25 results on '"Doyle MW"'
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2. Observed Warming Trends at U.S. Army Basic Combat Training Installations and Implications for Future Recruit Training.
- Author
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Patton EM and Doyle MW
- Subjects
- Humans, United States epidemiology, Hot Temperature adverse effects, Military Personnel statistics & numerical data, Heat Stress Disorders epidemiology
- Abstract
Introduction: Army recruits conducting BCT are among the most susceptible population of military personnel to experience exertional heat illness, a concern expected to become increasingly urgent due to steadily rising temperatures. In this study, we provide an empirical analysis of wet bulb globe temperature (WBGT) index trends at U.S. Army BCT installations and quantify the magnitude of these trends. Assuming these warming trends continue, the anticipated effects of increasing temperature trends are discussed in relation to potential impacts on recruit heat illness incidence and training disruption., Materials and Methods: We obtained weather data beginning in the early 1960s, including WBGT index measurements derived by the U.S. Air Force 14th Weather Squadron. We apply these datasets to two classifications for high WBGT index days, including one classification accounting for heat illness susceptibility based on prior day heat exposure, to determine when recruits are most at risk of heat illness. The daily likelihood of extreme WBGT index values is described at each installation using a 30-year climatological average. Trends in the WBGT index are evaluated quantitatively during the warm season (May 1-September 30) and full year and compared between decades and by individual BCT classes., Results: Trends in the WBGT index have increased at all four BCT installations. Between January 1960 and October 2022, the mean WBGT index value increased most quickly at Ft Jackson, SC (0.272°C decade-1, CI: 0.255-0.289) and least at Ft Moore, GA (0.190°C decade-1, CI: 0.170-0.210). Ft Moore experiences the greatest heat burden, with the daily likelihood of experiencing a "black flag" event (≥90°F WBGT index) peaking at nearly 50% in late July, while Ft Leonard Wood, MO, experiences the least heat burden. This heat burden is spread unevenly across installations and dependent on BCT class start date. Recruits beginning in mid-June will experience approximately 200 hours of hazardous heat during BCT at Ft Moore, GA; 100 hours at Ft Jackson, SC; 80 hours at Ft Sill, OK; and 61 hours at Ft Leonard Wood, MO., Conclusions: Temperatures measured on the WBGT index have steadily increased at US Army basic training installations since at least 1960. In the future, adaptation to the BCT program will be required to maintain rigorous standards without incurring unacceptable risk of recruit heat illness. The analysis provided by this study can help inform medical, training, and policy implementations needed to ensure continued BCT in a warming world., (© The Association of Military Surgeons of the United States 2023. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
- Published
- 2024
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3. 5-HT 3 R-sourced calcium enhances glutamate release from a distinct vesicle pool.
- Author
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Fawley JA, Doyle MW, and Andresen MC
- Subjects
- Action Potentials physiology, Animals, Capsaicin pharmacology, Excitatory Postsynaptic Potentials drug effects, Male, Neurons metabolism, Patch-Clamp Techniques, Rats, Rats, Sprague-Dawley, Serotonin metabolism, Solitary Nucleus drug effects, Synapses metabolism, Synaptic Transmission physiology, TRPV Cation Channels metabolism, Calcium metabolism, Glutamic Acid metabolism, Receptors, Serotonin, 5-HT3 metabolism
- Abstract
The serotonin 3 receptor (5-HT
3 R) is a calcium-permeant channel heterogeneously expressed in solitary tract (ST) afferents. ST afferents synapse in the nucleus of the solitary tract (NTS) and rely on a mix of voltage-dependent calcium channels (CaVs) to control synchronous glutamate release (ST-EPSCs). CaV activation triggers additional, delayed release of glutamate (asynchronous EPSCs) that trails after the ST-EPSCs but only from afferents expressing the calcium-permeable, transient receptor potential vanilloid type 1 receptor (TRPV1). Most afferents express TRPV1 and have high rates of spontaneous glutamate release (sEPSCs) that is independent of CaVs. Here, we tested whether 5-HT3 R-sourced calcium contributes to these different forms of glutamate release in horizontal NTS slices from rats. The 5-HT3 R selective agonist, m-chlorophenyl biguanide hydrochloride (PBG), enhanced sEPSCs and/or delayed the arrival times of ST-EPSCs (i.e. increased latency). The specific 5-HT3 R antagonist, ondansetron, attenuated these effects consistent with direct activation of 5-HT3 Rs. PBG did not alter ST-EPSC amplitude or asynchronous EPSCs. These independent actions suggest two distinct 5-HT3 R locations; axonal expression that impedes conduction and terminal expression that mobilizes a spontaneous vesicle pool. Calcium chelation with EGTA-AM attenuated the frequency of 5-HT3 R-activated sEPSCs by half. The mixture of chelation-sensitive and resistant sEPSCs suggests that 5-HT3 R-activated vesicles span calcium diffusion distances that are both distal (micro-) and proximal (nanodomains) to the channel. Our results demonstrate that the calcium domains of 5-HT3 Rs do not overlap other calcium sources or their respective vesicle pools. 5-HT3 Rs add a unique calcium source on ST afferents as part of multiple independent synaptic signaling mechanisms., (Copyright © 2019 Elsevier B.V. All rights reserved.)- Published
- 2019
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4. Causes and consequences of habitat fragmentation in river networks.
- Author
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Fuller MR, Doyle MW, and Strayer DL
- Subjects
- Animals, Humans, Hydrobiology trends, Ecosystem, Hydrobiology methods, Rivers
- Abstract
Increases in river fragmentation globally threaten freshwater biodiversity. Rivers are fragmented by many agents, both natural and anthropogenic. We review the distribution and frequency of these major agents, along with their effects on connectivity and habitat quality. Most fragmentation research has focused on terrestrial habitats, but theories and generalizations developed in terrestrial habitats do not always apply well to river networks. For example, terrestrial habitats are usually conceptualized as two-dimensional, whereas rivers often are conceptualized as one-dimensional or dendritic. In addition, river flow often leads to highly asymmetric effects of barriers on habitat and permeability. New approaches tailored to river networks can be applied to describe the network-wide effects of multiple barriers on both connectivity and habitat quality. The net effects of anthropogenic fragmentation on freshwater biodiversity are likely underestimated, because of time lags in effects and the difficulty of generating a single, simple signal of fragmentation that applies to all aquatic species. We conclude by presenting a decision tree for managing freshwater fragmentation, as well as some research horizons for evaluating fragmented riverscapes., (© 2015 New York Academy of Sciences.)
- Published
- 2015
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5. Environmental management strategy: four forces analysis.
- Author
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Doyle MW and Von Windheim J
- Subjects
- Animals, Ecology legislation & jurisprudence, Ecology methods, Ecology organization & administration, Environmental Monitoring economics, Environmental Monitoring legislation & jurisprudence, Government, Environmental Monitoring methods
- Abstract
We develop an analytical approach for more systematically analyzing environmental management problems in order to develop strategic plans. This approach can be deployed by agencies, non-profit organizations, corporations, or other organizations and institutions tasked with improving environmental quality. The analysis relies on assessing the underlying natural processes followed by articulation of the relevant societal forces causing environmental change: (1) science and technology, (2) governance, (3) markets and the economy, and (4) public behavior. The four forces analysis is then used to strategize which types of actions might be most effective at influencing environmental quality. Such strategy has been under-used and under-valued in environmental management outside of the corporate sector, and we suggest that this four forces analysis is a useful analytic to begin developing such strategy.
- Published
- 2015
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6. Rangeland management and fluvial geomorphology in northern Tanzania.
- Author
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Miller BW and Doyle MW
- Abstract
Researchers have independently documented the effects of land use on rivers and threats to river management institutions, but the relationship between changes in institutional context and river condition is not well described. This study assesses the connections between resource management institutions, land use, and rivers by integrating social science, geospatial analysis, and geomorphology. In particular, we measured hydraulic geometry, sediment size distributions, and estimated sediment yield for four rivers in northern Tanzania and conducted semistructured interviews that assessed corresponding resource management institutions. Communities managed rivers through both customary (traditional, nonstate) and government institutions, but the differences in the resource management policies and practices of the study rivers themselves were fairly subtle. Clearer differences were found at broader scales; the four watersheds exhibited substantial differences in land cover change and sediment yield associated with the location of settlements, roadways, and cultivation. Unexpectedly, these recent land use changes did not initiate a geomorphic response in rivers. The long history of grazing by domestic and wild ungulates may have influenced water and sediment supplies such that river channel dimensions are more resistant to changes in land use than other systems or have already adjusted to predominant changes in boundary conditions. This would suggest that not all rivers will have the anticipated responses to contemporary land use changes because of antecedent land use patterns; over long time scales (centuries to millennia), the presence of grazers may actually increase the ability of rivers to withstand changes in land use. Our findings point to a need for further interdisciplinary study of dryland rivers and their shifts between system states, especially in areas with a long history of grazing, relatively recent changes in land use, and a dynamic social and institutional context.
- Published
- 2014
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7. Integrating mission into physician practices.
- Author
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Doyle MW
- Subjects
- Organizational Case Studies, Organizational Objectives, Catholicism, General Practice
- Published
- 2014
8. How wide is a stream? Spatial extent of the potential "stream signature" in terrestrial food webs using meta-analysis.
- Author
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Muehlbauer JD, Collins SF, Doyle MW, and Tockner K
- Subjects
- Animals, Models, Biological, Plants, Food Chain, Rivers
- Abstract
The magnitude of cross-ecosystem resource subsidies is increasingly well recognized; however, less is known about the distance these subsidies travel into the recipient landscape. In streams and rivers, this distance can delimit the "biological stream width," complementary to hydro-geomorphic measures (e.g., channel banks) that have typically defined stream ecosystem boundaries. In this study we used meta-analysis to define a "stream signature" on land that relates the stream-to-land subsidy to distance. The 50% stream signature, for example, identifies the point on the landscape where subsidy resources are still at half of their maximum (in- or near-stream) level. The decay curve for these data was best fit by a negative power function in which the 50% stream signature was concentrated near stream banks (1.5 m), but a non-trivial (10%) portion of the maximum subsidy level was still found > 0.5 km from the water's edge. The meta-analysis also identified explanatory variables that affect the stream signature. This improves our understanding of ecosystem conditions that permit spatially extensive subsidy transmission, such as in highly productive, middle-order streams and rivers. Resultant multivariate models from this analysis may be useful to managers implementing buffer rules and conservation strategies for stream and riparian function, as they facilitate prediction of the extent of subsidies. Our results stress that much of the subsidy remains near the stream, but also that subsidies (and aquatic organisms) are capable of long-distance dispersal into adjacent environments, and that the effective "biological stream width" of stream and river ecosystems is often much larger than has been defined by hydro-geomorphic metrics alone. Limited data available from marine and lake sources overlap well with the stream signature data, indicating that the "signature" approach may also be applicable to subsidy spatial dynamics across other ecosystems.
- Published
- 2014
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9. What is a stream?
- Author
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Doyle MW and Bernhardt ES
- Subjects
- Conservation of Natural Resources legislation & jurisprudence, Environmental Policy, Legislation as Topic, United States, Water Cycle, Water Pollution legislation & jurisprudence, Water Pollution prevention & control, Water Supply standards, Rivers, Water Supply legislation & jurisprudence
- Published
- 2011
- Full Text
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10. Landscape characteristics of a stream and wetland mitigation banking program.
- Author
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BenDor T, Sholtes J, and Doyle MW
- Subjects
- Animals, Environmental Monitoring, North Carolina, Conservation of Natural Resources methods, Rivers, Wetlands
- Abstract
In the United States, stream restoration is an increasing part of environmental and land management programs, particularly under the auspices of compensatory mitigation regulations. Markets and regulations surrounding stream mitigation are beginning to mirror those of the well-established wetland mitigation industry. Recent studies have shown that wetland mitigation programs commonly shift wetlands across space from urban to rural areas, thereby changing the functional characteristics and benefits of wetlands in the landscape. However, it is not yet known if stream mitigation mirrors this behavior, and if so, what effects this may have on landscape-scale ecological and hydrological processes. This project addresses three primary research questions. (1) What are the spatial relationships between stream and wetland impact and compensation sites as a result of regulations requiring stream and wetland mitigation in the State of North Carolina? (2) How do stream impacts come about due to the actions of different types of developers, and how do the characteristics of impacts sites compare with compensation sites? (3) To what extent does stream compensation relocate high-quality streams within the river network, and how does this affect localized (intrawatershed) loss or gain of aquatic resources? Using geospatial data collected from the North Carolina Division of Water Quality and the Army Corps of Engineers' Wilmington District, we analyzed the behavior of the North Carolina Ecosystem Enhancement Program in providing stream and wetland mitigation for the State of North Carolina. Our results suggest that this program provides mitigation (1) in different ways for different types of permittees; (2) at great distances (both Euclidean and within the stream network) from original impacts; (3) in significantly different places than impacts within watersheds; and (4) in many cases, in different watersheds from original impacts. Our analysis also reveals problems with regulator data collection, storage, and quality control. These results have significant implications given new federal requirements for ecological consistency within mitigation programs. Our results also indicate some of the landscape-scale implications of using market-based approaches to ecological restoration in general.
- Published
- 2009
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11. Environmental markets: the power of regulation.
- Author
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Riggsbee A and Doyle MW
- Subjects
- United States, United States Government Agencies, Conservation of Natural Resources economics, Conservation of Natural Resources legislation & jurisprudence, Ecosystem, Environment
- Published
- 2009
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12. Environmental science. Aging infrastructure and ecosystem restoration.
- Author
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Doyle MW, Stanley EH, Havlick DG, Kaiser MJ, Steinbach G, Graf WL, Galloway GE, and Riggsbee JA
- Subjects
- Animals, Public Policy, United States, Ecology, Ecosystem
- Published
- 2008
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13. Vasopressin inhibits glutamate release via two distinct modes in the brainstem.
- Author
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Bailey TW, Jin YH, Doyle MW, Smith SM, and Andresen MC
- Subjects
- Animals, Arginine Vasopressin pharmacology, Drug Resistance, Excitatory Postsynaptic Potentials drug effects, In Vitro Techniques, Male, Neurons, Afferent drug effects, Neurons, Afferent metabolism, Neurons, Afferent physiology, Pressoreceptors drug effects, Probability, Rats, Rats, Sprague-Dawley, Receptors, Vasopressin metabolism, Solitary Nucleus cytology, Synaptic Transmission drug effects, Arginine Vasopressin physiology, Glutamic Acid metabolism, Solitary Nucleus metabolism
- Abstract
The hypothalamus coordinates autonomic responses in part through arginine vasopressin (AVP) released in medial nucleus tractus solitarius (NTS). However, the mechanisms and sites of AVP action within NTS pathways are uncertain. In brainstem slices, we activated solitary tract (ST) primary afferents to release glutamate and tested whether AVP modulated synaptic transmission to second-order neurons. NTS neurons were classified as second order by ST synaptic characteristics or the presence of anterograde tracers from peripheral baroreceptor afferents. Stimulus recruitment curves indicated ST-EPSCs on individual neurons were evoked by stimulation of single ST axons. Variance-mean (V-M) analysis of ST-EPSCs in individual neurons revealed uniformly high release probability (p approximately 0.9) from an average of 19 release sites (N) and a quantal size (q) of 34.0 +/- 4.7 pA. In 26 of 49 neurons, AVP inhibited afferent synaptic transmission. In most neurons, AVP reduced ST-EPSC amplitudes (n = 20) by decreasing p to 0.65, whereas q, N, and conduction times were unaffected. The V1a antagonist SR49059 alone decreased ST-EPSC V and increased M, suggesting tonic AVP actions, and blocked exogenous AVP action (n = 4). In other neurons with identical ST release properties, AVP induced synaptic failures and increased conduction time without altering the V-M relationship of successful ST-EPSCs (n = 6). Interestingly, frequency-depressed ST-EPSCs were not affected by AVP. AVP failed to alter holding or voltage-dependent potassium currents. Thus, AVP regulates NTS neurons by two distinct novel and state-dependent mechanisms: one, an analog, graded presynaptic inhibition of terminal glutamate release and the other, a binary, extraterminal block of conducted excitation.
- Published
- 2006
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14. Proopiomelanocortin neurons in nucleus tractus solitarius are activated by visceral afferents: regulation by cholecystokinin and opioids.
- Author
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Appleyard SM, Bailey TW, Doyle MW, Jin YH, Smart JL, Low MJ, and Andresen MC
- Subjects
- Animals, Cell Count methods, Dose-Response Relationship, Drug, Drug Interactions, Electric Stimulation methods, Enkephalin, Ala(2)-MePhe(4)-Gly(5)- pharmacology, Enkephalin, Methionine pharmacology, Excitatory Amino Acid Antagonists pharmacology, Excitatory Postsynaptic Potentials drug effects, Excitatory Postsynaptic Potentials physiology, Excitatory Postsynaptic Potentials radiation effects, Gene Expression Regulation drug effects, Green Fluorescent Proteins genetics, Hormone Antagonists pharmacology, Immunohistochemistry methods, In Vitro Techniques, Membrane Potentials drug effects, Membrane Potentials physiology, Membrane Potentials radiation effects, Mice, Mice, Transgenic, Neurons metabolism, Patch-Clamp Techniques methods, Pro-Opiomelanocortin genetics, Proglumide analogs & derivatives, Proglumide pharmacology, Proto-Oncogene Proteins c-fos metabolism, Quinoxalines pharmacology, Time Factors, Cholecystokinin pharmacology, Narcotics pharmacology, Neurons drug effects, Pro-Opiomelanocortin metabolism, Solitary Nucleus cytology, Visceral Afferents physiology
- Abstract
The nucleus tractus solitarius (NTS) receives dense terminations from cranial visceral afferents, including those from the gastrointestinal (GI) system. Although the NTS integrates peripheral satiety signals and relays this signal to central feeding centers, little is known about which NTS neurons are involved or what mechanisms are responsible. Proopiomelanocortin (POMC) neurons are good candidates for GI integration, because disruption of the POMC gene leads to severe obesity and hyperphagia. Here, we used POMC-enhanced green fluorescent protein (EGFP) transgenic mice to identify NTS POMC neurons. Intraperitoneal administration of cholecystokinin (CCK) induced c-fos gene expression in NTS POMC-EGFP neurons, suggesting that they are activated by afferents stimulated by the satiety hormone. We tested the synaptic relationship of these neurons to visceral afferents and their modulation by CCK and opioids using patch recordings in horizontal brain slices. Electrical activation of the solitary tract (ST) evoked EPSCs in NTS POMC-EGFP neurons. The invariant latencies, low failure rates, and substantial paired-pulse depression of the ST-evoked EPSCs indicate that NTS POMC-EGFP neurons are second-order neurons directly contacted by afferent terminals. The EPSCs were blocked by the glutamate antagonist 2,3-dihydroxy-6-nitro-7-sulfonyl-benzo[f]quinoxaline. CCK increased the amplitude of the ST-stimulated EPSCs and the frequency of miniature EPSCs, effects attenuated by the CCK1 receptor antagonist lorglumide. In contrast, the orexigenic opioid agonists [D-Ala(2), N-Me-Phe(4), Gly-ol(5)]-enkephalin and met-enkephalin inhibited both ST-stimulated EPSCs and the frequency of miniature EPSCs. These findings identify a potential satiety pathway in which visceral afferents directly activate NTS POMC-EGFP neurons with excitatory inputs that are appropriately modulated by appetite regulators.
- Published
- 2005
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15. Strategies for cellular identification in nucleus tractus solitarius slices.
- Author
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Doyle MW, Bailey TW, Jin YH, Appleyard SM, Low MJ, and Andresen MC
- Subjects
- Animals, Axonal Transport physiology, Dissection instrumentation, Electrophysiology instrumentation, Excitatory Postsynaptic Potentials physiology, Fluorescent Dyes, Male, Mice, Mice, Transgenic, Microscopy, Fluorescence instrumentation, Microscopy, Fluorescence methods, Microtomy instrumentation, Microtomy methods, Neural Pathways cytology, Neural Pathways physiology, Neurons classification, Neurons cytology, Neurons physiology, Neurophysiology instrumentation, Organ Culture Techniques instrumentation, Rats, Rats, Sprague-Dawley, Reaction Time drug effects, Reaction Time physiology, Solitary Nucleus cytology, Spectrophotometry, Infrared instrumentation, Spectrophotometry, Infrared methods, Staining and Labeling instrumentation, Synaptic Transmission physiology, Dissection methods, Electrophysiology methods, Neurophysiology methods, Organ Culture Techniques methods, Solitary Nucleus physiology, Staining and Labeling methods
- Abstract
The indistinct regional anatomy and intermixing of second order neurons with projection and interneurons make cellular studies more difficult within the nucleus tractus solitarius (NTS). Here, we outline experimental strategies to join in vitro electrophysiological with neuroanatomical protocols to discriminate specific subpopulations of NTS neurons. Horizontally cutting the brain stem produces slices in which electrical activation of the solitary tract (ST) is free of local interneuron contamination. Such ST excitatory synaptic currents (EPSCs) functionally identify second order NTS neurons by their minimal variation of latency (jitter). Sapphire blades, cold cutting temperatures and a mechanically stable microtome were critical to consistently obtain viable slices that were optimized for infrared and fluorescence microscopy. Anterogradely transported carbocyanine dye implanted on the aortic depressor nerve anatomically identified second order NTS neurons and their ST synaptic performance conformed to the minimal jitter signature of second order neurons. Retrograde tracers and green fluorescent protein labeled neurons afford two additional promising approaches for discriminating NTS neuron phenotypes in broader system contexts. Detailed methods and troubleshooting are described. Coupling tracing techniques with electrophysiology adds important new dimensions to NTS studies and such strategies provide bridging information between cellular mechanisms, neuroanatomy and systems integration.
- Published
- 2004
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16. Differentiation of autonomic reflex control begins with cellular mechanisms at the first synapse within the nucleus tractus solitarius.
- Author
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Andresen MC, Doyle MW, Bailey TW, and Jin YH
- Subjects
- Humans, Baroreflex physiology, Cardiovascular System innervation, Solitary Nucleus physiology, Synaptic Transmission physiology, Visceral Afferents physiology
- Abstract
Visceral afferents send information via cranial nerves to the nucleus tractus solitarius (NTS). The NTS is the initial step of information processing that culminates in homeostatic reflex responses. Recent evidence suggests that strong afferent synaptic responses in the NTS are most often modulated by depression and this forms a basic principle of central integration of these autonomic pathways. The visceral afferent synapse is uncommonly powerful at the NTS with large unitary response amplitudes and depression rather than facilitation at moderate to high frequencies of activation. Substantial signal depression occurs through multiple mechanisms at this very first brainstem synapse onto second order NTS neurons. This review highlights new approaches to the study of these basic processes featuring patch clamp recordings in NTS brain slices and optical techniques with fluorescent tracers. The vanilloid receptor agonist, capsaicin, distinguishes two classes of second order neurons (capsaicin sensitive or capsaicin resistant) that appear to reflect unmyelinated and myelinated afferent pathways. The differences in cellular properties of these two classes of NTS neurons indicate clear functional differentiation at both the pre- and postsynaptic portions of these first synapses. By virtue of their position at the earliest stage of these pathways, such mechanistic differences probably impart important differentiation in the performance over the entire reflex pathways.
- Published
- 2004
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17. Toward policies and decision-making for dam removal.
- Author
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Doyle MW, Harbor JM, and Stanley EH
- Subjects
- Conservation of Natural Resources, Engineering, Humans, Decision Making, Environment, Policy Making, Water Supply
- Abstract
Dam removal has emerged as a critical issue in environmental management. Agencies responsible for dams face a drastic increase in the number of potential dam removals in the near future. Given limited resources, these agencies need to develop ways to decide which dams should be removed and in what order. The underlying science of dam removal is relatively undeveloped and most agencies faced with dam removal lack a coherent purpose for removing dams. These shortcomings can be overcome by the implementation of two policies by agencies faced with dam removal: (1) the development and adoption of a prioritization scheme for what constitutes an important dam removal, and (2) the establishment of minimum levels of analysis prior to decision-making about a dam removal. Federal and state agencies and the scientific community must encourage an initial experimental phase of dam removal during which only a few dams are removed, and these are studied intensively. This will allow for the development of the fundamental scientific understanding needed to support effective decision-making in the future and minimize the risk of disasters arising from poorly thought out dam removal decisions.
- Published
- 2003
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18. Ketamine differentially blocks sensory afferent synaptic transmission in medial nucleus tractus solitarius (mNTS).
- Author
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Jin YH, Bailey TW, Doyle MW, Li BY, Chang KS, Schild JH, Mendelowitz D, and Andresen MC
- Subjects
- Action Potentials drug effects, Animals, Autonomic Nervous System drug effects, Brain Stem drug effects, Capsaicin pharmacology, Coronary Circulation drug effects, Electrophysiology, Male, Nodose Ganglion cytology, Nodose Ganglion drug effects, Patch-Clamp Techniques, Rats, Rats, Sprague-Dawley, Receptors, N-Methyl-D-Aspartate antagonists & inhibitors, Vascular Resistance drug effects, Anesthetics, Dissociative pharmacology, Ketamine pharmacology, Neurons, Afferent drug effects, Solitary Nucleus drug effects, Synaptic Transmission drug effects
- Abstract
Background: Ketamine increases blood pressure and heart rate by unknown mechanisms, but studies suggest that an intact central nervous system and arterial baroreceptors are required. In the brain stem, medial nucleus tractus solitarius receives afferents from nodose neurons that initiate cardiovascular autonomic reflexes. Here, the authors assessed ketamine actions on afferent medial nucleus tractus solitarius synaptic transmission., Methods: Ketamine was applied to horizontally sliced brain stems. Solitary tract (ST) stimulation evoked excitatory postsynaptic currents (eEPSCs) in medial nucleus tractus solitarius neurons. Capsaicin (200 nm) block of ST eEPSCs sorted neurons into sensitive (n = 19) and resistant (n = 23). In nodose ganglion slices, shocks to the peripheral vagal trunk activated afferent action potentials in sensory neurons classified by conduction velocities and capsaicin., Results: Ketamine potently (10-100 mciro m) blocked small, ST-evoked -methyl-d-aspartate synaptic currents found only in a subset of capsaicin-resistant neurons (6 of 12). Surprisingly, ketamine reversibly inhibited ST eEPSC amplitudes and induced synaptic failure at lower concentrations in capsaicin-sensitive than in capsaicin-resistant neurons (P < 0.005; n = 11 and 11). Spontaneous EPSCs using non- -methyl-d-aspartate receptors were insensitive even to 1-3 mm ketamine, suggesting that ST responses were blocked presynaptically. Similarly, ketamine blocked C-type action potential conduction at lower concentrations than A-type nodose sensory neurons., Conclusion: The authors conclude that ketamine inhibits postsynaptic -methyl-d-aspartate receptors and presynaptic afferent processes in medial nucleus tractus solitarius. Unexpectedly, capsaicin-sensitive (C-type), unmyelinated afferents are significantly more susceptible to block than capsaicin-resistant (A-type), myelinated afferents. This differentiation may be related to tetrodotoxin-resistant sodium currents. Since C-type afferents mediate powerful arterial baroreflexes effects, these differential actions may contribute to ketamine-induced cardiovascular dysfunction.
- Published
- 2003
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19. Vanilloid-sensitive afferents activate neurons with prominent A-type potassium currents in nucleus tractus solitarius.
- Author
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Bailey TW, Jin YH, Doyle MW, and Andresen MC
- Subjects
- Action Potentials drug effects, Action Potentials physiology, Animals, Electric Stimulation, Excitatory Postsynaptic Potentials drug effects, Excitatory Postsynaptic Potentials physiology, Head innervation, In Vitro Techniques, Male, Nerve Fibers physiology, Nerve Fibers, Myelinated physiology, Neurons classification, Neurons, Afferent drug effects, Neurons, Afferent physiology, Patch-Clamp Techniques, Potassium metabolism, Potassium Channel Blockers pharmacology, Rats, Rats, Sprague-Dawley, Reaction Time drug effects, Reaction Time physiology, Solitary Nucleus cytology, Synaptic Transmission drug effects, Synaptic Transmission physiology, Capsaicin pharmacology, Neurons drug effects, Neurons metabolism, Potassium Channels metabolism, Solitary Nucleus metabolism
- Abstract
Cranial visceral afferents innervate second-order nucleus tractus solitarius (NTS) neurons via myelinated (A-type) and unmyelinated (C-type) axons in the solitary tract (ST). A- and C-type afferents often evoke reflexes with distinct performance differences, especially with regard to their frequency-dependent properties. In horizontal brainstem slices, we used the vanilloid receptor 1 agonist capsaicin (CAP; 100 nm) to identify CAP-sensitive and CAP-resistant ST afferent pathways to second-order NTS neurons and tested whether these two groups of neurons had similar intrinsic potassium currents. ST stimulation evoked monosynaptic EPSCs identified by minimal synaptic jitter (<150 microsec) and divided into two groups: CAP-sensitive (n = 37) and CAP-resistant (n = 22). EPSCs in CAP-sensitive neurons had longer latencies (5.1 +/- 0.3 vs 3.6 +/- 0.3 msec; p = 0.001) but similar jitter (p = 0.57) compared with CAP-resistant neurons, respectively. Transient outward currents (TOCs) were significantly greater in CAP-sensitive than in CAP-resistant neurons. Steady-state currents were similar in both groups. 4-Aminopyridine or depolarized conditioning blocked the TOC, but tetraethylammonium had no effect. Voltage-dependent activation and inactivation of TOC were consistent with an A-type K+ current, I(KA). In current clamp, the activation of I(KA) reduced neuronal excitability and action potential responses to ST transmission. Our results suggest that the potassium-channel differences of second-order NTS neurons contribute to the differential processing of A- and C-type cranial visceral afferents beginning as early as this first central neuron. I(KA) can act as a frequency transmission filter and may represent a key target for the modulation of temporal processing of reflex responsiveness such as within the baroreflex arc.
- Published
- 2002
20. Vanilloid receptors presynaptically modulate cranial visceral afferent synaptic transmission in nucleus tractus solitarius.
- Author
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Doyle MW, Bailey TW, Jin YH, and Andresen MC
- Subjects
- Animals, Baroreflex physiology, Capsaicin pharmacology, Electric Stimulation, Excitatory Amino Acid Antagonists pharmacology, Excitatory Postsynaptic Potentials drug effects, Excitatory Postsynaptic Potentials physiology, Head physiology, In Vitro Techniques, Male, Patch-Clamp Techniques, Pressoreceptors physiology, Pyridinium Compounds, Rats, Rats, Sprague-Dawley, Reaction Time physiology, Receptors, Drug antagonists & inhibitors, Receptors, Glutamate drug effects, Receptors, Glutamate metabolism, Rhombencephalon physiology, Solitary Nucleus drug effects, Synaptic Transmission drug effects, Visceral Afferents drug effects, Capsaicin analogs & derivatives, Head innervation, Presynaptic Terminals metabolism, Receptors, Drug metabolism, Solitary Nucleus physiology, Synaptic Transmission physiology, Visceral Afferents physiology
- Abstract
Although the central terminals of cranial visceral afferents express vanilloid receptor 1 (VR1), little is known about their functional properties at this first synapse within the nucleus tractus solitarius (NTS). Here, we examined whether VR1 modulates afferent synaptic transmission. In horizontal brainstem slices, solitary tract (ST) activation evoked EPSCs. Monosynaptic EPSCs had low synaptic jitter (SD of latency to successive shocks) averaging 84.03 +/- 3.74 microsec (n = 72) and were completely blocked by the non-NMDA antagonist 2,3-dihydroxy-6-nitro-7-sulfonyl-benzo[f]quinoxaline (NBQX). Sustained exposure to the VR1 agonist capsaicin (CAP; 100 nm) blocked ST EPSCs (CAP-sensitive) in some neurons but not others (CAP-resistant). CAP-sensitive EPSCs had longer latencies than CAP-resistant EPSCs (4.65 +/- 0.27 msec, n = 48 vs 3.53 +/- 0.28 msec, n = 24, respectively; p = 0.011), but they had similar jitter. CAP evoked two transient responses in CAP-sensitive neurons: a rapidly developing inward current (I(cap)) (108.1 +/- 22.9 pA; n = 21) and an increase in spontaneous synaptic activity. After 3-5 min in CAP, I(cap) subsided and ST EPSCs disappeared. NBQX completely blocked I(cap). The VR1 antagonist capsazepine (10-20 microm) attenuated CAP responses. Anatomically, second-order NTS neurons were identified by 4-(4-dihexadecylamino)styryl)-N-methylpyridinium iodide transported from the cervical aortic depressor nerve (ADN) to stain central terminals. Neurons with fluorescent ADN contacts had CAP-sensitive EPSCs (n = 5) with latencies and jitter similar to those of unlabeled monosynaptic neurons. Thus, consistent with presynaptic VR1 localization, CAP selectively activates a subset of ST axons to release glutamate that acts on non-NMDA receptors. Because the CAP sensitivity of cranial afferents is exclusively associated with unmyelinated axons, VR1 identifies C-fiber afferent pathways within the brainstem.
- Published
- 2002
21. Cellular mechanisms of baroreceptor integration at the nucleus tractus solitarius.
- Author
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Andresen MC, Doyle MW, Jin YH, and Bailey TW
- Subjects
- Animals, Baroreflex physiology, Glutamic Acid physiology, Neural Pathways physiology, Neurons, Afferent physiology, Synapses physiology, Synaptic Transmission physiology, Pressoreceptors physiology, Solitary Nucleus physiology
- Abstract
The autonomic nervous system makes important contributions to the homeostatic regulation of the heart and blood vessels through arterial baroreflexes, and yet our understanding of the central nervous system mechanisms is limited. The sensory synapse of baroreceptors in the nucleus tractus solitarius (NTS) is unique because its participation is obligatory in the baroreflex. Here we describe experiments targeting this synapse to provide greater understanding of the cellular mechanisms at the earliest stages of the baroreflex. Our approach utilizes electrophysiology, pharmacology, and anatomical tracers to identify and evaluate key elements of the sensory information processing in NTS.
- Published
- 2001
- Full Text
- View/download PDF
22. Reliability of monosynaptic sensory transmission in brain stem neurons in vitro.
- Author
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Doyle MW and Andresen MC
- Subjects
- Action Potentials, Afferent Pathways drug effects, Afferent Pathways physiology, Animals, Cells, Cultured drug effects, Cells, Cultured physiology, Excitatory Amino Acid Antagonists pharmacology, Excitatory Postsynaptic Potentials drug effects, Excitatory Postsynaptic Potentials physiology, Nerve Tissue Proteins drug effects, Nerve Tissue Proteins physiology, Neurons drug effects, Patch-Clamp Techniques, Quinoxalines pharmacology, Rats, Rats, Sprague-Dawley, Receptors, GABA-A drug effects, Receptors, GABA-A physiology, Reproducibility of Results, Synaptic Transmission drug effects, Time Factors, Vagus Nerve physiology, Neurons physiology, Reaction Time physiology, Solitary Nucleus cytology, Synaptic Transmission physiology
- Abstract
The timing of events within the nervous system is a critical feature of signal processing and integration. In neurotransmission, the synaptic latency, the time between stimulus delivery and appearance of the synaptic event, is generally thought to be directly related to the complexity of that pathway. In horizontal brain stem slices, we examined synaptic latency and its shock-to-shock variability (synaptic jitter) in medial nucleus tractus solitarius (NTS) neurons in response to solitary tract (ST) electrical activation. Using a visualized patch recording approach, we activated ST 1-3 mm from the recorded neuron with short trains (50-200 Hz) and measured synaptic currents under voltage clamp. Latencies ranged from 1.5 to 8.6 ms, and jitter values (SD of intraneuronal latency) ranged from 26 to 764 micros (n = 49). Surprisingly, frequency of synaptic failure was not correlated with either latency or jitter (P > 0.147; n = 49). Despite conventional expectations, no clear divisions in latency were found from the earliest arriving excitatory postsynaptic currents (EPSCs) to late pharmacologically polysynaptic responses. Shortest latency EPSCs (<3 ms) were mediated by non-N-methyl-D-aspartate (non-NMDA) glutamate receptors. Longer latency responses were a mix of excitatory and inhibitory currents including non-NMDA EPSCs and GABAa receptor-mediated currents (IPSC). All synaptic responses exhibited prominent frequency-dependent depression. In a subset of neurons, we labeled sensory boutons by the anterograde fluorescent tracer, DiA, from aortic nerve baroreceptors and then recorded from anatomically identified second-order neurons. In identified second-order NTS neurons, ST activation evoked EPSCs with short to moderate latency (1.9-4.8 ms) but uniformly minimal jitter (31 to 61 micros) that were mediated by non-NMDA receptors but had failure rates as high as 39%. These monosynaptic EPSCs in identified second-order neurons were significantly different in latency and jitter than GABAergic IPSCs (latency, 2.95 +/- 0.71 vs. 5.56 +/- 0.74 ms, mean +/- SE, P = 0.027; jitter, 42.3 +/- 6.5 vs. 416.3 +/- 94.4 micros, P = 0.013, n = 4, 6, respectively), but failure rates were similar (27.8 +/- 9.0 vs. 9.7 +/- 4.4%, P = 0.08, respectively). Such results suggest that jitter and not absolute latency or failure rate is the most reliable discriminator of mono- versus polysynaptic pathways. The results suggest that brain stem sensory pathways may differ in their principles of integration compared with cortical models and that this importantly impacts synaptic performance. The unique performance properties of the sensory-NTS pathway may reflect stronger axosomatic synaptic processing in brain stem compared with dendritically weighted models typical in cortical structures and thus may reflect very different strategies of spatio-temporal integration in this NTS region and for autonomic regulation.
- Published
- 2001
- Full Text
- View/download PDF
23. Expression of the orphan receptor steroidogenic factor-1 mRNA in the rat medial basal hypothalamus.
- Author
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Roselli CE, Jorgensen EZ, Doyle MW, and Rønnekleiv OK
- Subjects
- Age Factors, Analysis of Variance, Animals, Female, Fushi Tarazu Transcription Factors, Homeodomain Proteins, Male, RNA, Messenger metabolism, Rats, Rats, Sprague-Dawley, Receptors, Cytoplasmic and Nuclear, Sex Factors, Steroidogenic Factor 1, DNA-Binding Proteins metabolism, Hypothalamus, Middle metabolism, Receptors, Cell Surface metabolism, Transcription Factors metabolism
- Abstract
Steroidogenic factor-1 (SF-1), an orphan receptor of the nuclear hormone receptor family, binds to the AAGGTCA motif in the promoter elements of several diverse target genes, including some that mediate steroidogenesis and sexual differentiation. In addition, SF-1 is expressed in embryonic forebrain, suggesting that it plays a role in neural development. This study was undertaken to study the distribution and regulation of SF-1 mRNA expression in the rat brain. SF-1 mRNA levels were measured in tissue dissections by ribonuclease protection assay. A 452 nt 32P-labeled cRNA probe, complementary to the putative ligand-binding domain of the rat SF-1 mRNA, was synthesized from the rat SF-1 cDNA inserted into pBluescript II KS, using a Sty 1 fragment and T3 polymerase. The probe protected a single 390 nt transcript in the medial basal hypothalamus (MBH) and peripheral steroidogenic tissues of the male rat. The size of this protected band corresponded to that of the protected sense RNA standard (HindIII fragment of the SF-1 cDNA transcribed with T7 polymerase). No SF-1 mRNA was detected in the preoptic area, amygdala or cingulate cortex. The levels of SF-1 mRNA in MBH were not affected by gonadectomy or androgen treatment, nor was there a sex difference in its expression in adults. In situ hybridization histochemistry revealed that SF-1 was localized to the ventromedial nucleus of the adult hypothalamus. The levels of SF-1 mRNA were high on gestational day 18 after which they fell by approximately 30% and remained constant throughout gestation, the first week of neonatal life, and into adulthood. These results demonstrate that the gene encoding SF-1 is expressed in a discrete region of the rat hypothalamus and appears to be developmentally regulated, but not affected by gonadal hormones in adults.
- Published
- 1997
- Full Text
- View/download PDF
24. Effect of physiological factors on proximal flow convergence upstream of an incompetent valve: an in-vitro study.
- Author
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Guenet FS, Walker PG, Doyle MW, Pohost GM, and Yoganathan AP
- Subjects
- Aortic Valve Insufficiency diagnosis, Bias, Computer Simulation, Hemorheology, Humans, Magnetic Resonance Imaging, Predictive Value of Tests, Reproducibility of Results, Software, Aortic Valve Insufficiency physiopathology, Blood Flow Velocity, Models, Cardiovascular
- Abstract
The flow (Q) through regurgitant valves may be quantified by multiplying the area of an isovelocity contour (isovel) by its velocity. This was tested computationally and experimentally (using MRI). Q = 14 to 141 ml/s, using flat and conical orifice plates. Plotting Q versus isovelocity radius, a plateau was found which, for low flow, corresponded to the true Q. At higher flow or large confinement, Q was overestimated. For conical plates, angle correction worked at low Q but not at higher values due to the formation of separation regions. These converted the cone plate into a flat plate. MRI produced similar results at 57 ml/s in that Q was correct with no angle correction. At low flow, MRI was too noisy to produce a clear plateau consistently.
- Published
- 1997
- Full Text
- View/download PDF
25. Multiple use of progesterone releasing intravaginal devices for synchronisation of oestrus and ovulation in cattle.
- Author
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McPhee SR, Doyle MW, Davis IF, and Chamley WA
- Subjects
- Animals, Cloprostenol administration & dosage, Cloprostenol pharmacology, Delayed-Action Preparations, Female, Pregnancy, Progesterone blood, Progesterone pharmacology, Cattle physiology, Estrus Synchronization drug effects, Ovulation drug effects, Progesterone administration & dosage
- Published
- 1983
- Full Text
- View/download PDF
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