bluuebunny/crossref_metadata_2025 huggingface dataset:
Transient Ca2+ currents in neurons isolated from rat lateral habenula
Authors: Huguenard J. R. , Gutnick M. J. , Prince D. A.
Published: December 2017

1. The properties of the low-voltage-activated transient Ca2+ current (LVA, IT) that underlies rhythmic burst firing in neurons of the lateral habenula (LHb) were examined to further our understanding of mechanisms that promote rhythmogenesis in the CNS. We compared these properties with those of IT in thalamic ventrobasal relay neurons (IVB) and of the more slowly inactivating ITs of thalamic reticular neurons (InRt). 2. Patch-clamp techniques were used to record whole cell Ca2+ currents in LHb cells acutely isolated from rats ranging in age from postnatal days 6 to 34 (P6-P34). The LVA current in LHb (ILHb) had a number of properties similar to those of IVB, including activation threshold (near -65 mV) and voltage-dependent steady-state activation [half-activation voltage (V1/2) = -58.5 mV, slope = 3.4 mV-1] and inactivation (V1/2 = -83.5 mV, slope = 5.0 mV-1) functions. 3. ILHb was characterized by biphasic inactivation, with a fast, voltage-dependent time constant (20-50 ms) similar to that of IVB and a slower, voltage-independent decay phase (time constant approximately 120 ms) that was much more prominent than in IVB. Recovery of ILHb from inactivation was monophasic (time constant, 507 ms at -90 mV), and was slower than for IVB and about the same as for InRt. 4. ILHb was relatively insensitive to equimolar substitution of Ba2+ for Ca2+, in contrast to IVB, which was decreased, and InRt, which was enhanced. 5. In computer simulations, these results could not be accounted for by a mixture of the two previously described IT types (IVB and InRt) in individual LHb cells.(ABSTRACT TRUNCATED AT 250 WORDS)
A variable-threshold motoneuron model that incorporates time- and voltage-dependent potassium and calcium conductances
Authors: Powers R. K.
Published: December 2017

1. A "threshold-crossing" motoneuron model was developed to relate recently described biophysical features of cat alpha-motoneurons to motoneuron discharge behavior. This model incorporated three features not included in precedent models: 1) a low-threshold, persistent calcium current; 2) realistic voltage dependencies of the major ionic conductances; and 3) a variable spike threshold. The effects of these additional biophysical features on model behavior were investigated by successively adding them to a fixed threshold model with a single potassium conductance. 2. Fixed-threshold models with either one or two potassium conductances could not produce appropriate discharge behavior. Steady-state frequency-current (F-I) relations were characterized by a continuously increasing slope, unlike the piecewise linear relations observed in real motoneurons. These models also produced unrealistically high discharge rates at the highest levels of "injected" current. 3. The addition of a variable spike threshold, which was made to increase linearly with the magnitude of injected current, could limit maximum discharge rates to more realistic levels. However, steady-state F-I relations still did not exhibit the appropriate shape. 4. The incorporation of a low-threshold calcium current led to a good quantitative agreement between the steady-state F-I relations produced by the model and those obtained in real motoneurons. In addition, the steady-state relation between total membrane current and membrane voltage (I-V relation) of the model was very similar to those measured in real motoneurons. The model's I-V and F-I relations were both very sensitive to the exact form of the steady-state relation between the magnitude of the calcium conductance and membrane voltage. 5. Additional modifications, which included a second calcium conductance and a factor relating spike threshold to membrane voltage, helped to produce more realistic afterhyperpolarizations and first-interval F-I relations. 6. Bistable discharge behavior could be produced by reducing the slow potassium conductance and increasing the time constants governing the activation and deactivation of the low-threshold calcium conductance. 7. The final model thus reproduces a wide range of motoneuron behaviors including subthreshold rectification, piecewise linear first interval and steady-state F-I relations, and, with appropriate modifications, bistable discharge behavior. Nonetheless, by simplifying the representation of fast spike conductances as well as the kinetics of the other ionic conductances, the model remains simple enough to be incorporated into a larger neural network.
Plateau pattern of afferent discharge rate from frog muscle spindles
Authors: Sokabe M. , Nunogaki K. , Naruse K. , Soga H. , Fujitsuka N. , Yoshimura A. , Ito F.
Published: December 2017

1. A characteristic plateau pattern was observed in the rate of afferent discharges during ramp-and-hold stretch of spindles isolated from semitendinosus muscles of frogs. The plateau pattern was more frequent in summer frogs (84%) than winter frogs (11%). 2. The plateau pattern consisted of a discharge rate around 120 imp/s at the end of dynamic stretch, followed by second and third steps of plateau rates around 60 and 40 imp/s, respectively. The intervals of impulses in lower steps were approximately n times those of the top step. 3. The plateau pattern was not sensitive to cutting extracapsular myelinated branches or lowering temperature from 23 to 12 degrees C. However, the number of the plateau was reduced in both cases. 4. Application of depolarizing current to the sensory terminal abolished the plateau pattern. In contrast, in spindles that did not show a plateau pattern, hyperpolarizing current induced such a pattern. 5. Calcium channel blockers and protein kinase C inhibitors abolished the plateau pattern. The plateau pattern could be established in quiescent spindles by drugs eliciting Ca2+ entry, raising cytosolic-free Ca2+, and activating protein kinase C. 6. The most striking aspect of the present study is the stability in the discharge rate at each step of the plateau, irrespective of different experimental conditions. This suggests that the spindle sensory terminal possesses a stable intrinsic rhythm generator in excitation, of which maximum frequency is 120 imp/s. The generator seems to be triggered by stretch stimulus and to be regulated by cytoplasmic Ca2+ and protein kinase C.
Agonists for neuropeptide Y receptor subtypes NPY-1 and NPY-2 have opposite actions on rat nodose neuron calcium currents
Authors: Wiley J. W. , Gross R. A. , MacDonald R. L.
Published: December 2017

1. The whole-cell variation of the patch-clamp technique was used to study the effect of neuropeptide Y (NPY) and preferential agonists for the NPY-1 and NPY-2 receptor subtypes on voltage-dependent calcium currents in acutely dissociated postnatal rat nodose ganglion neurons. 2. Both low- and high-threshold calcium current components were present. NPY altered voltage-dependent calcium currents in approximately 50% of neurons studied. NPY (0.1-100 nM, ED50 6 nM) decreased the peak amplitude of transient high-threshold calcium currents in approximately 45% of the neurons. NPY (100 nM) decreased the peak amplitude of these currents 31 +/- 5% (mean +/- SE). However, in approximately 5% of the neurons NPY (100 nM) caused a reversible and reproducible increase in transient high-threshold calcium currents of 21 +/- 4%. NPY did not affect either transient low-threshold or slowly inactivating high-threshold calcium current components. 3. Application of the C-terminal fragment NPY 13-36 (100 nM), a preferential agonist for NPY-2 receptors, reversibly decreased the peak amplitude of transient high-threshold calcium currents by 26 +/- 5% in 9 of 20 cells (45%). Application of [Pro34]-NPY (100 nM), a preferential agonist for NPY-1 receptors, reversibly increased the peak amplitude of transient high-threshold calcium currents 20 +/- 4% in 23 out of 48 neurons (48%). Six of 20 neurons (30%) responded to application of both agonists. Neither the NPY-1 nor NPY-2 agonists affected transient low-threshold or slowly inactivating high-threshold calcium current components.(ABSTRACT TRUNCATED AT 250 WORDS)
Covert orienting of attention in macaques. I. Effects of behavioral context
Authors: Bowman E. M. , Brown V. J. , Kertzman C. , Schwarz U. , Robinson D. L.
Published: December 2017

1. A task was used by Posner (1980) to measure shifts of attention that occurred covertly, in the absence of an eye movement or other orienting response. This paradigm was used here to assess the nature of covert attentional orienting in monkeys to develop an animal model for neurophysiological studies. Shifts of attention were measurable in monkeys and were consistent across a variety of experimental conditions. 2. The paradigm required that monkeys fixate and release a bar at the appearance of a target, which was preceded by a cue. Reaction times to targets that followed peripheral cues at the same location (validly cued) were significantly faster than those that followed cues in the opposite visual field (invalidly cued). This difference was defined as the validity effect, which as in humans, is used as the measure of a covert attentional shift. 3. When the proportion of validly to invalidly cued targets was decreased, no change was seen in the validity effect of the monkeys. This is in contrast to humans, for whom the ratio of validly to invalidly cued targets affected the magnitude of the validity effect. When 80% of the targets were preceded by cues at the same location, the validity effect was greatest. The effect was reversed when the proportions were reversed. From this result, it is concluded that cognitive processes can affect covert orienting to peripheral cues in humans, whereas in trained monkeys, performance was automatic. 4. To test whether cognitive influences on attention could be demonstrated in the monkey, an animal was taught to use symbolic, foveal signals to covertly direct attention. The magnitude of this validity effect was greater than that obtained with peripheral cues. 5. The effects of motivational and perceptual processes were tested. Although overall reaction times could be modified, the facilitating effects of the cues persisted. This constancy across motivational and perceptual levels supports the notion that the monkeys were performing the task in an automatic way, under the exogenous control of peripheral cues. 6. Most visual cuing has been tested with visual landmarks at the locations of cues and targets. These monkeys were trained with such landmarks, and when tested without them, the attentional effect of the cues was nearly abolished. These data suggest that local visual features can be important for covert orienting. 7. To determine the spatial extent of the effect of the cue, monkeys and humans were tested with four cue-target distances (0-60 degrees).(ABSTRACT TRUNCATED AT 400 WORDS)
High-frequency neurons in the inferior colliculus that are sensitive to interaural delays of amplitude-modulated tones: evidence for dual binaural influences
Authors: Batra R. , Kuwada S. , Stanford T. R.
Published: December 2017

1. Localization of sounds has traditionally been considered to be performed by a duplex mechanism utilizing interaural temporal differences (ITDs) at low frequencies and interaural intensity differences at higher frequencies. More recently, it has been found that listeners can detect ITDs at high frequencies if the amplitude of the sound varies and an ITD is present in the envelope. Here we report the responses of neurons in the inferior colliculi of unanesthetized rabbits to ITDs of the envelopes of sinusoidally amplitude-modulated (SAM) tones. 2. Neurons were studied extracellularly with glass-coated Pt-Ir or Pt-W microelectrodes. Their sensitivity to ITDs in the envelopes of high-frequency sounds (> or = 2 kHz) was assessed using SAM tones that were presented binaurally. The tones at the two ears had the same carrier frequency but modulation frequencies that differed by 1 Hz. This caused a cyclic variation in the ITD produced by the envelope. In this "binaural SAM" stimulus, the carriers caused no ITD because they were in phase. In addition to the binaural SAM stimulus, pure tones were used to investigate responses to ipsilateral and contralateral stimulation and the nature of the interaction during binaural stimulation. 3. Neurons tended to display one of two kinds of sensitivity to ITDs. Some neurons discharged maximally at the same ITD at all modulation frequencies > 250 Hz (peak-type neurons), whereas others were maximally suppressed at the same ITD (trough-type neurons). 4. At these higher modulation frequencies (> 250 Hz), the characteristic delays that neurons exhibited tended to lie within the range that a rabbit might normally encounter (+/- 300 microseconds). The peak-type neurons favored ipsilateral delays, which correspond to sounds in the contralateral sound field. The trough-type neurons showed no such preference. 5. The preference of peak-type neurons for a particular delay was sharper than that of trough-type neurons and was comparable to that observed in neurons of the inferior colliculus that are sensitive to delays of low-frequency pure tones. 6. At lower modulation frequencies (< 150 Hz) characteristic delays often lay beyond +/- 300 microseconds. 7. Increasing the ipsilateral intensity tended to shift the preferred delay ipsilaterally at lower (< 250 Hz), but not at higher, modulation frequencies. 8. When tested with pure tones, a substantial number of peak-type neurons were found to be excited by contralateral stimulation but inhibited by ipsilateral stimulation.(ABSTRACT TRUNCATED AT 400 WORDS)
Contribution of edema to the sensitization of high-threshold mechanoreceptors of the goat palatal mucosa
Authors: Cooper B.
Published: December 2017

1. Carrageenan has been shown to alter transduction capacities of high-threshold mechanoreceptors of the goat palatal mucosa. Assessments were made of the contributions of carrageenan-induced edema to the sensitization of mechanonociceptors (mechanically insensitive afferents) and intense pressure receptors of the palatal mucosa of the goat. The degree of edema was assessed by measurement of changes in tissue compliance produced by carrageenan. The impact of a simulated edema on both dynamic and static aspects of transduction were examined. The following observations were made. 2. Tissue compliance of the ventral zone of the incisal papilla (IP) was decreased after carrageenan treatment (0.042-0.014 mm/g). Tissue compliance changes were large for small displacements (< 1.4 mm), where displacement curves were substantially linear. For large displacements (> 1.4 mm), there was an exponential relationship between displacement and reactive force, and the compliance was unchanged. The exponential component may have represented the contribution of the maxillary bone compliance measures. 3. A simulated edema was created to assess the effects of edema on afferent reactivity. Saline was used to create the simulated edema by using changes in tissue compliance as a means of matching simulated to carrageenan-induced edema. An analysis of linear and exponential phases of saline or carrageenan-induced changes in tissue compliance indicated that saline injections produced a good approximation of the changes in linear properties, but diverged from a match of the exponential phase of carrageenan edema. 4. Assessments were made of modifications in nociceptor reactivity after simulated edema or retested controls (n = 47). There was little indication that edema influenced quantitative aspects of either static or dynamic force transduction. Mechanonociceptors, but not intense pressure receptors, sensitized after repeated intense stimulation (mean decline of dynamic activation threshold of 42 +/- 16 g/mm2, mean +/- SE). Artificial edema did not further contribute to this sensitization. 5. Qualitative features of stimulus transduction were modified by simulated edema. Eleven of 17 afferents without initial static or dynamic transduction capacity acquired the capacity after artificial edema. 6. Although most aspects of force transduction were unaffected by artificial edema, displacement transduction was considerably shifted. Artificial edema decreased the threshold and shifted the displacement range over which nociceptors transduced dynamic and static aspects of force (threshold decreased from 1,894 +/- 229 to 1,456 +/- 194 microns; range decreased 239 +/- 99 microns). 7. It was concluded the contribution of edema to allodynia and hyperalgesia is best understood in terms of its contribution to population-coding mechanisms that are brought about by changes in transmission properties.(ABSTRACT TRUNCATED AT 400 WORDS)
Multifunctional properties of ambiguous neurons identified electrophysiologically during vocalization in the awake monkey
Authors: Yajima Y. , Larson C. R.
Published: December 2017

1. The nucleus ambiguus (NA) of the medulla contains motoneurons (MNs) for muscles of the larynx, palate, pharynx, and esophagus. Previous studies in anesthetized animals have demonstrated neural discharge correlated closely with respiration, swallowing, and electrical stimulation-elicited vocalization. A preliminary study confirming the above findings was done by recording NA motoneuron extracellular potentials from awake vocalizing monkeys. The present study was undertaken to quantitatively describe discharge properties of a large number of NA neurons recorded from awake, vocalizing monkeys (Macaca nemestrina). 2. In monkeys trained to vocalize for a food reward, extracellular recordings of neurons in and around the nucleus ambiguus were correlated with laryngeal electromyographic activity during vocalization. A nerve cuff electrode on the ipsilateral recurrent laryngeal nerve allowed identification of laryngeal MNs by antidromic activation of laryngeal MNs and the collision test. 3. Most laryngeal MNs became active 100-200 ms before vocalization. They ceased discharging during or immediately after vocalization. Some MNs discharged in close synchrony with bursts of EMG associated with variations in the vocalization. The mean discharge rate of MNs during vocalization was 18 Hz, and the maximum rate in many cells was over 100 Hz. MNs were also active during swallowing. One MN was related only to respiration and one exclusively to swallowing. 4. Some non-motoneurons (Non-MNs) and cells that may possibly be MNs (PossMNs), recorded in and near the NA, showed properties similar to MNs. Many (147) were active only with vocalization, whereas others were active with swallowing (23); respiration (9); vocalization and swallowing (32); vocalization and respiration (40); or vocalization, swallowing, and respiration (17). 5. The present study demonstrates the importance of studying laryngeal MNs in the chronic preparation. Namely, it is shown that both MNs and Non-MNs of the NA are active with more than one activity. Moreover, some Non-MNs are active for only one activity, e.g., vocalization or swallowing. These findings imply the existence of subsets of medullary neurons involved in multiple behaviors for control of generalized laryngeal functions and other subsets related to specific behaviors.
Modulation of monosynaptic excitation in the neonatal rat spinal cord
Authors: Pinco M. , Lev-Tov A.
Published: December 2017

1. The effects of high-frequency (5-50 Hz) stimulation of dorsal root afferents on monosynaptic excitation of alpha motoneurons was studied in the in vitro spinal cord preparation of the neonatal rat, using sharp-electrode intracellular recordings. 2. Double pulse stimulation of dorsal root afferents induced severe depression of testing excitatory postsynaptic potentials (EPSPs) at each of the tested interstimulus intervals (15 ms-5 s). After perfusion of the preparation with low-calcium, high-magnesium Krebs saline, the amplitude of the conditioning EPSPs was markedly decreased and the testing EPSPs exhibited substantial facilitation that was maximal at the 20-ms interval and that was accompanied by depression at intervals > or = 60-100 ms. 3. Short-duration stimulus trains applied to dorsal root afferents normally induced tetanic depression of the intracellularly recorded monosynaptic EPSPs. Switching the bathing solution to low-calcium, high-magnesium saline decreased the control EPSP and induced facilitation and then tetanic potentiation (TP) of the EPSPs within the applied train. The magnitude of potentiation (% potentiation) of these EPSPs depended on the interpulse interval of the short stimulus train and on the degree of attenuation of the unpotentiated control EPSP after the solution was changed from normal- to low-calcium Krebs solution. 4. Long-duration stimulus trains applied to dorsal root afferents at 5-10 Hz induced marked depression of monosynaptic EPSPs during the train. The depression was alleviated after cessation of the tetanic stimulation and was followed in some cases by slight posttetanic potentiation.(ABSTRACT TRUNCATED AT 250 WORDS)
Spatial distribution of excitatory and inhibitory synapses on a Purkinje cell in a rat cerebellar culture
Authors: Hirano T. , Kasono K.
Published: December 2017

1. The spatial distribution of excitatory and inhibitory synapses on cultured Purkinje cells was studied with fluorescence, scanning electron microscopy (SEM), and electrophysiological techniques. 2. Presynaptic terminals were identified with immunohistochemical staining of synaptophysin and the results were correlated with SEM micrographs. 3. Excitatory and inhibitory inputs onto the Purkinje cell were identified from the direction and pharmacology of the postsynaptic current. 4. The localization of the presynaptic terminals on the Purkinje cell was observed after electrophysiological identification by filling the presynaptic neuron with Lucifer yellow and the Purkinje cell with Texas red. 5. The axon and presynaptic terminals of excitatory and inhibitory inputs had a different spatial organization. Excitatory inputs from granule cells were exclusively localized on the dendrites of Purkinje cells, whereas inhibitory contacts were found on both the soma and dendrites. This result is similar to that described in vivo.
Membrane currents evoked by excitatory amino acid agonists in ON bipolar cells of the mudpuppy retina
Authors: Thoreson W. B. , Miller R. F.
Published: December 2017

1. Whole-cell patch-clamp recordings were obtained from ON bipolar cells in a retinal slice preparation of the mudpuppy, Necturus maculosus. The effects of excitatory amino acid (EAA) agonists applied in the presence of cobalt (2-5 mM) were examined. 2. At the holding potential of -50 mV, L-2-amino-4-phosphonobutanoic acid (L-AP4, 5-10 microM) evoked an outward current accompanied by a conductance decrease. The zero current potential of the L-AP4-evoked current was near 0 mV independent of whether the intracellular Ringer solution contained CsCl or CsCH3SO4. The currents evoked by light were also accompanied by a conductance decrease and reversed near 0 mV. Replacing external sodium with choline or N-methyl-D-glucamine generated an outward current and suppressed the response to L-AP4. The response to L-AP4 was enhanced by removing extracellular calcium and suppressed by increasing extracellular calcium. These results indicate that L-AP4 closes nonspecific cation channels that are blocked by extracellular calcium. 3. In 2 mM cobalt, alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA, 50-100 microM) evoked membrane currents that were accompanied by a conductance increase. AMPA-evoked currents exhibited a significant chloride dependence and were suppressed by gamma-aminobutyric acid-A (GABAA) antagonists bicuculline and picrotoxin; a GABA uptake blocker, nipecotic acid; and a glycine antagonist, strychnine. AMPA-induced currents were virtually absent in the presence of 5 mM cobalt and nominally 0 mM extracellular calcium. These results indicate that the conductance increase induced by AMPA in the presence of 2 mM cobalt is largely the result of calcium-dependent synaptic inputs onto GABAA and glycine receptors of ON bipolar cells. 4. N-methyl-D-aspartic acid (250 microM) was ineffective when applied in the presence of 100 microM cadmium or 2 mM cobalt. 5. 1S,3R/1R,3S-1-aminocyclopentane-1,3-dicarboxylic acid (100-200 microM) evoked an outward current accompanied by a conductance decrease and appears to be an agonist at the L-AP4 receptor. 6. The findings of this study suggest that the only type of EAA receptor in mudpuppy ON bipolar cells is the L-AP4 receptor and that L-AP4 receptor activation results in the closing of nonspecific cation channels that are blocked by extracellular calcium.
Cholinergic and noradrenergic modulation of the slow (approximately 0.3 Hz) oscillation in neocortical cells
Authors: Steriade M. , Amzica F. , Nunez A.
Published: December 2017

1. The pedunculopontine tegmental (PPT) cholinergic nucleus and the locus coeruleus (LC) noradrenergic nucleus were electrically stimulated to investigate their effects on the recently described slow oscillation (approximately 0.3 Hz) of neocortical neurons. Intracellular recordings of slowly oscillating, regular-spiking and intrinsically bursting neurons from cortical association areas 5 and 7 (n = 140) were performed in anesthetized cats. 2. Pulse trains to the PPT nucleus produced the blockage of rhythmic (approximately 0.3 Hz) depolarizing-hyperpolarizing sequences in 79% of tested cortical neurons and transformed this slow cellular rhythm into tonic firing. The latency of the cortical cellular response to PPT stimulation was 1.2 +/- 0.5 (SE) s and its duration was 15.9 +/- 1.9 s. The PPT-elicited suppression of the slow cellular oscillation was accompanied by an activation of the electroencephalogram (EEG) having a similar time course. Fast Fourier transform analyses of EEG activities before and after PPT stimulation showed that the PPT-evoked changes consisted of decreased power of slow rhythms (0-8 Hz) and increased power of fast rhythms (24-33 Hz); these changes were statistically significant. 3. The blockage of the slow cellular oscillation was mainly achieved through the diminution or suppression of the long-lasting hyperpolarizations separating the rhythmic depolarizing envelopes. This effect was observed even when PPT pulse trains disrupted the oscillation without inducing overt depolarization and increased firing rate. The durations of the prolonged hyperpolarizations were measured during a 40-s window (20 s before and 20 s after the PPT pulse train) and were found to decrease from 1.5 +/- 0.2 to 0.7 +/- 0.1 s. The values of the product resulting from the duration (in seconds), the amplitude (in millivolts), and number of such hyperpolarizing events within 20-s periods were 51.5 +/- 5 and 5.1 +/- 1.9 before and after PPT stimulation, respectively. 4. The PPT effect was suppressed by systemic administration of a muscarinic antagonist, scopolamine, but not by mecamylamine, a nicotinic antagonist. 5. The PPT effect on cellular and EEG cortical slow oscillation survived, although its duration was reduced, in animals with kainate-induced lesions of thalamic nuclei projecting to areas 5 and 7 (n = 3) as well as in animals with similar excitotoxic lesions leading to extensive neuronal loss in nucleus basalis (n = 2). These data indicate that the PPT effect is transmitted to neocortex through either thalamic or basal forebrain relays.(ABSTRACT TRUNCATED AT 400 WORDS)
Differential neuromodulation of calcium currents by norepinephrine in rat sympathetic neurons
Authors: Chen C. , Schofield G. G.
Published: December 2017

1. Differences in the neuromodulation of Ca2+ currents between superior cervical ganglion (SCG) and more caudal paravertebral ganglion (PVG) neurons acutely isolated from the same rats were investigated using the whole-cell patch-clamp technique. 2. Norepinephrine (NE) induced a concentration-dependent inhibition of Ca2+ currents in both SCG and PVG neurons. The concentration producing 50% inhibition (IC50) for NE estimated from concentration-response curves was similar between SCG and PVG neurons but the maximal inhibition estimated from the concentration-response curve for PVG neurons was decreased compared with that of SCG neurons. 3. Tail current activation curves of both SCG and PVG neurons in the absence and presence of NE (5 microM) could be fitted to a double Boltzmann equation. In the presence of NE, the activation curves for both SCG and PVG neurons were shifted toward more depolarized potentials. The magnitude of the shift was greater in SCG than in PVG neurons, which could be accounted for by a greater decrease (P < 0.05) in the fractional amplitude of the first current component of SCG neurons (delta 1.4 +/- 0.4 nA, mean +/- SE, 39%) compared with that of PVG neurons (delta 0.9 +/- 0.1 nA, 16%). 4. Ca2+ current density, expressed as maximal tail current amplitude normalized to cell capacitance, was greater in PVG neurons than that in SCG neurons. 5. In SCG neurons, a saturating concentration of omega-conotoxin GVIA (omega-CgTx) produced a greater decrease of Ca2+ current amplitude at +20 mV (77.4 +/- 1.9%) than in PVG neurons (71.2 +/- 1.5%, P < 0.05). 6. After pretreatment with 15 microM omega-CgTx, NE still decreased the Ca2+ currents in both populations of neurons; however, the inhibition was greater in SCG neurons (31.1 +/- 3.4%) than in PVG neurons (12.8 +/- 3.6%, P < 0.01). 7. The dihydropyridine Ca2+ channel "agonist" Bay K 8644 (10 microM) prolonged Ca2+ tail currents in both SCG and PVG neurons. After normalizing to cell capacitance, there was no significant difference in Bay K 8644-induced tail current amplitude between the two populations of neurons. Moreover, NE (5 microM) increased the prolonged Ca2+ tail current amplitude induced by Bay K 8644 (10 microM) by 44.7 +/- 13.5% in SCG and 41.9 +/- 11.9% in PVG neurons. 8. Under control conditions, Ca2+ currents were facilitated by a depolarizing conditioning pulse (50 ms to +100 mV) in both PVG neurons (29.2 +/- 5.1%) and SCG neurons (20.1 +/- 4.0%).(ABSTRACT TRUNCATED AT 400 WORDS)
Modulation of synaptic transmission and long-term potentiation: effects on paired pulse facilitation and EPSC variance in the CA1 region of the hippocampus
Authors: Manabe T. , Wyllie D. J. , Perkel D. J. , Nicoll R. A.
Published: December 2017

1. Whole-cell patch-clamp recordings of excitatory postsynaptic currents (EPSCs) were made from guinea pig hippocampal CA1 pyramidal cells. The sensitivity of paired pulse facilitation (PPF) and EPSC variance to changes in synaptic transmission was investigated and the results were compared with the changes in these parameters evoked by long-term potentiation (LTP). 2. Presynaptic manipulations, such as activation of presynaptic gamma-aminobutyric acid-B receptors by baclofen, blockade of presynaptic adenosine receptors by theophylline, blockade of presynaptic potassium channels by cesium, and increasing the Ca(2+)-Mg2+ ratio in the external recording solution, each reliably changed PPF in a fashion reciprocal to the change in the EPSC amplitude. However, recruitment of additional synaptic release sites by increasing stimulus strength and antagonism of non-N-methyl-D-aspartate (NMDA) glutamate receptors by 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) failed to alter PPF. 3. Presynaptic manipulations including increased stimulus strength gave the predicted changes in the value of mean 2/variance (M2/sigma 2). Moreover, postsynaptic manipulations that altered EPSC amplitude, including blockade of non-NMDA receptors by CNQX, or changing the holding potential of the postsynaptic cell, gave little change in M2/sigma 2, as would be predicted for manipulations resulting in a uniform postsynaptic change. 4. LTP caused no change in PPF, whereas the presynaptic manipulations, which caused a similar amount of potentiation to that induced by LTP, significantly decreased PPF. On the other hand, LTP did increase M2/sigma 2, although the increase was less than that predicted for a purely presynaptic mechanism.(ABSTRACT TRUNCATED AT 250 WORDS)
Generation and transmission of respiratory oscillations in medullary slices: role of excitatory amino acids
Authors: Funk G. D. , Smith J. C. , Feldman J. L.
Published: December 2017

1. The involvement of excitatory amino acid (EAA) receptors in the generation of respiratory rhythm and transmission of inspiratory drive to hypoglossal (XII) motoneurons was examined in an in vitro neonatal rat medullary slice preparation. Slices generated rhythmic inspiratory activity in XII nerves. The role of EAAs in rhythm generation was determined by analyzing perturbations of respiratory network activity after bath application of EAA receptor antagonists or local microinjection of antagonists into the main column of respiratory neurons in the ventrolateral medulla (ventral respiratory group), particularly in the pre-Botzinger complex (pre-BotC). The involvement of EAAs in drive transmission to XII motoneurons was examined by recording perturbations in XII nerve discharge or motoneuron synaptic inputs after microinjection of EAA receptor antagonists into either the XII motor nuclei or sites in the ventrolateral medulla containing interneurons of the drive transmission circuit. 2. Block of non-N-methyl-D-aspartate (non-NMDA) receptors by bath application of 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) reversibly reduced XII nerve burst frequency and amplitude in a concentration-dependent manner, completely blocking respiratory motor output at concentrations > 4 microM. Activation of 2-amino-4-phosphonobutyric acid (AP-4)-sensitive receptors with D,L AP-4 reduced XII nerve burst amplitude by 30% but did not alter burst frequency. Block of NMDA receptor channels by bath application of (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d] cyclohepten-5,10-iminemaleate (MK-801) did not perturb the frequency or amplitude of motor output. Inhibition of EAA uptake in the slices by bath application of dihydrokainic acid reversibly increased the frequency and amplitude of XII motor discharge. 3. Block of non-NMDA receptors at multiple sites along the main column of respiratory neurons in the ventrolateral medulla, including the pre-BotC, by unilateral microinjection of CNQX produced a dose-dependent, bilateral reduction in XII nerve burst amplitude without substantial perturbations of the frequency of respiratory oscillations. Block of non-NMDA receptors within the pre-BotC at sites ventral to amplitude altering sites produced a reduction in frequency and ultimately bilateral block of respiratory network oscillations. 4. Non-NMDA receptor block within the XII motor nucleus by unilateral microinjection of CNQX produced a dose-dependent reduction in ipsilateral XII nerve discharge amplitude without perturbing the frequency of respiratory oscillations. Perturbations of contralateral XII nerve burst amplitude were significantly smaller. NMDA channel block within the XII motor nucleus did not affect inspiratory burst amplitude, whereas activation of AP-4 receptors caused a 30% reduction in amplitude.
Computer simulations of the effects of different synaptic input systems on motor unit recruitment
Authors: Heckman C. J. , Binder M. D.
Published: December 2017

1. The effects of four different synaptic input systems on the recruitment order within a mammalian motoneuron pool were investigated using computer simulations. The synaptic inputs and motor unit properties in the model were based as closely as possible on the available experimental data for the cat medial gastrocnemius pool and muscle. Monte Carlo techniques were employed to add random variance to the motor unit thresholds and forces and to sample the resulting recruitment orders. 2. The effects of the synaptic inputs on recruitment order depended on how they modified the range of recruitment thresholds established by differences in the intrinsic current thresholds of the motoneurons. Application of a uniform synaptic input to the pool (i.e., distributed equally to all motoneurons) resulted in a recruitment sequence that was quite stable even with the addition of large amounts of random variance. With 50% added random variance, the recruitment reversals did not exceed 8%. 3. The simulated monosynaptic input from homonymous Ia afferent fibers generated a twofold expansion of the range of recruitment thresholds beyond that attributed to the differences in the intrinsic current thresholds. The Ia input generated a small reduction in the number of recruitment reversals due to random variance (6% reversals at 50% random variance). The simulated monosynaptic vestibulospinal input generated a twofold compression of the range of recruitment thresholds that exerted a modest increase in the number of recruitment reversals (12% reversals at 50% random variance). 4. In comparison with the modest effects of the two monosynaptic inputs, the simulated oligosynpatic rubrospinal excitatory input exerted a nine-fold compression in the recruitment threshold range that resulted in a recruitment sequence that was highly sensitive to random variance. With 50% added random variance, the sequence became nearly random (40% reversals). 5. Reciprocal Ia inhibition was simulated by a uniform distribution within the pool, but its effects on recruitment order were highly dependent on the distribution of the excitatory input. Reciprocal inhibition exerted only minor effects on recruitment order when combined with the Ia or vestibulospinal inputs. However, when the excitatory drive was supplied by the rubrospinal input, even small amounts of reciprocal inhibition were sufficient to completely reverse the normal recruitment sequence. 6. The simulated monosynaptic Ia input was highly effective in compensating for the disruptive effects of rubrospinal excitation on recruitment order. Even a small Ia bias combined with the rubrospinal excitation was sufficient to halve the effects of random variance and to restore the normal recruitment sequence in the presence of rather large amounts of reciprocal inhibition.(ABSTRACT TRUNCATED AT 400 WORDS)
Expression of voltage-activated ion channels by astrocytes and oligodendrocytes in the hippocampal slice
Authors: Sontheimer H. , Waxman S. G.
Published: December 2017

1. Using patch-clamp recordings, expression of voltage-activated ion channels by identified glial cells in situ was studied in hippocampal slices derived from 5- to 24-day-old rats. Glial cells were filled with Lucifer yellow during recording, and were identified by staining for glial fibrillary acidic protein (GFAP). Of 105 cells presumed to be glial cells from which recordings were obtained, 40 were identified as astrocytes and 22 as oligodendrocytes. 2. Astrocytes in the hippocampal slice express three types of K+ current, singly or in combination: delayed rectifying currents (Kd), transient "A"-type currents (Ka) and inward-rectifying currents (Kir). Kd-like currents were observed in 88% of astrocytes recorded; these currents activated rapidly with a threshold of -40 mV and did not inactivate during a 10- to 30-ms pulse. A-type transient K+ currents were identified in 43% of astrocytes and required a negative holding potential (-110 mV) for activation. These activated at about -50 mV, and their time constant of inactivation was close to 10 ms. In 20% of astrocytes recorded in slices from animals > 7 days old, inwardly rectifying K+ currents were observed in addition to Kd or Ka. 3. Voltage-activated Na+ currents were observed in 11 of the 105 cells, and 5 of these were identified as astrocytes by GFAP staining. These were located in either stratum oriens or close to the granule cell layer in CA3. Na+ current densities ranged from 1.5 to 90 pA/pF. Voltage steps more positive than -40 mV were required for activation, peaks were close to -10 mV, and time to peak was between 300 and 800 microseconds. Extrapolated current reversal potentials were close to the theoretical Na+ equilibrium potential. 4. Spontaneous action potentials were never observed in any of the hippocampal astrocytes recorded, including those astrocytes that expressed Na+ currents. Additionally, action potentials could not be induced by current injections. By contrast, 26 hippocampal neurons recorded in the same slices showed both spontaneous and elicited action potentials as well as synaptic currents. 5. Oligodendrocytes, identified by lack of GFAP staining and cell morphology, had resting potentials ranging between -25 and -82 mV in 5 mM KCl. In approximately 50% of oligodendrocytes, time-dependent currents were not observed and only time-independent currents with linear current-voltage curves were recorded. In the remaining 50% of oligodendrocytes, time- and voltage-dependent K+ currents characterized by inward rectification were present.(ABSTRACT TRUNCATED AT 400 WORDS)
Morphology and topography of identified primary afferents in trigeminal subnuclei principalis and oralis
Authors: Jacquin M. F. , Renehan W. E. , Rhoades R. W. , Panneton W. M.
Published: December 2017

1. Intra-axonal recording, receptive field mapping, horseradish peroxidase injection, cytochrome oxidase staining, and computer-assisted reconstruction/morphometric methods were used to elucidate the structure and topography of trigeminal primary afferent collaterals in the normal adult rat. Prior studies focused on trigeminal brain stem subnuclei interpolaris and caudalis. This work is extended here to the remaining 2 subnuclei, principalis (PrV) and oralis (SpVo), where collaterals from 66 axons in 37 adult rats were studied. In nine rats, three to five axons were stained for within-nucleus comparisons of different fibers. Quantitative analyses were restricted to vibrissa sensitive fibers. 2. All of the axons conducted rapidly with small, low-threshold receptive fields. The majority responded to vibrissa deflection (n = 47); the remainder responded to guard hair deflection; gentle pressure applied to hairy skin, glabrous skin, lingual mucosa, or an incisor; or jaw movement. All descended in the trigeminal sensory root where some bifurcated into ascending and descending branches. Each well-stained fiber gave rise to transversely oriented collaterals in PrV and SpVo. 3. Within PrV and SpVo, fibers with differing adaptation properties and receptive fields had indistinguishable collateral morphologies. Arbors from single axons were rostrocaudally discontinuous, small relative to collaterals in subnuclei interpolaris and caudalis, circumscribed and topographically organized in a manner consistent with cytochrome oxidase and bulk-labeled primary afferent staining patterns. In SpVo and caudal PrV, the map is inverted with the nose pointing medially. In rostral PrV, the map turns 90 degrees such that the nose points dorsally. 4. Axons had different quantitative properties along the rostrocaudal axis of the trigeminal brain stem complex. Whereas arbors subtended similar transverse areas throughout PrV and SpVo, collaterals in the rostral third of PrV had a relatively low bouton density. Arbors in the caudal two thirds of PrV had the highest bouton density. Arbors in SpVo tended to be more variable in size and shape than those of caudal PrV, and their bouton numbers were significantly lower than in PrV. 5. In PrV, arbors were largely confined to somatotopically corresponding cytochrome oxidase patches, precluding significant overlap of neighboring whisker projections. In SpVo, termination sites were not as strictly confined and numerous examples of within- and between-row overlap were obtained for whisker afferents in cases where multiple axons were stained.(ABSTRACT TRUNCATED AT 400 WORDS)
Responses of medullary raphe neurons to electrical and chemical activation of vagal afferent nerve fibers
Authors: Evans A. R. , Blair R. W.
Published: December 2017

1. Various intensities, frequencies, and pulse widths of electrical stimulation of vagal afferent fibers were used to assess the responses of 87 medullary raphe neurons to vagal afferent fiber input in pentobarbital sodium-anesthetized, barodenervated paralyzed cats. Thirty-seven neurons were antidromically activated from the T2-T3 segments of the thoracic spinal cord, and 40 neurons could not be antidromically activated. Neurons were located in the nucleus raphe magnus (79%) and the nucleus raphe obscurus (15%). The remaining 6% of the neurons were not found; however, their locations were comparable in depth and position on the midline with other neurons in the same animals whose locations were identified. 2. The responses of 60 neurons to electrical stimulation of vagal afferent fibers were classified as excitatory (38%), inhibitory (24%), or mixed, (7%). The mixed responses were characterized by excitation at one frequency or intensity and inhibition at another frequency or intensity. The remaining 27 neurons did not clearly respond. 3. The excitatory responses to electrical stimulation of the cervical vagus nerve were intensity and frequency dependent. Inhibitory responses were frequency dependent at lower frequencies of stimulation and both frequency and intensity dependent at higher frequencies. The mixed responses were frequency dependent. Overall, longer pulse widths produced significantly greater responses than shorter pulse widths. 4. Thirty-three neurons were tested for responses to chemical stimulation of vagal afferents with intra-atrial injections of three doses of veratridine. Twenty-one percent were excited, 55% were inhibited, and 6% had mixed responses. For the mixed responses, excitation occurred at one dose and inhibition at another. The remaining 18% of the neurons were unresponsive to veratridine. The excitatory responses were dose dependent, but the inhibitory responses were not. Three doses of phenybiguanide (PBG) were also used to chemically activate vagal afferents in 27 neurons. Eleven percent were excited, 44% were inhibited, and 4% had mixed responses. The remaining 41% were unresponsive to PBG. The excitatory and inhibitory responses were dose dependent. 5. When comparing responses in projection and nonprojection neurons, inhibition was seen significantly more often in projection neurons and excitation in nonprojection neurons. Sixty-three percent of the neurons inhibited by electrical stimulation were raphespinal neurons, and 78% of the neurons excited by vagal stimulation were nonprojection neurons. Similar observations were made with the responses to chemical activation of the vagus. 6. Neurons with lower spontaneous discharge rates were more often excited by vagal stimulation and neurons with higher rates were more often inhibited.(ABSTRACT TRUNCATED AT 400 WORDS)