Chemosensor-Driven Artificial Antennal Lobe Transient Dynamics Enable Fast Recognition and Working Memory

The speed and accuracy of odor recognition in insects can hardly be resolved by the raw descriptors provided by olfactory receptors alone due to their slow time constant and high variability. The animal overcomes these barriers by means of the antennal lobe (AL) dynamics, which consolidates the classificatory information in receptor signal with a spatiotemporal code that is enriched in odor sensitivity, particularly in its transient. Inspired by this fact, we propose an easily implementable AL-like network and show that it significantly expedites and enhances the identification of odors from slow and noisy artificial polymer sensor responses. The device owes its efficiency to two intrinsic mechanisms: inhibition (which triggers a competition) and integration (due to the dynamical nature of the network). The former functions as a sharpening filter extracting the features of receptor signal that favor odor separation, whereas the latter implements a working memory by accumulating the extracted features in trajectories. This cooperation boosts the odor specificity during the receptor transient, which is essential for fast odor recognition.

Amine Modulation of Ih in a Small Neural Network

We studied the functional role and modulation of the hyperpolarization-activated inward current ( Ih) in the pyloric network of the lobster stomatogastric ganglion. In isolated neurons, Ih is a small current with a hyperpolarized voltage of half-activation ( VAct) and a slow time constant of activation (τAct). Bath application of dopamine (DA), octopamine (OCT), or serotonin (5HT) modified Ih in selected synaptically isolated pyloric neurons. DA significantly enhanced Ih in the anterior burster (AB) neuron by depolarizing its VAct, accelerating its τAct, and enhancing its maximal conductance ( gmax). DA more weakly enhanced Ih in the pyloric constrictor (PY) and ventricular dilator (VD) neurons. OCT weakly depolarized VAct and accelerated τAct in the VD and inferior cardiac (IC) neurons. 5HT depolarized VAct in the IC neuron. Under control conditions with intact modulatory inputs from other ganglia, the pyloric rhythm cycles strongly at about 1–2 Hz. Bath application of the Ih blocker cesium (Cs+) caused a mean increase in the period of 8%, although this effect was highly variable. When Cs+ was applied to an isolated ganglion where the pyloric rhythm had been activated only by DA, the cycle period was consistently increased by 13.5%, with no other strong changes in rhythm parameters. These results suggest that Ih regulates the pyloric rhythm by accelerating AB pacemaker frequency, but that this effect can vary with the modulatory conditions.

Short-term potentiation of ventilation after different levels of hypoxia

Short-term potentiation of ventilation (VSTP) may be observed in healthy subjects on sudden termination of an hypoxic stimulus. We hypothesized that the level of hypoxia preceding normoxia would modify the duration and magnitude of the ensuing ventilatory decay. Ten healthy adults were studied on two different occasions, during which they were randomly exposed to isocapnic 6 or 10% O2for 60 s and then switched to an isocapnic normoxic gas mixture. Both hypoxic gases induced significant ventilatory responses, and mean peak minute ventilation before the isocapnic normoxic switch was higher in 6% O2( P < 0.001). The fast time constant of the two-exponential equation representing the best fit for ventilatory decay was unaffected by the magnitude of the hypoxic stimulus. However, the slow time constant, which is considered to represent VSTP, was markedly prolonged in 6% compared with 10% O2 [106.7 ± 11.3 vs. 38.2 ± 6.1 (SD) s, respectively; P< 0.0001]. This result indicates that VSTP is stimulus dependent. We conclude that the magnitude of hypoxia preceding a normoxic transient modifies VSTP characteristics. We speculate that the interdependence function of ventilatory stimulus and short-term potentiation is crucial for preservation of system stability during transitions from high to low ventilatory drives.

Modulation of Voltage-dependent Properties of a Swelling-activated Cl− Current

We used the patch-clamp technique to study the voltage-dependent properties of the swelling-activated Cl− current (ICl,swell) in BC3H1 myoblasts. This Cl− current is outwardly rectifying and exhibits time-dependent inactivation at positive potentials (potential for half-maximal inactivation of +75 mV). Single-channel Cl− currents with similar voltage-dependent characteristics could be measured in outside-out patches pulled from swollen cells. The estimated single-channel slope conductance in the region between +60 and +140 mV was 47 pS. The time course of inactivation was well described by a double exponential function, with a voltage-independent fast time constant (∼60 ms) and a voltage-dependent slow time constant (&gt;200 ms). Recovery from inactivation, which occurred over the physiological voltage range, was also well described by a double exponential function, with a voltage-dependent fast time constant (10–80 ms) and a voltage-dependent slow time constant (&gt;100 ms). The inactivation process was significantly accelerated by reducing the pH, increasing the Mg2+ concentration or reducing the Cl− concentration of the extracellular solution. Replacing extracellular Cl− by other permeant anions shifted the inactivation curve in parallel with their relative permeabilities (SCN− &gt; I− &gt; NO3− &gt; Cl− &gt;&gt; gluconate). A leftward shift of the inactivation curve could also be induced by channel blockers. Additionally, the permeant anion and the channel blockers, but not external pH or Mg2+, modulated the recovery from inactivation. In conclusion, our results show that the voltage-dependent properties of ICl,swell are strongly influenced by external pH , external divalent cations, and by the nature of the permeant anion.

Stretch-activated channels in airway epithelial cells

Two type of stretch-activated (SA) ion channels were identified in the basolateral membrane of isolated rabbit airway epithelial cells by patch-clamp techniques. Pressure activation and deactivation of one channel, which had a conductance of 29 pS, occurred after a delay of approximately 20-30 s. The open probability of this delayed stretch-activated (DSA) channel was increased from < 0.01 to 0.45 at 50 mmHg of suction. The reversal potential of the DSA channel, calculated from the pipette potential at which membrane currents reversed [-31.3 +/- 3.6 (SD) mV] and the resting membrane potential (-27.8 +/- 3.3 mV) was +3.5 +/- 3.3 mV. None of the equilibrium potentials of the ions used were similar to the calculated reversal potential of the DSA channel, suggesting that this channel is nonselective for cations. The DSA channel gating behavior was characterized by bursts of rapid transitions between open and closed states. The distribution of the open and closed times revealed that this gating behavior could be fitted with two open states and two closed states. Only the slow time constant of the closed state was decreased by suction. The second SA channel was selective for K+ and had a conductance of 65 pS but a long delay was not associated with the pressure sensitivity of this channel. The open probability of the K(+)-selective SA channel was increased from < 0.01 to 0.30 by 50 mmHg of suction. The K(+)-selective SA channel was distinct from the well-characterized basolateral K+ channel.

Analysis of venous flow transients for estimation of vascular resistance, compliance, and blood flow distribution

We analysed venous flow transients using a long venous circuit and right heart bypass in 17 dogs after a rapid decrease in atrial pressure. A biphase curve was obtained which we decomposed into a two-compartmental model, one with a fast time constant for venous return (0.069 min) and 52% of total circulating flow [Formula: see text], and one with a slower time constant (0.456 min) and 48% of [Formula: see text]. Subsequently, separate drainage from splanchnic and peripheral beds (with the renal venous return in the peripheral bed drainage) allowed comparison of time constants and venous outflow in these beds. The sum of the venous outflow volumes over time during separate drainage was indistinguishable from the single biphasic venous outflow volume curve over time observed with a long circuit and single reservoir. The fast time constant of the biphasic curve was not different from that determined by separate drainage from the peripheral circulation. The slow time constant of the single biphasic curve of 0.456 min was hybrid of two time constants, 0.216 min in the splanchnic bed and 0.862 min in the peripheral bed. Separate drainage from peripheral and splanchnic vascular beds demonstrated that the peripheral bed constituted 70% of venous outflow in the fast time constant compartment using Caldini's technique, whereas the splanchnic bed constituted 63% of venous outflow in the slow time constant compartment. It is concluded that, although Caldini's technique demonstrates biphasic venous flow transients, neither the fast nor the slow time constant compartments resolved from this analysis represent a particular anatomical region or vascular bed.

Comparative effects of vasodilator drugs on flow distribution and venous return

Systemic vascular effects of hydralazine, prazosin, captopril, and nifedipine were studied in 115 anesthetized dogs. Blood flow [Formula: see text] and right atrial pressure (Pra) were independently controlled by a right heart bypass. Transient changes in central blood volume after an acute reduction in Pra at a constant [Formula: see text] showed that blood was draining from two vascular compartments with different time constants, one fast and the other slow. At three dose levels producing comparable reductions in systemic arterial pressure (30–40% at the highest dose), these drugs had different effects on flow distribution and venous return. Hydralazine and prazosin had parallel and balanced effects on arterial resistance of the two vascular compartments, and flow distribution was unaltered. Captopril preferentially reduced arterial resistance of the compartment with a slow time constant for venous return (−26 ± 6%, −30 ± 6%, −50 ± 5% at 0.02, 0.10, and 0.50 mg∙kg−1∙h−1, respectively; [Formula: see text]) without altering arterial resistance of the fast time-constant compartment. Blood flow to the slow time-constant compartment was increased 43 ± 14% at the highest dose, and central blood volume was reduced 108 ± 15 mL. In contrast, nifedipine had a balanced effect on arterial resistance with the lowest dose (0.025 mg/kg) but caused a preferential reduction in arterial resistance of the fast time-constant compartment at higher doses (−38 ± 4% and −55 ± 2% at 0.05 and 0.10 mg/kg, respectively). Blood flow to the slow time-constant compartment was reduced 36 ± 5% at the highest dose of nifedipine, and central blood volume was increased 66 ± 12 mL. Total systemic venous compliance was unaltered or slightly reduced by each of the four drugs. These results add further evidence to the hypothesis that peripheral blood flow distribution is a major determinant of venous return to the heart.

Time-constant histograms from the forced expired volume signal

The forced expired volume signal was analyzed using a parallel compartment model in which each compartment emptied exponentially. With this model the forced expired volume signal was represented by a histogram showing the fraction of the vital capacity as a functional of compartmental time constants. We developed an algorithm to compute this histogram from the volume signal. The algorithm used the least-squares criterion function with both smoothness and nonnegativity constraints. In a stimulation study reasonable histograms were obtained even in the presence of realistic random error. Three dependent forced expired volume signals from 16 subjects were analyzed, and the histograms were reproducible. Most histograms were bimodal with fast time constants of 0.12–0.55 s and slow time constants of 1.3–2.7 s. In all normal subjects and patients with restrictive disease more than 75% of the vital capacity was in the fast time-constant mode. Subjects with obstructive disease had more than 40% of the vital capacity in the slow time-constant mode.