bluuebunny/crossref_metadata_2025 huggingface dataset:
Hebbian induction of LTP in visual cortex: perforated patch-clamp study in cultured neurons
Authors: Otsu Y. , Kimura F. , Tsumoto T.
Published: December 2017

1. To see whether presynaptic activation paired with postsynaptic depolarization is necessary for the induction of long-term potentiation (LTP) in visual cortex or whether an activation of postsynaptic receptors in conjunction with depolarization is sufficient, we carried out perforated patch-clamp recordings with nystatin from cultured cortical neurons of rats. 2. Recorded neurons were monosynaptically activated either by electrical stimulation of an adjacent neuron or by direct activation of glutamate on "hot spots" of dendrites through iontophoresis or pressure ejection. In experiments in which cultured neurons were stained immunocytochemically with antibody against synaptophysin after electrophysiological recordings, hot spots were found to correspond to probable synaptic sites. 3. Excitatory postsynaptic currents (EPSCs) evoked by test stimulation applied to the adjacent neuron at 0.1 Hz were recorded at a holding potential of -60 or -70 mV for 5-10 min after an establishment of the whole cell recording configuration. Then, stimulation was paired with postsynaptic depolarization (0 mV for 200 ms) at 1 Hz for 30 or 60 s. LTP of EPSCs was induced in 7 of the 15 cells from which stable recordings were obtained for 18-30 min after pairing. 4. When postsynaptic depolarization was paired with direct glutamate application in the absence of presynaptic stimulation in 12 cells, only 1 showed LTP. Postsynaptic depolarization alone did not induce LTP in any of the six cells tested. Also, presynaptic stimulation alone did not induce LTP in any of the five cells tested. 5. These results suggest that the concurrent activation of presynaptic elements with postsynaptic depolarization is necessary for the induction of LTP in visual cortex.
Transduction and adaptation in spider slit sense organ mechanoreceptors
Authors: Juusola M. , French A. S.
Published: December 2017

1. Mechanoreceptor neurons in spider (Cupiennlus salei) slit sense organ were examined by intracellular current- and voltageclarry recordings. Steps and pseudorandomly modulated displacement stimuli were delivered to the mechanosensitive cuticular slits. The resulting responses were used to determine the response dynamics and signal-to-noise ratio (SNR) of mechanoelectrical transduction. 2. Neurons were separated into two groups that, in terms of their afferent discharges, displayed different adaptations to displacement stimuli. Both responded at the onset of the step but then adapted fully, either immediately or within 10-200 ms. Voltage-clamp recordings showed only small differences in the receptor currents of the two groups. 3. Displacement of the slit caused a large inward current that decayed in seconds to a steady level of approximately 10-25% of the initial transient. When adapted to a steady displacement, the neurons responded to superimposed displacements in the same direction with additional transient currents, whose decay could be fitted by two exponentials with time constants of approximately 10 and 100 ms. In contrast, displacement in the opposite direction caused small "outward" currents without obvious adaptation. This behavior persisted with increasing background displacements, suggesting a shift in the displacement-response curve along the displacement axis. 4. White noise stimulation supported the step data and confirmed that the receptor's sensitivity was independent of mean slit membrane displacement. When the relative displacement of the stimulus (i.e., strain) was held constant at different maintained backgrounds, the SNR of the neurons remained fairly constant at approximately 2-10 over the frequency range from 4 to 450 Hz. The receptor current frequency responses showed high-pass characteristics, with a two- to sevenfold enhancement of the response amplitude and a phase lag relative to the stimulus of 90 degrees at 300 Hz. Low coherence values in the frequency range of 0.5-125 Hz were explained by nonlinear adaptation. 5. We conclude that, by rapidly adapting to the mean displacement of the slit membrane, slit organ mechanoreceptor neurons maintain a high sensitivity and SNR that allow the detection of small and rapid changes in cuticular strain.
Nonlinear models of the first synapse in the light-adapted fly retina
Authors: Juusola M. , Weckstrom M. , Uusitalo R. O. , Korenberg M. J. , French A. S.
Published: December 2017

1. Randomly modulated light stimuli were used to characterize the nonlinear dynamic properties of the synapse between photoreceptors and large monopolar neurons (LMC) in the fly retina. Membrane potential fluctuations produced by constant variance contrast stimuli were recorded at eight different levels of background light intensity. 2. Representation of the photoreceptor-LMC input-output data in the form of traditional characteristic curves indicated that synaptic gain was reduced by light adaptation. However, this representation did not include the time-dependent properties of the synaptic function, which are known to be nonlinear. Therefore nonlinear systems analysis was used to characterize the synapse. 3. The responses of photoreceptors and LMCs to random light fluctuations were characterized by second-order Volterra series, with kernel estimation by the parallel cascade method. Photoreceptor responses were approximately linear, but LMC responses were clearly nonlinear. 4. Synaptic input-output relationships were measured by passing the light stimuli to LMCs through the measured photoreceptor characteristics to obtain an estimate of the synaptic input. The resulting nonlinear synaptic functions were well characterized by second-order Volterra series. They could not be modeled by a linear-nonlinear-linear cascade but were better approximated by a nonlinear-linear-nonlinear cascade. 5. These results support two possible structural models of the synapse, the first having two parallel paths for signal flow between the photoreceptor and LMC, and the second having two distinct nonlinear operations, occurring before and after chemical transmission. 6. The two models were cach used to calculate the synaptic gain to a brief change in photoreceptor membrane potential. Both models predicted that synaptic gain is reduced by light adaptation.
Adaptation of carotid chemoreceptors to step increases in PaCO2 in anesthetized cats
Authors: Linton R. A. , Band D. M. , McLoughlin P.
Published: December 2017

1. The rate of change sensitivity of some carotid chemoreceptors to within-breath changes in PaCO2 would suggest that the half-life of adaptation of these receptors to a step increase is shorter than the 5-10 s previously reported. 2. In six anesthetized cats, step increases in PaCO2 (10 in each cat) were produced by injection of CO2 into the inspired gas during high-frequency jet ventilation. Chemoreceptor discharge was recorded from single-fiber preparations of the divided carotid sinus nerve, and the changes in PaCO2 were followed with the use of an in vivo pH electrode. 3. The adaptation half-lives were 0.3, 0.8, 1.2, 1.3, 1.6, and 8.6 s. The physiological significance of these findings in terms of respiratory control and the mechanism of chemotransduction are discussed. The receptors with the shortest and longest half-lives showed corresponding differences in response to sine-wave oscillations in PaCO2. 4. In a further group of five cats, chemoreceptor responses to step increases in PaCO2 were tested before and during infusion of KCl to produce a mean arterial [K-] of 6.8 +/- 0.2 (SE) mM. Under these conditions the hyperkalemia caused no further increase in discharge. 5. We conclude that adaptation of the chemoreceptor response to increases in PaCO2 is much faster than previously reported and that this finding is consistent with observations of chemoreceptor responses to respiratory PaCO2 oscillations.
Benzolamide inhibits low-threshold calcium currents in hippocampal pyramidal neurons
Authors: Gottfried J. A. , Chesler M.
Published: December 2017

1. Benzolamide is a poorly permeant sulfonamide inhibitor of the enzyme carbonic anhydrase. We studied the effect of benzolamide on low-threshold (LT) Ca currents in neonatal hippocampal CAl neurons. 2. In hippocampal slices, benzolamide (2-10 microM) inhibited the LT current 30-75% in voltage-clamped CAl pyramidal cells (n = 6). In slices bathed in N-2-hydroxypiperazine-N'-2-ethane-sulfonic acid (HEPES)-buffered Ringer, benzolamide also reduced the LT current, indicating that the action of the drug was not bicarbonate dependent. 3. Benzolamide inhibited LT Ca currents 20-75% in acutely dissociated CAl neurons in HEPES (n = 18): inhibition was 36 +/- 8% (mean +/- SE; n = 7) and 50 +/- 8% (n = 7) at 10 and 50 microM benzolamide, respectively. By contrast, high-threshold calcium currents recorded in CAl pyramidal cells (n = 18) and dorsal root ganglion neurons (n = 4) were virtually unaffected by benzolamide. 4. These results indicate that benzolamide inhibits LT Ca channels in central neurons and suggest caution in the use of this agent to inhibit extracellular carbonic anhydrase in excitable tissues.
Nerve growth factor (NGF) acutely enhances high-voltage-activated calcium currents in molluscan neurons
Authors: Wildering W. C. , Lodder J. C. , Kits K. S. , Bulloch A. G.
Published: December 2017

1. Nerve growth factor (NGF) is a member of a family of molecules (the neurotrophins) that can regulate the survival and/or outgrowth of many vertebrate cells. NGF also induces outgrowth from Lymnaea neurons under experimental conditions. Recent studies have shown that the neurotrophins can also acutely modulate some physiological properties of adult neurons. Here we examined the actions of NGF on high-voltage-activated (HVA) Ca2+ currents in Lymnaea motoneurons. 2. NGF induced a dose-dependent and reversible increase in HVA Ca2+ currents within 2 min. 3. The threshold dose of the NGF-induced enhancement of HVA Ca2+ currents ranged between 1 and 1,000 pg/ml. In the most sensitive cells, the response saturated at doses higher than 1 ng/ml. 4. The results indicate that neurotrophins acutely modulate voltage-gated Ca2+ currents in molluscan neurons through a high affinity signal transduction pathway. The data support the existence of neurotrophins in invertebrates. Moreover, this property of NGF may explain the neuromodulatory actions of neurotrophins observed in various preparations.
Burst characteristics of dentate gyrus granule cells: evidence for endogenous and nonsynaptic properties
Authors: Pan E. , Stringer J. L.
Published: December 2017

1. Hippocampal slices bathed in 8 mM potassium and 0-added calcium exhibited spontaneous epileptiform activity in the dentate gyrus. Extracellular recording revealed recurrent prolonged bursts of population spikes and an associated negative DC shift. These episodes were very similar to the in vivo phenomenon termed maximal dentate activation (MDA). Therefore this in vitro activity will be referred to as MDA-like activity or events. 2. During the MDA-like activity, the individual granule cells exhibited a sustained depolarization that matched the duration of the negative extracellular DC shift. At the beginning of the MDA-like activity, there was a burst of action potentials. After the burst, most granule cells either continued to fire action potentials regularly or in bursts. Some cells exhibited this initial burst of activity and then a dramatic reduction in firing rate. This reduction in rate was followed by a gradual increase in the amplitude and frequency of the epileptiform activity recorded during the remainder of the MDA-like event. 3. Before and between MDA-like events, spontaneous cellular activity consisted of single action potentials and bursts of action potentials on a depolarizing envelope. In addition, depolarizing potentials, up to 13 mV, were recorded. There were no extracellular field potentials associated with these intracellularly recorded potentials. 4. In the 8 mM potassium, 0-added calcium test solution, the membrane potential threshold for burst production was significantly lower than in normal potassium and calcium medium. 5. The effect of depolarizing and hyperpolarizing current injections on the amplitude and frequency of the epileptiform activity was tested. Current injection had no effect on the frequency of the epileptiform activity recorded during the MDA-like events. However, the frequency of the cellular bursts between MDA-like events was very sensitive to current injection. Depolarizing current increased the frequency, and hyperpolarizing current decreased the frequency of the spontaneous activity. 6. This study has shown that in 8 mM potassium and 0-added calcium the granule cells of the dentate gyrus are capable of generating spontaneous bursts that appear to be mediated by endogenous mechanisms. In addition, synchronized epileptiform discharges were recorded from the granule cells at regular intervals that appear were recorded from the granule cells at regular intervals that appear to be mediated by exogenous nonsynaptic mechanisms.
Neuroplastic effects of neonatal capsaicin on neurons in adult rat trigeminal nucleus principalis and subnucleus oralis
Authors: Kwan C. L. , Hu J. W. , Sessle B. J.
Published: December 2017

1. The effects of C-fiber depletion induced by neonatal capsaicin treatment on the functional properties of low-threshold mechanoreceptive (LTM) neurons in the rat trigeminal (V) subnucleus oralis and nucleus principalis were examined. Neonatal rats were injected with capsaicin within 48 h of birth. The mechanoreceptive field (RF) and response properties of 184 oralis LTM neurons and 185 principalis LTM neurons were studied in adult capsaicin-treated rats. These properties were compared with those of 200 oralis LTM neurons and 253 principalis LTM neurons from untreated or vehicle-treated (control) adult rats. 2. The effectiveness of neonatal capsaicin in depleting C fibers was tested by determining the plasma extravasation of Evans blue dye that was induced in the hindlimb skin by the cutaneous application of the C-fiber excitant and inflammatory irritant mustard oil. The amount of extravasation in capsaicin-treated rats was significantly less than that of control rats. 3. Neonatal capsaicin treatment was associated with significant increases in neuronal RF size and in the percentage of neurons with convergent inputs from more than one type of peripheral tissue (e.g., nonsinus hair, vibrissae, glabrous skin/mucosa, subcutaneous structures such as joint or muscle, periodontal ligament) in both subnucleus oralis and nucleus principalis. In subnucleus oralis, neonatal capsaicin treatment produced a significant increase in the percentage of neurons with a RF involving both V1 and V2 divisions, and a significant decrease in the percentage of neurons with a RF restricted to the V1 division. Analogous changes were not observed in nucleus principalis, although for principalis vibrissa-sensitive neurons, neonatal capsaicin treatment was associated with significant increases in the total number of vibrissae per neuronal RF and in the maximal length of the vibrissal row (i.e., the number of vibrissae in the longest row of vibrissae, stimulation of which was effective in activating a given neuron). 4. Neonatal capsaicin treatment did not significantly affect other oralis or principalis neuronal properties, including the percentage of neurons exhibiting spontaneous activity or abnormal response properties (such as habituating tap sensitivity, discontinuous RF, or mixed adaptation properties within the RF). 5. The changes in the functional properties of oralis and principalis LTM neurons induced by neonatal capsaicin treatment are consistent with those previously reported at other levels of the rodent CNS. They provide additional support to the view that C fibers may have an important role in shaping the functional properties of central LTM somatosensory neurons.
Responses to light of starburst amacrine cells
Authors: Peters B. N. , Masland R. H.
Published: December 2017

1. Starburst amacrine cells were studied using whole cell patch recording. Displaced starburst cells were labeled in rabbit retinas by intraocular injection of 4,6-diamidino-2-phenylindole. The retinas were isolated and maintained in vitro. The inner limiting membrane and Muller cell endfeet were removed mechanically from small areas above the starburst cell bodies, allowing an unimpeded approach under visual control to the cells. A total of 104 cells was studied. 2. In voltage-clamp recordings, the cells responded to light with slow, graded inward and outward currents on which were superimposed smaller, rapid inward currents. The rapid inward currents appeared to be postsynaptic currents. 3. The receptive fields of the cells were mapped using small spots. They had an on-center, off-surround organization. Visualizing the dendrites by including Lucifer yellow in the patch pipette showed that the receptive fields' centers closely approximated the dendritic spread of the neurons. 4. The cells' responses to movement were tested with smooth movements or with two-spot apparent motion. No directional preference was seen for spots swept across the whole receptive field, for centrifugal movements, or for centripetal movements. 5. Bath-applied tetrodotoxin (TTX) or intracellularly applied lidocaine N-ethyl bromide (QX-314) had no effect on any component of the spontaneous or light-evoked activity. Depolarization of the cell bodies by injected current showed evidence of active conductances, but they were unaffected by TTX or QX-314. 6. 6-Cyano-7-nitroquionxyline-2,3-dione eliminated the small rapid currents, indicating that they depend on alpha-amino-3-hydroxy-5-methyl-4- isoxazolepropionic acid/kainate glutamate receptors. 7. Because it is unlikely that we voltage clamped the distalmost dendrites of these wide-field cells, uncertainties remain about rapid electrical events occurring in the dendrites. From a functional point of view, though, the fact that slow responses to distal photic stimulation were recorded at the soma suggests that the starburst cells could in principle integrate inputs across fairly substantial fractions of their total dendritic arbors. The extent to which this actually occurs remains to be learned.
Information theoretic analysis of dynamical encoding by filiform mechanoreceptors in the cricket cercal system
Authors: Roddey J. C. , Jacobs G. A.
Published: December 2017

1. The stimulus/response properties of 20 mechanosensory receptors in the cricket cercal sensory system were studied using electrophysiological techniques. These receptors innervated filiform hairs of various lengths and directional selectivities. Previous studies have characterized the sensitivity of such cells to the direction of air currents and to the amplitude of sinusoidal stimuli. In the experiments reported here, the quantity and quality of information encoded in the receptors' elicited responses about the dynamics of more complex air current waveforms were characterized. 2. Based on a white analysis of receptor response properties, the median frequency of each receptor's frequency tuning curve was found to be strongly correlated with the length of its associated mechanosensory hair. The receptors connected to hairs > 900 microns encoded frequencies below approximately 150 Hz very accurately and the receptors connected to shorter hairs encoded progressively higher bands of frequencies. These results were interpreted within the constraints imposed by the biomechanics of the air current-to-cercus boundary. 3. The encoding accuracy was expressed in the information theoretic units of bits/second, which characterizes the information transmission rate of a receptor. The information rates of the neuronal spike trains ranged from 75 to 220 bits/s. The information transmission rate was not correlated with the length of the mechanosensory hair. The average amount of information transmitted per action potential was negatively correlated with receptor hair length and ranged between 0.6 and 3.1 bits/spike. Decoding of the receptor responses was restricted to linear transformations of the spike trains. 4. The stimulus/response latencies of the different receptors ranged between 5 and 11 ms, and the integration time of the receptors ranged between 8 and 30 ms. The latency of a receptor was only weakly correlated with the length of its associated hair, and a receptor's integration time was correlated with hair length. 5. The stimulus/response phase difference for receptor cells that innervated hairs longer than approximately 800 microns increased with frequency > 50 Hz. The phase responses for receptor cells connected to hairs < 800 microns did not vary for frequencies > 50 Hz.
Physiological properties of rat ventral pallidal neurons recorded intracellularly in vivo
Authors: Lavin A. , Grace A. A.
Published: December 2017

1. The physiology of ventral pallidal (VP) cells was investigated using in vivo intracellular recording and staining techniques in adult rats. Based on electrophysiological criteria, three different types of cells were found: type A cells, which fired phasic spikes that did not exhibit a substantial afterhyperpolarization (AHP), type B cells, which exhibited a slow ramplike depolarization that preceded the short-duration action potential; the spike was followed by a prominent AHP, and type C cells, which were the only cells that fired spikes in couplets or bursts, with the spikes in a burst exhibiting a progressive increase in duration and a decrease in amplitude. These cells also exhibited a rebound low threshold spikelike event. Furthermore, 18% of the VP cells recorded exhibited a slow subthreshold oscillation of the membrane potential (< 1 Hz). 2. The response of VP cells to stimulation of fibers arising from the prefrontal cortex, nucleus accumbens, and mediodorsal thalamic nucleus (MD) was examined. In contrast to our initial predictions, all cells responded to nucleus accumbens stimulation with excitation. Type A and B cells responded to nucleus accumbens stimulation with excitation and to MD stimulation with antidromic-like responses, orthodromic excitation, or evoked inhibitory postsynaptic potentials. Only type A cells responded to prefrontal cortical stimulation. Type C cells only responded to stimulation of the nucleus accumbens, which resulted in evoked excitatory postsynaptic potentials. 3. The cells in the VP therefore can be segregated into three physiologically defined groups according to action potential discharge patterns and their response to afferent fiber stimulation.
Motor patterns for two distinct rhythmic behaviors evoked by excitatory amino acid agonists in the Xenopus embryo spinal cord
Authors: Soffe S. R.
Published: December 2017

1. Mechanisms underlying the selective expression of different motor patterns in vertebrates are poorly understood. Immobilized, spinal Xenopus embryos are used here to examine the motor patterns evoked by various concentrations of excitatory amino acids. 2. Relatively low concentrations of N-methyl-D-aspartate (NMDA) (40-60 microM), kainate (7-8 microM), and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) (5 microM) evoked motor root discharge characteristic of swimming. Brief applications of higher concentrations of kainate (20-40 microM), AMPA (25-30 microM), quisqualate (5 microM), and glutamate (1-4 mM) evoked sequences of a different motor pattern: struggling. This is characterized by a longer cycle period, increased burst duration, and a reversed longitudinal pattern of motor root discharge. The struggling pattern was never evoked by higher concentrations of NMDA (300-500 microM), but was evoked by 30 microM AMPA or 5 microM quisqualate in the presence of 50 microM D-2-amino-5-phosphonopentanoic acid. 3. Intracellular recordings from presumed spinal motoneurons showed different patterns of activity during agonist-evoked swimming and struggling. The patterns were like those described previously during sensory-evoked behavior. 4. Caudal applications of excitatory amino acids that produced struggling discharge did so only at caudal motor roots, whereas caudal applications of NMDA evoked swimming activity throughout the spinal cord. 5. During excitatory-amino-acid-evoked struggling, sensory Rohon-Beard neurons depolarized up to 7 mV, but did not fire. 6. The results show that expression of the struggling pattern, like swimming, is not critically dependent on sensory discharge. The results are also consistent with the idea that expression of the two very different motor patterns for swimming or struggling in this simple vertebrate preparation can be controlled by the level of excitation within the spinal motor circuitry, and need not involve the activity of a specific external neuromodulator.
A voltage-dependent and calcium-permeable ion channel in fused presynaptic terminals of Torpedo
Authors: Meir A. , Rahamimoff R.
Published: December 2017

1. We used a preparation of fused presynaptic nerve terminals of Torpedo electromotor nerve and the patch-clamp technique for characterization of single ion channels. We report here of a large, nonselective ion channel which is highly voltage dependent. 2. The slope conductance of the I-V relation was estimated by either direct measurement of the single-channel current amplitude at different voltages (850 +/- 18 pS (SE); n = 9) or by variance analysis (834 +/- 23 pS; n = 5). 3. The voltage dependence was examined in three ways. At steady-state DC voltage conditions, NPo (the open probability times the number of channels in the patch) was estimated. At potentials < 0 mV, the probability of the channel to open is negligible and increases dramatically, within a very narrow voltage range, to > 50% at +8 mV (n = 8). 4. In pulse experiments, the activation time delay is shorter as the voltage step reaches more positive values. The mean time for half activation (T1/2) decreases from 15 ms at +10 mV to 4 ms at +30 mV (n = 5). 5. Ensemble currents exhibit rectification in response to voltage ramps at negative potentials (n = 10). 6. The channel was found to be nonselective. Its permeability to Na+, K+, Cl-, glutamate, Ba+2, and Ca+2, relative to Na+, was 1.00, 1.00, 1.22, 1.07, 0.85, and 0.62, respectively. 7. Based on the transport number of calcium, the calculated driving force, and the mean channel open time, we estimated the number of calcium ions entering the nerve terminal upon depolarization. This number is not substantially different from the number of ions entering through voltage-dependent, calcium-selective channels in other cells. 8. We speculate that this nonselective ion channel, may serve as a calcium entry route into the nerve terminal and hence be involved in transmitter release.
Stretch-sensitive afferent neurons in cat knee joint capsule: sensitivity to axial and compression stresses and strains
Authors: Grigg P. , Hoffman A. H.
Published: December 2017

1. Experiments were performed to determine whether the response of stretch-sensitive mechanoreceptors to tissue deformation is caused by the axial stretching of the tissue or by the associated transverse compression of the tissue caused by the Poisson effect. 2. Single, stretch-sensitive mechanoreceptors were recorded in vitro in a preparation of innervated, isolated capsule from the cat knee. Afferents were isolated in a ligamentous capsule thickening that has a uniform geometry and parallel collagen fibers. The tissue was loaded axially while simultaneously stretching it around the surface of a cylinder to produce compression stresses and strains. Axial stresses and strains were measured or estimated. 3. By altering the diameter of the cylinder, given axial stresses and strains produced different levels of compression stresses and strains. It was possible to compare the neuronal response to pure uniaxial tension with the response when both axial stretching and transverse compression was applied. 4. In 8 of 11 experiments, transverse compression did not significantly change the response (P > 0.05). In one experiment, the response was decreased by compression. In the other two experiments, the response was increased but was not a function of the magnitude of the compressive stress. 5. Compressive strain was not significantly correlated with neuron response in any experiment. 6. The data do not sustain the model that the responses of stretch-sensitive neurons are due to local compression of the afferent ending.
Transient and sustained depolarization of retinal ganglion cells by Ih
Authors: Tabata T. , Ishida A. T.
Published: December 2017

1. Using whole cell patch-clamp methods, we have identified an inward cationic current activated by hyperpolarization (Ih) in somata of goldfish retinal ganglion cells. 2. Ih activated at test potentials between -70 and -105 mV, and did not appear to inactivate during prolonged hyperpolarizations under voltage clamp. During step hyperpolarizations from holding potentials between -70 and -40 mV, apparent activation was faster at more negative test potentials. On repolarization from -105 mV to holding potentials between -75 and -55 mV, Ih deactivated exponentially at rates showing no marked voltage dependence (tau = approximately 100 ms). 3. Ih tail currents reversed at membrane potentials consistent with a relative permeability to Na+ and K+ of roughly 0.5, when pipette and bath solutions both contained Na+ and K+. 4. Ih was readily blocked by extracellular Cs+ (3 mM), but was resistant to block by tetraethylammonium (30 mM), Ba2+ (1 mM), or Co2+ (2.4 mM). 5. Time-dependent voltage rectification developed during injection of hyperpolarizing current under current clamp. After current injection ceased, membrane potential depolarized beyond resting potential, often leading to anode-break-like spikes. Both voltage rectification and voltage overshoot were suppressed by extracellular Cs+. 6. Voltage-clamp measurements in the presence and absence of Cs+ were used to model membrane potential changes produced by exogenous current injections, by hyperpolarizing synaptic inputs, and by termination of both. Modeled responses resembled membrane potential changes measured under current clamp when terms for activation and deactivation of Ih were included. 7. The voltage rectification and anode-break-like spikes observed in isolated cells resemble those recorded during and after light-evoked hyperpolarizations of retinal ganglion cells in situ. Ih may transiently augment retinal ganglion cell excitability after termination of hyperpolarizing light stimuli, and thus promote encoding of stimulus timing.
Subjective scaling of smooth surface friction
Authors: Smith A. M. , Scott S. H.
Published: December 2017

1. Six men and four women, 30-51 yr of age, were asked to use the tip of the washed and dried index finger to stroke six different featureless, flat surfaces mounted on a three-dimensional force platform. The six surfaces were rosin-coated glass, glass, satin-finished aluminum, poly-vinyl chloride (PVC) plastic, Teflon, and nyloprint (polyamide plastic). The subjects were requested to indicate where the sensation produced by each surface should be placed on an unidimensional scale represented by an 18cm line labeled at one end by the words "most slippery" and at the other end by the words "most sticky." The coefficients of friction for each surface and for each subject were subsequently assessed by asking each subject to stroke the surfaces as if they were assessing its slipperiness for 5 s. 2. The finger forces normal and tangential to the stroked surfaces were digitized at 250 Hz and stored on a laboratory computer. The ratio of the mean tangential force to the mean perpendicular force during stroking was used to calculate the mean coefficient of kinetic friction. The mean friction for all subjects ranged from 0.43 for the nyloprint surface to 2.79 for the rosin-coated glass. Correlation coefficients calculated between the subjective estimates of friction and the measured coefficients of friction for each subject individually resulted in a mean correlation of 0.85 (n = 10, P < 0.001). 3. These data indicate that subjects can accurately scale relative differences in the friction of macroscopically smooth, flat surfaces, by modulating the tangential force applied to the finger while keeping the normal force relatively constant. The fact that subjects maintained a relatively constant normal force and instead varied the tangential force across different surfaces suggests that receptors sensitive to these tangential forces are important in the perception of smooth surface friction.
Taste-mixture suppression: functional dissection of cellular and paracellular origins
Authors: Stewart R. E. , Heck G. L. , Desimone J. A.
Published: December 2017

1. Chorda tympani (CT) nerve responses were recorded during simultaneous current and voltage clamping of the lingual receptive-field epithelium to examine the role of field potential in taste mixture suppression between sodium gluconate (NaG) and potassium gluconate (KG). 2. Under zero current-clamp conditions, CT responses to 100 mM NaG were suppressed by 63% when presented in mixture with 250 mM KG. At this concentration, KG alone elicited no measurable neural activity, but produced a large submucosal-positive field potential. 3. When CT responses to 100 mM NaG were obtained with voltage clamp at the zero-current clamp field potential of the NaG/KG mixture, they were suppressed by only 30% relative to NaG responses under zero-current clamp. Similarly, CT responses to the mixture of NaG and KG measured while voltage was clamped at the field potential of NaG alone were slightly elevated, but not to the magnitude of zero-current clamp responses to NaG. Therefore field potential-mediated suppression of CT responses to NaG accounts for only a part of the total mixture suppression between NaG and KG. 4. Analysis of the voltage dependence of CT responses to NaG indicated that the moderate field potential increase (8.9 mV) caused by the presence of KG in the mixture equates to a 43% increase in the apparent Km for NaG, from 110 to 157 mM. Use of this effective Km obviated the effect of field potential on CT responses to the NaG/KG mixture and permitted kinetic analysis of K+ blockade of Na+ responses. These analyses suggested that K ions block Na+ movement through apical Na+ channels in a voltage-independent manner with an apparent Ko of 405 mM. Importantly, direct inhibition of Na+ transduction by K+ can account for the part of mixture suppression not mediated by field potential. 5. These experiments reveal that mixture suppression between NaG and KG is derived from two distinct sources. Field potential, triggered largely by the limited mobility of both K+ and Na+ through taste bud tight junctions, globally modulates Na+ transduction. In addition, at the level of the apical Na+ channel, K ions directly block movement of depolarizing Na+ across taste receptor apical membranes.
Computer simulations of voltage clamping retinal ganglion cells through whole-cell electrodes in the soma
Authors: Velte T. J. , Miller R. F.
Published: December 2017

1. Computer simulations of voltage-clamp experiments in retinal ganglion cells were implemented to better understand the insights that can be obtained with this physiological approach. 2. Simulation studies of voltage clamping were based on the contemporary approach of using whole-cell recordings with low resistance electrodes attached to the soma. Realistic ganglion cell morphologies were provided by cell staining experiments in the mudpuppy retina; selected cells included small-, medium-, and large-field neurons whose morphologies were entered into a computer through a neuron tracing program. 3. Values for the specific membrane resistance (Rm) varied from 5,000 to 100,000 omega/cm2 to conform to the range of Rm values obtained with intracellular sharp electrodes and whole-cell recordings. 4. Synaptic input currents were simulated by injecting current with and without an underlying conductance change into different regions of the dendritic tree. The time-variant waveform of the current included a combined transient and sustained component similar to the waveform of ON-bipolar activation. 5. Simulations were base on 1) intact structures, which included the soma and the entire dendritic tree, and 2) a more limited cell geometry that included representation of the soma, but only part of the dendritic tree, to represent the restricted morphology that might be rendered after cutting the retina into 150-microns cross sections for retinal slice experiments. 6. The results of this study indicate that voltage clamping from the soma, with optimal, low resistance electrodes and series resistance compensation, provides an error-free voltage clamp for slow signals that are generated within a small electrotonic distance from the soma (approximately 0.1 lambda). 7. The ideal voltage-clamp conditions are optimized when synaptic conductances are small and nonlinear membrane elements are minimally activated: small-field neurons best approximate these conditions, but clamping errors are evident in these cells when more distal branches are activated. The degree of error in voltage clamping was much greater when medium-and large-field neurons were evaluated. 8. It was not possible to clamp action potentials (nonpropagating) even when they were generated near the soma in any of the three model cells examined. 9. Experimental paradigms were developed to demonstrate that inadequate voltage clamping can lead to errors in the interpretation of experimental data when relevant variables are not taken into consideration. Suggestions are made for determining and optimizing favorable clamp conditions.
Intracellular blockade of inhibitory synaptic responses in visual cortical layer IV neurons
Authors: Dudek S. M. , Friedlander M. J.
Published: December 2017

1. Inhibitory postsynaptic potentials (IPSPs) evoked by stimulation at the white-matter/layer VI border were recorded intracellularly from visual cortical layer IV neurons maintained in vitro. These IPSPs, typically not apparent at resting membrane potentials, were measured at membrane potentials 15-25 mV depolarized from resting levels. The effects of two chloride channel blockers on these IPSPs were investigated. 2. 4,4'-Dinitro-stilbene-2,2'-disulfonic acid (DNDS) was found to inhibit IPSPs as it diffused into the postsynaptic cell from an intracellular micropipette, leaving only the presumed pure excitatory postsynaptic potential (EPSP) component of the evoked compound PSP. Input resistance, resting membrane potential, spike accommodation, and EPSPs at resting membrane potentials were not significantly affected. 3. A novel chloride channel blocker 5,11,17,23-tetrasulfonato-25,26,27,28-tetramethoxy-calix[4]a rene (TS-TM-calix[4]arene) was found to potently inhibit IPSPs recorded at depolarized membrane potentials. The TS-TM-calix[4]arene, similar to DNDS, did not affect input resistance, resting membrane potential, spike accommodation, and EPSPs at resting membrane potentials. 4. To confirm that DNDS and TS-TM-calix[4]arene were indeed blocking IPSPs, similar experiments were performed on monosynaptic IPSPs evoked by stimulation of layer V in the presence of 2-amino-5-phosphonovaleric acid (APV) and 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX). Both DNDS and TS-TM-calix[4]arene were effective in blocking monosynaptic IPSPs. 5. Consistent with the notion that DNDS and TS-TM-calix[4]arene block IPSPs by inhibiting gamma-aminobutyric acid-A (GABAA) receptor channels, the decrease in input resistance caused by extracellular application of muscimol was also significantly inhibited by intracellular use of these compounds. 6. These data suggest that DNDS and TS-TM-calix[4]arene applied intracellularly may be useful for the study of the function of GABAA-mediated synaptic inhibition of cortical neurons. Because only neurons impaled by the recording electrodes are influenced by the drugs, this method offers an advantage over extracellular application of GABAA blockers in that entire networks of neurons are not influenced.
Visually guided saccade versus eye-hand reach: contrasting neuronal activity in the cortical supplementary and frontal eye fields
Authors: Mushiake H. , Fujii N. , Tanji J.
Published: December 2017

1. We studied neuronal activity in the supplementary eye field (SEF) and frontal eye field (FEF) of a monkey during performance of a conditional motor task that required capturing of a target either with a saccadic eye movement (the saccade-only condition) or with an eye-hand reach (the saccade-and-reach condition), according to visual instructions. 2. Among 106 SEF neurons that showed presaccadic activity, more than one-half of them (54%) were active preferentially under the saccade-only condition (n = 12) or under the saccade-and-reach condition (n = 45), while the remaining 49 neurons were equally active in both conditions. 3. By contrast, most (97%) of the 109 neurons in the FEF exhibited approximately equal activity in relation to saccades under the two conditions. 4. The present results suggest the possibility that SEF neurons, at least in part, are involved in signaling whether the motor task is oculomotor or combined eye-arm movements, whereas FEF neurons are mostly related to oculomotor control.
Effect of ibotenic acid lesions of the omnipause neurons on saccadic eye movements in rhesus macaques
Authors: Kaneko C. R.
Published: December 2017

1. Although much is known about the neurons that control saccadic eye movements, the precise manner in which they interact is still uncertain. To test the validity of competing models of the pontine saccade generator, neurotoxic lesions were made in the nucleus raphe interpositus (rip), which contains one of the principal types of saccade-related neurons, the omnipause neurons (OPNs). The correlated changes in eye movement were quantified in three juvenile rhesus macaques and compared with the results predicted by different models. 2. After the location of the OPNs was mapped, the rip was subjected to sequential, punctate pressure injections of ibotenic acid. The resulting progressive damage was correlated with changes in saccade metrics, including a decrease in peak saccadic velocity and an increase in saccade duration. 3. The damage to rip and presumably to the OPNs was not associated with a change in the animals' ability to maintain steady fixation of a stationary target. 4. The results suggest that Robinson's original local feedback model of saccade generation should be modified. Either a second integrator should be added or the concept of local feedback should be abandoned entirely. 5. The suggestion that the OPNs are primarily responsible for fixation is probably incorrect. OPNs may contribute to fixation stability along with a number of other sources.
Fast-twitch muscle unit properties in different rat medial gastrocnemius muscle compartments
Authors: DeRuiter C. J. , De Haan A. , Sargeant A. J.
Published: December 2017

1. The effect of muscle unit (MU) localization on physiological properties was investigated within the fast-twitch fatigue-resistant (FR) and fast-fatigable (FF) MU populations of rat medial gastrocnemius (MG) muscle. Single MG MUs were functionally isolated by microdissection of the ventral roots. FR and FF MU properties of the most proximal and distal muscle compartments were compared. The most proximal and distal compartment are subvolumes of the MG innervated by the most proximal and distal primary nerve branch, respectively. A subsample of the isolated units was glycogen depleted and muscle cross sections were stained for glycogen and myosin-adenosinetriphosphatase. 2. It was shown that proximal FF and FR units reached optimum length for force production at shorter muscle lengths compared with the distal FR and FF units. 3. The fast MUs of the proximal compartment had small territories that were located close to and/or within the mixed region (containing type I, IIA, IIX, and IIB fibers) of the muscle. The fast MUs of the distal compartment had greater territories that were located in the more superficial muscle part (containing only type IIX and IIB fibers) and in some cases spanned the entire area of the distal muscle compartment. 4. FR and FF MUs consisted of muscle fibers identified histochemically as type IIX and IIB, respectively. 5. Within each of the FR and FF MU populations, MUs that were located in the most proximal muscle compartment were more resistant to fatigue compared with the units located in the most distal compartment. 6. Cross-sectional fiber areas were smaller for the proximal FR and FF fibers, but specific force did not differ among units. Consequently, when account was taken of the innervation ratio, the proximal FR and FF units produced less force than distal units of the same type. Tetanic forces were 87 +/- 27 (SD) mN (proximal FR), 154 +/- 53 (SD) mN (distal FR), 142 +/- 25 (SD) mN (proximal FF), and 229 +/- 86 (SD) mN (distal FF). 7. The present findings suggest that with increasing demand placed on rat MG during in vivo locomotion, recruitment is likely to proceed from proximal to distal muscle parts within the FR and FF MU populations.
Properties of the nociceptive neurons of the leech segmental ganglion
Authors: Pastor J. , Soria B. , Belmonte C.
Published: December 2017

1. The electrical responses of nociceptive (N) lateral and N medial neurons of the leech segmental ganglion to mechanical, chemical, and thermal stimulation of the skin were studied in a superfused ganglion-body wall preparation. 2. Mechanical indentation of the skin > 10 mN evoked in both types of cells a sustained discharge of impulses; afterdischarge was often observed with suprathreshold stimulations. 3. Application to the cutaneous receptive area of 10-100 mM acetic acid or of NaCI crystals and solutions also elicited a firing response in N medial and N lateral cells. In contrast, capsaicin applied to the skin (3.3 x 10(-5) to 3.3 x 10(-2) M) excited N lateral but not N medial neurons. Likewise, impulse discharges were obtained when capsaicin was applied to the cell bodies of N lateral but not of N medial neurons. 4. In both types of N neurons, heating of the skin above 39 degrees C evoked a discharge of impulses whose frequency was roughly proportional to temperature values. 5. Application of repeated suprathreshold heating cycles at 10-min intervals enhanced the impulse frequency of the response (sensitization). Shorter time intervals between heating cycles depressed the response to heat. Sensitization could not be obtained by equivalent soma depolarizations obtained by intracellular current injection. 6. Impulse discharges evoked by irritant agents were also augmented by previous application of noxious heat. 7. N lateral neurons fired in response to low-pH solutions and capsaicin directly applied onto the ganglion. N medial neurons responded inconsistently to acid and were insensitive to capsaicin. Action potentials evoked in N lateral cells by capsaicin had a slow rise, a prominent hump, and a prolonged afterhyperpolarization. 8. It is concluded that N neurons of the leech segmental ganglion respond to different modalities of noxious stimuli applied to their peripheral receptive fields and develop sensitization after repeated noxious stimulation. These properties are typical of mammalian polymodal nociceptors; thus N neurons may be a simple model for analysis of membrane mechanisms associated with polymodality of nociceptive neurons.