bluuebunny/crossref_metadata_2025 huggingface dataset:
Oscillatory pressure-flow relationships of canine airways: a steady-state model for different gases
Authors: Sato J. , Davey B. L. , Suki B. , Bates J. H.
Published: December 2017

We measured the airway pressure drop (delta Paw) between the trachea and the alveolus in three normal anesthetized paralyzed dogs, together with flow (V) at the trachea. Alveolar pressure was measured using a closed-chest modification of the standard alveolar capsule technique. Measurements were made during a period of sinusoidal ventilation at 0.83 Hz with a tidal volume of 35 ml/kg, after a 30-s period of apnea. We found that the amplitude of the swings in delta Paw decreased transiently after onset of sinusoidal ventilation. We established that this decrease was due to a reflex bronchodilatation by making additional measurements on vagotomized dogs. We developed a mathematical model to account for the steady-state data that included both laminar and turbulent flow, airway wall elastance, airway gas inertance, and the Bernoulli effect at the site of tracheal pressure measurement. The model accurately described the data obtained from each dog with four different gas mixtures containing air, helium, neon, and sulfur hexafluoride. We also constructed Moody plots from the measured delta Paw-V relationships, after removing the estimated contributions of gas inertance and the Bernoulli effect from delta Paw, and found evidence of the effects of changing airway dimensions throughout a breath, V unsteadiness, and differences between inspiratory and expiratory resistances.
Advantage of normalizing force production to myofibrillar protein in skeletal muscle cross-sectional area
Authors: Taylor J. A. , Kandarian S. C.
Published: December 2017

When maximum isometric force (Po) is normalized to muscle cross-sectional area (CSA), intrinsic differences in force production among muscles may be masked by alterations in myofibrillar protein concentration or extracellular space. We tested the hypothesis that there is a greater deficit in Po when normalized to the average whole muscle CSA than when normalized to the myofibrillar protein CSA under conditions known to alter the concentration of myofibrils or connective tissue protein or interstitial fluid volume. Rats underwent either hindlimb unweighting (HU) to induce atrophy in the soleus muscle, sciatic nerve denervation to induce atrophy in the soleus and extensor digitorum longus (EDL) muscles, or ablation of gastrocnemius and plantaris muscles to induce hypertrophy in the soleus muscle. Po of the soleus muscle normalized to the muscle CSA (specific Po) was 58, 25, and 72% of control muscles with HU, denervation, and hypertrophy, respectively, whereas denervated EDL muscle specific Po was 60% of control muscles (P < 0.05). Soleus muscle Po normalized to the myofibrillar CSA was 80, 53, and 75% of control muscles with HU, denervation, and hypertrophy, respectively, whereas the denervated EDL muscle value was 82% of control muscles (P < 0.05). Both approaches to normalizing Po show force deficits, but normalization to the average myofibrillar protein in the muscle cross section gives values substantially closer to control values for HU and denervated muscles only. Data support the hypothesis because myofibrillar protein concentration is decreased in HU and denervation and interstitial space is increased in HU but neither parameter is altered with hypertrophy.(ABSTRACT TRUNCATED AT 250 WORDS)
Identification of Mechanoafferent Neurons in Terrestrial Snail: Response Properties and Synaptic Connections
Authors: Malyshev Aleksey Y. , Balaban Pavel M.
Published: December 2017

In this study, we describe the putative mechanosensory neurons, which are involved in the control of avoidance behavior of the terrestrial snail Helix lucorum. These neurons, which were termed pleural ventrolateral (PlVL) neurons, mediated part of the withdrawal response of the animal via activation of the withdrawal interneurons. Between 15 and 30 pleural mechanosensory neurons were located on the ventrolateral side of each pleural ganglion. Intracellular injection of neurobiotin revealed that all PlVL neurons sent their axons into the skin nerves. The PlVL neurons had no spontaneous spike activity or fast synaptic potentials. In the reduced “CNS-foot” preparations, mechanical stimulation of the skin covering the dorsal surface of the foot elicited spikes in the PlVL neurons without any noticeable prepotential activity. Mechanical stimulus-induced action potentials in these cells persisted in the presence of high-Mg2+/zero-Ca2+saline. Each neuron had oval-shaped receptive field 5–20 mm in length located on the dorsal surface of the foot. Partial overlapping of the receptive fields of different neurons was observed. Intracellular stimulation of the PlVL neurons produced excitatory inputs to the parietal and pleural withdrawal interneurons, which are known to control avoidance behavior. The excitatory postsynaptic potentials (EPSPs) in the withdrawal interneurons were induced in 1:1 ratio to the PlVL neuron spikes, and spike-EPSP latency was short and highly stable. These EPSPs also persisted in the high-Mg2+/high-Ca2+saline, suggesting monosynaptic connections. All these data suggest that PlVL cells were the primary mechanosensory neurons.
Weakly Modulated Spike Trains: Significance, Precision, and Correction for Sample Size
Authors: Hung Chou P. , Ramsden Benjamin M. , Roe Anna Wang
Published: December 2017

Many single-unit electrophysiological studies of visual cortex have investigated strong evoked responses to simple stimuli such as oriented gratings. Experiments involving other types of stimuli, such as natural scenes, higher-order features, and surface brightness, produce single-unit responses that are more difficult to interpret. Experiments with brightness, in particular, evoke single-unit responses that are typically weakly modulated. When the brightness is generated by a visual illusion such as the Cornsweet illusion, statistical tests are often necessary to distinguish true responses from baseline fluctuations. Here, using data collected from cat Areas 17 and 18 in response to real and illusory brightness stimuli, we provide a method for detecting and quantifying weak but significant periodic responses. By randomizing spike trains (via bootstrap methods), we provide confidence levels for response significance, permitting the evaluation of both weak and strong responses. We show that because of a strong dependence on total spike number, response significance can only be appropriately determined with randomized spike trains of similar spike number. Such randomizations can be performed for both stimulus-elicited and spontaneously occurring spike trains. By developing a method for generating randomized modulated spike trains (phase-restricted randomization) from actual recordings, we calculate upper and lower confidence limits of modulated spike trains and describe how measurement precision varies as a function of total spike count. Finally, using this randomization method, we describe how a correction function can be determined to correct for measurement bias introduced at low spike counts. These methods may also be useful in the study of small but potentially significant responses in other systems.
Eye-Hand Coordination: Saccades Are Faster When Accompanied by a Coordinated Arm Movement
Authors: Snyder Lawrence H. , Calton Jeffrey L. , Dickinson Anthony R. , Lawrence Bonnie M.
Published: December 2017

When primates reach for an object, they very often direct an eye movement toward the object as well. This pattern of directing both eye and limb movements to the same object appears to be fundamental to eye-hand coordination. We investigated interactions between saccades and reaching movements in a rhesus monkey model system. The amplitude and peak velocity of isolated eye movements are positively correlated with one another. This relationship is called the main sequence. We now report that the main sequence relationship for saccades is changed during coordinated eye and arm movements. In particular, peak eye velocity is approximately 4% faster for the same size saccade when the saccade is accompanied by a coordinated arm movement. Saccade duration is reduced by an equivalent amount. The main sequence relationship is unperturbed when the arm moves simultaneously but in the opposite direction as the eyes, suggesting that eye and arm movements must be tightly coordinated to produce the effect. Candidate areas mediating this interaction include the posterior parietal cortex and the superior colliculus.
Mechanosensitive Properties of Gastric Vagal Afferent Fibers in the Rat
Authors: Ozaki Noriyuki , Sengupta J. N. , Gebhart G. F.
Published: December 2017

Single, teased fiber recordings were made from the decentralized right cervical vagus nerve (hyponodal) of the rat. A total of 67 afferent fibers that responded to gastric distension (GD) were studied: 9 fibers were stimulated by phasic balloon GD, 58 by more natural fluid GD. All balloon GD–responsive fibers had resting activity (3.1 imp/s), and 57/58 fluid GD responsive fibers had resting activity (1.3 imp/s). All balloon GD–responsive fibers exhibited a dynamic response to phasic distension followed by slow adaptation, whereas fluid GD–responsive fibers exhibited increasing responses as intragastric pressure increased, followed typically by slow adaptation. Responses to graded GD were studied in all fibers, and all gave increasing responses to increasing pressures (5–60 mmHg). Thresholds for response varied between 0 and 18 mmHg. Mean response thresholds for two durations of fluid GD (30 and 60 s) were 5.6 and 3.9 mmHg; the mean response threshold to phasic balloon GD (30 s duration) was 5.3 mmHg. The potential sensitizing effect of platelet activating factor (PAF, 50 or 100 ng · kg−1 · min−1 for 20 min) infused into the gastric artery was studied in 20 fibers. Fifteen fibers exhibited an increase in spontaneous activity; intragastric pressure also slightly increased during PAF infusion. The increase in activity produced by PAF was attenuated in the presence of the PAF receptor antagonist WEB 2086. After PAF-induced acute inflammation of the stomach, three of five fibers studied did not exhibit any change in response to graded GD. The present study characterized distension-sensitive afferent fibers in the right cervical vagus innervating the stomach of the rat by balloon GD and fluid GD. The results document that all distension-sensitive gastric vagal afferent fibers encoded the intensity of GD, but none had response thresholds in what might be considered the noxious range. PAF infusion activated mechanosensitive gastric vagal afferent fibers, but acute inflammation produced by PAF did not sensitize responses to GD.
Androgens Modulate NMDA Receptor–Mediated EPSCs in the Zebra Finch Song System
Authors: White Stephanie A. , Livingston Frederick S. , Mooney Richard
Published: December 2017

Androgens potently regulate the development of learned vocalizations of songbirds. We sought to determine whether one action of androgens is to functionally modulate the development of synaptic transmission in two brain nuclei, the lateral part of the magnocellular nucleus of the anterior neostriatum (LMAN) and the robust nucleus of the archistriatum (RA), that are critical for song learning and production. We focused on N-methyl-d-aspartate–excitatory postsynaptic currents (NMDA-EPSCs), because NMDA receptor activity in LMAN is crucial to song learning, and because the LMAN synapses onto RA neurons are almost entirely mediated by NMDA receptors. Whole cell recordings from in vitro brain slice preparations revealed that the time course of NMDA-EPSCs was developmentally regulated in RA, as had been shown previously for LMAN. Specifically, in both nuclei, NMDA-EPSCs become faster over development. We found that this developmental transition can be modulated by androgens, because testosterone treatment of young animals caused NMDA-EPSCs in LMAN and RA to become prematurely fast. These androgen-induced effects were limited to fledgling and juvenile periods and were spatially restricted, in that androgens did not accelerate developmental changes in NMDA-EPSCs recorded in a nonsong area, the Wulst. To determine whether androgens had additional effects on LMAN or RA neurons, we examined several other physiological and morphological parameters. In LMAN, testosterone affected α-amino-3-hydroxy-5-methyl-4-isoxazoleproprianate–EPSC (AMPA-EPSC) decay times and the ratio of peak synaptic glutamate to AMPA currents, as well as dendritic length and spine density but did not alter soma size or dendritic complexity. In contrast, testosterone did not affect any of these parameters in RA, which demonstrates that exogenous androgens can have selective actions on different song system neurons. These data are the first evidence for any effect of sex steroids on synaptic transmission within the song system. Our results support the idea that endogenous androgens limit sensitive periods for song learning by functionally altering synaptic transmission in song nuclei.
Motor Dynamics Encoding in Cat Cerebellar Flocculus Middle Zone During Optokinetic Eye Movements
Authors: Kitama Toshihiro , Omata Tomohiro , Mizukoshi Akihito , Ueno Takehiko , Sato Yu
Published: December 2017

We investigated the relationship between eye movement and simple-spike (SS) frequency of Purkinje cells in the cerebellar flocculus middle zone during the optokinetic response (OKR) in alert cats. The OKR was elicited by a sequence of a constant-speed visual pattern movement in one direction for 1 s and then in the opposite direction for 1 s. Quick-phase-free trials were selected. Sixty-six cells had direction-selective complex spike (CS) activity that was modulated during horizontal (preferring contraversive) but not vertical stimuli. The SS activity was modulated during horizontal OKR, preferring ipsiversive stimuli. Forty-one cells had well-modulated activity and were suitable for the regression model. In these cells, an inverse dynamics approach was applied, and the time course of the SS rate was reconstructed, with mean coefficient of determination 0.76, by a linear weighted superposition of the eye acceleration (mean coefficient, 0.056 spikes/s per deg/s2), velocity (5.10 spikes/s per deg/s), position (−2.40 spikes/s per deg), and constant (mean 34.3 spikes/s) terms, using a time delay (mean 11 ms) from the unit response to the eye response. The velocity and acceleration terms contributed to the increase in the reconstructed SS rates during ipsilateral movements, whereas the position term contributed during contralateral movements. The standard regression coefficient analyses revealed that the contribution of the velocity term (mean coefficient 0.81) was predominant over the acceleration (0.03) and position (−0.17) terms. Forward selection analysis revealed three cell types: Velocity-Position-Acceleration type ( n = 27): velocity, position, and acceleration terms are significant ( P < 0.05); Velocity-Position type ( n = 12): velocity and position terms are significant; and Velocity-Acceleration type ( n = 2): velocity and acceleration terms are significant. Using the set of coefficients obtained by regression of the response to a 5 deg/s stimulus velocity, the SS rates during higher (10, 20, and 40 deg/s) stimulus velocities were successfully reconstructed, suggesting generality of the model. The eye-position information encoded in the SS firing during the OKR was relative but not absolute in the sense that the magnitude of the position shift from the initial eye position (0 deg/s velocity) contributed to firing rate changes, but the initial eye position did not. It is concluded that 1) the SS firing frequency in the cat middle zone encodes the velocity and acceleration information for counteracting the viscosity and inertia forces respectively, during short-duration horizontal OKR and 2) the apparent position information encoded in the SS firing is not appropriate for counteracting the elastic force during the OKR.
Developmental Changes in Leg Coordination of the Chick at Embryonic Days 9, 11, and 13: Uncoupling of Ankle Movements
Authors: Sharp Andrew A. , Ma Edna , Bekoff Anne
Published: December 2017

To understand changes in motor behavior during development, kinematic measurements were made of the right leg during embryonic motility in chicks on embryonic (E) days 9, 11, and 13. This is an interesting developmental period during which the embryo first becomes large enough to be physically constrained by the shell. Additionally, sensory systems are incorporated at that time into the spinal motor circuitry. Previous electromyographic (EMG) recordings have shown that the basic pattern of muscle activity seen at E9, composed of half-center–type alternation of extensor and flexor activation, breaks down by E13. This breakdown in organization could be because of disruption of motor patterns by the immature sensory system and/or new spatial constraints on the embryo. The current article describes several changes in leg movement patterns during this period. Episodes of motility increase in duration and the intervals of time between episodes of motility decrease in length. The range of motion of the leg increases, but the overall posture of the leg becomes more flexed. It was found that in-phase coordination of movement among the hip, knee, and ankle decreased between E9 and E13 in agreement with the previous EMG recordings. However, it was also found that the decrease of in-phase coordination among the three joints was accompanied by an increase in the time any two joints were moving in the same manner. Furthermore, examination of in-phase coordination within pairs of joints showed that all three pairs were well coordinated at E9, but that at E13 the in-phase coordination of the ankle with the other two joints decreased, whereas the knee and hip coordination was maintained. This suggests that the hip-knee synergy was closely coupled and that coupling of the ankle with other joints was more labile. The authors conclude that embryos respond to the reduction of free space in the egg during this period not by decreasing the amplitude or coordination of leg movements in general, but instead by differentially controlling the movements of the ankle from those of the hip and knee. Additionally, the changes in movement patterns do not represent a decrease in organization, but rather an alteration of motor coordination possibly as the result of information from the newly acquired sensory systems. These data also support theories that limb central pattern generators (CPGs) are composed of unit CPGs for each joint that can be modulated individually and that this organization is already established early in embryogenesis.
LVA and HVA Ca2+Currents in Ventricular Muscle Cells of theLymnaeaHeart
Authors: Yeoman M. S. , Brezden B. L. , Benjamin P. R.
Published: December 2017

The single-electrode voltage-clamp technique was used to characterize voltage-gated Ca2+currents in dissociated Lymnaea heart ventricular cells. In the presence of 30 mM tetraethylammonium (TEA), two distinct Ca2+currents could be identified. The first current activated between −70 and −60 mV. It was fully available for activation at potentials more negative than −80 mV. The current was fast to activate and inactivate. The inactivation of the current was voltage dependent. The current was larger when it was carried by Ca2+compared with Ba2+, although changing the permeant ion had no observable effect on the kinetics of the evoked currents. The current was blocked by Co2+and La3+(1 mM) but was particularly sensitive to Ni2+ions (≈50% block with 100 μM Ni2+) and insensitive to low doses of the dihydropyridine Ca2+channel antagonist, nifedipine. All these properties classify this current as a member of the low-voltage–activated (LVA) T-type family of Ca2+currents. The activation threshold of the current (−70 mV) suggests that it has a role in pacemaking and action potential generation. Muscle contractions were first seen at −50 mV, indicating that this current might supply some of the Ca2+necessary for excitation-contraction coupling. The second, a high-voltage–activated (HVA) current, activated at potentials between −40 and −30 mV and was fully available for activation at potentials more negative than −60 mV. This current was also fast to activate and with Ca2+as the permeant ion, inactivated completely during the 200-ms voltage step. Substitution of Ba2+for Ca2+increased the amplitude of the current and significantly slowed the rate of inactivation. The inactivation of this current appeared to be current rather than voltage dependent. This current was blocked by Co2+and La3+ions (1 mM) but was sensitive to micromolar concentrations of nifedipine (≈50% block 10 μM nifedipine) that were ineffective at blocking the LVA current. These properties characterize this current as a L-type Ca2+current. The voltage sensitivity of this current suggests that it is also important in generating the spontaneous action potentials, and in providing some of the Ca2+necessary for excitation-contraction coupling. These data provide the first detailed description of the voltage-dependent Ca2+currents present in the heart muscle cells of an invertebrate and indicate that pacemaking in the molluscan heart has some similarities with that of the mammalian heart.
Motor Cortical Activity During Drawing Movements: Population Representation During Spiral Tracing
Authors: Moran Daniel W. , Schwartz Andrew B.
Published: December 2017

Monkeys traced spirals on a planar surface as unitary activity was recorded from either premotor or primary motor cortex. Using the population vector algorithm, the hand's trajectory could be accurately visualized with the cortical activity throughout the task. The time interval between this prediction and the corresponding movement varied linearly with the instantaneous radius of curvature; the prediction interval was longer when the path of the finger was more curved (smaller radius). The intervals in the premotor cortex fell into two groups, whereas those in the primary motor cortex formed a single group. This suggests that the change in prediction interval is a property of a single population in primary motor cortex, with the possibility that this outcome is due to the different properties generated by the simultaneous action of separate subpopulations in premotor cortex. Electromyographic (EMG) activity and joint kinematics were also measured in this task. These parameters varied harmonically throughout the task with many of the same characteristics as those of single cortical cells. Neither the lags between joint-angular velocities and hand velocity nor the lags between EMG and hand velocity could explain the changes in prediction interval between cortical activity and hand velocity. The simple spatial and temporal relationship between cortical activity and finger trajectory suggests that the figural aspects of this task are major components of cortical activity.
Upregulation of a Silent Sodium Channel After Peripheral, but not Central, Nerve Injury in DRG Neurons
Authors: Black J. A. , Cummins T. R. , Plumpton C. , Chen Y. H. , Hormuzdiar W. , Clare J. J. , Waxman S. G.
Published: December 2017

After transection of their axons within the sciatic nerve, DRG neurons become hyperexcitable. Recent studies have demonstrated the emergence of a rapidly repriming tetrodotoxin (TTX)-sensitive sodium current that may account for this hyperexcitability in axotomized small (<27 μm diam) DRG neurons, but its molecular basis has remained unexplained. It has been shown previously that sciatic nerve transection leads to an upregulation of sodium channel III transcripts, which normally are present at very low levels in DRG neurons, in adult rats. We show here that TTX-sensitive currents in small DRG neurons, after transection of their peripheral axonal projections, reprime more rapidly than those in control neurons throughout a voltage range of −140 to −60 mV, a finding that suggests that these currents are produced by a different sodium channel. After transection of the central axonal projections (dorsal rhizotomy) of these small DRG neurons, in contrast, the repriming kinetics of TTX-sensitive sodium currents remain similar to those of control (uninjured) neurons. We also demonstrate, with two distinct antibodies directed against different regions of the type III sodium channel, that small DRG neurons display increased brain type III immunostaining when studied 7–12 days after transection of their peripheral, but not central, projections. Type III sodium channel immunoreactivity is present within somata and neurites of peripherally axotomized, but not centrally axotomized, neurons studied after <24 h in vitro. Peripherally axotomized DRG neurons in situ also exhibit enhanced type III staining compared with control neurons, including an accumulation of type III sodium channels in the distal portion of the ligated and transected sciatic nerve, but these changes are not seen in centrally axotomized neurons. These observations are consistent with a contribution of type III sodium channels to the rapidly repriming sodium currents observed in peripherally axotomized DRG neurons and suggest that type III channels may at least partially account for the hyperexcitibility of these neurons after injury.
Inhibition of Rapid Heat Responses in Nociceptive Primary Sensory Neurons of Rats by Vanilloid Receptor Antagonists
Authors: Kirschstein Timo , Greffrath Wolfgang , Büsselberg Dietrich , Treede Rolf-Detlef
Published: December 2017

Recent studies demonstrated that heat-sensitive nociceptive primary sensory neurons respond to the vanilloid receptor (VR) agonist capsaicin, and the first cloned VR is a heat-sensitive ion channel. Therefore we studied to what extent heat-evoked currents in nociceptive dorsal root ganglion (DRG) neurons can be attributed to the activation of native vanilloid receptors. Heat-evoked currents were investigated in 89 neurons acutely dissociated from adult rat DRGs as models for their own terminals using the whole cell patch-clamp technique. Locally applied heated extracellular solution (effective temperature ∼53°C) rapidly activated reversible and reproducible inward currents in 80% (62/80) of small neurons (≤32.5 μm), but in none of nine large neurons ( P < 0.001, χ2 test). Heat and capsaicin sensitivity were significantly coexpressed in this subpopulation of small DRG neurons ( P < 0.001, χ2 test). Heat-evoked currents were accompanied by an increase of membrane conductance (320 ± 115%; mean ± SE, n = 7), had a reversal potential of 5 ± 2 mV ( n = 5), which did not differ from that of capsaicin-induced currents in the same neurons (4 ± 3 mV), and were carried at least by Na+ and Ca2+(pCa2+ > pNa+). These observations are consistent with the opening of temperature-operated nonselective cation channels. The duration of action potentials was significantly higher in heat-sensitive (10–90% decay time: 4.45 ± 0.39 ms, n = 12) compared with heat-insensitive neurons (2.18 ± 0.19 ms, n = 6; P< 0.005, Student's t-test), due to an inflection in the repolarizing phase. This property as well as capsaicin sensitivity and small cell size are characteristics of nociceptive DRG neurons. When coadministered with heat stimuli, the competitive VR antagonist capsazepine (1 μM to 1 mM) significantly reduced heat-evoked currents in a dose-dependent manner (IC50 13 μM, Hill slope −0.58, maximum effect 75%). Preincubation for 12–15 s shifted the IC50 by ∼0.5 log10 units to an estimated IC50 of ∼4 μM. The noncompetitive VR antagonist ruthenium red (5 μM) significantly reduced heat-evoked currents by 33 ± 6%. The effects of both VR antagonists were rapidly reversible. Our results provide evidence for a specific activation of native VRs in nociceptive primary sensory neurons by noxious heat. The major proportion of the rapid heat-evoked currents can be attributed to the activation of these temperature-operated channels, and noxious heat may be the signal detected by VRs under physiological conditions.
Effect of Phasic Activation on Endplate Potential in Rat Diaphragm
Authors: Moyer Michelle , van Lunteren Erik
Published: December 2017

Neuromuscular junction endplate potentials (EPPs) decrease quickly and to a large extent during continuous stimulation. The present study examined the hypothesis that EPP rundown recovers rapidly, thereby substantially preserving neurotransmission during intermittent compared with continuous stimulation. Studies were performed in vitro on rat diaphragm, using μ-conotoxin to allow recording of normal-sized EPPs from intact fibers. During continuous 5- to 100-Hz stimulation, EPP amplitude declined with a biphasic time course. The initial fast rate of decline was modulated substantially by stimulation frequency, whereas the subsequent slow rate of decline was relatively frequency independent. During intermittent 5- to 100-Hz stimulation (duty cycle 0.33), EPP amplitude declined rapidly during each train, but recovered substantially by the onset of the following train. The intra-train declines were substantially greater than the inter-train declines in EPP amplitude. Intra-train reductions in EPP amplitude were stimulation frequency dependent, based on both the total decline and rate constant of EPP decline. In contrast, the degree of recovery from train to train was independent of stimulation frequency, indicating low frequency dependence of inter-train rundown. The substantial recovery of EPP amplitude in between trains resulted in greater cumulative EPP size during intermittent compared with continuous stimulation. During continuous stimulation, EPP drop-out was only seen during 100-Hz stimulation; this was completed mitigated during intermittent stimulation. Miniature EPP size was unaffected by either continuous or intermittent stimulation. The pattern of rapid intra-train rundown and slow inter-train rundown of EPP size during intermittent stimulation is therefore due to rapid changes in the magnitude of neurotransmitter release rather than to axonal block or postsynaptic receptor desensitization. These findings indicate considerable rundown of EPP amplitudes within a stimulus train, with near complete recovery by the onset of the next train. This substantially attenuates the decrement in EPP amplitude during intermittent compared with continuous stimulation, thereby preserving the integrity of neurotransmission during phasic activation.
Activation of Spinal Wide Dynamic Range Neurons by Intracutaneous Microinjection of Nicotine
Authors: Jinks Steven L. , Carstens E.
Published: December 2017

Nicotine evokes pain in the skin and oral mucosa and excites a subpopulation of cutaneous nociceptors, but little is known about the central transmission of chemogenic pain. We have investigated the responses of lumbar spinal wide dynamic range (WDR)-type dorsal horn neurons to intracutaneous (ic) microinjection of nicotine in pentobarbital-anesthetized rats. Nearly all (97%) units responded to nicotine microinjected ic (1 μl) into the low-threshold region of the hind-paw mechanosensitive receptive field in a concentration-related manner (0.01–10%). Responses to repeated injections of 10% nicotine exhibited tachyphylaxis at 5-, 10-, and 15-min interstimulus intervals. Significant tachyphylaxis was not seen with 1% nicotine. All nicotine-responsive units tested ( n = 30) also responded to ic histamine (1 μl, 3%) and did not exhibit tachyphylaxis to repeated histamine. However, there was significant cross-tachyphylaxis of nicotine to histamine. Thus 5 min after ic nicotine, histamine-evoked responses were attenuated significantly compared with the initial histamine-evoked response prior to nicotine, with partial recovery over the ensuing 15 min. Neuronal excitation by ic nicotine was not mediated by histamine H1 receptors because ic injection of the H1 receptor antagonist, cetirizine, had no effect on ic nicotine-evoked responses, whereas it significantly attenuated ic histamine-evoked responses in the same neurons. The lowest-threshold portion of cutaneous receptive fields showed a significant expansion in area at 20 min after ic nicotine 10%, indicative of sensitization. Responses to 1% nicotine were significantly reduced after ic injection of the nicotinic antagonist, mecamylamine (0.1% ic), with no recovery over the ensuing 40–60 min. These data indicate that nicotine ic excites spinal WDR neurons, partly via neuronal nicotinic acetylcholine receptors that are presumably expressed in cutaneous nociceptor terminals. Repeated injections of high concentrations of nicotine led to tachyphylaxis and cross-tachyphylaxis with histamine, possibly relevant to peripheral analgesic effects of nicotine.
Intracellular Study of Excitability in the Seizure-Prone Neocortex In Vivo
Authors: Steriade Mircea , Amzica Florin
Published: December 2017

The excitability of neocortical neurons from cat association areas 5–7 was investigated during spontaneously occurring seizures with spike-wave (SW) complexes at 2–3 Hz. We tested the antidromic and orthodromic responsiveness of neocortical neurons during the “spike” and “wave” components of SW complexes, and we placed emphasis on the dynamics of excitability changes from sleeplike patterns to seizures. At the resting membrane potential, an overwhelming majority of neurons displayed seizures over a depolarizing envelope. Cortical as well as thalamic stimuli triggered isolated paroxysmal depolarizing shifts (PDSs) that eventually developed into SW seizures. PDSs could also be elicited by cortical or thalamic volleys during the wave-related hyperpolarization of neurons, but not during the spike-related depolarization. The latencies of evoked excitatory postsynaptic potentials (EPSPs) progressively decreased, and their slope and depolarization surface increased, from the control period preceding the seizure to the climax of paroxysm. Before the occurrence of full-blown seizures, thalamic stimuli evoked PDSs arising from the postinhibitory rebound excitation, whereas cortical stimuli triggered PDSs immediately after the early EPSP. These data shed light on the differential excitability of cortical neurons during the spike and wave components of SW seizures, and on the differential effects of cortical and thalamic volleys leading to such paroxysms. We conclude that the wave-related hyperpolarization does not represent GABA-mediated inhibitory postsynaptic potentials (IPSPs), and we suggest that it is a mixture of disfacilitation and Ca2+-dependent K+ currents, similar to the prolonged hyperpolarization of the slow sleep oscillation.
Passive Normalization of Synaptic Integration Influenced by Dendritic Architecture
Authors: Jaffe David B. , Carnevale Nicholas T.
Published: December 2017

We examined how biophysical properties and neuronal morphology affect the propagation of individual postsynaptic potentials (PSPs) from synaptic inputs to the soma. This analysis is based on evidence that individual synaptic activations do not reduce local driving force significantly in most central neurons, so each synapse acts approximately as a current source. Therefore the spread of PSPs throughout a dendritic tree can be described in terms of transfer impedance ( Zc ), which reflects how a current applied at one location affects membrane potential at other locations. We addressed this topic through four lines of study and uncovered new implications of neuronal morphology for synaptic integration. First, Zc was considered in terms of two-port theory and contrasted with dendrosomatic voltage transfer. Second, equivalent cylinder models were used to compare the spatial profiles of Zc and dendrosomatic voltage transfer. These simulations showed that Zc is less affected by dendritic location than voltage transfer is. Third, compartmental models based on morphological reconstructions of five different neuron types were used to calculate Zc , input impedance ( ZN ), and voltage transfer throughout the dendritic tree. For all neurons, there was no significant variation of Zc with location within higher-order dendrites. Furthermore, Zc was relatively independent of synaptic location throughout the entire cell in three of the five neuron types (CA3 interneurons, CA3 pyramidal neurons, and dentate granule cells). This was quite unlike ZN , which increased with distance from the soma and was responsible for a parallel decrease of voltage transfer. Fourth, simulations of fast excitatory PSPs (EPSPs) were consistent with the analysis of Zc ; peak EPSP amplitude varied <20% in the same three neuron types, a phenomenon that we call “passive synaptic normalization” to underscore the fact that it does not require active currents. We conclude that the presence of a long primary dendrite, as in CA1 or neocortical pyramidal cells, favors substantial location-dependent variability of somatic PSP amplitude. In neurons that lack long primary dendrites, however, PSP amplitude at the soma will be much less dependent on synaptic location.
Chemical Activation of Cervical Cell Bodies: Effects on Responses to Colorectal Distension in Lumbosacral Spinal Cord of Rats
Authors: Qin Chao , Chandler Margaret J. , Miller Kenneth E. , Foreman Robert D.
Published: December 2017

We have shown that stimulation of cardiopulmonary sympathetic afferent fibers activates relays in upper cervical segments to suppress activity of lumbosacral spinal cells. The purpose of this study was to determine if chemical excitation (glutamate) of upper cervical cell bodies changes the spontaneous activity and evoked responses of lumbosacral spinal cells to colorectal distension (CRD). Extracellular potentials were recorded in pentobarbital-anesthetized male rats. CRD (80 mmHg) was produced by inflating a balloon inserted in the descending colon and rectum. A total of 135 cells in the lumbosacral segments (L6–S2) were activated by CRD. Seventy-five percent (95/126) of tested cells received convergent somatic input from the scrotum, perianal region, hindlimb, and tail; 99/135 (73%) cells were excited or excited/inhibited by CRD; and 36 (27%) cells were inhibited or inhibited/excited by CRD. A glutamate (1 M) pledget placed on the surface of C1–C2 segments decreased spontaneous activity and excitatory CRD responses of 33/56 cells and increased spontaneous activity of 13/19 cells inhibited by CRD. Glutamate applied to C6–C7 segments decreased activity of 10/18 cells excited by CRD, and 9 of these also were inhibited by glutamate at C1–C2 segments. Glutamate at C6–C7 increased activity of 4/6 cells inhibited by CRD and excited by glutamate at C1–C2 segments. After transection at rostral C1 segment, glutamate at C1–C2still reduced excitatory responses of 7/10 cells. Further, inhibitory effects of C6–C7 glutamate on excitatory responses to CRD still occurred after rostral C1transection but were abolished after a rostral C6transection in 4/4 cells. These data showed that C1–C2 cells activated with glutamate primarily produced inhibition of evoked responses to visceral stimulation of lumbosacral spinal cells. Inhibition resulting from activation of cells in C6–C7 segments required connections in the upper cervical segments. These results provide evidence that upper cervical cells integrate information that modulates activity of distant spinal neurons responding to visceral input.
Temporal Dynamics of Acoustic Stimuli Enhance Amplitude Tuning of Inferior Colliculus Neurons
Authors: Galazyuk Alexander V. , Llano Daniel , Feng Albert S.
Published: December 2017

Sounds in real-world situations seldom occur in isolation. In spite of this, most studies in the auditory system have employed sounds that serve to isolate physiological responses, namely, at low rates of stimulation. It is unclear, however, whether the basic response properties of a neuron derived thereof, such as its amplitude and frequency selectivities, are applicable to real-world situations where sounds occur in rapid succession. In the present study, we investigated one of the basic response properties of neurons in the bat inferior colliculus (IC), i.e., the rate-level function, to tone pulses in three different configurations: individual tone pulses of constant amplitude at different rates of stimulation, random-amplitude pulse trains, and dynamic-amplitude-modulated pulse trains the temporal pattern of which was similar to what bats encounter in a behavioral context. We reported that for the majority of IC neurons, amplitude selectivity to tone pulses was dependent on the rate of stimulation. In general, the selectivity was greater at high rates or in a behavioral context than at low rates. For a small population of IC neurons, however, the rate of stimulation had little or no effect on their rate-level functions. Thus for IC neurons, responses to sounds presented at low rates may or may not be used to predict the responses to the same stimuli presented at high rates or in a behavioral context. The possible neural mechanisms underlying the rate-dependent effects are discussed.
Corticotropin-Releasing Factor Produces a Protein Synthesis–Dependent Long-Lasting Potentiation in Dentate Gyrus Neurons
Authors: Wang Hai L. , Tsai Li Y. , Lee Eminy H. Y.
Published: December 2017

Corticotropin-releasing factor (CRF) was shown to produce a long-lasting potentiation of synaptic efficacy in dentate gyrus neurons of the rat hippocampus in vivo. This potentiation was shown to share some similarities with tetanization-induced long-term potentiation (LTP). In the present study, we further examined the mechanism underlying CRF-induced long-lasting potentiation in rat hippocampus in vivo. Results indicated that the RNA synthesis inhibitor actinomycin-D, at a concentration that did not change basal synaptic transmission alone (5 μg), significantly decreased CRF-induced potentiation. Similarly, the protein synthesis inhibitor emetine, at a concentration that did not affect hippocampal synaptic transmission alone (5 μg), also markedly inhibited CRF-induced potentiation. These results suggest that like the late phase of LTP, CRF-induced long-lasting potentiation also critically depend on protein synthesis. Further, prior maximum excitation of dentate gyrus neurons with tetanization occluded further potentiation of these neurons produced by CRF and vise versa. Moreover, quantitative reverse transcription-polymerase chain reaction analysis revealed that CRF mRNA level in the dentate gyrus was significantly increased 1 h after LTP recording. Together with our previous findings that CRF antagonist dose-dependently diminishes tetanization-induced LTP, these results suggest that both CRF-induced long-lasting potentiation and tetanization-induced LTP require protein synthesis and that CRF neurons are possibly involved in the neural circuits underlying LTP.
Characterization With Barium of Potassium Currents in Turtle Retinal Müller Cells
Authors: Solessio Eduardo , Linn David M. , Perlman Ido , Lasater Eric M.
Published: December 2017

Müller cells are highly permeable to potassium ions and play a crucial role in maintaining potassium homeostasis in the vertebrate retina. The potassium current found in turtle Müller cells consists of two components: an inwardly rectifying component and a linear, passive component. These currents are insensitive to broadband potassium channel blockers, tetraethylammonium (TEA) and 4-aminopyridine (4-AP) and well blocked by barium. Differential block by the polyamine spermine suggests that these currents flow through different channels. In this study, we used barium ions as a probe to investigate the properties of these currents by whole cell, voltage-clamp recordings from isolated cells. Current-voltage ( I-V) relationships generated from current responses to short (35 ms) and long (3.5 s) voltage pulses were fit with the Hill equation. With extracellular barium, the time course of block and unblock was voltage and concentration dependent and could be fit with single exponential functions and time constants larger than 100 ms. Blocking effects by extracellular barium on the two types of currents were indistinguishable. The decrease of the outward current originates in part due to charge effects. We also found that intracellular barium was an effective blocker of the potassium currents. The relative block of the inward rectifier by intracellular barium suggests the existence of two “apparent” binding sites available for barium within the channel. Under depolarizing conditions favoring the block by internal polyamines, the Hill coefficient for barium binding was 1, indicating a single apparent binding site for barium within the pore of the passive linear conductance. The difference in the steepness of the blocking functions suggests that the potassium currents flow through two different types of channels, an inward rectifier and a linear passive conductance. Last, we consider the use of barium as an intracellular K+ channel blocker for voltage-clamp experiments.
Presynaptic Ca2+Influx at the Inhibitor of the Crayfish Neuromuscular Junction: A Photometric Study at a High Time Resolution
Authors: Vyshedskiy Andrey , Lin Jen-Wei
Published: December 2017

Presynaptic calcium influx at the inhibitor of the crayfish neuromuscular junction was investigated by measuring fluorescence transients generated by calcium-sensitive dyes. This approach allowed us to correlate presynaptic calcium influx with transmitter release at a high time resolution. Systematic testing of the calcium indicators showed that only low-affinity dyes, with affinities in the range of micromolar, should be used to avoid saturation of dye binding and interference with transmitter release. Presynaptic calcium influx was regulated by slowly increasing the duration of the action potential through progressive block of potassium channels. The amplitude of the calcium transient, measured from a cluster of varicosities, was linearly related to the duration of the action potential with a slope of 1.2. Gradual changes in potassium channel block allowed us to estimate the calcium cooperativity of transmitter release over a 10-fold range in presynaptic calcium influx. Calcium cooperativity measured here exhibited one component with an average value of 3.1. Inspection of simultaneously recorded presynaptic calcium transients and inhibitory postsynaptic currents (IPSCs) showed that prolonged action potentials were associated with a slow rising phase of presynaptic calcium transients, which were matched by a slow rate of rise of IPSCs. The close correlation suggests that fluorescence transients provide information on the rate of calcium influx. Because there is an anatomic mismatch between the presynaptic calcium transient, measured from a cluster of varicosities, and IPSC, measured with two-electrode voltage clamp, macropatch recording was used to monitor inhibitory postsynaptic responses from the same cluster of varicosities from which the calcium transient was measured. Inhibitory postsynaptic responses recorded with the macropatch method exhibited a faster rising phase than that recorded with two-electrode voltage clamp. This difference could be attributed to slight asynchrony of transmitter release due to action potential conduction along fine branches. In conclusion, this report shows that fluorescence transients generated by calcium-sensitive dyes can provide insights to the properties of presynaptic calcium influx, and its correlation with transmitter release, at a high time resolution.