PubMed Health⌕ Search

Biomedical subjects

R Miles

Publications and source records attributed to R Miles.

At least 37 records · Page 2Linked to original sources
PubMed1998

How many subtypes of inhibitory cells in the hippocampus?

Hippocampal inhibitory cells are diverse. It is supposed that they fall into functionally distinct subsets defined by a similar morphology and physiology. Switching between functions could be accomplished by activating receptors for modulating transmitters expressed selectively by different subsets of interneurons. We tested this hypothesis by comparing morphology, physiology, and neurotransmitter receptor expression for CA1 hippocampal interneurons. We distinguished 16 distinct morphological phenotypes and 3 different modes of discharge. Subsets of inhibitory cells were excited or inhibited by agonists at receptors for noradrenaline, muscarine, serotonin, and mGluRs. Most cells responded to 2 or 3 agonists, and 25 different response combinations were detected. Subsets defined by morphology, physiology, and receptor expression did not coincide, suggesting that hippocampal interneurons cannot easily be segregated into a few well-defined groups.

2-Amino-5-phosphonovalerate↗
PubMed1998

AMPA receptor-mediated alterations of intracellular calcium homeostasis in rat cerebellar Purkinje cells in vitro: correlates to dark cell degeneration.

In the rat cerebellar slice preparation in vitro, excessive DL-amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid (AMPA)-receptor activation elicits a characteristic type of excitotoxicity of Purkinje cells (PCs) known as dark cell degeneration (DCD). DCD models neurotoxicity of PCs and hippocampal pyramidal neurons in vivo following hyperexcitable states. The intent of this study was to: a) determine whether AMPA-induced neurotoxicity of PCs is correlated with temporally and spatially restricted rises in intracellular Ca2+ and b) whether GYKI 52466 and nominal external Ca2+, conditions that reduced expression of AMPA-elicited DCD, altered the induced Ca2+ patterns. Employing the Ca2+-sensitive dye Fluo-3 and a confocal laser scanning microscope, we evaluated changes in intracellular Ca2+ within PCs in a cerebellar slice preparation. AMPA application alone (30 microM for 30 min) caused a significant initial rise in perinuclear and cytoplasmic Ca2+ that returned to control levels during the latter part of the AMPA exposure period. Following removal of AMPA (expression period), perinuclear and cytoplasmic Ca2+ displayed a significant delayed rise peaking transiently 60 min after AMPA removal. The efficacy of GYKI 52466 and nominal external Ca2+ conditions to attenuate AMPA-induced DCD was correlated to reductions in AMPA-induced transient elevations in perinuclear and cytoplasmic Ca2+ levels during the expression phase and to a lesser extent during the exposure period. The present data suggest that during the expression phase, the delayed perinuclear and cytoplasmic Ca2+ transient may be the harbinger of impending loss of Ca2+ homeostasis and cell damage.

Aniline Compounds↗
PubMed1998

Antibiotic prophylaxis in the initial management of severe acute pancreatitis.

BACKGROUND: The role of antibiotic prophylaxis in the initial management of patients with acute pancreatitis is an area of major controversy. Contrary to earlier clinical trials, recent experimental and clinical studies have accrued evidence that warrants reappraisal of current clinical practice. This article reviews these recent advances in knowledge. METHODS: All papers derived from a Medline search for the years 1990-1997 inclusive using the text words 'acute', 'pancreatitis', 'antibiotic' and 'antibiotics' were studied. Additional papers were derived from reference lists within papers identified by the Medline search. Only experimental and clinical papers relevant to the issue of prophylactic antibiotic therapy in acute pancreatitis are included in the review. RESULTS AND CONCLUSION: Current experimental evidence favours the use of prophylactic antibiotics in severe acute pancreatitis. The results of contemporary randomized clinical trials restricted to patients with prognostically severe acute pancreatitis have demonstrated improvement in outcome associated with antibiotic treatment.

Acute Disease↗
PubMed1997

Disinhibition of rat hippocampal pyramidal cells by GABAergic afferents from the septum.

1. Slices were prepared from rat forebrain to include both the septum and the hippocampus in order to examine the effects of septal stimulation on hippocampal inhibitory circuits. 2. Repetitive stimulation of septo-hippocampal fibres caused a maintained decrease in the frequency of spontaneous IPSPs recorded from CA3 pyramidal cells in the presence of antagonists of excitatory amino acid receptors and of muscarine receptors. 3. In records made from pyramidal cells with CsCl-filled electrodes, IPSPs were examined at potentials both more positive and more negative than their reversal potential. Single septal stimuli hyperpolarized pyramidal cells when IPSPs were depolarizing events and depolarized them when IPSPs were hyperpolarizing. The GABAA receptor antagonist picrotoxin abolished the effects of septal stimulation. 4. Activation of septal afferents initiated an IPSP in hippocampal inhibitory cells but not in pyramidal cells. Septal IPSPs had similar kinetics to those initiated by local hippocampal stimulation and could suppress inhibitory cell discharge. 5. In pyramidal cells recorded with potassium acetate-filled electrodes, septal stimuli initiated a depolarization that increased with the driving force for Cl- and that could cause firing. 6. Rhythmic stimulation of septo-hippocampal fibres at 5 Hz initiated, in the hippocampus, a maintained out-of-phase oscillation of pyramidal cell discharge and inhibitory cell firing, as detected by the occurrence of spontaneous IPSPs. 7. These results suggest that GABAergic septo-hippocampal afferents selectively inhibit hippocampal inhibitory cells and so disinhibit pyramidal cells. This disinhibition could contribute to the transmission of the theta rhythm from the septum to the hippocampus.

Afferent Pathways↗
PubMed1997

Psychopathology in preadolescent sons of fathers with substance use disorders.

OBJECTIVE: While preadolescent children of parents with substance use disorders (SUDs) are known to have more behavior problems, depression, and anxiety than expected, psychiatric disorders in these children and their relationships with parental disorders have not been systematically investigated. This study compares the psychiatric disorders of preadolescent boys of fathers with and without SUDs and examines the relationships between offspring and parental psychopathology. METHOD: Fathers (i.e., probands) of boys 10 through 12 years old were recruited to represent families of boys with paternal SUD (high risk or HR: n = 113) and boys without paternal SUD (low average risk or LAR: n = 170). These boys (i.e., index cases) and their biological parents participated in structured diagnostic interviews, and diagnoses were determined by the best-estimate method. RESULTS: Disruptive behavior disorders and anxiety disorders were more prevalent in HR than in LAR index cases. Logistic regression analyses examining the relationships between parental and index case psychopathology indicated that parental childhood psychiatric disorders were more strongly predictive of index case psychiatric disorders than parental adulthood psychiatric disorders, including SUDs. CONCLUSIONS: Inasmuch as HR boys had increased rates of disruptive behavior disorders and anxiety disorders, these disorders may be important targets for early intervention to prevent the development of SUD, as well as the morbidity associated with these disorders. Prevention efforts and studies of the transmission of liability for psychiatric disorders in children should carefully consider parental childhood characteristics.

Case-Control Studies↗
PubMed1996

Inhibition of estrogen-stimulated growth of uterine leiomyomas by selective estrogen receptor modulators.

Uterine leiomyoma is the most frequent gynecologic neoplasm in women. By using a panel of cell lines derived from spontaneous Eker rat leiomyomas, we examined the estrogen-responsive phenotype of these tumor cells. Leiomyoma-derived ELT cell lines proliferated in response to estrogen, and estrogen-induced cell proliferation could be inhibited by the estrogen antagonist ICI 182780 and the selective estrogen-receptor modulators (SERMs) raloxifene and tamoxifen. In addition to inhibiting cell growth, these antagonists also inhibited estrogen-induced increases in progesterone-receptor expression. These data indicate that SERMs such as raloxifene and tamoxifen act as estrogen antagonists in uterine myometrial cells and suggest that this class of compounds may be effective for treatment of this important gynecologic neoplasm.

Animals↗
PubMed1996

Differences between somatic and dendritic inhibition in the hippocampus.

Hippocampal synaptic inhibition is mediated by distinct groups of inhibitory cells. Some contact pyramidal cells perisomatically, while others terminate exclusively on their dendrites. We examined perisomatic and dendritic inhibition by recording from CA3 inhibitory and pyramidal cells and injecting biocytin to visualize both cells in light and electron microscopy. Single perisomatic inhibitory cells made 2-6 terminals clustered around the soma and proximal pyramidal cell processes. Dendritic cells established 5-17 terminals, usually on different dendrites of a pyramidal cells. Perisomatic terminals were larger than those facing dendritic membrane. Perisomatic inhibitory cells initiated the majority of simultaneous IPSPs seen in nearby pyramidal cells. Single IPSPs initiated by perisomatic sodium-dependent action potentials. Activation of inhibitory fibers terminating on dendrites could suppress calcium-dependent spikes. Thus, distinct inhibitory cells may differentially control dendritic electrogenesis and axonal output of hippocampal pyramidal cells.

Action Potentials↗
PubMed1996

Paired recordings from neurones.

Paired recording is a powerful and versatile tool to examine communication between and within neurones. This technique has provided new insights in studies of synaptic function and plasticity, of neuronal integration, and of the decoding of neuronal circuits. Recent studies using dual recordings in combination with morphology have successfully determined the number of transmitter release sites between synaptically connected neurones. Important progress in understanding the dynamics of signal transmission within individual cells has been made possible using infra-red microscopy, which permits dual recordings from visualized somatic and dendritic sites on a single neurone.

Animals↗
PubMed1996

Long distance transmission of diagnostic cardiovascular information.

Availability of advanced cardiac diagnostic procedures has proven to decrease the morbidity and mortality associated with common cardiovascular diseases. It was requested that the University of Nebraska Medical Center (UNMC) provide a rural hospital with advanced cardiology services. The services included monitoring of inpatients and rapid interpretation of cardiac diagnostic tests. UNMC proposed to solve this problem by building a computer-based system to transmit diagnostic cardiac information from a rural hospital to UNMC for interpretation by a cardiologist. The information transmitted to UNMC was grouped into two categories: 1) cardiovascular ultrasound, 2) ambulatory and 12-lead electrocardiograms. The information consisted of digital and analog waveform information, static images, and 30 fps video. The system provided rapid data transmission to UNMC over a T-1 line. The system utilized a compression technology which did not degrade the interpretation quality of the data. This system has increased the availability of advanced cardiac diagnostic services to general medical practitioners in a rural hospital. In addition, the system has significantly reduced the time and cost to transmit vital cardiac diagnostic information, thus improving the quality of care received by rural patients.

Cardiovascular Diseases↗
PubMed1996

Review of cardiac events in USAF aviators.

INTRODUCTION: The purpose of this study was to define the cardiac event rate in the U.S. Air Force (USAF) aviator population. METHODS: Several sources of information were reviewed to search for individual USAF active duty pilots and navigators who had cardiac events (defined as myocardial infarction, angina and sudden cardiac death), while on unrestricted flying duties during the years 1988-92. Source investigated included: USAF physical disability, casualty and medical evaluation board records, and records from the Aeromedical Consultation Service at Brooks AFB, TX. RESULTS: There were 38 total cardiac events, with an average of 7.6 events per year. Myocardial infarctions occurred in 23 aviators, angina in 7 and sudden death in 8. The ages ranged from 31-53 yr with an average age of 44 yr. The 5-yr average annual event rate by age group was 0.0054% (30-34 yr), 0.018% (35-39 yr), 0.038% (40-44 yr), 0.14% (45-49 yr), and 0.13% (50-54 yr). CONCLUSIONS: Although the total number of cardiac events in our aviator population is low, the cardiac event rate in the older age groups is of concern and may warrant a more intensive screening program for that population.

Adult↗
PubMed1995

Dual modulation of synaptic inhibition by distinct metabotropic glutamate receptors in the rat hippocampus.

1. The effects of metabotropic glutamate receptor (mGluR) activation on synaptic inhibition were examined using whole-cell recordings of spontaneous and miniature inhibitory synaptic currents from CA3 pyramidal cells in rat hippocampal slices. 2. The mGluR agonist (1S,3R)trans-1-aminocyclopentane-1,3-dicarboxylic acid (tACPD) increased spontaneous IPSC (spIPSC) frequency by up to 5-fold. At doses above 5 microM the increase was transient (15-45 s) and was followed by a decline to control frequency. In these conditions, elevating external K+ from 2 to 8 mM could still increase spIPSC frequency. 3. Miniature IPSCs (mIPSCs) were recorded in the presence of 1 microM TTX, 5 mM Mg2+ and nominally zero Ca2+. At concentrations above 50 microM, tACPD induced a sustained, reversible reduction in mIPSC frequency by up to 43%. 4. Quisqualate, at doses as low as 50 nM, increased spIPSC frequency, but did not affect mIPSC frequency at concentrations up to 10 microM. 5. The specific mGluR2 and 3 agonist (2S,1'R,2'R,3'R)-2-(2,3-dicarboxycyclopropyl)glycine (DCG-IV, 3 microM) reduced mIPSC frequency by 40 +/- 4% but did not increase spIPSC frequency. 6. The putative mGluR antagonist L-2-amino-3-phosphonopropionate (L-AP3, 1 mM) blocked the effect of tACPD on mIPSC but not spIPSC frequency. The broad-spectrum antagonist (RS)-alpha-methyl-4-carboxyphenylglycine (MCPG, 500 microM) blocked both responses. 7. mGluR activation also had dual effects on IPSCs evoked by focal extracellular stimulation. Application of 5 microM tACPD increased the mean amplitude of evoked IPSCs by 112 +/- 9%, largely by reducing the proportion of response failures. In contrast, IPSC amplitude was reduced to 44 +/- 1% of control values by 3 microM DCG-IV. 8. These results suggest hippocampal inhibitory cells express two distinct mGluR subtypes. One receptor (possibly mGluR1 or 5) is located on somato-dendritic membrane and enhances cell excitability. Another (mGluR2 or 3) is present at inhibitory terminals and reduces the probability of GABA release.

2-Amino-5-phosphonovalerate↗
PubMed1995

Fast and slow excitation of inhibitory cells in the CA3 region of the hippocampus.

Pyramidal cells form excitatory synaptic connections with local inhibitory neurons in the hippocampus. This recurrent synapse plays a crucial stabilizing role in the control of hippocampal activity, since it transforms pyramidal cell activity into inhibition of the same pyramidal cell population. Using a combination of dual recording from presynaptic and postsynaptic cells and anatomical techniques, we show that these synaptic connections often comprise a single site for liberation of excitatory transmitter. The resulting excitatory postsynaptic potentials (EPSCs) have a fast time course and a similar amplitude to miniature EPSCs recorded in tetrodotoxin and cobalt. In contrast, activation of metabotropic glutamate receptors (mGluRs) by transmitter liberated during repetitive activation of these synapses produces an excitation with a much slower time course. In addition to somatodendritic mGluRs, which excite inhibitory cells, a different species of mGluR is present on inhibitory cell terminals. This mGluR is activated by higher concentrations of the agonist t-1-amino-cyclopentyl-1,3-decarboxylate and acts to reduce gamma-aminobutyric acid release. mGluRs, thus, have a dual action to enhance and to depress synaptic inhibition in the hippocampus.

Animals↗
PubMed1995

Pyramidal cell-to-inhibitory cell spike transduction explicable by active dendritic conductances in inhibitory cell.

In the guinea-pig hippocampal CA3 region, the synaptic connection from pyramidal neurons to stratum pyramidale inhibitory neurons is remarkable. Anatomically, the connection usually consists of a single release site on an interneuronal dendrite, sometimes 200 microns or more from the soma. Nevertheless, the connection is physiologically powerful, in that a single presynaptic action potential can evoke, with probability 0.1 to 0.6, a postsynaptic action potential with latency 2 to 6 ms. We construct a model interneuron and show that the anatomical and physiological observations can be reconciled if the interneuron dendrites are electrically excitable. Excitable dendrites could also account for depolarization-induced amplification of the pyramidal cell-interneuron EPSP in the voltage range subthreshold for spike generation.

Action Potentials↗
PubMed1994

Excitatory synaptic connections onto rat hippocampal inhibitory cells may involve a single transmitter release site.

1. Whole-cell tight-seal records of excitatory postsynaptic currents (EPSCs) were made from inhibitory cells in the CA3 region of thin hippocampal slices. We tested the hypothesis that excitatory synaptic connections made on inhibitory cells involve few transmitter release sites. 2. EPSCs impinging on inhibitory cells had a time to peak of 0.4-3.8 ms and an amplitude of 8-90 pA at a holding potential of -60 mV. They were suppressed by the excitatory amino acid antagonists 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) and DL-2-amino-5-phosphonovaleric acid (APV). 3. Addition of tetrodotoxin (TTX) and Co2+ to the external solution reduced the frequency of EPSCs from 0.90 to 0.25 s-1 (n = 24 cells). In the majority of cells EPSC amplitude distributions were not significantly changed. 4. Increasing Ca2+ and reducing Mg2+ in the external solution, in order to enhance the probability of transmitter release, did not change EPSC amplitude distributions. In contrast, amplitude histograms for IPSCs recorded from pyramidal cells were shifted to higher mean values in this solution. 5. EPSCs were elicited in inhibitory cells by electrical stimulation via a glass pipette placed near to pyramidal cells in stratum pyramidale. EPSCs elicited by weak stimuli had similar amplitude distributions to excitatory synaptic events recorded in the presence of TTX and Co2+. 6. These findings suggest excitatory synaptic connections made with CA3 inhibitory cells involve few or possibly just one transmitter release site.

2-Amino-5-phosphonovalerate↗
PubMed1994

A branching dendritic model of a rodent CA3 pyramidal neurone.

1. We constructed a branching dendritic compartmental model of a CA3 pyramidal neurone, using experimental data from guinea-pig and rat cells obtained in vitro. The goal was to understand interactions between synaptic events impinging on dendritic branches and voltage- and calcium-dependent currents. The model contained sixty-four soma-dendrite (SD) compartments, an axon initial segment (IS), and four axonal compartments. There were six active conductances in the SD membrane, including a sodium conductance (gNa) and a high-threshold calcium conductance (gCa), with kinetic properties similar to those reported in a previous study. 2. The distribution of conductance densities across the IS and SD was adjusted by testing the model response to antidromic stimulation and current pulses or sustained currents injected into the soma or apical dendrites. As before, gNa was concentrated on and near the soma with lower density in the dendrites, while gCa had a higher density in apical dendrites than at the soma. 3. The model predicts that CA3 pyramidal neurones in media blocking synaptic transmission should fire a burst of action potentials following antidromic stimulation. This was confirmed experimentally in hippocampal slices. 4. Both in the model and in guinea-pig neurones, dendritic IPSCs can delay the onset of bursting. If an IPSC begins soon enough after the first fast action potential, the later burst envelope is attenuated. This effect results from suppression of dendritic Ca2+ electrogenesis. 5. The model predicts that an appropriately timed dendritic IPSC (after the first somatic spike but before the dendritic Ca2+ spike) may suppress the transient local [Ca2+] signal, while having a negligible effect on the electrical output of the neurone. This phenomenon has been reported in guinea-pig Purkinje cells. 6. We conclude that active dendritic currents are critical for regulation of the electrical output of CA3 pyramidal neurones. We suggest also that dendritic [Ca2+] signals might be controlled in individual dendrites independently of action potential outputs, an effect of possible importance for synaptic plasticity.

Action Potentials↗
PubMed1993

Hippocampal pyramidal cells excite inhibitory neurons through a single release site.

Morphologically a synapse consists of a presynaptic release site containing vesicles, a postsynaptic element with membrane specialization, and a synaptic cleft between them. The number of release sites shapes the properties of synaptic transmission between neurons. Although excitatory interactions between cortical neurons have been examined, the number of release sites remains unknown. We have now recorded excitatory postsynaptic potentials evoked by single pyramidal cells in hippocampal interneurons and visualized both cells using biocytin injections. Light and electron microscopy showed that excitatory postsynaptic potentials were mediated by a single synapse. We also reconstructed the entire axon arborization of single pyramidal cells, filled in vivo, in sections counterstained for parvalbumin, which selectively marks basket and axo-axonic cells. Single synaptic contacts between pyramidal cells and parvalbumin-containing neurons were dominant (> 80%), providing evidence for high convergence and divergence in hippocampal networks.

Animals↗