bluuebunny/crossref_metadata_2025 huggingface dataset:
Synaptic and Nonsynaptic Ictogenesis Occurs at Different Temperatures in Submerged and Interface Rat Brain Slices
Authors: Schuchmann S. , Meierkord H. , Stenkamp K. , Breustedt J. , Windmüller O. , Heinemann U. , Buchheim K.
Published: December 2017

To investigate the temperature sensitivity of low-Ca2+-induced nonsynaptic and low-Mg2+-induced synaptic ictogenesis under submerged and interface conditions, we compared changes of extracellular field potential and extracellular potassium concentration at room temperature (23 ± 1°C; mean ± SD) and at 35 ± 1°C in hippocampal-entorhinal cortex slices. The induction of spontaneous epileptiform activity under interface conditions occurred at 35 ± 1°C in both models. In contrast, under submerged conditions, spontaneous epileptiform activity in low-Mg2+ artificial cerebrospinal fluid (ACSF) was observed at 35 ± 1°C, whereas epileptiform discharges induced by low-Ca2+ ACSF occurred only at room temperature. To investigate the different temperature effects under submerged and interface conditions, measurements of extra- and intracellular pH and extracellular space volume were performed. Lowering the temperature from 35 ± 1°C to room temperature effected a reduction in extracellular pH under submerged and interface conditions. Under submerged conditions, temperature changes had no significant influence on the intracellular pH in presence of either normal or low-Mg2+ ACSF. In contrast, application of low-Ca2+ ACSF effected a significant increase in intracellular pH at room temperature but not at 35 ± 1°C under submerged conditions. Therefore increasing intracellular pH by lowering the temperature in low-Ca2+ ACSF may push slices to spontaneous epileptiform activity by opening gap junctions. Finally, extracellular space volume significantly decreased by switching from submerged to interface conditions. The reduced extracellular space volume under interface conditions may lead to an enlarged ephaptic transmission and therefore promotes low-Mg2+- and low-Ca2+-induced spontaneous epileptiform activity. The results of the study indicate that gas-liquid interface and total-liquid submerged slice states impart distinct physiological parameters on brain tissue.
Contrast Sensitivity in Human Visual Areas and Its Relationship to Object Recognition
Authors: Avidan Galia , Harel Michal , Hendler Talma , Ben-Bashat Dafna , Zohary Ehud , Malach Rafael
Published: December 2017

An important characteristic of visual perception is the fact that object recognition is largely immune to changes in viewing conditions. This invariance is obtained within a sequence of ventral stream visual areas beginning in area V1 and ending in high order occipito-temporal object areas (the lateral occipital complex, LOC). Here we studied whether this transformation could be observed in the contrast response of these areas. Subjects were presented with line drawings of common objects and faces in five different contrast levels (0, 4, 6, 10, and 100%). Our results show that indeed there was a gradual trend of increasing contrast invariance moving from area V1, which manifested high sensitivity to contrast changes, to the LOC, which showed a significantly higher degree of invariance at suprathreshold contrasts (from 10 to 100%). The trend toward increased invariance could be observed for both face and object images; however, it was more complete for the face images, while object images still manifested substantial sensitivity to contrast changes. Control experiments ruled out the involvement of attention effects or hemodynamic “ceiling” in producing the contrast invariance. The transition from V1 to LOC was gradual with areas along the ventral stream becoming increasingly contrast-invariant. These results further stress the hierarchical and gradual nature of the transition from early retinotopic areas to high order ones, in the build-up of abstract object representations.
Role of Apamin-Sensitive KCa Channels for Reticulospinal Synaptic Transmission to Motoneuron and for the Afterhyperpolarization
Authors: Cangiano Lorenzo , Wallén Peter , Grillner Sten
Published: December 2017

Single motoneurons and pairs of a presynaptic reticulospinal axon and a postsynaptic motoneuron were recorded in the isolated lamprey spinal cord, to investigate the role of calcium-dependent K+ channels (KCa) during the afterhyperpolarization following the action potential (AHP), and glutamatergic synaptic transmission on the dendritic level. The AHP consists of a fast phase due to transient K+ channels (fAHP) and a slower phase lasting 100–200 ms (sAHP), being the main determinant of spike frequency regulation. We now present evidence that the sAHP has two components. The larger part, around 80%, is abolished by superfusion of Cd2+ (blocker of voltage-dependent Ca2+ channels), by intracellular injection of 1,2-bis-( 2-aminophenoxy)-ethane- N,N,N′,N′-tetraacetic acid (BAPTA; fast Ca2+ chelator), and by apamin (selective toxin for KCa channels of the SK subtype). While 80% of the sAHP is thus due to KCa channels, the remaining 20% is not mediated by Ca2+, either entering through voltage-dependent Ca2+ channels or released from intracellular Ca2+ stores. This Ca2+-independent sAHP component has a similar time course as the KCa portion and is not due to a Cl− conductance. It may be caused by Na+-activated K+ channels. Glutamatergic excitatory postsynaptic potentials (EPSPs) evoked by single reticulospinal axons give rise to a local Ca2+ increase in the postsynaptic dendrite, mediated in part by N-methyl-d-aspartate (NMDA) receptors. The Ca2+ levels remain elevated for several hundred milliseconds and could be expected to activate KCa channels. If so, this activation should cause a local conductance increase in the dendrite that would shunt EPSPs following the first EPSP in a spike train. We have tested this in reticulospinal/motoneuronal pairs, by stimulating the presynaptic axon with spike trains at different frequencies. We compared the first EPSP and the following EPSPs in the control and after blockade with apamin. No difference was observed in EPSP amplitude or shape before and after apamin, either in normal Ringer or in Mg2+-free Ringer removing the voltage-dependent block of NMDA receptors. In conclusion, the local Ca2+ entry during reticulospinal EPSPs does not cause an activation of KCa channels sufficient to affect the efficacy of synaptic transmission. Thus the integration of synaptic signals at the dendritic level in motoneurons appears simpler than would otherwise have been the case.
Auditory-Visual Interactions Subserving Goal-Directed Saccades in a Complex Scene
Authors: Corneil B. D. , Van Wanrooij M. , Munoz D. P. , Van Opstal A. J.
Published: December 2017

This study addresses the integration of auditory and visual stimuli subserving the generation of saccades in a complex scene. Previous studies have shown that saccadic reaction times (SRTs) to combined auditory-visual stimuli are reduced when compared with SRTs to either stimulus alone. However, these results have been typically obtained with high-intensity stimuli distributed over a limited number of positions in the horizontal plane. It is less clear how auditory-visual interactions influence saccades under more complex but arguably more natural conditions, when low-intensity stimuli are embedded in complex backgrounds and distributed throughout two-dimensional (2-D) space. To study this problem, human subjects made saccades to visual-only (V-saccades), auditory-only (A-saccades), or spatially coincident auditory-visual (AV-saccades) targets. In each trial, the low-intensity target was embedded within a complex auditory-visual background, and subjects were allowed over 3 s to search for and foveate the target at 1 of 24 possible locations within the 2-D oculomotor range. We varied systematically the onset times of the targets and the intensity of the auditory target relative to background [i.e., the signal-to-noise (S/N) ratio] to examine their effects on both SRT and saccadic accuracy. Subjects were often able to localize the target within one or two saccades, but in about 15% of the trials they generated scanning patterns that consisted of many saccades. The present study reports only the SRT and accuracy of the first saccade in each trial. In all subjects, A-saccades had shorter SRTs than V-saccades, but were more inaccurate than V-saccades when generated to auditory targets presented at low S/N ratios. AV-saccades were at least as accurate as V-saccades but were generated at SRTs typical of A-saccades. The properties of AV-saccades depended systematically on both stimulus timing and S/N ratio of the auditory target. Compared with unimodal A- and V-saccades, the improvements in SRT and accuracy of AV-saccades were greatest when the visual target was synchronous with or leading the auditory target, and when the S/N ratio of the auditory target was lowest. Further, the improvements in saccade accuracy were greater in elevation than in azimuth. A control experiment demonstrated that a portion of the improvements in SRT could be attributable to a warning-cue mechanism, but that the improvements in saccade accuracy depended on the spatial register of the stimuli. These results agree well with earlier electrophysiological results obtained from the midbrain superior colliculus (SC) of anesthetized preparations, and we argue that they demonstrate multisensory integration of auditory and visual signals in a complex, quasi-natural environment. A conceptual model incorporating the SC is presented to explain the observed data.
Spatial Structure and Symmetry of Simple-Cell Receptive Fields in Macaque Primary Visual Cortex
Authors: Ringach Dario L.
Published: December 2017

I present measurements of the spatial structure of simple-cell receptive fields in macaque primary visual cortex (area V1). Similar to previous findings in cat area 17, the spatial profile of simple-cell receptive fields in the macaque is well described by two-dimensional Gabor functions. A population analysis reveals that the distribution of spatial profiles in primary visual cortex lies approximately on a one-parameter family of filter shapes. Surprisingly, the receptive fields cluster into even- and odd-symmetry classes with a tendency for neurons that are well tuned in orientation and spatial frequency to have odd-symmetric receptive fields. The filter shapes predicted by two recent theories of simple-cell receptive field function, independent component analysis and sparse coding, are compared with the data. Both theories predict receptive fields with a larger number of subfields than observed in the experimental data. In addition, these theories do not generate receptive fields that are broadly tuned in orientation and low-pass in spatial frequency, which are commonly seen in monkey V1. The implications of these results for our understanding of image coding and representation in primary visual cortex are discussed.
Bradykinin Lowers the Threshold Temperature for Heat Activation of Vanilloid Receptor 1
Authors: Sugiura Takeshi , Tominaga Makoto , Katsuya Hirotada , Mizumura Kazue
Published: December 2017

Bradykinin (BK) is an inflammatory mediator that plays a pivotal role in pain and hyperalgesia to heat in inflamed tissues by exciting nociceptors and sensitizing them to heat through activation of protein kinase C (PKC). It has been suggested that the capsaicin receptor (VR1), a nociceptor-specific cation channel sensitive to noxious heat, protons, and capsaicin, is a channel that is modified by BK in these effects. In this study, we examined how BK modulates the activity of VR1. We measured VR1 currents using the patch-clamp technique in human embryonic kidney-derived (HEK293) cells expressing VR1 and B2 BK receptor. We found that BK lowered the threshold temperature for activation of VR1 currents in HEK cells down to well below the physiological body temperature in a concentration-dependent manner through PKC activation. We also demonstrated that in capsaicin-sensitive dorsal root ganglion (DRG) neurons the activation threshold of heat-induced current, which is considered to be VR-1 mediated, was lowered by BK and that this effect was also mediated by PKC. These data further support the supposition that modulation of VR1 is a mechanism for the BK-induced excitation of nociceptors and their sensitization to heat.
Postsynaptic Action of BDNF on GABAergic Synaptic Transmission in the Superficial Layers of the Mouse Superior Colliculus
Authors: Henneberger Christian , Jüttner René , Rothe Thomas , Grantyn Rosemarie
Published: December 2017

The neurotrophin brain-derived neurotrophic factor (BDNF) is involved in numerous aspects of synapse development and plasticity. The present study was aimed at clarifying the significance of endogenous BDNF for the synaptically driven spontaneous network activity and GABAergic inhibition in the superficial layers of the mouse superior colliculus. In this structure neuron survival is unaffected by the absence of BDNF. Two experimental approaches were used: comparison of BDNF-deficient (–/–) and wild-type (+/+) mice and blockade of BDNF receptor signaling by the tyrosine kinase inhibitor K-252a. Patch-clamp recordings were performed on horizontal slices during postnatal days 15 and 16. The lack of BDNF in –/– mice caused a significant reduction of the spontaneous action potential frequency and an increase in the pharmacologically induced disinhibition of spike discharge. This change was accompanied by an increase in the amplitudes of GABAergic evoked, spontaneous, and miniature inhibitory postsynaptic currents (IPSCs). BDNF gene inactivation had no effect on the degree of paired-pulse facilitation or the frequency of miniature IPSCs. The increase of IPSC amplitudes by chronic BDNF deprivation was completely mimicked by acute exposure to K-252a in +/+ animals. The enhancement of GABAergic IPSCs in –/– animals was reversed by acute application of 100 ng/ml BDNF, but this rescue was completely prevented by blocking postsynaptic protein kinase C (PKC) activation with the PKC inhibitor peptide 19–31. From these results we conclude that BDNF increases spontaneous network activity by suppressing GABAergic inhibition, the site of action of BDNF is predominantly postsynaptic, BDNF-induced suppression of GABAergic synaptic transmission is caused by acute downregulation of GABAAreceptors, and BDNF effects are mediated by its TrkB receptor and require PKC activation in the postsynaptic cell.
Experimental and Modeling Studies of Novel Bursts Induced by Blocking Na+ Pump and Synaptic Inhibition in the Rat Spinal Cord
Authors: Rozzo Aldo , Ballerini Laura , Abbate Gilda , Nistri Andrea
Published: December 2017

This study addressed some electrophysiological mechanisms enabling neonatal rat spinal networks in vitro to generate spontaneous rhythmicity. Networks, made up by excitatory connections only after block of GABAergic and glycinergic transmission, develop regular bursting (disinhibited bursts) suppressed by the Na+ pump blocker strophanthidin. Thus the Na+ pump is considered important to control bursts. This study, however, shows that, after about 1 h in strophanthidin solution, networks of the rat isolated spinal cord surprisingly resumed spontaneous bursting (“strophanthidin bursting”), which consisted of slow depolarizations with repeated oscillations. This pattern, recorded from lumbar ventral roots, was synchronous on both sides, of irregular periodicity, and lasted for ≥12 h. Assays of 86Rb+uptake by spinal tissue confirmed Na+ pump block by strophanthidin. The strophanthidin rhythm was abolished by glutamate receptor antagonists or tetrodotoxin, indicating its network origin. N-methyl-d-aspartate (NMDA), serotonin, or high K+ could not accelerate it. The size of each burst was linearly related to the length of the preceding pause. Bursts could also be generated by dorsal root electrical stimulation and possessed similar dependence on the preceding pause. Conversely, disinhibited bursts could be evoked at short intervals from the preceding one unless repeated pulses were applied in close sequence. These data suggest that rhythmicity expressed by excitatory spinal networks could be controlled by Na+ pump activity or slow synaptic depression. A model based on the differential time course of pump operation and synaptic depression could simulate disinhibited and strophanthidin bursting, indicating two fundamental, activity-dependent processes for regulating network discharge.
Cisplatin-Induced Hyperactivity in the Dorsal Cochlear Nucleus and Its Relation to Outer Hair Cell Loss: Relevance to Tinnitus
Authors: Kaltenbach James A. , Rachel John D. , Mathog T. Alecia , Zhang Jinsheng , Falzarano Pamela R. , Lewandowski Matthew
Published: December 2017

Cisplatin causes both acute and chronic forms of tinnitus as well as increases in spontaneous neural activity (hyperactivity) in the dorsal cochlear nucleus (DCN) of hamsters. It has been hypothesized that the induction of hyperactivity in the DCN may be a consequence of cisplatin's effects on cochlear outer hair cells (OHCs); however, systematic studies testing this hypothesis have yet to appear in the literature. In the present investigation, the relationship between hyperactivity and OHC loss, induced by cisplatin, was examined in detail. Hamsters received five treatments of cisplatin at doses ranging from 1.5 to 3 mg · kg−1 · day−1, every other day. Beginning 1 mo after initiation of treatment, electrophysiological recordings were carried out on the surface of the DCN to measure spontaneous multiunit activity along a set of coordinates spanning the medial-lateral (tonotopic) axis of the DCN. After recordings, cochleas were removed and studied histologically using a scanning electron microscope. The results revealed that cisplatin-treated animals with little or no loss of OHCs displayed levels of activity similar to those seen in saline-treated controls. In contrast, the majority (75%) of cisplatin-treated animals with severe OHC loss displayed well-developed hyperactivity in the DCN. The induced hyperactivity was seen mainly in the medial (high-frequency) half of the DCN of treated animals. This pattern was consistent with the observation that OHC loss was distributed mainly in the basal half of the cochlea. In several of the animals with severe OHC loss and hyperactivity, there was no significant damage to IHC stereocilia nor any observable irregularities of the reticular lamina that might have interfered with normal IHC function. Hyperactivity was also observed in the DCN of animals showing severe losses of OHCs accompanied by damage to IHCs, although the degree of hyperactivity in these animals was less than in animals with severe OHC loss but intact IHCs. These results support the view that loss of OHC function may be a trigger of tinnitus-related hyperactivity in the DCN and suggest that this hyperactivity may be somewhat offset by damage to IHCs.
Visual Cortex Neurons of Monkeys and Cats: Temporal Dynamics of the Contrast Response Function
Authors: Albrecht Duane G. , Geisler Wilson S. , Frazor Robert A. , Crane Alison M.
Published: December 2017

Cortical neurons display two fundamental nonlinear response characteristics: contrast-set gain control (also termed contrast normalization) and response expansion (also termed half-squaring). These nonlinearities could play an important role in forming and maintaining stimulus selectivity during natural viewing, but only if they operate well within the time frame of a single fixation. To analyze the temporal dynamics of these nonlinearities, we measured the responses of individual neurons, recorded from the primary visual cortex of monkeys and cats, as a function of the contrast of transient stationary gratings that were presented for a brief interval (200 ms). We then examined 1) the temporal response profile (i.e., the post stimulus time histogram) as a function of contrast and 2) the contrast response function throughout the course of the temporal response. We found that the shape and complexity of the temporal response profile varies considerably from cell to cell. However, within a given cell, the shape remains relatively invariant as a function of contrast and appears to be simply scaled and shifted. Stated quantitatively, approximately 95% of the variation in the temporal responses as a function of contrast could be accounted for by scaling and shifting the average poststimulus time histogram. Equivalently, we found that the overall shape of the contrast response function (measured every 2 ms) remains relatively invariant from the onset through the entire temporal response. Further, the contrast-set gain control and the response expansion are fully expressed within the first 10 ms after the onset of the response. Stated quantitatively, the same, scaled Naka-Rushton equation (with the same half-saturation contrast and expansive response exponent) provides a good fit to the contrast response function from the first 10 ms through the last 10 ms of the temporal response. Based upon these measurements, it appears as though the two nonlinear properties, contrast-set gain control and response expansion, are present in full strength, virtually instantaneously, at the onset of the response. This observation suggests that response expansion and contrast-set gain control can influence the performance of visual cortex neurons very early in a single fixation, based on the contrast within that fixation. In the discussion, we consider the implications of the results within the context of 1) slower types of contrast gain control, 2) discrimination performance, 3) drifting steady-state measurements, 4) functional models that incorporate response expansion and contrast normalization, and 5) structural models of the biochemical and biophysical neural mechanisms.
Coexistence of Functional IP3and Ryanodine Receptors in Vagal Sensory Neurons and Their Activation by ATP
Authors: Hoesch Robert E. , Yienger Katherine , Weinreich Daniel , Kao Joseph P. Y.
Published: December 2017

Intracellular photorelease of cagedd- myo-inositol 1,4,5-trisphosphate (IP3), caffeine application, and immunofluorescence confocal microscopy were used to determine thatd- myo-inositol 1,4,5-trisphosphate receptors (IP3Rs) and ryanodine receptors (RyRs) coexist in rabbit vagal sensory nodose ganglion neurons (NGNs). ATP, an extracellular physiological signaling molecule, consistently evoked robust transient increases in cytosolic free Ca2+concentration (Ca2+transients). ATP applied in Ca2+-free physiological saline elicited Ca2+transients that averaged approximately 70% of the amplitude of transients evoked in the presence of extracellular Ca2+. The component of the ATP-evoked Ca2+transient that was independent of extracellular Ca2+corresponds to Ca2+release from intracellular stores. This release component was sensitive to the pharmacological antagonists pyridoxalphosphate-6-azophenyl-2′,4′-disulphonic acid (PPADS), U73122 , neomycin, and heparin (13.5–15 kD), indicating that P2 purinoreceptors (P2Y) and the IP3signaling pathway are required for ATP-evoked Ca2+release. Additionally, a portion of ATP-evoked Ca2+release was inhibited by ryanodine, a selective blocker of RyRs. The ryanodine-insensitive component (approximately 70%) of ATP-evoked Ca2+release corresponds to IP3-induced Ca2+release via IP3Rs, while the ryanodine-sensitive component (approximately 30%) corresponds to consequent Ca2+-induced Ca2+release (CICR) via RyRs. These results indicate that functional IP3Rs and RyRs coexist in nodose neurons and that both IP3-induced Ca2+release and CICR can be activated by ATP.
Prostaglandin E2 Modulates TTX-RI Na in Rat Colonic Sensory Neurons
Authors: Gold Michael S. , Zhang Lei , Wrigley Dena L. , Traub Richard J.
Published: December 2017

This study was performed to determine the impact of the inflammatory mediator prostaglandin E2 (PGE2) on the biophysical properties of tetrodotoxin resistant voltage-gated Na+ currents (TTX-R I Na) in colonic dorsal root ganglion (DRG) neurons. TTX-R I Na was studied in DRG neurons from thoracolumbar (TL: T13–L2) and lumbosacral (LS: L6–S2) DRG retrogradely labeled following the injection of DiIC18 (DiI) into the wall of the descending colon of adult male rats. TTX-R I Na in colonic DRG neurons had a high threshold for activation [ V 0.5 of conductance-voltage ( G-V) curve = −3.1 ± 1.0 (SE) mV] and steady-state availability ( V 0.5 for H-infinity curve = −18.4 ± 1.4 mV), was slowly inactivating (10.6 ± 1.4 ms at 0 mV), and recovered rapidly from inactivation (83.5 ± 5.0% of the current recovered with a time constant of 1.3 ± 0.1 ms at −80 mV). TTX-R I Na was present in every colonic DRG neuron studied ( n = 62). PGE2induced a rapid (<15 s) increase in TTX-R I Na that was associated with a hyperpolarizing shift in the G-V curve (3.4 ± 0.7 mV), an increase in the rate of inactivation (4.21 ± 0.7 ms at 0 mV), and no change in steady-state availability. There was no statistically significant difference ( P > 0.05) between TL and LS colonic DRG neurons with respect to the biophysical properties of TTX-R I Na, the current density or the magnitude of PGE2-induced changes in the current. However, both the proportion of TL and LS neurons in which TTX-R I Na was modulated by PGE2 (16 of 16 TL neurons and 12 of 14 LS neurons) as well as the magnitude of PGE2-induced changes in the current were significantly larger in colonic DRG neurons than in the total population of DRG neurons. These results suggest that changes in nociceptive processing associated with inflammation of the colon does not reflect differences between TL and LS neurons with respect to the properties of TTX-R INa, distribution of current, or magnitude of inflammatory mediator-induced changes in the current. However, these results do suggest modulation of TTX-R I Na in colonic afferents is an underlying mechanism of hyperalgesia and pain associated with inflammation of the colon and that this current constitutes a novel target for therapeutic relief of visceral inflammatory pain.
Long-Range Synchronization of γ and β Oscillations and the Plasticity of Excitatory and Inhibitory Synapses: A Network Model
Authors: Bibbig Andrea , Traub Roger D. , Whittington Miles A.
Published: December 2017

The ability of oscillating networks to synchronize despite significant separation in space, and thus time, is of biological significance, given that human γ activity can synchronize over distances of several millimeters to centimeters during perceptual and learning tasks. We use computer simulations of networks consisting of excitatory pyramidal cells (e-cells) and inhibitory interneurons (i-cells), modeling two tonically driven assemblies separated by large (≥8 ms) conduction delays. The results are as follows. 1) Two assemblies separated by large conduction delays can fire synchronously at β frequency (with i-cells firing at γ frequency) under two timing conditions: e-cells of (say) assembly 2 are still inhibited “delay + spike generation milliseconds” after the e-cell beat of assembly 1; this means that the e-cell inhibitory postsynaptic potential (IPSP) cannot be significantly shorter than the delay (2-site effect). This implies for a given decay time constant that the interneuron → pyramidal cell conductances must be large enough. The e-cell IPSP must last longer than the i-cell IPSP, i.e., the interneuron → pyramidal cell conductance must be sufficiently large and the interneuron → interneuron conductance sufficiently small (local effect). 2) We define a “ long-interval doublet” as a pair of interneuron action potentials—separated by approximately “delay milliseconds”—in which a) the first spike is induced by tonic inputs and/or excitation from nearby e-cells, while b) the second spike is induced by (delayed) excitation from distant e-cells. “Long-interval population doublets” (long-interval doublets of the i-cell population) are necessary for synchronized firing in our networks. Failure to produce them leads to almost anti-phase activity at γ frequency. 3) An (almost) anti-phase oscillation is the most stable oscillation pattern of two assemblies that are separated by axonal conduction delays of approximately one-half a γ period (delays from 8 to 17 ms in our simulations) and that are firing at γ frequency. 4) Two assemblies separated by large conduction delays can synchronize their activity with the help of interneuron plasticity. They can also synchronize without pyramidal cell → pyramidal cell connections being present. The presence of pyramidal cell → pyramidal cell connections allows, however, for synchronization if other parameters are at inappropriate values for synchronization to occur. 5) Synchronization of two assemblies separated by large conduction delays with the help of interneuron plasticity is not simply due to slowing down of the oscillation frequency. It is reached with the help of a “ synchronizing-weak-beat,” which induces sudden changes in the oscillation period length of the two assemblies.
Is the Functional Connectivity Within Temporal Lobe Influenced By Saccadic Eye Movements?
Authors: Sobotka Stanislaw , Zuo Wei , Ringo James L.
Published: December 2017

Local evoked potentials (LEPs), recorded in response to electrical stimulation, were used to study functional connectivity between different sites of the temporal lobe. Permanent electrodes were implanted in anterior and posterior positions of both inferotemporal cortex (IT) and hippocampal formation (HF). In each experimental session, one of these four sites was stimulated and LEPs were recorded in the others. Clear LEPs were found in the anterior and posterior IT sites in response to stimulation of the anterior as well as posterior HF. Bidirectional connections (as judged by the potentials) were found between the anterior and posterior sites of the same structure (IT or HF). The timing of the LEPs indicates that much of the response was carried in multisynaptic circuits. Stimulation delivered just after the monkey made a saccade produced larger late components in the LEPs than the same stimulation delivered without a saccade. The influence was maximal when the delay between the end of the saccade and the electrical stimulation was in the range of 50–100 ms. This saccadic modulation of the functional connectivity was observed within IT (bidirectional) and between posterior HF and IT (unidirectional).
Cellular Mechanisms of Nociception in the Frog
Authors: Kuffler D. P. , Lyfenko A. , Vyklický L. , Vlachová V.
Published: December 2017

Cellular mechanisms underlying defense reactions induced by noxious heat and acids were studied in frogs ( Rana pipiens) by measuring whole cell membrane currents in cultured dorsal root ganglion (DRG) neurons. Seventy-eight of 82 DRG neurons exposed to 3-s ramps of increasing temperature to 48°C exhibited an inward current ( I HEAT) of 490 ± 70 pA at −70 mV. I HEAT exhibited reversal at ∼10 mV with a pronounced outward rectification, suggesting opening of nonselective cation channels. In frogs, in contrast to mammals, I HEAT was not influenced by capsaicin (5 μM), capsazepine (10 μM), or ruthenium red (10 μM). In a large proportion (∼80%) of heat-sensitive DRG neurons, acids produced a large slowly inactivating sodium carried current ( I ACID) with average pH50 5.7. I ACIDwas blocked by 1 mM amiloride (to 22%) and was absent if extracellular Na+ was substituted by Cs+. Elevating temperature to 38°C increased I ACID, whereas temperatures >40°C profoundly inhibited it (by 82 ± 2%; n = 42). The inhibition was long-lasting (>30 s) but fully reversible. Phorbol ester myristate acetate (PMA, 1 μM) and forskolin (1 μM) inhibited I ACID to 37 ± 5% ( n = 5) and 78 ± 8% ( n = 4), respectively. It is suggested that I HEAT in frog DRG neurons is carried through capsaicin-insensitive nonselective cation channels distinct from vanilloid receptor in mammals, whereas I ACID is carried through amiloride-sensitive sodium channels that are strongly inhibited by noxious heat, possibly due to activation of the intracellular messenger systems.
Spectral Determination of Responses to Species-Specific Calls in the Dorsal Nucleus of the Lateral Lemniscus
Authors: Bauer Eric E. , Klug Achim , Pollak George D.
Published: December 2017

This study evaluated how neurons in the dorsal nucleus of the lateral lemniscus (DNLL) in Mexican free-tailed bats respond to both tone bursts and species-specific calls. Up to 20 calls were presented to each neuron, of which 18 were social communication and 2 were echolocation calls. We also measured excitatory response regions (ERRs): the range of tone burst frequencies that evoked discharges at a fixed intensity. Neurons were unselective for one or another call in that each neuron responded to any call so long as the call had energy that encroached on its ERR. Additionally, responses were evoked by the same set of calls, and with similar spike counts, when they were presented normally or reversed. By convolving activity in the ERRs with the spectrogram of each call, we showed that responses to tones accurately predicted discharge patterns evoked by species-specific calls. DNLL cells are remarkably homogeneous in that neurons having similar BFs responded to each of the species-specific calls with similar response profiles. The homogeneity was further illustrated by the ability to accurately predict the response profiles of a particular DNLL cell to species-specific calls from the ERR of another similarly tuned DNLL cell. Thus DNLL neurons tuned to the same or similar frequencies responded to species-specific calls with latencies and temporal discharge patterns that were so similar as to be virtually interchangeable. What this suggests is that DNLL responses evoked by complex sounds can be largely explained by a simple summation of the excitation in each neuron's ERR. Finally, superimposing the spectrograms of each call on the responses evoked by that call revealed that the DNLL population response re-creates both the spectral and the temporal features of each signal.
Inter-Bouton Variability of Synaptic Strength Correlates With Heterogeneity of Presynaptic Ca2+ Signals
Authors: Kirischuk Sergei , Grantyn Rosemarie
Published: December 2017

The elevation of presynaptic calcium concentration is a crucial step in excitation-secretion coupling. However, the amplitudes of action-potential-induced presynaptic calcium transients can display high variability among different terminals. The aim of this study was to clarify whether, at individual boutons, synaptic strength correlates with the average amplitude of presynaptic calcium transients. Low-density collicular cultures were loaded with the calcium indicator Oregon Green bis-( o-aminophenoxy)- N,N,N′,N′-tetraacetic acid (BAPTA) 1. Action potentials were blocked with tetrodotoxin. Presynaptic terminals were identified with FM4–64, a use-dependent vesicle marker. Presynaptic calcium influx was elicited by a focal electrical stimulation of single boutons. Whole cell patch-clamp and calcium imaging techniques were used to record GABAergic evoked inhibitory postsynaptic currents (eIPSCs) and presynaptic fluorescence changes in the stimulated terminal. To make the eIPSCs from different boutons comparable, they were normalized to the mean value of miniature IPSCs (mIPSCs) of the postsynaptic cell. Records from 47 boutons showed that eIPSCs varied between 0.5 and 3.0 and presynaptic calcium transients varied between 0.1 and 1.3. However, there was a strong correlation between the mean amplitudes of eIPSCs and presynaptic calcium responses. The eIPSC-[Ca2+]prerelationship allows to use the amplitudes of presynaptic calcium transients as an indicator of release efficacy and, in a set of contacts made by one axon, to predict the relative impact of individual terminals.
Impact on the Quality of Erections after Completing a Low-Intensity Extracorporeal Shock Wave Treatment Cycle on a Group of 710 Patients
Authors: Ayala Héctor A. Corredor , Cuartas José Pablo Saffon , Cleves Diana Cerquera
Published: December 2017

Objective. The aim of this study is to evaluate the response to low-intensity extracorporeal shock wave therapy in a group of patients with organic vascular erectile dysfunction. Materials and Methods. This is an observational retrospective study. The researchers reviewed 710 patients with a clinical diagnosis of organic vascular erectile dysfunction (ED) of more than 3-month duration from male sexual health clinics of the Boston Medical Group from 12 cities in Spain and 4 in Mexico. Patients received 5 outpatient shock wave therapy sessions. They were evaluated with the erection hardness score (EHS) before the first session (n = 710), at the end of the last session (n = 710), and one month after the last session (n = 412). Results. In the first examination, the EHS improved in 43.1% (306/710) of subjects compared to the baseline measurement and ability to penetrate increased from 26.8% to 44% (p<0.0001). In the second examination, the ability to penetrate was 37.9%, lower than in the first (p=0.042) but higher than the baseline (p=0.0001). Conclusions. The results suggest that the shock wave therapy with or without concomitant treatments improved the quality of erections in patients with erectile dysfunction treated in specialised male sexual health clinics. This trial is registered with NCT03237143.
Structural Failure of a Modern Knee Tumor Megaendoprosthesis
Authors: Koch Katrin , Kohn Dieter , Anagnostakos Konstantinos
Published: December 2017

Modular knee megaendoprotheses are commonly used devices for distal femur or proximal tibia replacement in tumor surgery as well as for treatment of some periprosthetic fractures around a loose or failed total knee arthroplasty. Structural failures of the prosthesis are well-known postoperative complications and have been reported for various prosthesis types. In the majority of the cases, the polyethylene parts fail. We would like to present an unusual case of a broken femoral component of an MRH® endoprosthesis four years after implantation.
On the Resistance-Harary Index of Graphs Given Cut Edges
Authors: Wang Hongzhuan , Hua Hongbo , Zhang Libing , Wen Shu
Published: December 2017

Graphs are often used to describe the structure of compounds and drugs. Each vertex in the graph represents the molecule and each edge represents the bond between the atoms. The resistance distance between any two vertices is equal to the resistance between the two points of an electrical network. The Resistance-Harary index is defined as the sum of reciprocals of resistance distances between all pairs of vertices. In this paper, the extremal graphs with maximum Resistance-Harary index are determined in connected graphs with given vertices and cut edges.
NADPH Oxidase Deficiency: A Multisystem Approach
Authors: Giardino Giuliana , Cicalese Maria Pia , Delmonte Ottavia , Migliavacca Maddalena , Palterer Boaz , Loffredo Lorenzo , Cirillo Emilia , Gallo Vera , Violi Francesco , Pignata Claudio
Published: December 2017

The immune system is a complex system able to recognize a wide variety of host agents, through different biological processes. For example, controlled changes in the redox state are able to start different pathways in immune cells and are involved in the killing of microbes. The generation and release of ROS in the form of an “oxidative burst” represent the pivotal mechanism by which phagocytic cells are able to destroy pathogens. On the other hand, impaired oxidative balance is also implicated in the pathogenesis of inflammatory complications, which may affect the function of many body systems. NADPH oxidase (NOX) plays a pivotal role in the production of ROS, and the defect of its different subunits leads to the development of chronic granulomatous disease (CGD). The defect of the different NOX subunits in CGD affects different organs. In this context, this review will be focused on the description of the effect of NOX2 deficiency in different body systems. Moreover, we will also focus our attention on the novel insight in the pathogenesis of immunodeficiency and inflammation‐related manifestations and on the protective role of NOX2 deficiency against the development of atherosclerosis.
A Network Diffusion Model of Food Safety Scare Behavior considering Information Transparency
Authors: Chen Tingqiang , Wang Lei , Wang Jining , Yang Qi
Published: December 2017

This study constructs the network diffusion model of food safety scare behavior under the effect of information transparency and examines the network topology and evolution characteristics of food safety scare behavior in a numerical simulation. The main conclusions of this study are as follows. (1) Under the effect of information transparency, the network degree distribution of food safety scare behavior diffusion demonstrates the decreasing characteristics of diminishing margins. (2) Food safety scare behavior diffusion increases with the information dissemination rate and consumer concern about food safety incidents and shows the characteristics of monotone increasing. And with the increasing of the government food safety supervision information transparency and media food safety supervision information transparency, the whole is declining characteristic of diminishing marginal. In addition, the extinction of food safety scare behavior cannot be achieved gradually given a single regulation of government food safety supervision information transparency and media food safety supervision information transparency. (3) The interaction effects between improving government food safety supervision information transparency or media food safety supervision information transparency and declining consumer concerns about food safety incidents or information transmission rate can engender the suppression of food safety scare behavior diffusion.
Seasonal Microbial Conditions of Locally Made Yoghurt (Shalom) Marketed in Some Regions of Cameroon
Authors: Moh Lamye Glory , Keilah Lunga Paul , Etienne Pamo Tedonkeng , Jules-Roger Kuiate
Published: December 2017

The microbial conditions of locally made yoghurt (shalom) marketed in three areas of Cameroon were evaluated during the dry and rainy seasons alongside three commercial brands. A total of ninety-six samples were collected and the microbial conditions were based on total aerobic bacteria (TEB), coliforms, yeasts, and moulds counts as well as the identification of coliforms and yeasts using identification kits. Generally, there was a significant increase (p≤0.05) in total aerobic and coliform counts (especially samples from Bamenda), but a decrease in yeast and mould counts of the same samples during the rainy season when compared to those obtained during the dry season. These counts were mostly greater than the recommended standards. Twenty-one Enterobacteriaceae species belonging to 15 genera were identified from 72 bacterial isolates previously considered as all coliforms.Pantoeasp. (27.77%) was highly represented, found in 41% (dry season) and 50% (rainy season) of samples. In addition, sixteen yeast species belonging to 8 genera were equally identified from 55 yeast isolates andCandidasp. (76.36%) was the most represented. This result suggests that unhygienic practices during production, ignorance, warmer weather, duration of selling, and inadequate refrigeration are the principal causes of higher levels of contamination and unsafe yoghurts.
Comparison of Host Gene Expression Profiles in Spleen Tissues of Genetically Susceptible and Resistant Mice during ECTV Infection
Authors: Cheng Wen-Yu , Jia Huai-Jie , He Xiao-Bing , Chen Guo-Hua , Feng Yuan , Wang Chun-Yan , Wang Xiao-Xia , Jing Zhi-Zhong
Published: December 2017

Ectromelia virus (ECTV), the causative agent of mousepox, has emerged as a valuable model for investigating the host-Orthopoxvirusrelationship as it relates to pathogenesis and the immune response. ECTV is a mouse-specific virus and causes high mortality in susceptible mice strains, including BALB/c and C3H, whereas C57BL/6 and 129 strains are resistant to the disease. To understand the host genetic factors in different mouse strains during the ECTV infection, we carried out a microarray analysis of spleen tissues derived from BALB/c and C57BL/6 mice, respectively, at 3 and 10 days after ECTV infection. Differential Expression of Genes (DEGs) analyses revealed distinct differences in the gene profiles of susceptible and resistant mice. The susceptible BALB/c mice generated more DEGs than the resistant C57BL/6 mice. Additionally, gene ontology and KEGG pathway analysis showed the DEGs of susceptible mice were involved in innate immunity, apoptosis, metabolism, and cancer-related pathways, while the DEGs of resistant mice were largely involved in MAPK signaling and leukocyte transendothelial migration. Furthermore, the BALB/c mice showed a strong induction of interferon-induced genes, which, however, were weaker in the C57BL/6 mice. Collectively, the differential transcriptome profiles of susceptible and resistant mouse strains with ECTV infection will be crucial for further uncovering the molecular mechanisms of the host-Orthopoxvirusinteraction.
Pre- and Postintervention Factor Structure of Functional Independence Measure in Patients with Spinal Cord Injury
Authors: Saltychev Mikhail , Lähdesmäki Janne , Jokinen Petteri , Laimi Katri
Published: December 2017

Objective. To evaluate the factor structure of Functional Independence Measure (FIM®) scale amongst people with spinal cord injury (SCI). Methods. This was a retrospective, register-based cohort study on 155 rehabilitants with SCI. FIM was assessed at the beginning and at the end of multidisciplinary inpatient rehabilitation. The internal consistency of the FIM was assessed with Cronbach’s alpha and exploratory factor analysis was employed to approximate the construct structure of FIM. Results. The internal consistency demonstrated high Cronbach’s alpha of 0.95 to 0.96. For both pre- and postintervention assessments, the exploratory factor analysis resulted in 3-factor structures. Except for two items (“walking or using a wheelchair” and “expression”), the structures of the identified three factors remained the same from the beginning to the end of rehabilitation. The loadings of all items were sufficient, exceeding 0.3. Both pre- and postintervention chi-square tests showed significant p values < 0.0001. The “motor” domain was divided into two factors with this 2-factor structure enduring through the intervention period. Conclusions. Amongst rehabilitants with SCI, FIM failed to demonstrate unidimensionality. Instead, it showed a 3-factor structure that fluctuated only little depending on the timing of measurement. Additionally, when measured separately, also motor score was 2-dimensional, not 1-dimensional. Using a total or subscale FIM, scores seem to be unjustified in the studied population.
A Carotenoid Extract from a Southern Italian Cultivar of Pumpkin Triggers Nonprotective Autophagy in Malignant Cells
Authors: Russo Maria , Moccia Stefania , Bilotto Stefania , Spagnuolo Carmela , Durante Miriana , Lenucci Marcello Salvatore , Mita Giovanni , Volpe Maria Grazia , Aquino Rita Patrizia , Russo Gian Luigi
Published: December 2017

Carotenoids, including β‐carotene, lycopene, and derivatives, such as retinoic acid, have been studied for their significant antiproliferative and differentiating activity on cancer cells in experimental models and in clinics. We are presenting here data on the mechanism of action of a carotenoid‐enriched extract obtained from the pumpkin Cucurbita moschata, variety “long of Naples,” on two malignant human cell lines, Caco‐2 and SAOs, derived from a colon adenocarcinoma and an osteosarcoma, respectively. The carotenoid extract has been obtained from pumpkin pulp and seeds by supercritical CO2 extraction and employed to prepare oil‐in‐water nanoemulsions. The nanoemulsions, applied at a final carotenoid concentration of 200–400 μg/ml, were not cytotoxic, but induced a delay in cell growth of about 40% in both SAOs and Caco‐2 cell lines. This effect was associated with the activation of a “nonprotective” form of autophagy and, in SAOs cells, to the induction of cell differentiation via a mechanism that involved AMPK activation. Our data suggest the presence of a pool of bioactive compounds in the carotenoid‐enriched extract, acting additively, or synergistically, to delay cell growth in cancer cells.