Integration of the effects of a single stimulus applied to the vagus nerve on the right and the left, in the rabbit heart

It was reported by the literature that a train stimulation, simultaneously delivered on the two vagi, resulted in a decrement of the negative chronotropic effect, when it was compared to the sum of the effects obtained by the stimulation of the two nerves, separately. Our data indicate that the size of the chronotropic effect obtained by the simultaneous application on the two vagi of a single supraliminar stimulus, randomly applied within the P-P cycle, in rabbits, can be equal, higher or lower than the sum of the same stimulation separately delivered to the two nerves. The results could depend upon the different amount of acetylcholine released during stimulation. The hypothesis is put forward that different patterns of the neuro-cardiac junction regulation might be activated according to the quantity of released neuromediator.     

High plasma norepinephrine attenuates the dynamic heart rate response to vagal stimulation

To better understand the pathophysiological significance of high plasma norepinephrine (NE) concentration in regulating heart rate (HR), we examined the interactions between high plasma NE and dynamic vagal control of HR. In anesthetized rabbits with sinoaortic denervation and vagotomy, using a binary white noise sequence (0-10 Hz) for 10 min, we stimulated the right vagus and estimated the transfer function from vagal stimulation to HR response. The transfer function approximated a first-order low-pass filter with pure delay. Infusion of NE (100 microg. kg(-1) x h(-1) iv) attenuated the dynamic gain from 6.2 +/- 0.8 to 3.9 +/- 1.2 beats x min(-1) x Hz(-1) (n = 7, P < 0.05) without affecting the corner frequency or pure delay. Simultaneous intravenous administration of phentolamine (1 mg x kg(-1) x h(-1)) and NE (100 microg x kg(-1) x h(-1)) abolished the inhibitory effect of NE on the dynamic gain (6.3 +/- 0.8 vs. 6.4 +/- 1.3 beats x min(-1) x Hz(-1), not significant, n = 7). The inhibitory effect of NE at infusion rates of 10, 50, and 100 microg x kg(-1) x h(-1) on dynamic vagal control of HR was dose-dependent (n = 5). In conclusion, high plasma NE attenuated the dynamic HR response to vagal stimulation, probably via activation of alpha-adrenergic receptors on the preganglionic and/or postganglionic cardiac vagal nerve terminals.     

The dynamics of the chronotropic effect of a single vagal stimulus in cats under the action of met-enkephalin and neurotensin]

Following a burst of pulses applied to the vagus nerve with progressively incremental delay after the P wave of the ECG, the narrow zone of the cardiac cycle was identified where even a small shift of the vagal burst position evoked an abrupt alteration of the chronotropic effect magnitude. Met-enkephalin potentiated the phase-dependent vagal chronotropic effect, whereas neurotensin moved its limits toward the initial part of the P-P interval.     

Quantifying the information transmitted in a single stimulus

Information theory - in particular mutual information- has been widely used to investigate neural processing in various brain areas. Shannon mutual information quantifies how much information is, on average, contained in a set of neural activities about a set of stimuli. To extend a similar approach to single stimulus encoding, we need to introduce a quantity specific for a single stimulus. This quantity has been defined in literature by four different measures, but none of them satisfies the same intuitive properties (non-negativity, additivity), that characterize mutual information. We present here a detailed analysis of the different meanings and properties of these four definitions. We show that all these measures satisfy, at least, a weaker additivity condition, i.e. limited to the response set. This allows us to use them for analysing correlated coding, as we illustrate in a toy-example from hippocampal place cells.     

Exercise training augments the dynamic heart rate response to vagal but not sympathetic stimulation in rats

We examined the transfer function of autonomic heart rate (HR) control in anesthetized sedentary and exercise-trained (16 wk, treadmill for 1 h, 5 times/wk at 15 m/min and 15-degree grade) rats for comparison to HR variability assessed in the conscious resting state. The transfer function from sympathetic stimulation to HR response was similar between groups (gain, 4.2 ± 1.5 vs. 4.5 ± 1.5 beats·min(-1)·Hz(-1); natural frequency, 0.07 ± 0.01 vs. 0.08 ± 0.01 Hz; damping coefficient, 1.96 ± 0.55 vs. 1.69 ± 0.15; and lag time, 0.7 ± 0.1 vs. 0.6 ± 0.1 s; sedentary vs. exercise trained, respectively, means ± SD). The transfer gain from vagal stimulation to HR response was 6.1 ± 3.0 in the sedentary and 9.7 ± 5.1 beats·min(-1)·Hz(-1) in the exercise-trained group (P = 0.06). The corner frequency (0.11 ± 0.05 vs. 0.17 ± 0.09 Hz) and lag time (0.1 ± 0.1 vs. 0.2 ± 0.1 s) did not differ between groups. When the sympathetic transfer gain was averaged for very-low-frequency and low-frequency bands, no significant group effect was observed. In contrast, when the vagal transfer gain was averaged for very-low-frequency, low-frequency, and high-frequency bands, exercise training produced a significant group effect (P < 0.05 by two-way, repeated-measures ANOVA). These findings suggest that, in the frequency domain, exercise training augments the dynamic HR response to vagal stimulation but not sympathetic stimulation, regardless of the frequency bands.     

Interaction between vagal and chemoreceptors afferents in ventilatory response to transient hypercapnia (anaesthetized rabbit).

In rabbits anaesthetized with ethyl-carbamate, stimulation of chemoreceptors afferents was allowed by transient hypercapnia, before and after vagal blockade by DC current. In these relatively fast breathing animals, the transient hypercapnia produced light changes of inspiratory tidal volume (VI), inspiratory (TI) and expiratory durations (TE). Despite the identity of transient hypercapnia, it ensued that: (1) the higher the spontaneous VI and the lower the respiratory frequency (fR), the greater their respective changes (deltaVI and deltafR) during the ventilatory response; (2) after vagal blockade, greater changes in VI, TI, TE and mean inspiratory flow rate (VI/TI) occurred than in control state, while the relation between deltafR and fR was more significant than in control state. Respective roles played by vagal and chemoreceptors afferents in the ventilatory response to transient hypercapnia are discussed.     

On the effects of a constant sub-threshold conditioning stimulus upon the response to a constant current test stimulus

The strength of a test stimulus, which is just adequate to produce a response after a sub-threshold conditioning stimulus, is calculated on the basis of Rashevsky's two-factor theory as a function of the strength and duration of the conditioning stimulus. The results are compared with available data for one of a family of curves and found to be in satisfactory agreement.     

Properties of vagal excitation transfer to the heart atrium]

A mathematical model of pre- and postganglionic parasympathetic nerve fiber excitation transfer is developed. This model gives a measure Q of acetylcholine (ACh) release from presynaptic preganglionic boutons and postganglionic varicosities. When increasing Ca++ the measure Q increases too. Na-ions exert a competitive inhibition. The relationship between Q and the Ca/Na2-quotient is a hyperbolic one. Mn++ inhibits the release of ACh non-competitively. Q increases both by excess potassium and Cs+ depolarization. The ACh release is diminished by Mg++. Ba++ cannot replace the effect of Ca++ on ACh release in Ca++ depleting conditions. Q increases with decreasing pH-level. The ACh release is not significantly influenced by increasing pH, Verapamil (4 mg/l), prostaglandins E2 and F2alpha (20 ng/ml) and substitution of nonpermeable anions for Cl-.     

P300 from a single auditory stimulus

The P3(00) event-related brain potential (ERP) was elicited with auditory stimuli to compare 2 different discrimination tasks. The oddball paradigm presented both target and standard tones; the single-stimulus paradigm presented at target but no standard tone stimulus. Experiment 1 manipulated target stimulus probability (0.20, 0.50, 0.80) and produced highly similar P3 amplitude and latency results across probability levels for each paradigm. Experiment 2 factorially varied inter-stimulus interval (2 sec, 6 sec) and target stimulus probability (0.20, 0.80). P3 amplitude and latency were highly similar for both the oddball and single-stimulus procedures across all conditions.     

Role of vagal C-fiber afferents in respiratory response to hypercapnia

The respiratory response to hypercapnia has been investigated in 10 anesthetized rabbits by use of a rebreathing technique. The responses were obtained in three situations: with one intact vagus nerve (control), during differential block of conduction, and after vagotomy. Differential block was achieved using anodal hyperpolarization by application of a direct current to the cervical vagus nerve. Great care was taken during the differential block to establish that all impulse conduction in myelinated fibers of the cervical vagus nerve was abolished but that the nonmyelinated fibers conducted normally. Additionally, in five more rabbits the nature of the differential block was confirmed from single-fiber recordings of activity in both myelinated and nonmyelinated fibers. The same increase in tidal volume in response to hypercapnia was present in all three experimental situations, indicating that it was not vagally mediated. The increase in frequency in response to hypercapnia in the control state was abolished by vagotomy but preserved when only the nonmyelinated fibers were functioning during the differential block. This increased frequency response, attributable to decreases in both inspiratory and expiratory durations, was usually enhanced during the differential block, despite the slower deeper pattern of breathing attributed to loss of activity in myelinated fibers. The implications of this reflex increase in frequency in response to hypercapnia, mediated by nonmyelinated vagal endings in the lung, are discussed.     

Changes in the phase response curve of the circadian clock to a phase-shifting stimulus.

Experiments were conducted in hamsters to determine whether the phase response curve (PRC) to injections of the short-acting benzodiazepine triazolam is a fixed or a labile property of the circadian clock. The results indicated that (1) both the shape and the amplitude of the PRC to triazolam generated on the first day of transfer from a light-dark cycle (LD 14:10) to constant darkness (DD) (i.e., PRCLD) were different from those of the PRC generated after many days in DD (PRCDD); and (2) the phase-shifting effects of triazolam on the activity rhythms of hamsters transferred from LD 14:10 or 12:12 to DD changed dramatically within the first 8-9 days spent in DD. In an attempt to accelerate the resynchronization of the circadian clock of hamsters subjected to an 8-hr advance in the LD cycle, triazolam was given to the animals at a time selected on the basis of the characteristics of PRCLD. The activity rhythms of five of eight triazolam-treated animals were resynchronized to the new LD cycle within 2-4 days after the shift, whereas those of most of the control animals were resynchronized 21-29 days after the shift. These findings suggest that attempts to use pharmacological or nonpharmacological tools to phase-shift circadian clocks under entrained conditions should take into account information derived from PRCs generated at the time of transition from entrained to free-running conditions.     

Calcium response in single osteocytes to locally applied mechanical stimulus: Differences in cell process and cell body

It is proposed that osteocytes embedded in the bone matrix have the ability to sense deformation and/or damage to the matrix and to feed these mechanical signals back to the adaptive bone remodeling process. When osteoblasts differentiate into osteocytes during the bone formation process, they change their morphology to a stellate form with many slender processes. This characteristic cell shape may underlie the differences in mechanosensitivity between the cell processes and cell body. To elucidate the mechanism of cellular response to mechanical stimulus in osteocytes, we investigated the site-dependent response to quantitatively controlled local mechanical stimulus in single osteocytes isolated from chick embryos, using the technique of calcium imaging. A mechanical stimulus was applied to a single osteocyte using a glass microneedle targeting a microparticle adhered to the cell membrane by modification with a monoclonal antibody OB7.3. Application of the local deformation induced calcium transients in the vicinity of the stimulated point and caused diffusive wave propagation of the calcium transient to the entire intracellular region. The rate of cell response to the stimulus was higher when applied to the cell processes than when applied to the cell body. In addition, a large deformation was necessary at the cell body to induce calcium transients, whereas a relatively small deformation was sufficient at the cell processes, suggesting that the mechanosensitivity of the cell processes was higher than that of the cell body. These results suggest that the cell shape with slender processes contributes to the site-dependent mechanosensitivity in osteocytes.     

Glycerylprostaglandin synthesis by resident peritoneal macrophages in response to a zymosan stimulus

Cyclooxygenase (COX)-2 oxygenates arachidonic acid (AA) and 2-arachidonylglycerol (2-AG) to endoperoxides, which are subsequently transformed to prostaglandins (PGs) and glycerylprostaglandins (PG-Gs). PG-G formation has not been demonstrated in intact cells treated with a physiological agonist. Resident peritoneal macrophages, which express COX-1, were pretreated with lipopolysaccharide to induce COX-2. Addition of zymosan caused release of 2-AG and production of the glyceryl esters of PGE2 and PGI2 over 60 min. The total quantity of PG-Gs (16 +/- 6 pmol/10(7) cells) was much lower than that of the corresponding PGs produced from AA (21,000 +/- 7,000 pmol/10(7) cells). The differences in PG-G and PG production were partially explained by differences in the amounts of 2-AG and AA released in response to zymosan. The selective COX-2 inhibitor, SC236, reduced PG-G and PG production by 49 and 17%, respectively, indicating a significant role for COX-1 in PG-G and especially PG synthesis. Time course studies indicated that COX-2-dependent oxygenation rapidly declined 20 min after zymosan addition. When exogenous 2-AG was added to macrophages, a substantial portion was hydrolyzed to AA and converted to PGs; 1 microm 2-AG yielded 820 +/- 200 pmol of PGs/10(7) cells and 78 +/- 41 pmol of PG-Gs/10(7) cells. SC236 reduced PG-G and PG production from exogenous 2-AG by 88 and 76%, respectively, indicating a more significant role for COX-2 in the utilization of exogenous substrate. In conclusion, lipopolysaccharide-pretreated macrophages produce PG-Gs from endogenous 2-AG during zymosan phagocytosis, but PG-G formation is limited by substrate hydrolysis and inactivation of COX-2.     

The development of a febrile response to pyrogen in the thyroid-deficient rabbit

The development of the febrile response to E. coli lipopolysaccharide (1.5 micrograms/kg, i.v.) in thyroid-deficient rabbits has been studied. Twenty-eight New Zealand White rabbits weighing 2.1-2.3 kg were used. Hypothyroidism was induced by treatment with propylthiouracil (100 or 200 mg/kg body wt./15 days). Thyroid-deficient animals showed a reduction in the febrile response to lipopolysaccharide, but the effect was significantly different (p less than 0.01) from the control only for rabbits treated with 200 mg/kg of propylthiouracil. Propranolol (2 mg/kg, i.p.) given 30 min before lipopolysaccharide also reduced (p less than 0.01) the fever response in control rabbits. The results of this experiment are consistent with the hypothesis that the reduction in the febrile response of thyroid-deficient rabbits is due to the reduced number of beta-adrenergic receptors, or to a change in the availability of neurotransmitter in thermogenically active tissues, such as brown fat.     

Chemosensory behavior: the path from stimulus to response

In the past year, candidates have been identified for two long-sought classes of molecules, insect odorant receptors and mammalian taste receptors. In addition, genes directing receptor gene expression and the development of specific chemosensory neurons have been described in Drosophila melanogaster and Caenorhabditis elegans. Finally, recent physiological experiments have provided new insights into the mechanisms by which chemosensory information is processed.