bluuebunny/crossref_metadata_2025 huggingface dataset:
Time Course of Determination of Movement Direction in the Reaction Time Task in Humans
Authors: Sommer Martin , Classen Joseph , Cohen Leonardo G. , Hallett Mark
Published: December 2017

The primary motor cortex produces motor commands that include encoding the direction of movement. Excitability of the motor cortex in the reaction time (RT) task can be assessed using transcranial magnetic stimulation (TMS). To elucidate the timing of the increase in cortical excitability and of the determination of movement direction before movement onset, we asked six right-handed, healthy subjects to either abduct or extend their right thumb after a go-signal indicated the appropriate direction. Between the go-signal and movement onset, single TMS pulses were delivered to the contralateral motor cortex. We recorded the direction of the TMS-induced thumb movement and the amplitude of motor-evoked potentials (MEPs) from the abductor pollicis brevis and extensor pollicis brevis muscles. Facilitation of MEPs from the prime mover, as early as 200 ms before the end of the reaction time, preceded facilitation of MEPs from the nonprime mover, and both preceded measurable directional change. Compared with a control condition in which no voluntary movement was required, the direction of the TMS-induced thumb movement started to change in the direction of the intended movement as early as 90 ms before the end of the RT, and maximum changes were seen shortly before the end of reaction time. Movement acceleration also increased with maxima shortly before the end of the RT. We conclude that in concentric movements a change of the movement direction encoded in the primary motor cortex occurs in the 200 ms prior to movement onset, which is as early as increased excitability itself can be detected.
Glutamate Receptors Form Hot Spots on Apical Dendrites of Neocortical Pyramidal Neurons
Authors: Frick A. , Zieglgänsberger W. , Dodt H.-U.
Published: December 2017

Apical dendrites of layer V cortical pyramidal neurons are a major target for glutamatergic synaptic inputs from cortical and subcortical brain regions. Because innervation from these regions is somewhat laminar along the dendrites, knowing the distribution of glutamate receptors on the apical dendrites is of prime importance for understanding the function of neural circuits in the neocortex. To examine this issue, we used infrared-guided laser stimulation combined with whole cell recordings to quantify the spatial distribution of glutamate receptors along the apical dendrites of layer V pyramidal neurons. Focally applied (<10 μm) flash photolysis of caged glutamate on the soma and along the apical dendrite revealed a highly nonuniform distribution of glutamate responsivity. Up to four membrane areas (extent 22 μm) of enhanced glutamate responsivity (hot spots) were detected on the dendrites with the amplitude and integral of glutamate-evoked responses at hot spots being three times larger than responses evoked at neighboring sites. We found no association of these physiological hot spots with dendritic branch points. It appeared that the larger responses evoked at hot spots resulted from an increase in activation of both α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and N-methyl-d-aspartate (NMDA) receptors and not a recruitment of voltage-activated sodium or calcium conductances. Stimulation of hot spots did, however, facilitate the triggering of both Na+ spikes and Ca2+ spikes, suggesting that hot spots may serve as dendritic initiation zones for regenerative spikes.
Responses to Task-Irrelevant Visual Features by Primate Prefrontal Neurons
Authors: Lauwereyns Johan , Sakagami Masamichi , Tsutsui Ken-Ichiro , Kobayashi Shunsuke , Koizumi Masashi , Hikosaka Okihide
Published: December 2017

The primate brain is equipped with prefrontal circuits for interpreting visual information, but how these circuits deal with competing stimulus-response (S-R) associations remains unknown. Here we show different types of responses to task-irrelevant visual features in three functionally dissociated groups of primate prefrontal neurons. Two Japanese macaques participated in a go/no-go task in which they had to discriminate either the color or the motion direction of a visual target to make a correct manual response. Prior to the experiment, the monkeys had been trained extensively so that they acquired fixed associations between visual features and required responses (e.g., “green = go”; “downward motion = no-go”). In this design, the monkey was confronted with a visual target from which it had to extract relevant information (e.g., color in the color-discrimination condition) while ignoring irrelevant information (e.g., motion direction in the color-discrimination condition). We recorded from 436 task-related prefrontal neurons while the monkey performed the multidimensional go/no-go task: 139 (32%) neurons showed go/no-go discrimination based on color as well as motion direction (“integration cells”); 192 neurons (44%) showed go/no-go discrimination only based on color (“color-feature cells”); and 105 neurons (24%) showed go/no-go discrimination only based on motion direction (“motion-feature cells”). Overall, however, 162 neurons (37%) were influenced by irrelevant information: 53 neurons (38%) among integration cells, 71 neurons (37%) among color-feature cells, and 38 neurons (36%) among motion-feature cells. Across all types of neurons, the response to an irrelevant feature was positively correlated with the response to the same feature when it was relevant, indicating that the influence from irrelevant information is a residual from S-R associations that are relevant in a different context. Temporal and anatomical differences among integration, color-feature and motion-feature cells suggested a sequential mode of information processing in prefrontal cortex, with integration cells situated toward the output of the decision-making process. In these cells, the response to irrelevant information appears as a congruency effect, with better go/no-go discrimination when both the relevant and irrelevant feature are associated with the same response than when they are associated with different responses. This congruency effect could be the result of the combined input from color- and motion-feature cells. Thus these data suggest that irrelevant features lead to partial activation of neurons even toward the output of the decision-making process in primate prefrontal cortex.
Modulatory Actions of Serotonin, Norepinephrine, Dopamine, and Acetylcholine in Spinal Cord Deep Dorsal Horn Neurons
Authors: Garraway Sandra M. , Hochman Shawn
Published: December 2017

The deep dorsal horn represents a major site for the integration of spinal sensory information. The bulbospinal monoamine transmitters, released from serotonergic, noradrenergic, and dopaminergic systems, exert modulatory control over spinal sensory systems as does acetylcholine, an intrinsic spinal cord biogenic amine transmitter. Whole cell recordings of deep dorsal horn neurons in the rat spinal cord slice preparation were used to compare the cellular actions of serotonin, norepinephrine, dopamine, and acetylcholine on dorsal root stimulation-evoked afferent input and membrane cellular properties. In the majority of neurons, evoked excitatory postsynaptic potentials were depressed by the bulbospinal transmitters serotonin, norepinephrine, and dopamine. Although, the three descending transmitters could evoke common actions, in some neurons, individual transmitters evoked opposing actions. In comparison, acetylcholine generally facilitated the evoked responses, particularly the late, presumably N-methyl-d-aspartate receptor-mediated component. None of the transmitters modified neuronal passive membrane properties. In contrast, in response to depolarizing current steps, the biogenic amines significantly increased the number of spikes in 14/19 neurons that originally fired phasically ( P < 0.01). Together, these results demonstrate that even though the deep dorsal horn contains many functionally distinct subpopulations of neurons, the bulbospinal monoamine transmitters can act at both synaptic and cellular sites to alter neuronal sensory integrative properties in a rather predictable manner, and clearly distinct from the actions of acetylcholine.
Auditory Detection and Discrimination in Deaf Cats: Psychophysical and Neural Thresholds for Intracochlear Electrical Signals
Authors: Vollmer Maike , Beitel Ralph E. , Snyder Russell L.
Published: December 2017

More than 30,000 hearing-impaired human subjects have learned to use cochlear implants for speech perception and speech discrimination. To understand the basic mechanisms underlying the successful application of contemporary speech processing strategies, it is important to investigate how complex electrical stimuli delivered to the cochlea are processed and represented in the central auditory system. A deaf animal model has been developed that allows direct comparison of psychophysical thresholds with central auditory neuronal thresholds to temporally modulated intracochlear electrical signals in the same animals. Behavioral detection thresholds were estimated in neonatally deafened cats for unmodulated pulse trains (e.g., 30 pulses/s or pps) and sinusoidal amplitude-modulated (SAM) pulse trains (e.g., 300 pps, SAM at 30 Hz; 300/30 AM). Animals were trained subsequently in a discrimination task to respond to changes in the modulation frequency of successive SAM signals (e.g., 300/8 AM vs. 300/30 AM). During acute physiological experiments, neural thresholds to pulse trains were estimated in the inferior colliculus (IC) and the primary auditory cortex (A1) of the anesthetized animals. Psychophysical detection thresholds for unmodulated and SAM pulse trains were virtually identical. Single IC neuron thresholds for SAM pulse trains showed a small but significant increase in threshold (0.4 dB or 15.5 μA) when compared with thresholds for unmodulated pulse trains. The mean difference between psychophysical and minimum neural thresholds within animals was not significant (mean = 0.3 dB). Importantly, cats also successfully discriminated changes in the modulation frequencies of the SAM signals. Performance on the discrimination task was not affected by carrier rate (100, 300, 500, 1,000, or 1,500 pps). These findings indicate that 1) behavioral and neural response thresholds are based on detection of the peak pulse amplitudes of the modulated and unmodulated signals, and 2) discrimination of successive SAM pulse trains is based on temporal resolution of the envelope frequencies. Overall, our animal model provides a robust framework for future studies of behavioral discrimination and central neural temporal processing of electrical signals applied to the deaf cochlea by a cochlear implant.
Ethanol Inhibition of Glycine-Activated Responses in Neurons of Ventral Tegmental Area of Neonatal Rats
Authors: Ye Jiang Hong , Tao Liang , Zhu Li , Krnjević Kres̆imir , McArdle Joseph J.
Published: December 2017

The brain is particularly sensitive to alcohol during the period of its rapid growth. To better understand the mechanism(s) involved, we studied ethanol effects on glycine-activated responses of ventral tegmental area (VTA) neurons isolated from the newborn rat, using whole cell and gramicidin perforated patch-clamp techniques. Previously we reported that 0.1–40 mM ethanol enhances glycine-induced responses of 35% of VTA neurons ( Ye et al. 2001 ). We now direct our attention to the inhibitory effects of ethanol observed in 45% (312 of 694) of neonatal VTA neurons. Under current-clamp conditions, 1 mM ethanol had no effect on the membrane potential of these cells, but it decreased glycine-induced membrane depolarization and the frequency of spontaneous action potentials. Under voltage-clamp conditions, 0.1–10 mM ethanol did not elicit a current but depressed the glycine-induced currents. The ethanol-induced inhibition of glycine current was independent of membrane potential (between −60 and +60 mV). Likewise, ethanol did not alter the reversal potential of the glycine-activated currents. Ethanol-mediated inhibition of glycine current depended on the glycine concentration. While ethanol strongly depressed currents activated by 30 μM glycine, it had no appreciable effect on maximal currents activated by 1 mM glycine. In the presence of ethanol (1 mM), the EC50 for glycine increased from 32 ± 5 to 60 ± 3 μM. Thus ethanol may decrease the agonist affinity of glycine receptors. A kinetic analysis indicated that ethanol shortens the time constant of glycine current deactivation but has no effect on activation. In conclusion, by altering VTA neuronal function, ethanol-induced changes in glycine receptors may contribute to neurobehavioral manifestations of the fetal alcohol syndrome.
Intracellular pH Response to Anoxia in Acutely Dissociated Adult Rat Hippocampal CA1 Neurons
Authors: Sheldon Claire , Church John
Published: December 2017

The effects of anoxia on intracellular pH (pHi) were examined in acutely isolated adult rat hippocampal CA1 neurons loaded with the H+-sensitive fluorophore, 2′,7′-bis-(2-carboxyethyl)-5-(and-6)-carboxyfluorescein. During perfusion with HCO[Formula: see text]/CO2- or HEPES-buffered media (pH 7.35) at 37°C, 5- or 10-min anoxic insults were typified by an intracellular acidification on the induction of anoxia, a subsequent rise in pHiin the continued absence of O2, and a further internal alkalinization on the return to normoxia. The steady-state pHichanges were not consequent on changes in [Ca2+]iand, examined in the presence of HCO[Formula: see text], were not significantly affected by (DIDS). In the absence of HCO[Formula: see text], the magnitude of the postanoxic alkalinization was attenuated when external Na+was reduced by substitution with N-methyl-d-glucamine (NMDG+), but not Li+, suggesting that increased Na+/H+exchange activity contributes to this phase of the pHiresponse. In contrast, 100–500 μM Zn2+, a known blocker of H+-conductive pathways, reduced the magnitudes of the internal alkalinizations that occurred both during and following anoxia. The effects of NMDG+-substituted medium and Zn2+to reduce the increase in pHithat occurred after anoxia were additive. Consistent with the steady-state pHichanges, rates of pHirecovery from internal acid loads imposed immediately after anoxia were increased, and the application of Zn2+and/or perfusion with NMDG+-substituted medium slowed pHirecovery. Reducing extracellular pH from 7.35 to 6.60, or reducing ambient temperature from 37°C to room temperature, also attenuated the increases in steady-state pHiobserved during and after anoxia and reduced rates of pHirecovery from acid loads imposed in the immediate postanoxic period. Finally, inhibition of the cAMP/protein kinase A second-messenger system reduced the magnitude of the rise in pHiafter anoxia in a manner that was dependent on external Na+; conversely, activation of the system with isoproterenol increased the postanoxic alkalinization, an effect that was attenuated by pretreatment with propranolol, Rp-cAMPS, or when NMDG+(but not Li+) was employed as an external Na+substitute. The results suggest that a Zn2+-sensitive acid efflux mechanism, possibly a H+-conductive pathway activated by membrane depolarization, contributes to the internal alkalinization observed during anoxia in adult rat CA1 neurons. The rise in pHiafter anoxia reflects acid extrusion via the H+-conductive pathway and also Na+/H+exchange, activation of the latter being mediated, at least in part, through a cAMP-dependent signaling pathway.
Stimulation Pattern That Maximizes Force in Paralyzed and Control Whole Thenar Muscles
Authors: Griffin Lisa , Godfrey Sharlene , Thomas Christine K.
Published: December 2017

The pattern of seven pulses that elicited maximal thenar force was determined for control muscles and those that have been paralyzed chronically by spinal cord injury. For each subject group ( n = 6), the peak force evoked by two pulses occurred at a short interval (5–15 ms; a “doublet”), but higher mean relative forces were achieved in paralyzed versus control muscles (41.4 ± 3.9% vs. 22.7 ± 2.0% maximal). Thereafter, longer intervals evoked peak force in each type of muscle (mean: 35 ± 1 ms, 36 ± 2 ms, respectively). With seven pulses, paralyzed and control muscles reached 76.4 ± 5.6% and 57.0 ± 2.6% maximal force, respectively. These force differences resulted from significantly greater doublet/twitch and doublet/tetanic force ratios in paralyzed (2.73 ± 0.08, 0.35 ± 0.03) compared with control muscles (2.07 ± 0.07, 0.25 ± 0.01). The greater force enhancement produced in paralyzed muscles with two closely spaced pulses may relate to changes in muscle stiffness and calcium metabolism. Peak force-time integrals were also achieved with an initial short interpulse interval, followed by longer intervals. The postdoublet intervals that produced peak force-time integrals in paralyzed and control muscles were longer than those for peak force, however (77 ± 3 ms, 95 ± 4 ms, respectively). These data show that the pulse patterns that maximize force and force-time integral in paralyzed muscles are similar to those that maximize these parameters in single motor units and various whole muscles across species. Thus the changes in neuromuscular properties that occur with chronic paralysis do not strongly influence the pulse pattern that optimizes muscle force or force-time integral.
Collicular Microstimulation During Passive Rotation Does Not Generate Fixed Gaze Shifts
Authors: Van Beuzekom A. D. , Van Gisbergen J.A.M.
Published: December 2017

We investigated whether saccades evoked by electrical stimulation (E-saccades) in the superior colliculus can compensate for passive sinusoidal head rotation in yaw so as to keep the rapid gaze shift constant. After accounting for variations in E-saccade onset position, we found significant horizontal metric changes, proportional to head velocity, in 31 of 37 experiments in 2 monkeys. Vertical effects were small. In a substantial fraction of the experiments (14/37), these metric changes represented significant but often insufficient compensatory adjustments in the horizontal component, opposite to the direction of head movement. However, very robust violations of gaze-shift constancy were remarkably common: significant anticompensatory changes in the horizontal component occurred in 17/37 experiments. In these cases, typically involving larger E-saccades, the horizontal component increased in size with rotation into the half field containing the E-saccade and became smaller during opposite rotation. Further analysis showed that, instead of showing a dichotomy, the metric effect actually varied along a continuum from compensatory to strongly anticompensatory. In addition to these metric changes, we found a robust kinematic effect of head rotation in metrically matched E-saccades. In all experiments where the effect was significant (34/37), horizontal peak velocity increased for rotation into the half field where the E-saccade was directed and decreased for opposite rotation. This kinematic effect was again proportional to head velocity and predominant in the horizontal component. Comparison of yaw and pitch rotation at the same stimulation site showed that both expressions of vestibular-saccade interaction (metric and kinematic) tended to align with the direction of rotation. The component-specific nature of the modulation suggests that the effects may have been caused by convergence of saccadic and vestibular signals at a component-coding stage downstream of the colliculus. We suggest that the quick-phase system got access to the common pulse generator as soon as the collicular stimulation had opened the pause-cell gate. Adding such an anticompensatory signal would act to increase the E-saccade horizontal component when the monkey was rotated in the same direction and bring about a decrease in size and peak velocity when it was opposite. In the large majority of experiments the metric changes failed to maintain gaze-shift constancy, either because they were in the wrong direction or because they were too small. Possible reasons for this major departure from the properties of natural gaze shifts are discussed.
Postsynaptic Application of a cAMP Analogue Reverses Long-Term Potentiation in Hippocampal CA1 Pyramidal Neurons
Authors: Otmakhov Nikolai , Lisman John E.
Published: December 2017

The molecular mechanisms that underlie the maintenance of long-term potentiation (LTP) remain unclear. We have examined the influence of postsynaptic cAMP-dependent processes on LTP maintenance in CA1 hippocampal cells. After LTP induction, drugs affecting cAMP-dependent processes were perfused into the cell through a patch pipette. A cAMP analogue, Rp-cAMPS (4 mM), dramatically decreased the amplitude of potentiated synaptic responses. The amplitude of responses in the control pathway was also decreased but to a lesser extent, indicating a specific effect on the potentiation process. This specific effect was not due to the larger amplitude of potentiated responses, was not use-dependent and, unlike other factors that affect LTP maintenance, did not depend on the delay (2, 10, or 25 min) of drug application after LTP induction. Lower concentrations of Rp-cAMPS (1.0 and 0.4 mM) also produced an inhibitory effect but reduced the LTP and control pathways comparably. One possible action of Rp-cAMPS is competitive inhibition of protein kinase A (PKA). Surprisingly, a potent and noncompetitive PKA inhibitor, regulatory type II subunit of PKA, produced only a weak depression of potentiated and control responses indicating there must be other targets for Rp-cAMPS. Moreover, Sp-8-OH-cAMPS, which is an activator of PKA, and Rp-8-OH-cAMPS, which is a weak inhibitor of PKA, both produced effects similar to those of Rp-cAMPS. We conclude that there are postsynaptic cyclic nucleotide-dependent processes that can specifically alter the mechanisms that maintain LTP and that are not primarily dependent on PKA.
Participation of the Thalamic CM-Pf Complex in Attentional Orienting
Authors: Minamimoto Takafumi , Kimura Minoru
Published: December 2017

The centre médian-parafascicular (CM-Pf) complex is located at the posterior intralaminar nuclei of the thalamus and forms part of the nonspecific thalamocortical projection system and the internal circuit of the basal ganglia. However, the functional roles of this complex remain to be fully elucidated. Here we have examined whether the CM-Pf complex is involved in the process of covert attention. We trained two macaque monkeys to perform a task in which a visual target stimulus for button release appeared at either the same location as the preceding visual instruction cue (a “validly cued target”) or a location on the opposite side (an “invalidly cued target”). Reaction times (RTs) to a validly cued target were significantly shorter than those to an invalidly cued target, leading to a “validity effect” of about 20 ms. We recorded the activity of 97 neurons in the CM-Pf while the monkeys performed the attention task with the hand that was contralateral to the neuronal recording. Seventy CM-Pf neurons showed task-related activity after the appearance of either the instruction cue or the target stimulus: 33 neurons responded with a prominent short-latency facilitation (SLF), whereas 37 responded with a short-latency suppression followed by a long-latency facilitation (LLF). Most of the SLF neurons responded preferentially to a cue appearing on the contralateral side (76%) and to an invalidly cued target appearing on the contralateral side (61%). In contrast, LLF neurons showed a short-latency suppression after the cue stimulus, regardless of whether the cue appeared on the contra- or ipsilateral side (84%). Inactivating the CM-Pf complex by local injection (1 μl) of the GABAA receptor agonist muscimol (1–5 μg/μl) resulted in a significant increase in the RT to a validly cued target presented on the contra- but not the ipsilateral side. In contrast, inactivating the CM-Pf complex did not affect RTs to invalidly cued targets on either the contra- or the ipsilateral side. Thus the validity effect was abolished only on the contralateral side. We conclude that the CM-Pf complex plays a specific and essential role in the process of attentional orienting to external events occurring on the contralateral side, probably through the projection of primary outputs to the striatum, which is involved in the action-selection mechanisms of the basal ganglia.
AMPA Receptor-Mediated Miniature Synaptic Calcium Transients in GluR2 Null Mice
Authors: Wang Sabrina , Jia Zhengping , Roder John , Murphy Timothy H.
Published: December 2017

AMPA-type glutamate receptors are normally Ca2+ impermeable due to the expression of the GluR2 receptor subunit. By using GluR2 null mice we were able to detect miniature synaptic Ca2+ transients (MSCTs) associated with AMPA-type receptor-mediated miniature synaptic currents at single synapses in primary cortical cultures. MSCTs and associated Ca2+ transients were monitored under conditions that isolated responses mediated by AMPA or N-methyl-d-aspartate (NMDA) receptors. As expected, addition of the antagonist 6-cyano-7-nitroquinoxalene-2,3-dione (CNQX, 3 μM) blocked the AMPA receptor-mediated MSCTs. Voltage-gated Ca2+channels did not contribute to AMPA MSCTs because CdCl2 (0.1–0.2 mM) did not significantly alter the frequency or the amplitude of the MSCTs. The amplitude of AMPA MSCTs appeared to be regulated independently from event frequency since the two measures were not correlated ( R = 0.023). Synapses were identified that only expressed MSCTs attributed to either NMDA or AMPA receptors. At synapses with only NMDA responses, MSCT amplitude was significantly lower (by 40%) than synapses expressing both NMDA and AMPA responses. At synapses that showed MSCTs mediated by both AMPA and NMDA receptors, the amplitude of the transients in each condition was positively correlated ( R = 0.94). Our results suggest that when AMPA and NMDA receptors are co-expressed at synapses, mechanisms exist to ensure proportional scaling of each receptor type that are distinct from the presynaptic factors controlling the frequency of miniature release.
Pattern Generation in Caudal-Lumbar and Sacrococcygeal Segments of the Neonatal Rat Spinal Cord
Authors: Gabbay H. , Delvolvé I. , Lev-Tov A.
Published: December 2017

The rhythmogenic capacity of the tail-innervating segments (L4-Co3) of the spinal cord was studied in isolated spinal cord and tail–spinal cord preparations of neonatal rats. Bath-applied serotonin/ N-methyl-d-aspartate (NMDA) failed to produce a robust sacrococcygeal rhythmicity following midlumbar transection of the spinal cord. By contrast, a regular alternating left–right rhythm could be induced in the sacrococcygeal segments by application of noradrenaline (NA) or NA and NMDA before and after midlumbar transection of the cord. This rhythm was accelerated with the concentration of NMDA and was blocked by α1 or α2 adrenoceptor antagonists. The efferent bursts induced by NA/NMDA were accompanied by rhythmic tail movements produced by alternating activation of the left and right tail muscles and by coactivation of flexors, extensors, and abductors on a given side of the tail. This coactivation implies that reciprocal inhibitory pathways were not activated during the rhythm. Lesion experiments revealed that the rhythmogenic circuitry is distributed along all or most of the sacrococcygeal segments. The NA/NMDA-induced rhythm persisted in the isolated sacrococcygeal (S1-Co3), sacral (S1-S4), coccygeal (Co1-Co3), and smaller isolated regions of the sacrococcygeal cord. The rhythm also could be maintained in longitudinally split sacrococcygeal hemicords in which flexor, extensor, and abductor motoneurons are coactivated. This finding indicates that neither left/right nor flexor/extensor inhibitory interactions are required for rhythmogenesis in the sacrococcygeal cord. A slow rhythm lacking the alternating left–right pattern was induced by NA/NMDA in tail-innervating caudal lumbar segments of isolated L4-Co3 preparations. This rhythm was independent of the concurrent sacrococcygeal rhythm and the activity pattern of the tail musculature and it does not seem to contribute to rhythmic tail movements under these conditions. Comparative studies of the rhythm produced in the isolated caudal lumbar, sacrococcygeal cord, and caudal thoracic–rostral lumbar segments revealed that the S1-Co3 rhythm was faster than the L4-L6 pattern and slower than the T6-L3 rhythm. It is suggested that the caudal lumbar and sacrococcygeal segments of the cord are normally driven by the faster rostral lumbar central pattern generators. The relevance of the findings described above to pattern generation in the mammalian spinal cord is discussed.
Local Field Potential Oscillations in Primate Cerebellar Cortex: Modulation During Active and Passive Expectancy
Authors: Courtemanche Richard , Pellerin Jean-Pierre , Lamarre Yves
Published: December 2017

Cerebellar local field potential (LFP) oscillations were recorded in the paramedian lobule of one hemisphere, while monkeys were in two behavioral conditions: actively performing an elbow flexion-extension or a lever-press task in response to an auditory or visual stimulus to get reward (active condition), or waiting quietly for the reward to come in the same time window after the appearance of the stimulus (passive condition). The oscillations in the paramedian lobule were first characterized in four monkeys, and they showed an idiosyncratic frequency for each monkey, between 13 and 25 Hz. The granule cell layer multi-unit activity was phase-locked with the negative phase of the LFP oscillations, while Purkinje cell simple spikes were also sometimes phase-locked with the LFP. Three monkeys were trained to perform the motor tasks: the LFP oscillations were modulated, in the active condition, in a systematic manner in relation to the lever-press or elbow flexion-extension tasks. During periods when the monkey was waiting to initiate movement, LFP oscillations appeared and then stopped with movement initiation. This modulation was valid for the task being executed with either hand. Surprisingly, the LFP oscillations were also systematically modulated during the passive condition; as the monkey was waiting for the usual time to get a reward passively, oscillations appeared stronger and were stopped by the end of the usual delay, whether the monkey was rewarded or not. This type of modulation was not affected by the length of the stimulus, as long as the reward window was known to the monkey. If the monkey had not been previously trained to the active condition, the modulation appeared in the passive condition. These results show that cerebellar LFP oscillations in the paramedian lobule are reliably present when the monkey is involved in a waiting period, whether this period ends with an active or passive event. This study provides electrophysiological evidence for a specific pattern of activity in the cerebellum for the expectancy of events that are known to be bound to happen, either externally, or from voluntary action.
Synaptic Precedence During Synapse Formation Between Reciprocally Connected Neurons Involves Transmitter-Receptor Interactions and AA Metabolites
Authors: Lovell P. , McMahon B. , Syed N. I.
Published: December 2017

The cellular mechanisms that determine specificity of synaptic connections between mutually connected neurons in the nervous system have not yet been fully examined in vertebrate and invertebrate species. Here we report on a novel form of synaptic interaction during early stages of synapse formation between reciprocally connected Lymnaea neurons. Specifically, using soma-soma synapses between an identified dopaminergic neuron (also known as the giant dopamine cell), right pedal dorsal 1 (RPeD1), and a FMRFamidergic neuron, visceral dorsal 4 (VD4), we demonstrate that although reciprocal inhibitory synapses re-form between the somata after 24–36 h of pairing, VD4 is, however, the first cell to establish synaptic contacts with RPeD1 (within 12–18 h). We show that VD4 “captures” RPeD1 first as a postsynaptic cell by suppressing its transmitter secretory machinery during early stages of cell-cell pairing. The VD4-induced suppression of transmitter release from RPeD1 was transient, and it required transcription and de novo protein synthesis dependent step in VD4 but not in RPeD1. The VD4-induced effects on RPeD1 were mimicked by a FMRFamide-like peptide. Perturbation of FMRFamide-activated metabolites of the arachidonic acid pathway in RPeD1 not only prevented FMRFamide-induced suppression of transmitter release from the giant dopamine cell but also shifted the synaptic balance in favor of RPeD1, thus making it the first cell to begin synaptic transmission with VD4 within 12–18 h. A single RPeD1 that had developed dopamine secretory capabilities overnight and was subsequently paired with VD4 for 12–18 h was, however, immune to VD4-induced suppression of transmitter release. Under these experimental conditions, both cells developed mutual inhibitory synapses concurrently. Taken together, our data provide evidence for novel synaptic interaction between reciprocally connected neurons and underscore the importance of transmitter-receptor interplay in regulating the timing of synapse formation in the nervous system.
Dynamic Coordination of Body Parts During Prism Adaptation
Authors: Martin Tod A. , Norris Scott A. , Greger Bradley E. , Thach W. Thomas
Published: December 2017

We studied coordination across body parts in throwing during adaptation to prisms. Human subjects threw balls at a target before, during, and after wearing laterally shifting prism eyeglasses. Positions of head, shoulders, arm, and ball were video-recorded continuously. We computed body angles of eyes-in-head, head-on-trunk, trunk-on-arm, and arm-on-ball. In each subject, the gaze-throw adjustment during adaptation was distributed across all sets of coupled body parts. The distribution of coupling changed unpredictably from throw to throw within a single session. The angular variation among coupled body parts was typically significantly larger than angular variation of on-target hits. Thus coupled body parts changed interdependently to account for the high accuracy of ball-on-target. Principal components and Monte Carlo analyses showed variability in body angles across throws with a wide range of variability/stereotypy across subjects. The data support a model of a dynamic and generalized solution as evidenced by the distribution of the gaze-throw adjustment across body parts.
A Case of Disseminated Hypopigmented Keratoses Improved with Oral Acitretin
Authors: Eskiocak Ali Haydar , Bassorgun Cumhur İbrahim , Uzun Sarp , Uzun Soner
Published: December 2017

Disseminated hypopigmented keratosis is a distinct clinical entity and only few cases have been reported so far. Here, we present a 21-year-old man with almost 10-year history of hypopigmented, nonfollicular, keratotic lichenoid papules occurring on the extensor surfaces of the extremities, back and lumber region. Histopathological examination showed orthohyperkeratosis, irregular acanthosis, and sporadic papillomatosis with a normal amount of melanin and number of melanocytes. In addition, no marked inflammation or melanophages were seen. In order to exclude other possible causes, we performed laboratory tests and radiological examination which were all found to be normal. As the clinical and histopathological features of our patient were taken into account, it was considered to be compatible with the diagnosis of disseminated hypopigmented keratoses. So far, only topical therapies have been used with failure in the previously reported cases except one patient. Considering the extensive lesions, we treated the present patient with 5% salicylic acid in addition to oral acitretin and significant regression in all lesions was achieved, particularly on the keratosis.
Absorption and Elimination of Oat Avenanthramides in Humans after Acute Consumption of Oat Cookies
Authors: Zhang Tianou , Shao Jing , Gao Yike , Chen Chi , Yao Dan , Chu Yi Fang , Johnson Jodee , Kang Chounghun , Yeo Dongwook , Ji Li Li
Published: December 2017

Background. Avenanthramides (AVA) are a group of diphenolic acids found only in oats that have anti‐inflammatory and antioxidant effects. Absorption of AVAs in humans after oral consumption of natural oat flour is unknown. Objective. To examine the appearance of AVAs in plasma after oral ingestion of oat cookies and estimate key pharmacokinetic parameters. Methods. Male and female nonobese participants (n = 16) consumed three cookies made with oat flour containing high (229.6 mg/kg, H‐AVA) or low (32.7 mg/kg, L‐AVA) amounts of AVAs, including AVA‐A, AVA‐B, and AVA‐C. Blood samples were collected at 0, 0.5, 1, 2, 3, 5, and 10 h after ingestion. Plasma total (conjugated and free) AVA concentrations were quantified using UPLC‐MS, and pharmacokinetic parameters for each AVA were estimated. Results. AVAs reached peak concentrations in plasma between 2 and 3 h for the H‐AVA group and between 1 and 2 h for the L‐AVA group. Maximal plasma concentrations for AVAs were higher in the H‐AVA than in the L‐AVA group. AVA‐B demonstrated a longer half‐life and slower elimination rate than AVA‐A and AVA‐C. Conclusions. AVAs found naturally in oats are absorbed in the plasma after oral administration in humans. AVA‐B has the slowest elimination rate and the longest half‐life compared to AVA‐A and AVA‐C, while AVA‐C demonstrated the lowest plasma concentrations. This study is registered with ClinicalTrials.gov identifier NCT02415374.
Association between Scale-Free Brain Dynamics and Behavioral Performance: Functional MRI Study in Resting State and Face Processing Task
Authors: Kasagi Masato , Huang Zirui , Narita Kosuke , Shitara Hitoshi , Motegi Tomokazu , Suzuki Yusuke , Fujihara Kazuyuki , Tanabe Sean , Kosaka Hirotaka , Ujita Koichi , Fukuda Masato , Northoff Georg
Published: December 2017

The scale-free dynamics of human brain activity, characterized by an elaborate temporal structure with scale-free properties, can be quantified using the power-law exponent (PLE) as an index. Power laws are well documented in nature in general, particularly in the brain. Some previous fMRI studies have demonstrated a lower PLE during cognitive-task-evoked activity than during resting state activity. However, PLE modulation during cognitive-task-evoked activity and its relationship with an associated behavior remain unclear. In this functional fMRI study in the resting state and face processing + control task, we investigated PLE during both the resting state and task-evoked activities, as well as its relationship with behavior measured using mean reaction time (mRT) during the task. We found that (1) face discrimination-induced BOLD signal changes in the medial prefrontal cortex (mPFC), posterior cingulate cortex (PCC), amygdala, and fusiform face area; (2) PLE significantly decreased during task-evoked activity specifically in mPFC compared with resting state activity; (3) most importantly, in mPFC, mRT significantly negatively correlated with both resting state PLE and the resting-task PLE difference. These results may lead to a better understanding of the associations between task performance parameters (e.g., mRT) and the scale-free dynamics of spontaneous and task-evoked brain activities.
Anomalous Coronary Artery Origin in a Young Patient with Marfan Syndrome
Authors: Duarte S. B. C. P. , Beraldo D. O. , Cesar L. A. M. , Mansur A. P. , Takada J. Y.
Published: December 2017

Marfan syndrome is an autosomal dominant genetic disorder that affects connective tissue and is caused by mutations in the fibrillin 1 gene present at chromosome 15. Aortic aneurysm is its main complication, and along the dilation of the aorta root and its descending portion (60–100%), with secondary aortic insufficiency, it increases risk of acute aortic dissection and death. Coronary artery anomalies affect between 0.3% and 1.6% of the general population and are the second leading cause of sudden death in young adults, especially if the anomalous coronary passes through aorta and pulmonary artery. The anomalous origin of the left main coronary artery in the right Valsalva sinus has a prevalence of 0.02%–0.05% and is commonly related to other congenital cardiac anomalies, such as transposition of great vessels, coronary fistulas, bicuspid aortic valve, and tetralogy of Fallot. Its association with Marfan syndrome is not known, and there is no previous report in the literature. We describe here a case of a female with Marfan syndrome diagnosed with symptomatic anomalous origin of the left coronary artery in the right Valsalva sinus.
Multiobjective Level-Wise Scientific Workflow Optimization in IaaS Public Cloud Environment
Authors: Thant Phyo Thandar , Powell Courtney , Schlueter Martin , Munetomo Masaharu
Published: December 2017

Cloud computing in the field of scientific applications such as scientific big data processing and big data analytics has become popular because of its service oriented model that provides a pool of abstracted, virtualized, dynamically scalable computing resources and services on demand over the Internet. However, resource selection to make the right choice of instances for a certain application of interest is a challenging problem for researchers. In addition, providing services with optimal performance at the lowest financial resource deployment cost based on users’ resource selection is quite challenging for cloud service providers. Consequently, it is necessary to develop an optimization system that can provide benefits to both users and service providers. In this paper, we conduct scientific workflow optimization on three perspectives: makespan minimization, virtual machine deployment cost minimization, and virtual machine failure minimization in the cloud infrastructure in a level-wise manner. Further, balanced task assignment to the virtual machine instances at each level of the workflow is also considered. Finally, system efficiency verification is conducted through evaluation of the results with different multiobjective optimization algorithms such as SPEA2 and NSGA-II.
Morphological Transformation of Myeloma Cells into Multilobated Plasma Cell Nuclei within 7 Days in a Case of Secondary Plasma Cell Leukemia That Finally Transformed as Anaplastic Myeloma
Authors: Fujimi Akihito , Nagamachi Yasuhiro , Yamauchi Naofumi , Kanisawa Yuji
Published: December 2017

A 48-year-old man was diagnosed with multiple myeloma (IgG-k) and was treated with high-dose dexamethasone as an induction therapy followed by thalidomide-based regimens. Approximately 22 months after the initial diagnosis, the patient developed secondary plasma cell leukemia (PCL) with a white blood cell (WBC) count of 20.2 × 109/L including 79.5% plasma cells. A G-banding chromosomal analysis in the bone marrow showed an t(11;14) abnormality of up to 5%, which was not detected at initial diagnosis. We immediately started bortezomib and dexamethasone therapy, but in just 7 days, the WBC count elevated to 48.5 × 109/L, and approximately 95% of them were medium-sized atypical lymphoid cells with multilobated nuclei. Although we subsequently initiated alternative regimens, the patient’s condition deteriorated, and he died 4 months after developing PCL. Approximately 2 months before his death, the diameter of myeloma cells in the bone marrow enlarged by approximately twofold, and pleomorphic nuclei were present, indicating an anaplastic myeloma transformation. Concurrently, a 100% increase of the t(11;14) clone frequency was observed in the G-banding-analyzed bone marrow cells. Morphological transformation of myeloma cells into multilobated plasma cell nuclei can be considered as the starting point of the sequential process leading to anaplastic myeloma.
On the Difference of Scaling Properties for Temperature and Precipitation over China
Authors: Jiang Lei , Zhao Liqing , Zhao Zihao
Published: December 2017

The daily air temperature and precipitation records of four meteorological observation stations over China are used to investigate the differences of scaling property employing the detrended fluctuation analysis (DFA) method. The results show that the values in DFA-exponent for temperature are higher than those for precipitation compared by different orders DFA1–3. A 95% significance test is also applied to verify LRCs by resampling the temperature and precipitation records 10000 times in Beijing. The values of scaling exponent from original temperature and precipitation records are larger than the upper range value of the interval threshold after shuffling the data records, which implies there are positive LRCs. For temperature records, the value of scaling exponent calculated by FA is greater than those by DFA1–3 at all four stations. This indicates that the FA curve overestimates the scaling behavior due to the effect of trends. By contrast, the values of scaling exponent in precipitation are almost the same by using FA and DFA1–3 for all time scales, respectively. Furthermore, there are crossovers on short time scales in different orders DFA1–3 for the temperature records, while the slopes keep almost consistent on all time scales for the precipitation records.
Antioxidant and Hepatoprotective Activities of Polysaccharides from Spent Mushroom Substrates (Laetiporus sulphureus) in Acute Alcohol‐Induced Mice
Authors: Zhao Huajie , Lan Yufei , Liu Hui , Zhu Yongfa , Liu Weiru , Zhang Jianjun , Jia Le
Published: December 2017

In order to contribute to the exploitation and utilization of spent mushroom substrates (SMS) of Laetiporus sulphureus, hot‐water‐extractable polysaccharides (H‐SMPS) and enzymatic‐extractable polysaccharides (E‐SMPS) were successfully isolated from SMS of L. sulphureus. Both H‐SMPS and E‐SMPS were found to have high reducing power and potential scavenging activities against hydroxyl, DPPH, and superoxide anion radicals. In vivo assays showed that the administration of H‐SMPS and E‐SMPS has potential hepatoprotective effects against alcohol‐induced alcoholic liver disease (ALD), possibly brought about by improving liver function, increasing antioxidant status, and reducing lipid peroxidation. Furthermore, monosaccharide composition analysis showed that fucose may play a vital role in guaranteeing stronger hepatoprotection. These results may provide references for the exploitation of the SMS of L. sulphureus as a source of H‐SMPS and E‐SMPS, which in turn can be used as functional foods or natural drugs for the prevention of ALD and other liver diseases.
Ginsenoside Rb1 for Myocardial Ischemia/Reperfusion Injury: Preclinical Evidence and Possible Mechanisms
Authors: Zheng Qun , Bao Xiao-Yi , Zhu Peng-Chong , Tong Qiang , Zheng Guo-Qing , Wang Yan
Published: December 2017

Ginseng is an important herbal drug that has been used worldwide for many years. Ginsenoside Rb1 (G‐Rb1), the major pharmacological extract from ginseng, possesses a variety of biological activities in the cardiovascular systems. Here, we conducted a preclinical systematic review to investigate the efficacy of G‐Rb1 for animal models of myocardial ischemia/reperfusion injury and its possible mechanisms. Ten studies involving 211 animals were identified by searching 6 databases from inception to May 2017. The methodological quality was assessed by using the CAMARADES 10‐item checklist. All the data were analyzed using RevMan 5.3 software. As a result, the score of study quality ranged from 3 to 7 points. Meta‐analyses showed that G‐Rb1 can significantly decrease the myocardial infarct size and cardiac enzymes (including lactate dehydrogenase, creatine kinase, and creatine kinase‐MB) when compared with control group (P < 0.01). Significant decrease in cardiac troponin T and improvement in the degree of ST‐segment depression were reported in one study (P < 0.05). Additionally, the possible mechanisms of G‐Rb1 for myocardial infarction are antioxidant, anti‐inflammatory, antiapoptosis, promoting angiogenesis and improving the circulation. Thus, G‐Rb1 is a potential cardioprotective candidate for further clinical trials of myocardial infarction.