Transmission In Different Regions Research Articles

Effects and interaction of temperature and relative humidity on the trend of influenza prevalence: A multi-central study based on 30 provinces in mainland China from 2013 to 2018.

Evidence is inefficient about how meteorological factors influence the trends of influenza transmission in different regions of China. We estimated the time-varying reproduction number (Rt) of influenza and explored the impact of temperature and relative humidity on Rt using generalized additive quasi-Poisson regression models combined with the distribution lag non-linear model (DLNM). The effect of temperature and humidity interaction on Rt of influenza was explored. The multiple random-meta analysis was used to evaluate region-specific association. The excess risk (ER) index was defined to investigate the correlation between Rt and each meteorological factor with the modification of seasonal and regional characteristics. Low temperature and low relative humidity contributed to influenza epidemics on the national level, while shapes of merged cumulative effect plots were different across regions. Compared to that of median temperature, the merged RR (95%CI) of low temperature in northern and southern regions were 1.40(1.24,1.45) and 1.20 (1.14,1.27), respectively, while those of high temperature were 1.10(1.03,1.17) and 1.00 (0.95,1.04), respectively. There were negative interactions between temperature and relative humidity on national (SI=0.59, 95%CI: 0.57-0.61), southern (SI=0.49, 95%CI: 0.17-0.80), and northern regions (SI=0.59, 95%CI: 0.56,0.62). In general, with the increase of the change of the two meteorological factors, the ER of Rt also gradually increased. Temperature and relative humidity have an effect on the influenza epidemics in China, and there is an interaction between the two meteorological factors, but the effect of each factor is heterogeneous among regions. Meteorological factors may be considered to predict the trend of influenza epidemic.

Spatio-temporal dynamics of three diseases caused by Aedes-borne arboviruses in Mexico

BackgroundThe intensity of transmission of Aedes-borne viruses is heterogeneous, and multiple factors can contribute to variation at small spatial scales. Illuminating drivers of heterogeneity in prevalence over time and space would provide information for public health authorities. The objective of this study is to detect the spatiotemporal clusters and determine the risk factors of three major Aedes-borne diseases, Chikungunya virus (CHIKV), Dengue virus (DENV), and Zika virus (ZIKV) clusters in Mexico.MethodsWe present an integrated analysis of Aedes-borne diseases (ABDs), the local climate, and the socio-demographic profiles of 2469 municipalities in Mexico. We used SaTScan to detect spatial clusters and utilize the Pearson correlation coefficient, Randomized Dependence Coefficient, and SHapley Additive exPlanations to analyze the influence of socio-demographic and climatic factors on the prevalence of ABDs. We also compare six machine learning techniques, including XGBoost, decision tree, Support Vector Machine with Radial Basis Function kernel, K nearest neighbors, random forest, and neural network to predict risk factors of ABDs clusters.ResultsDENV is the most prevalent of the three diseases throughout Mexico, with nearly 60.6% of the municipalities reported having DENV cases. For some spatiotemporal clusters, the influence of socio-economic attributes is larger than the influence of climate attributes for predicting the prevalence of ABDs. XGBoost performs the best in terms of precision-measure for ABDs prevalence.ConclusionsBoth socio-demographic and climatic factors influence ABDs transmission in different regions of Mexico. Future studies should build predictive models supporting early warning systems to anticipate the time and location of ABDs outbreaks and determine the stand-alone influence of individual risk factors and establish causal mechanisms.

Dengue, Chikungunya, and Zika: Spatial and Temporal Distribution in Rio de Janeiro State, 2015–2019

Simultaneous spatial circulation of urban arboviral diseases, such as dengue, chikungunya, and Zika, is a major challenge. In this ecological study of urban arboviruses performed from 2015 to 2019, we analyzed the spatial and temporal dynamics of these arboviruses in all 92 municipalities and nine health regions of Rio de Janeiro state. Annual cumulative incidences are presented for all three arboviruses throughout the study period. Spatial analyses of the three studied arboviruses showed distinct behaviors among municipalities and health regions. Co-circulation of the three arboviruses in the state and a heterogeneous spatiotemporal pattern was observed for each disease and region, with dengue having a higher annual incidence during the five years of the study, as well as two consecutive epidemic years in the state. The increase in transmission in different regions of the state in one year culminated in an epidemic in the state in the following year. A high annual cumulative incidence of chikungunya occurred in municipalities from 2017 to 2019 and of Zika only in 2016. Some municipalities with higher population densities showed higher incidences for some arboviruses and appeared to contribute to the dissemination to cities of lower demographic density and maintenance of these urban arboviruses. Thus, regions recording increased incidences of the three diseases in their territories for long periods should be considered municipal poles, as they initiated and sustained high transmission within their region.

Powassan Virus Experimental Infections in Three Wild Mammal Species.

Powassan virus (POWV) is a tick-borne virus maintained in sylvatic cycles between mammalian wildlife hosts and ticks (primarily Ixodes spp.). There are two currently recognized lineages, POWV-lineage 1 (POWV-L1) and deer tick virus (DTV; lineage 2), both of which can cause fatal neurologic disease in humans. Increased numbers of human case reports in the northeastern and north central United States in recent years have fueled questions into POWV epidemiology. We inoculated three candidate wildlife POWV reservoir hosts, groundhogs (Marmota monax), striped skunks (Mephitis mephitis), and fox squirrels (Sciurus niger), with either POWV-L1 or DTV. Resulting viremia, tissue tropism, and pathology were minimal in most inoculated individuals of all three species, with low (peak titer range, 101.7-103.3 plaque-forming units/mL serum) or undetectable viremia titers, lack of detection in tissues except for low titers in spleen, and seroconversion in most individuals by 21 days postinoculation (DPI). Pathology was limited and most commonly consisted of mild inflammation in the brain of POWV-L1- and DTV-inoculated skunks on four and 21 DPI, respectively. These results reveal variation in virulence and host competence among wild mammalian species, and a likely limited duration of host infectiousness to ticks during enzootic transmission cycles. However, POWV can transmit rapidly from tick to host, and tick co-feeding may be an additional transmission mechanism. The rare and low-level detections of viremia in these three, common, wild mammal species suggest that vector-host dynamics should continue to be explored, along with eco-epidemiological aspects of enzootic POWV transmission in different regions and virus lineages.

Estimating the time-varying reproduction number of SARS-CoV-2 using national and subnational case counts

Background: Interventions are now in place worldwide to reduce transmission of the novel coronavirus. Assessing temporal variations in transmission in different countries is essential for evaluating the effectiveness of public health interventions and the impact of changes in policy. Methods: We use case notification data to generate daily estimates of the time-dependent reproduction number in different regions and countries. Our modelling framework, based on open source tooling, accounts for reporting delays, so that temporal variations in reproduction number estimates can be compared directly with the times at which interventions are implemented. Results: We provide three example uses of our framework. First, we demonstrate how the toolset displays temporal changes in the reproduction number. Second, we show how the framework can be used to reconstruct case counts by date of infection from case counts by date of notification, as well as to estimate the reproduction number. Third, we show how maps can be generated to clearly show if case numbers are likely to decrease or increase in different regions. Results are shown for regions and countries worldwide on our website (https://epiforecasts.io/covid/) and are updated daily. Our tooling is provided as an open-source R package to allow replication by others. Conclusions: This decision-support tool can be used to assess changes in virus transmission in different regions and countries worldwide. This allows policymakers to assess the effectiveness of current interventions, and will be useful for inferring whether or not transmission will increase when interventions are lifted. As well as providing daily updates on our website, we also provide adaptable computing code so that our approach can be used directly by researchers and policymakers on confidential datasets. We hope that our tool will be used to support decisions in countries worldwide throughout the ongoing COVID-19 pandemic.

The impact of climate variability on infectious disease transmission in China: Current knowledge and further directions

BackgroundClimate change may lead to emerging and re-emerging infectious diseases and pose public health challenges to human health and the already overloaded healthcare system. It is therefore important to review current knowledge and identify further directions in China, the largest developing country in the world. MethodsA comprehensive literature review was conducted to examine the relationship between climate variability and infectious disease transmission in China in the new millennium. Literature was identified using the following MeSH terms and keywords: climatic variables [temperature, precipitation, rainfall, humidity, etc.] and infectious disease [viral, bacterial and parasitic diseases]. ResultsFifty-eight articles published from January 1, 2000 to May 30, 2018 were included in the final analysis, including bacterial diarrhea, dengue, malaria, Japanese encephalitis, HFRS, HFMD, Schistosomiasis. Each 1 °C rise may lead to 3.6%–14.8% increase in the incidence of bacillary dysentery disease in south China. A 1 °C rise was corresponded to an increase of 1.8%–5.9% in the weekly notified HFMD cases in west China. Each 1 °C rise of temperature, 1％ rise in relative humidity and one hour rise in sunshine led to an increase of 0.90%, 3.99% and 0.68% in the monthly malaria cases, respectively. Climate change with the increased temperature and irregular patterns of rainfall may affect the pathogen reproduction rate, their spread and geographical distribution, change human behavior and influence the ecology of vectors, and increase the rate of disease transmission in different regions of China. ConclusionExploring relevant adaptation strategies and the health burden of climate change will assist public health authorities to develop an early warning system and protect China's population health, especially in the new 1.5 °C scenario of the newly released IPCC special report.

NT-4/5 antagonizes the BDNF modulation of corticostriatal transmission: Role of the TrkB.T1 receptor.

SummaryNeurotrophins are related to survival, growth, differentiation and neurotrophic maintenance as well as modulation of synaptic transmission in different regions of the nervous system. BDNF effects have been studied in the striatum due to the trophic role of BDNF in medium spiny neurons; however, less is known about the effects of NT‐4/5, which is also present in the striatum and activates the TrkB receptor along with BDNF. If both neurotrophins are present in the striatum, the following question arises: What role do they play in striatal physiology? Thus, the aim of this study was to determine the physiological effect of the sequential application and coexistence of BDNF and NT‐4/5 on the modulation of corticostriatal synapses. Our data demonstrated that neurotrophins exhibit differential effects depending on exposure order. BDNF did not modify NT‐4/5 effect; however, NT‐4/5 inhibited the effects of BDNF. Experiments carried out in COS‐7 cells to understand the mechanisms of this antagonism, indicated that NT‐4/5 exerts its inhibitory effect on BDNF by upregulating the TrkB.T1 and downregulating the TrkB‐FL isoforms of the TrkB receptor.

Cost-Effective Management of Electricity Transmission in an Industrial Region

One of the worldwide modern instruments to increase power efficiency is the price-dependent electricity consumption. It is one of the elements in managing the demand for power consumption. The programs of price-dependent power consumption are globally relevant. However, in Russia, their development is still on a conceptual phase. This paper analyses regional tariffs for the power transmission from the perspective of encouraging consumers to price-dependent demand management for electricity consumption. We examine the structure of final electricity tariffs for various categories of consumers as well as identify the percentage rate for the electricity transmission for each category. We consider the methodology of single-part and two-part tariffs for electricity transmission, their structure, and advantages of application. On the example of Volga Federal District tariffs, we have calculated single-part and two-part tariffs for the power transmission in industrial enterprises in terms of three typical schedules of electricity consumption. To compare the efficiency of the price-dependent demand management for the electricity transmission in different regions of Russia, we have introduced the indicators “coefficient of the transmission tariff†and “integral coefficient of the transmission tariff†. Furthermore, we made calculations for 65 regions of Russia entering the price zones of power wholesale market. As a result of the analysis, we divided Russian regions of Russia according to the indicator of “integrated coefficient of transmission tariff†in 3 administrative groups. For each group, we have developed recommendations on pricedependent demand management for power transmission. The theoretical significance of the research consists in the development of methods for the analysis and selection of the most appropriate industrial enterprise tariff for electricity transmission. In practice, regional authorities can use the developed groups of regions to change the structure of regional tariffs in order to stimulate consumers to price-dependent power consumption. Moreover, the algorithm for calculating tariffs for electricity transmission can be applied by the industrial Russia enterprises in price-dependent demand management of power consumption to choose an optimum tariff and reduce costs on power transmission.

Spatiotemporal Anopheles Population Dynamics, Response to Climatic Conditions: The Case of Chabahar, South Baluchistan, Iran

BackgroundAn understanding of the factors that affect the abundance of Anopheline species provides an opportunity to better understand the dynamics of malaria transmission in different regions. Chabahar, located south east of Iran, is the most malarious region in the country. ObjectiveThe main aim of this study was to quantify the spatiotemporal Anopheles population dynamics, response to climatic conditions in Chabahar. MethodsSatellite-based and land-based climatic data were used as explanatory variables. Monthly caught mosquitoes in 6 village sites of Chabahar were used as dependent variable. The spatiotemporal associations were first investigated by inspection of scatter plots and single variable regression analysis. A multivariate linear regression model was developed to reveal the association between environmental variables and the monthly mosquito abundance at a 95% confidence level (P ≤ 0.5). FindingsResults indicated that Anopheles mosquitoes can be found all year in Chabahar with 2 significant seasonal peaks from March to June (primary peak) and September to November (secondary peak). Results of the present study showed that 0.77 of yearly mosquito abundance emerges in the thermal range of 24°C to 30°C and the humidity range of 0.70 to 0.80 in Chabahar. ConclusionAccording to the developed multivariate linear model, 0.88 of temporal variance of mosquito abundance, nighttime land surface temperature, and relative humidity of 15 Universal Time Coordinated (18.30 Iran) are the main drivers of mosquito population dynamics in Chabahar.

Epidemiology of hepatitis E virus in Iran.

Iran is known as an endemic country for hepatitis E virus (HEV) infection, while there are variations in the epidemiology of HEV infection throughout the country. The available epidemiological studies in different regions of Iran show HEV seroprevalence of 1.1%-14.2% among general population, 4.5% -14.3% among blood donors, 6.1%-22.8% among injecting drug users, 6.3%-28.3% among hemodialysis patients, 1.6%-11.3% among patients infected with other hepatitis viruses, 27.5% among patients with chronic liver disease, 30.8% among kidney transplant recipient patients, and 10%-16.4% among human immunodeficiency virus-infected patients. These variations reflect differences in the status of public health and hygiene, risk factors, and routes of transmission in different regions and groups. Therefore, it is necessary to review the epidemiology of HEV infection to determine the most prevalent risk factors and routes of transmission, and to evaluate the effectiveness of preventive strategies employed in the public health services of the country. Moreover, the other epidemiological aspects of HEV, including the genotypic pattern, extra hepatic manifestations, and incidence of chronic infection need to be investigated among Iranian population to expand the current knowledge on the epidemiology of HEV and to clarify the real burden of HEV infection. Therefore, this review was performed to provide a general overview regarding the epidemiology of HEV in Iran.

Temporal Changes in Ebola Transmission in Sierra Leone and Implications for Control Requirements: a Real-time Modelling Study.

Background: Between August and November 2014, the incidence of Ebola virus disease (EVD) rose dramatically in several districts of Sierra Leone. As a result, the number of cases exceeded the capacity of Ebola holding and treatment centres. During December, additional beds were introduced, and incidence declined in many areas. We aimed to measure patterns of transmission in different regions, and evaluate whether bed capacity is now sufficient to meet future demand. Methods: We used a mathematical model of EVD infection to estimate how the extent of transmission in the nine worst affected districts of Sierra Leone changed between 10th August 2014 and 18th January 2015. Using the model, we forecast the number of cases that could occur until the end of March 2015, and compared bed requirements with expected future capacity. Results: We found that the reproduction number, R, defined as the average number of secondary cases generated by a typical infectious individual, declined between August and December in all districts. We estimated that R was near the crucial control threshold value of 1 in December. We further estimated that bed capacity has lagged behind demand between August and December for most districts, but as a consequence of the decline in transmission, control measures caught up with the epidemic in early 2015. Conclusions: EVD incidence has exhibited substantial temporal and geographical variation in Sierra Leone, but our results suggest that the epidemic may have now peaked in Sierra Leone, and that current bed capacity appears to be sufficient to keep the epidemic under-control in most districts.

Spatial pattern of severe acute respiratory syndrome in-out flow in 2003 in Mainland China.

BackgroundSevere acute respiratory syndrome (SARS) spread to 32 countries and regions within a few months in 2003. There were 5327 SARS cases from November 2002 to May 2003 in Mainland China, which involved 29 provinces, resulted in 349 deaths, and directly caused economic losses of $18.3 billion.MethodsThis study used an in-out flow model and flow mapping to visualize and explore the spatial pattern of SARS transmission in different regions. In-out flow is measured by the in-out degree and clustering coefficient of SARS. Flow mapping is an exploratory method of spatial visualization for interaction data.ResultsThe findings were as follows. (1) SARS in-out flow had a clear hierarchy. It formed two main centers, Guangdong in South China and Beijing in North China, and two secondary centers, Shanxi and Inner Mongolia, both connected to Beijing. (2) “Spring Festival travel” strengthened external flow, but “SARS panic effect” played a more significant role and pushed the external flow to the peak. (3) External flow and its three typical kinds showed obvious spatial heterogeneity, such as self-spreading flow (spatial displacement of SARS cases only within the province or municipality of onset and medical locations); hospitalized flow (spatial displacement of SARS cases that had been seen by a hospital doctor); and migrant flow (spatial displacement of SARS cases among migrant workers). (4) Internal and external flow tended to occur in younger groups, and occupational differentiation was particularly evident. Low-income groups of male migrants aged 19–35 years were the main routes of external flow.ConclusionsDuring 2002–2003, SARS in-out flow played an important role in countrywide transmission of the disease in Mainland China. The flow had obvious spatial heterogeneity, which was influenced by migrants’ behavior characteristics. In addition, the Chinese holiday effect led to irregular spread of SARS, but the panic effect was more apparent in the middle and late stages of the epidemic. These findings constitute valuable input to prevent and control future serious infectious diseases like SARS.Electronic supplementary materialThe online version of this article (doi:10.1186/s12879-014-0721-y) contains supplementary material, which is available to authorized users.

Dengue transmission based on urban environmental gradients in different cities of Pakistan.

This study focuses on the dengue transmission in different regions of Pakistan. For this purpose, the data of dengue cases for 2009-2012 from four different cities (Rawalpindi, Islamabad, Lahore, and Karachi) of the country is collected, evaluated, and compiled. To identify the reasons and regions of higher risk of Dengue transmission, land use classification, analysis of climate covariates and drainage patterns was done. Analysis involves processing of SPOT 5 10m, Landsat TM 30m data sets, and SRTM 90m digital elevation models by using remote sensing and GIS techniques. The results are based on the change in urbanization and population density, analysis of temperature, rainfall, and wind speed; calculation of drainage patterns including stream features, flow accumulation, and drainage density of the study areas. Results suggest that the low elevation areas with calm winds and minimum temperatures higher than the normal, rapid increase in unplanned urbanization, low flow accumulation, and higher drainage density areas favor the dengue transmission.

Nitrergic and purinergic mechanisms evoke inhibitory neuromuscular transmission in the human small intestine

Inhibitory neuromuscular transmission in the human colon is due to nitrergic and purinergic (P2Y1 -mediated) inputs. The aim of this study was to determine the mechanisms of neuromuscular transmission in different regions of the human small intestine. Ileal (n = 6) and jejunal (n = 6) samples underwent histological examination and were studied using sharp microelectrodes in smooth muscle cells and conventional muscle bath techniques. Electrical field stimulation (EFS) was used to stimulate inhibitory neurons. No histological abnormalities were found. Resting membrane potential was -39.7 ± 1.5 and -45.5 ± 2.1 mV in the jejunum and ileum, respectively. Slow waves and spontaneous contractions were recorded at a frequency of about 8-9 and 6-7 cpm in the jejunum and ileum, respectively. In non-adrenergic, non-cholinergic conditions, EFS caused an inhibitory junction potential and mechanical relaxation. Both responses were blocked by tissue incubation with the nitric oxide synthase inhibitor (Nω-nitro-l-arginine 1 mM) and the P2Y1 receptor blocker 2'-deoxy-N(6) -methyladenosine 3',5'-bisphosphate tetrasodium salt (MRS2179; 10 μM). Both exogenous addition of sodium nitroprusside (1 μM) and the preferential P2Y1 receptor agonist ADPβS (1 μM) hyperpolarized and relaxed smooth muscle cells. MRS2179 (10 μM) blocked ADPβS-induced responses. Similar to colon, inhibitory neurotransmission in the human small intestine is mainly mediated by purinergic (via P2Y1 receptors) and nitrergic inhibitory neurotransmission. Similar mechanisms of inhibitory neurotransmission are present in different regions of the human intestine.

Epidemiology and prevention of hepatitis B virus infection in China

The concept of a hepatitis B vaccine was first introduced into China in 1978. China has been one of the first two developing countries to enact the universal hepatitis B vaccination programme for newborn babies in 1992, and has made tremendous achievements in the control of hepatitis B virus (HBV) infection since then. China now has both low and high endemic regions regarding HBV prevalence co-existing. Although China's drive to stop HBV spread has resulted in changes in HBV epidemic patterns, for the eventual elimination HBV infection in China, it is important to understand the current status of its epidemiology and the aspects of HBV transmission in different regions. More efforts are needed to improve and develop strategies for the control of HBV infection in China, particularly after implementing the policy of universal HBV immunization for all newborns.

Comparison of γ-aminobutyric acid effects in different parts of the cat ileum

The effects of γ-aminobutyric acid (GABA) and those of a GABA A (muscimol) and a GABA B (baclofen) receptor agonists were determined on the spontaneous activity of longitudinally or circularly oriented preparations (segments) isolated from terminal, proximal and distal parts of the cat ileum. GABA applied at 1 μM to 2 mM caused dose-dependent biphasic changes (relaxation and contraction) in spontaneous activity of the longitudinal and circular layers in the terminal and distal parts of the cat ileum and monophasic changes (contraction) in the proximal part. The potency of GABA to elicit relaxant and/or contractile effects in different parts of the ileum showed a proximal-to-terminal increasing pattern. In the longitudinal layer of the distal and terminal ileum, muscimol (100 μM) mimicked the relaxation phase of the GABA effect, while baclofen (100 μM) simulated the contractile phase. Bicuculline, atropine and tetrodotoxin abolished GABA- and muscimol-induced relaxation and suppressed, but failed to prevent GABA- and baclofen-induced contractions. In addition, 2-hydroxysaclofen antagonized the baclofen-induced contractile effect, reduced the GABA-induced contractile phase but failed to prevent GABA- and muscimol-induced relaxation. In the circular layer of the same regions, muscimol mimicked the biphasic GABA effects, while baclofen was without effect. Bicuculline, atropine and tetrodotoxin completely prevented the GABA- and muscimol effects, while 2-hydroxysaclofen failed to antagonize them. In the longitudinal and circular layers of the proximal ileum, muscimol (100 μM) exerted a `GABA-like' transient contractile effect, while baclofen (100 μM) did not elicit any response. Bicuculline, atropine and tetrodotoxin antagonized the GABA- and muscimol-induced contractile responses of longitudinal and circular layers, while 2-hydroxysaclofen was ineffective. The results suggested that the inhibitory and/or excitatory action of GABA on cholinergic transmission in different regions of cat ileum varies along an increasing gradient towards the terminal ileum and is mediated by GABA A and GABA B receptors in the terminal and distal ileum and by GABA A receptors in the proximal ileum.

Activation of pharmacologically distinct metabotropic glutamate receptors depresses reticulospinal-evoked monosynaptic EPSPs in the lamprey spinal cord.

1. Different metabotropic glutamate receptors (mGluRs) can modulate synaptic transmission in different regions in the CNS, but their roles at individual synaptic connections have not been detailed. We used paired intracellular recordings from reticulospinal axons and their postsynaptic target neurons in the lamprey spinal cord to investigate the effects of mGluR activation on glutamatergic synaptic transmission. 2. The mGluR agonists (1S,3R)-1-aminocyclopentane-1,3-dicarboxyylic acid [(1S,3R)-ACPD] and L(+)-2-amino-4-phosphonobutyric acid (L-AP4) both reduced the amplitude of monosynaptic excitatory postsynaptic potentials (EPSPs) elicited by stimulation of single reticulospinal axons. The depression of monosynaptic unitary EPSPs occurred without any apparent change in the input resistance of postsynaptic neurons. Furthermore, the mGluR agonists did not affect the amplitude of (RS)-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-induced depolarizations. Taken together, these results thus suggest that (1S,3R)-ACPD and L-AP4 depress reticulospinal synaptic transmission via presynaptic mechanisms. 3. (2S,1'S,2'S)-2-(carboxycyclopropyl) glycine (L-CCG-I), which selectively activates group II mGluRs, also reduced the amplitude of reticulospinal-evoked EPSPs without any apparent change in the input resistance or membrane potential of the postsynaptic neuron. 4. The mGluR antagonist alpha-methyl-L-AP4 blocked the depression induced by L-AP4 but not that induced by (1S,3R)-ACPD. Furthermore, the effects of coapplication of (1S,3R)-ACPD and L-AP4 were additive, suggesting that they inhibit synaptic transmission by an action on pharmacologically distinct mGluRs. 5. These results provide evidence for the colocalization of at least two different subtypes of presynaptic mGluRs on a single reticulospinal axon in the lamprey. These presynaptic mGluRs could serve as glutamatergic autoreceptors limiting the extent of reticulospinal-mediated excitation of spinal neurons.