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Biomedical subjects

W R See

Publications and source records attributed to W R See.

At least 19 recordsLinked to original sources

High-frequency oscillations in membrane potentials of medullary inspiratory and expiratory neurons (including laryngeal motoneurons).

1. In midcollicular decerebrate, unanesthetized, paralyzed cats ventilated with a cycle-triggered pump system, the properties of high-frequency oscillations (HFOs, 50-100 Hz) in membrane potentials (MPs) of medullary inspiratory (I) and expiratory (E) cells were studied. Simultaneous recordings were taken from bilateral phrenic and recurrent laryngeal (RL) nerves and from cells in the intermediate ventral respiratory group (intVRG, 0-1 mm rostral to the obex) or the caudal ventral respiratory group (cVRG, 2-4 mm caudal to the obex). 2. Spectral coherence analyses were used to detect the presence of HFOs during I in I and E cell MPs. Cross-correlation histograms (CCHs) between the cell and phrenic signals were used to ascertain cell-nerve HFO phase relations and to identify cells as RL motoneurons. Of the 103 cells that had significant HFOs (cell-phrenic coherences > or = 0.1), measurable HFO peak lags in the CCH were seen in 53 cells: 1) RL cells (9 I cells and 7 E cells); and 2) other types of cell (8 intVRG I cells, 18 intVRG E cells, and 11 cVRG E cells). These cells had high HFO correlations; the cell-phrenic coherence range was 0.35-0.94, with a mean HFO frequency of 58 Hz. 3. The cell-phrenic HFO lag (in ms) was measured in the CCH as the lag of the primary peak (peak located nearest to 0 lag). The phase lag was defined as (lag of primary peak in ms)/(HFO period in ms). The phase lags differed markedly between two subsets of cells: 1) RL I cells had HFO depolarization peaks that lagged the phrenic HFO peaks (average cell-phrenic phase lag = -0.18); and 2) the non-RL cells, regardless of location (intVRG or cVRG) and type (I or E), had HFO depolarization peaks leading (preceding) the phrenic HFO peaks (average cell-phrenic phase lag = 0.28). In addition, the cVRG E cells had significantly shorter cell-phrenic phase lags than the intVRG E cells (0.23 vs. 0.31, respectively). 4. These lags can be compared with the (I unit)-phrenic phase lags (average approximately 0.3) found in earlier extracellular studies. 1) There is a transmission delay of about one half HFO cycle from excitatory I cells to RL I cells. 2) Because a depolarization peak in the MP of an E cell corresponds to the start of a hyperpolarizing wave, the excitatory bulbospinal pathways from I cells have transmission times comparable with those of the inhibitory intramedullary pathways from I cells to E cells. 5. These results indicate that study of HFO phase relations can furnish useful information on functional connectivity of medullary respiratory neurons during the I phase.

Animals

Analysis of recurrent laryngeal inspiratory discharges in relation to fast rhythms.

1. Inspiratory (I) activities of recurrent laryngeal (RL) motoneurons and efferent nerves were studied by autospectral, interval, and coherence analyses, with emphasis on fast rhythms of two types: medium-frequency oscillations (MFO, usual range 20-50 Hz for nerve autospectral peaks) and high-frequency oscillations (HFO, usual range 50-100 Hz). 2. In decerebrate, paralyzed, and artificially ventilated cats, recordings were taken from 27 isolated single RL fibers (14 cats) and 8 identified RL motoneurons in the medulla (6 cats), together with recordings of phrenic (PHR) and RL whole-nerve activities. In another 50 cats, RL and PHR nerve discharges were recorded simultaneously. 3. The autospectra of RL units showed prominent MFO peaks with frequencies close to that of the RL nerve MFO spectral peak, indicating presence of this type of fast rhythm in the units' discharges. Spectral analysis of RL unit activity in different segments of the I phase showed that the frequency of a unit's MFO was very close to the peak (maintained) firing rate of the unit during the portion of I analyzed. Thus a motoneuron's MFO spectral peak reflected its rhythmic discharge arising from the cell's refractoriness (and possibly with the rate changing in the course of I). 4. The coherences of motoneurons' MFOs to nerve MFOs were very low or 0, indicating that correlations between unitary MFOs of the RL population were rare and/or weak. 5. In those cats (19/20) that had discernible PHR nerve HFO autospectral peaks, about half of the recorded RL motoneurons (16/34) had HFO. For these motoneurons, the unit-nerve HFO coherences were substantial, indicating widespread correlations between unitary HFOs. 6. In a fraction of cats, coherence peaks in the MFO frequency range were observed between bilateral RL nerves, and between RL and PHR nerves, at frequencies that were subharmonics of the HFO frequency. 7. In light of theoretical considerations on the generation of aggregate rhythms from superposition of unitary rhythms, these observations indicate that, similarly, to the case of PHR motoneurons and nerves. 1) RL nerve MFO arises from superposition of uncorrelated, or at most partially correlated, MFOs of RL units, representing the rhythmic discharges of the cells. It is manifested therefore as a spectral deflection with a maximum in the band of peak firing rates of the units. 2) RL nerve HFO arises from correlated, common-frequency HFOs in a subpopulation of RL units, caused by HFO inputs from antecedent medullary I neurons.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals

A fast graphics printing program for neurophysiological data.

A program was written in assembly language for fast graphics screen dump of neurophysiological data during and after experiments. This program takes approximately 3 s to plot a 1024 x 768 graphics image. A resident program has also been produced, which allows a screen graphics image to be printed by using a keyboard command. A Pascal-compatible object file is available to interface the program with Turbo-Pascal programs.

Computer Graphics

Timing of medullary late-inspiratory neuron discharges: vagal afferent effects indicate possible off-switch function.

1. In decerebrate paralyzed cats, we observed the responses of ventral and dorsal medullary inspiratory (I) neurons to two types of vagal afferent input that shorten neural I: lung inflation and vagal electrical stimulation. 2. A study population of 15 I neurons whose firing patterns suggested involvement in the inspiratory OFF-switch (IOS) was selected on the basis of two criteria: late onset of firing and excitation by vagal inputs. 3. Firing in relation to the end of I showed two types of response to vagal inputs. The pre-expiratory onset time (time from initial spike to end of I) was either unchanged (type 1 response in 5/15 neurons) or significantly changed (type 2 response in 10/15 neurons). 4. It is suggested that type 1 neurons, whose firing patterns remain closely locked to the end of I despite considerable changes of I duration, are involved in promoting the IOS, whereas type 2 neurons are either not involved (e.g., late-onset premotor neurons) or are involved at an earlier temporal processing stage.

Afferent Pathways

Sleep laboratory studies on the single-dose effects of serotonin reuptake inhibitors paroxetine and fluoxetine on human sleep and awakening qualities.

Paroxetine is a novel antidepressant drug with selective serotonin (5-HT) reuptake inhibitory properties. In a double-blind placebo-controlled crossover sleep laboratory study the single-dose effects on objective and subjective sleep and awakening qualities were investigated after paroxetine 20, 30 and 40 mg morning doses (PX 20, 30, 40), paroxetine 30 mg evening dose, fluoxetine 40 mg morning dose (FX 40) and placebo in 18 healthy young volunteers. The drugs were orally administered in 2-wk intervals. In addition to each drug night, the adaptation night and washout night were recorded. Polysomnographic investigations (10:30 p.m. to 6:00 a.m.) showed a delayed sleep onset only after the morning intake of paroxetine, PX 40 being statistically different from placebo. Total sleep time and sleep efficiency deteriorated under morning PX 30, PX 40 and evening PX 30 as compared to placebo. The nocturnal wake time and sleep stage 1 increased under the paroxetine. Rapid eye movement (REM) reduction (min and %) occurred dose dependently after all paroxetine doses, but the REM latency was lengthened only after the morning intake. The suppressant effect on REM sleep is characteristic for antidepressants and was still significant in the washout nights following PX 40 and evening PX 30. The only statistically relevant finding under 40 mg fluoxetine referred to the increase of REM latency in both drug and washout nights. In contrast to objective results, subjective sleep quality remained generally unchanged. Attention, concentration and reaction performance improved under paroxetine as compared to baseline. The deterioration of well-being under PX 40 might be related to the appearance of drowsiness and nausea. Blood pressure and pulse rate were unaffected.

Adult

Changes in frequency content of inspiratory neuron and nerve activities in the course of inspiration.

In decerebrate paralyzed cats, the spectra and coherences of inspiratory (I) nerve activities and of medullary I neuron discharges were compared between different stages of I. The correlated high-frequency oscillations (HFOs) in the activities had common time courses of frequency and strength, which were influenced by lung afferent input; whereas the time courses for the uncorrelated medium-frequency oscillations (MFOs) depended on individual activity patterns. These results indicate that HFOs are characteristic of the common I pattern generator, whereas MFOs are specific to individual activities.

Action Potentials

Fast rhythms in the discharges of medullary inspiratory neurons.

The discharges of 44 medullary inspiratory (I) neurons in decerebrate paralyzed cats were studied using interval and spectral analysis. Most neurons had a rhythm in their discharge. In 31 the rhythm was at the frequency of, and coherent to, the high-frequency oscillations (HFOs) of I nerves, and in 7 the rhythm was in the range of medium-frequency oscillations (MFOs), with no coherence to nerve MFOs. Thus, correlated HFOs are characteristic of the I system at all levels, whereas MFOs are uncommon in medullary neurons and seem to be unrelated to general mechanisms.

Action Potentials

Intracellular potentials and discharge patterns of expiratory neurons in the caudal ventral respiratory group: influence of phasic pulmonary afferent input.

In decerebrate paralyzed cats, the membrane potential (MP) patterns of 12 augmenting expiratory (E) neurons in the caudal ventral respiratory group, and phrenic and recurrent laryngeal activities, were compared for inspiratory (I) phases with and without lung inflation. No-inflation produced, in the MPs of E neurons, larger hyperpolarization during I and during early E (associated with increased early-E laryngeal activity), suggesting an increase of inhibitory inputs from I neurons and early-E neurons, respectively.

Action Potentials

High-frequency and medium-frequency components of different inspiratory nerve discharges and their modification by various inputs.

In decerebrate paralyzed cats, spectral analysis was performed on simultaneous recordings of efferent inspiratory nerves (phrenic, recurrent laryngeal, hypoglossal). Spectral peaks were present both in the high-frequency (HFO) range (50-100 Hz) and the medium-frequency (MFO) range (20-50 Hz). Different activities were coherent only in the HFO range, indicating that the HFOs arise in a common inspiratory pattern generator that drives the different motoneuron populations, whereas the MFOs are specific to different systems.

Animals

Role of chemical afferents in the maintenance of rhythmic respiratory movements.

In seven anesthetized cats central chemosensitivity was eliminated (cold block) and peripheral chemoreceptors were either stimulated or eliminated (sectioned) to test whether nonchemical vagal afferents can maintain rhythmic ventilation and to determine the relative contribution of the carotid and aortic chemoreceptors to ventilatory drive without central chemosensitivity. Elimination of all chemical afferents invariably induced apnea, whereas ventilation was reduced from 533 to 159 ml X min-1 during cold block of central chemosensitivity and to 478 ml X min-1 after sectioning both sinus nerves. Cold block with only the aortic chemoreceptors and vagal afferents intact produced apnea in four of six cases tested. Stimulation of peripheral chemoreceptors during cold block remained effective and interrupted apnea in three of the four cats with only aortic chemoreceptors intact. We conclude that the nonchemical vagal respiratory afferents alone are unable to maintain rhythmic ventilation. Respiratory rhythm generation is, under the conditions of our experiments, critically dependent on sufficient afferent input from chemical afferents. Of these, central chemosensitivity plays the major role, followed by carotid body and, least importantly, by aortic afferents.

Afferent Pathways

Effect of halothane anesthesia on end-tidal PCO and pattern of respiration in the rat.

End-tidal Pco2 (petco2) and ventilation of the rat anesthetized with halothane were measured. The Petco2 measured by an infrared analyzer agreed well with the simultaneously measured Paco2 in the range from 20-60mm Hg (2.7-8.0 kPa). When the level of anesthesia was deepened by increasing the halothane concentration from 0.9-3.0%, minute ventilation was decreased progressively accompanied by a rise in Petco2 and the CO2 output was reduced. Halothane induced a progressive decrease in frequency of respiration (f) with almost constant or even slight increase in tidal volume (VT)). Decrease in f was caused largely by the prolongation of expiratory duration (TE). Changes in inspiratory duration (T1) were small and the mean VT/T1 ratio remained unaltered at different levels of anesthesia. These changes in respiratory pattern induced by halothane anesthesia contrasted with the simultaneous decrease in VT, f and VT/T1 ratio and apparent changes of both T1 an TE reported in other species. Species differences in effects of anesthesia on ventilation were discussed. Restraining the rat on a stereotaxic apparatus with head holders, especially with ear bars, elicited an initial transient stimulation of ventilation which was followed by a strong depression.

Anesthesia, General

H+-sensitivity and pattern of discharge of neurons in the chemosensitive areas of the ventral medulla oblongata of rats in vitro.

Effect of H+ on neuronal activity in medullary chemosensitive structures was analyzed in brain slices of the rat in vitro. Spontaneous discharges of spikes were recorded from two populations of neurons in the ventral surface layer of the medulla oblongata. Neurons located in the rostro-lateral part of the hypoglossal nerve root (area II) fired irregular phasic and/or continuous tonic discharges. More rostral and medial to it, a population of 'H+-sensitive' tonic neurons was found previously (area I). The phasic activity of neurons in area II with variable bursting and silent periods (0.1--120 s) was either increased or decreased by H+. Some neurons firing tonically in area II started to show phasic burst under low pH conditions. After cutting the slice between area I and II, the number of neurons firing phasically in area II was reduced, and the activity of area II neurons was mostly depressed by H+. An increase in activity of area I neurons by H+ was kept intact even after section. The results suggest that neurons in area I play an important role not only in the excitatory response to H+ of area II neurons but also in the initiation of phasic neuronal discharges in area II.

Animals

Respiratory response to hypoxia and hypercapnia after elimination of central chemosensitivity.

Central respiratory drive responding to pH changes was eliminated by bilateral coagulation or cold block of area S (intermediate area) on the ventral medullary surface in 7 anaesthetized cats. Arterial pH, PCO2, and PO2 (4 cats) and the respiratory response to hypoxia and hypercapnia (6 cats) were observed before and after coagulation. After coagulation in hyperoxia the arterial pH dropped from 7.30 to 7.09, the arterial PCO2 was elevated from 4.80 kPa to 8.17 kPa (6 cats). Ventilation increased by 477 ml at a PCO2a of 6.58 kPa when PO2a was reduced from 39.5 kPa to 8.5 kPa before coagulation, after coagulation ventilation increased by 241 ml (4 cats). The peripheral chemoreceptors guaranteed spontaneous breathing even in hyperoxia. The data reveal that the loss of respiratory homeostasis by elimination of the S areas is due to the loss of central chemosensitive drive with concomitant reduction of peripheral chemoreceptor effect.

Animals