LTD occurred without changes in the waveforms of isolated AMPA and NMDA EPSPs. Reducing the number of release sites by lowering the stimulus strength or reducing the probability of transmitter release by an adenosine agonist N6-cyclohexyl-adenosine both mimicked the LTD-induced changes. Partial blockade of the AMPA receptors was also without effect on the waveforms of isolated AMPA EPSPs. In contrast, partial blockade of the NMDA receptors in several different ways resulted in waveform changes. A similar result could be inferred from experiments using composite field EPSPs. The synaptic attenuation caused by a partial blockade of NMDA receptors therefore appears to differ mechanistically from that involved in LTD, arguing against a postsynaptic locus of the modification involved in LTD. However, directly testing for alterations in transmitter release using the open channel blocker of NMDA receptors MK-801 failed in revealing such presynaptic changes during LTD. Our results therefore suggest that LTD might be due to a coordinated pre- and postsynaptic change instead of distinct pre- or postsynaptic modifications.

Activity-dependent decay of early LTP revealed by dual EPSP recording in hippocampal slices from young rats.

The early maintenance of long-term potentiation (LTP) was studied in the CA1 region of hippocampal slices from 12- to 18-day-old rats in a low-magnesium solution (0.1 mM). The alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) and N-methyl-D-aspartate (NMDA) receptor-mediated components of the field excitatory postsynaptic potential were estimated in parallel using early and late measurements of the composite potential. At the normal test stimulus frequency of 0.1 Hz, LTP was seen initially as a predominant increase in the AMPA component, but converted, via a substantial decay of this component and a gradual growth of the NMDA component, into nearly equal changes of the two components. Interrupting the test stimulation for 10 min, changing the test stimulus frequency to 1/60 Hz after LTP induction, or using a test stimulus frequency of 1/60 Hz during the entire experiment significantly reduced the decay of the potentiation of the AMPA component while enhancing the potentiation of the NMDA one. The ratio between the magnitudes of the two excitatory postsynaptic potential (EPSP) components showed a decaying time course that was independent of the manipulations used. Application of the NMDA antagonist D(-)-2-amino-5-phosphonopentanoic acid (50 microM) after LTP induction stabilized the LTP of the AMPA component until washout was started. On the other hand, the phosphatase inhibitor okadaic acid (1 microM) resulted in decay of the potentiation of both EPSP components back to around baseline and altered the time course of the ratio between the components. Our results show that the early maintenance of LTP is controlled in an activity-dependent and NMDA-dependent manner. This process accelerates the decay of LTP of both AMPA and NMDA components in parallel, suggesting that it is similar to homosynaptic long-term depression, although it operates at the normal test stimulus frequency. The data support a scenario in which LTP ensues as a selective AMPA receptor modification and subsequently converts to another modification, possibly a presynaptic one.

Long-term potentiation and paired-pulse facilitation in the hippocampal CA1 region.

We have investigated the interaction between long-term potentiation (LTP) and paired-pulse facilitation (PPF) in the hippocampal CA1 region under different conditions of initial PPF. PPF is a short lasting presynaptic alteration in synaptic efficacy, determined by the presynaptic release probability, where a high and low PPF indicate a low and high release probability, respectively. LTP was associated with no, or only little, change in PPF, independent of the initial value of PPF and of the time of measurement within the first hour of LTP. These results support the notion that the expression mechanism of LTP is not regulated by the initial release probability and that LTP is due to a single expression mechanism within its first hour.

The complementary nature of long-term depression and potentiation revealed by dual component excitatory postsynaptic potentials in hippocampal slices from young rats.

Homosynaptic long-term depression and long-term potentiation were studied in hippocampal slices from 12-18-day-old rats using field excitatory postsynaptic potentials recorded in the CA1 subfield (stratum radiatum). Independent estimates of the alpha-amino-3-hydroxy-5-methylisoxazolepropionic acid (AMPA) and the N-methyl-D-aspartate receptor-mediated components of the field excitatory postsynaptic potential were obtained in parallel using early and late measurements of a dual component excitatory postsynaptic potential in a solution containing low (0.1 mM) magnesium and 1 microM of the AMPA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX). Long-term depression, induced by 2 Hz stimulation for 10 min, was observed as an equal relative depression of the AMPA and N-methyl-D-aspartate receptor-mediated components of the field excitatory postsynaptic potential, whereas long-term potentiation induced by single or repeated high-frequency stimulation, was seen initially as a predominant potentiation of the AMPA receptor-mediated component. Within the first 30-60 min, long-term potentiation gradually changed to more equal increases of the two components of the excitatory postsynaptic potential. During alternating induction of long-term depression and long-term potentiation, the AMPA and N-methyl-D-aspartate receptor-mediated components could both be repeatedly regulated up and down. Long-term depression and long-term potentiation also showed several signs of interaction with each other during such experiments; e.g., long-term depression removed the occlusive effect of large long-term potentiation on a subsequent long-term potentiation, and long-term potentiation applied after the induction of long-term depression was found to be more stable than otherwise. The results support the notion that long-term depression and long-term potentiation employ changes in a common synaptic property. A tentative mechanism for this modification, expressed as equal changes of AMPA and N-methyl-D-aspartate receptor-mediated components of the excitatory postsynaptic potential, is an alteration in transmitter release, while the initial asymmetric part of long-term potentiation indicates involvement of an additional short-term modification.

On the linkage between AMPA and NMDA receptor-mediated EPSPs in homosynaptic long-term depression in the hippocampal CA1 region of young rats.

Homosynaptic long-term depression (LTD) was studied in hippocampal slices from 12-18-d-old rats using field EPSP recording in the apical dendritic layer of CA1 pyramidal cells. Independent estimates of the alpha-amino-3-hydroxy-5-methylisoxazolepropionic acid (AMPA) and the N-methyl-D-aspartic acid (NMDA) receptor-mediated components of the field EPSP were obtained in parallel using early and late measurements of a dual-component EPSP in a low-magnesium solution. LTD was induced by low-frequency stimulation (LFS; 2 Hz for 10 min), resulting in equal relative changes of the AMPA and NMDA receptor-mediated components. Under conditions when the AMPA receptor-mediated component was fully blocked, a similarly sized LTD was observed for the pure NMDA receptor-mediated EPSP (measured as initial slope or peak amplitude). Equal changes in AMPA and NMDA receptor-mediated components occurred also upon application of the adenosine agonist N6-cyclohexyladenosine (CHA), known to act by decreasing transmitter release. On the other hand, LTD was found to interact in a multiplicative manner with the presynaptic release changes induced by CHA and by paired-pulse facilitation. The induction of the LTDs of both AMPA and NMDA receptor-mediated EPSPs was blocked by the NMDA receptor antagonist D(-)-2-amino-5-phosphonopentanoic acid and by the phosphatase inhibitor okadaic acid. Partial blockade of LTD by okadaic acid resulted in equal partial blockade of the LTDs of the AMPA and NMDA receptor-mediated components. On the other hand, the L-type calcium channel blocker nifedipine, the metabotropic glutamate receptor antagonist (RS)-alpha-methyl-4-carboxyphenylglycine, the nitric oxide synthase inhibitor N omega-nitro-L-arginine, and the heme oxygenase inhibitor protoporphyrin IX zinc(II) had no effect on LTD of either the AMPA or the NMDA receptor-mediated component. These results of equal changes of AMPA and NMDA receptor-mediated components of the field EPSP in association with LTD, and the consistent parallelism of effects or noneffects on these components by various receptor antagonists and enzyme inhibitors, seem more easily explained by a presynaptic locus for LTD than by a postsynaptic one.

Effect of adenosine-induced changes in presynaptic release probability on long-term potentiation in the hippocampal CA1 region.

In the present study some characteristics of long-term potentiation (LTP) in the hippocampal CA1 region were examined under different conditions of transmitter release. Adenosine A1 agonist/antagonists, or in some instances changes in the extracellular calcium/magnesium ratio, were used to alter release probability. The overall LTP time course (onset latency, growth phase, and subsequent decay for both the non-NMDA and NMDA receptor-mediated EPSPs) following a brief tetanus was essentially the same over an almost 10-fold variation in release probability (measured as change in field EPSP magnitude). The major difference observed was a faster initial decay of LTP evoked at low levels of release probability, possibly related to impaired induction conditions. It was also observed that LTP induced at one level of release probability occluded that induced at a lower (or higher) level, and that changes in release probability induced by adenosine agonist/antagonists affected potentiated and "naive" EPSPs to an equal extent. Taken together, these data do not provide support for the notion of different locations for LTP expression at different conditions of release probability. The results are also more compatible with the notion of a single, rather than several, expression mechanism(s) within the first hour of LTP in the hippocampal CA1 region.