bluuebunny/crossref_metadata_2025 huggingface dataset:
EVALUATION OF THE LOOPING FORMATION AND PAIN DURING INSERTION INTO THE CECUM IN COLONOSCOPY
Authors: Sato Koichiro , Fujinuma Sumio , Sakai Yoshihiro
Published: May 2006

Introduction:  One of the causes of pain during insertion of the colonoscope is stretching of the mesenterium by loop formation. The degree of pain differs according to the type of loop formation. Our aims were to study the accuracy of the colonoscopist’s assessment of the presence and type of loop formation and to study the degree of pain in relation to the type of loop by administering the visual analog scale (VAS).

Methods:  Two hundred and fifty‐seven consecutive patients were enrolled. All procedures were performed by two experienced colonoscopists who were blind to magnetic endoscope imaging view. After the colonoscopy, the colonoscopist was asked to assess the presence and type of loop formation. The degree of pain was assessed using the VAS.

Results:  The accuracy of estimating N loop, alpha loop, absence of loop formation and U loop was each over 70%. The accuracy of estimating gamma and splenic loop was significantly lower than the accuracy of estimating U loop. Colonoscopy was significantly more painful in women than in men. The degree of pain was significantly higher upon formation of reverse alpha loop and gamma and splenic loop than upon formation of N loop and U loop.

Conclusions:  Upon formation of reverse alpha loop or gamma and splenic loop, patients experienced more pain and it was difficult for the endoscopists to assess these loops. As women had severe pain compared with men, the use of a pediatric colonoscope or higher dosage of sedation in women should be considered.
The importance of growth and mortality costs in the evolution of the optimal life history
Authors: Roff D. A. , Heibo E. , Vøllestad L. A.
Published: May 2006

A central assumption of life history theory is that the evolution of the component traits is determined in part by trade-offs between these traits. Whereas the existence of such trade-offs has been well demonstrated, the relative importance of these remains unclear. In this paper we use optimality theory to test the hypothesis that the trade-off between present and future fecundity induced by the costs of continued growth is a sufficient explanation for the optimal age at first reproduction, α, and the optimal allocation to reproduction, G, in 38 populations of perch and Arctic char. This hypothesis is rejected for both traits and we conclude that this trade-off, by itself, is an insufficient explanation for the observed values of α and G. Similarly, a fitness function that assumes a mortality cost to reproduction but no growth cost cannot account for the observed values of α. In contrast, under the assumption that fitness is maximized, the observed life histories can be accounted for by the joint action of trade-offs between growth and reproductive allocation and between mortality and reproductive allocation (Individual Juvenile Mortality model). Although the ability of the growth/mortality model to fit the data does not prove that this is the mechanism driving the evolution of the optimal age at first reproduction and allocation to reproduction, the fit does demonstrate that the hypothesis is consistent with the data and hence cannot at this time be rejected. We also examine two simpler versions of this model, one in which adult mortality is a constant proportion of juvenile mortality [Proportional Juvenile Mortality (PJM) model] and one in which the proportionality is constant within but not necessarily between species [Specific Juvenile Mortality (SSJM) model]. We find that the PJM model is unacceptable but that the SSJM model produces fits suggesting that, within the two species studied, juvenile mortality is proportional to adult mortality but the value differs between the two species.
Lower occurrence of idiopathic pulmonary fibrosis in Maori and Pacific Islanders
Authors: YOUNG Lisa M. , HOPKINS Raewyn , WILSHER Margaret L.
Published: May 2006

Objective:  Idiopathic pulmonary fibrosis (IPF), a chronic fibro‐proliferative interstitial pneumonia, has not been reported to occur more frequently in any particular race. We have observed that our patients with IPF comprise a proportionately lower number of Maori and Pacific Islanders and set out to evaluate this further.

Methods:  Retrospective analysis of an IPF database from a single tertiary respiratory institution was undertaken. Demographic and survival data were collected. Ethnicity was compared with 2001 New Zealand census data from the same catchment area.

Results:  Eighty‐seven cases of IPF were identified. Overall median survival was 46 months. Ethnicity data were available for 84 of the 87 cases. 76/84 (90%) were European, 6/84 (7%) were Asian or Indian, 2/84 (2%) were Maori, and 0/84 (0%) were Pacific Islanders. For Maori and Pacific Islanders, this represented a significant trend in difference when compared with ethnicity data from the hospital catchment population (P < 0.001).

Conclusions:  Our department is the tertiary referral centre for pulmonary disease in the upper North Island of New Zealand, and therefore referral centre bias is likely to be low. The preliminary observation that the occurrence of IPF is lower in those of Maori or Polynesian ethnicity warrants further study. This may, in part, help in our understanding of the pathogenic mechanisms in IPF.
Probabilistic Risk Assessment of Wastes Buried in the Ground
Authors: Cohen Bernard L.
Published: May 2006

The differences between probabilistic risk assessment (PRA) and safety analysis (SA) are discussed, and it is shown that PRA is more suitable than SA for determining the acceptability of a technology. Since a PRA by the fault tree‐event tree analysis method used for reactor safety studies does not seem to be practical for buried waste, an alternative approach is suggested using geochemical analogs. This method is illustrated for the cases of high‐level and low‐level radioactive waste and for chemical carcinogens released in coal burning.
Dopamine Modulation of Calcium Currents in Pyloric Neurons of the Lobster Stomatogastric Ganglion
Authors: Johnson Bruce R. , Kloppenburg Peter , Harris-Warrick Ronald M.
Published: May 2006

We examined the dopamine (DA) modulation of calcium currents (ICa) that could contribute to the plasticity of the pyloric network in the lobster stomatogastric ganglion. Pyloric somata were voltage-clamped under conditions designed to block voltage-gated Na+, K+, and H currents. Depolarizing steps from –60 mV generated voltage-dependent, inward currents that appeared to originate in electrotonically distal, imperfectly clamped regions of the cell. These currents were blocked by Cd2+ and enhanced by Ba2+ but unaffected by Ni2+. Dopamine enhanced the peak ICa in the pyloric constrictor (PY), lateral pyloric (LP), and inferior cardiac (IC) neurons and reduced peak ICa in the ventricular dilator (VD), pyloric dilator (PD), and anterior burster (AB) neurons. All of these effects, except for the AB, are consistent with DA's excitation or inhibition of firing in the pyloric neurons. Enhancement of ICa in PY and LP neurons and reduction of ICa in VD and PD neurons are also consistent with DA-induced synaptic strength changes via modulation of presynaptic ICa. However, the reduction of ICa in AB suggests that DA's enhancement of AB transmitter release is not directly mediated through presynaptic ICa. ICa in PY and PD neurons was more sensitive to nifedipine block than in AB neurons. In addition, nifedipine blocked DA's effects on ICa in the PY and PD neurons but not in the AB neuron. Thus the contribution of specific calcium channel subtypes carrying the total ICa may vary between pyloric neuron classes, and DA may act on different calcium channel subtypes in the different pyloric neurons.
Amplitude and Frequency Dependence of Spike Timing: Implications for Dynamic Regulation
Authors: Hunter John D. , Milton John G.
Published: May 2006

The spike-time reliability of motoneurons in the Aplysia buccal motor ganglion was studied as a function of the frequency content and the relative amplitude of the fluctuations in the neuronal input, calculated as the coefficient of variation (CV). Measurements of spike-time reliability to sinusoidal and aperiodic inputs, as well as simulations of a noisy leaky integrate-and-fire neuron stimulated by spike trains drawn from a periodically modulated process, demonstrate that there are three qualitatively different CV-dependent mechanisms that determine reliability: noise-dominated (CV < 0.05 for Aplysia motoneurons) where spike timing is unreliable regardless of frequency content; resonance-dominated (CV ≈ 0.05–0.25) where reliability is reduced by removal of input frequencies equal to motoneuron firing rate; and amplitude-dominated (CV >0.35) where reliability depends on input frequencies greater than motoneuron firing rate. In the resonance-dominated regime, changes in the activity of the presynaptic inhibitory interneuron B4/5 alter motoneuron spike-time reliability. The increases or decreases in reliability occur coincident with small changes in motoneuron spiking rate due to changes in interneuron activity. Injection of a hyperpolarizing current into the motoneuron reproduces the interneuron-induced changes in reliability. The rate-dependent changes in reliability can be understood from the phase-locking properties of regularly spiking motoneurons to periodic inputs. Our observations demonstrate that the ability of a neuron to support a spike-time code can be actively controlled by varying the properties of the neuron and its input.
Postnatal Development of Cochlear Function in the Mustached Bat,Pteronotus parnellii
Authors: Kössl M. , Foeller E. , Drexl M. , Vater M. , Mora E. , Coro F. , Russell I. J.
Published: May 2006

Postnatal development of the mustached bat's cochlea was studied by measuring cochlear microphonic and compound action potentials. In adults, a cochlear resonance is involved in enhanced tuning to the second harmonic constant frequency component (CF2) of their echolocation calls at ∼61 kHz This resonance is present immediately after birth in bats that do not yet echolocate. Its frequency is lower (46 kHz) and the corresponding threshold minimum of cochlear microphonic potentials is broader than in adults. Long-lasting ringing of the cochlear microphonic potential after tone stimulus offset that characterizes the adult auditory response close to CF2 is absent in newborns. In the course of the first 5 postnatal weeks, there is a concomitant upward shift of CF2 and the frequency of cochlear threshold minima. Up to the end of the third postnatal week, sensitivity of auditory threshold minima and the Q value of the cochlear resonance increase at a fast rate. Between 2 and 4 wk of age, two cochlear microphonic threshold minima are found consistently in the CF2 range that differ in their level-dependent dynamic growth behavior and are 1.5–5.7 kHz apart from each other. In older animals, there is a single minimum that approaches adult tuning in its sharpness. The data provide evidence to show that during maturation of the cochlea, the frequency and the sensitivity of the threshold minimum associated with CF2 increases and that these increases are associated with the fusion of two resonances that are partly dissociated in developing animals.
Calcium Sensitivity of a Sodium-Activated Nonselective Cation Channel in Lobster Olfactory Receptor Neurons
Authors: Bobkov Yuriy V. , Ache Barry W.
Published: May 2006

We report that a Na+-activated nonselective cation channel described previously in lobster olfactory neurons, in which phosphoinositide signaling mediates olfactory transduction, can also be activated by Ca2+. Ca2+activates the channel in the presence of Na+, increasing the open probability of the channel with a K1/2of 490 nM and a Hill coefficient of 1.3. Ca2+also increases the sensitivity of the channel to Na+. In some cells, the same channel is Ca2+insensitive in a cell-specific manner. The nonspecific activator of protein phosphatases, protamine, applied to the intracellular face of patches containing the channel irreversibly eliminates the sensitivity to Ca2+. This effect can be blocked by okadaic acid, a nonspecific blocker of protein phosphatases, and restored by the catalytic subunit of protein kinase A in the presence of MgATP. The Ca2+-sensitive form of the channel is predominantly expressed in the transduction zone of the cells in situ. These findings imply that the Ca2+sensitivity of the channel, and possibly its regulation by phosphorylation, play a role in olfactory transduction and help tie activation of the channel to the canonical phosphoinositide turnover pathway.
A Minimal Model for G Protein–Mediated Synaptic Facilitation and Depression
Authors: Bertram Richard , Swanson Jessica , Yousef Mohammad , Feng Zhong-Ping , Zamponi Gerald W.
Published: May 2006

G protein–coupled receptors are ubiquitous in neurons, as well as other cell types. Activation of receptors by hormones or neurotransmitters splits the G protein heterotrimer into Gα and Gβγ subunits. It is now clear that Gβγ directly inhibits Ca2+channels, putting them into a reluctant state. The effects of Gβγ depend on the specific β and γ subunits present, as well as the β subunit isoform of the N-type Ca2+channel. We describe a minimal mathematical model for the effects of G protein action on the dynamics of synaptic transmission. The model is calibrated by data obtained by transfecting G protein and Ca2+channel subunits into tsA-201 cells. We demonstrate with numerical simulations that G protein action can provide a mechanism for either short-term synaptic facilitation or depression, depending on the manner in which G protein–coupled receptors are activated. The G protein action performs high-pass filtering of the presynaptic signal, with a filter cutoff that depends on the combination of G protein and Ca2+channel subunits present. At stimulus frequencies above the cutoff, trains of single spikes are transmitted, while only doublets are transmitted at frequencies below the cutoff. Finally, we demonstrate that relief of G protein inhibition can contribute to paired-pulse facilitation.
Dissociation of Spatial-, Object-, and Sound-Coding Neurons in the Mediodorsal Nucleus of the Primate Thalamus
Authors: Tanibuchi Ikuo , Goldman-Rakic Patricia S.
Published: May 2006

The mediodorsal nucleus (MD) is the thalamic gateway to the prefrontal cortex, an area of the brain associated with spatial and object working memory functions. We have recorded single-neuron activities from the MD nucleus in monkeys trained to perform spatial tasks with peripheral visual stimuli and a nonspatial task with foveally presented pictures of objects and faces—tasks identical to those we have previously used to map regional specializations in the dorso- and ventro-lateral prefrontal cortex, respectively. We found that MD neurons exhibited categorical specificity—either responding selectively to locations in the spatial tasks or preferentially to specific representations of faces and objects in the nonspatial task. Spatially tuned neurons were located in parts of the MD connected with the dorsolateral prefrontal cortex while neurons responding to the identity of stimuli mainly occupied more ventral positions in the nucleus that has its connections with the inferior prefrontal convexity. Neuronal responses to auditory stimuli were also examined, and vocalization sensitive neurons were found in more posterior portions of the MD. We conclude that MD neurons are dissociable by their spatial and nonspatial coding properties in line with their cortical connections and that the principle of information segregation in cortico-cortical pathways extends to the “association” nuclei of the thalamus.
Differential Gurmarin Suppression of Sweet Taste Responses in Rat Solitary Nucleus Neurons
Authors: Lemon Christian H. , Imoto Toshiaki , Smith David V.
Published: May 2006

We examined the effect of the sweet transduction blocker gurmarin on taste responses recorded from neurons in the rat solitary nucleus (NST) to determine how gurmarin sensitivity is distributed across neuronal type. Initially, responses evoked by washing the anterior tongue and palate with 0.5 M sucrose, 0.1 M NaCl, 0.01 M HCl, and 0.01 M quinine-HCl were recorded from 35 neurons. For some cells, responses to a sucrose concentration series (0.01–1.0 M) or an array of sweet-tasting compounds were also measured. Gurmarin (10 μg/ml, 2–4 ml) was then applied to the tongue and palate. Stimuli were reapplied after 10–15 min. Neurons were segregated into groups based on similarities among their initial response profiles using hierarchical cluster analysis (HCA). Results indicated that sucrose responses recorded from neurons representative of each HCA-defined class were suppressed by gurmarin. However, a disproportionate percentage of cells in each group displayed sucrose responses that were substantially attenuated after gurmarin treatment. Postgurmarin sucrose responses recorded from neurons that composed 57% of class S, 40% of class N, and 33% of class H were suppressed by ≥50% relative to control. On average, attenuation was statistically significant only in class S and N neurons. Although the magnitude of gurmarin-induced response suppression did not differ across sucrose concentration, responses to different sweet-tasting compounds were differentially affected. Responses to NaCl, HCl, or quinine were not suppressed by gurmarin. Results suggest that information from gurmarin-sensitive and -insensitive receptor processes converges onto single NST neurons.
Relationship Between Membrane Potential Oscillations and Rhythmic Discharges in Identified Hippocampal Theta-Related Cells
Authors: Bland Brian H. , Konopacki Jan , Dyck Richard H.
Published: May 2006

Intracellular recordings of cells, classified according to the criteria of Colom and Bland as phasic theta-on or phasic theta-off cells, were carried out in the dorsal region of the hippocampal formation in urethan-anesthetized rats. Cells were studied during two spontaneously occurring hippocampal field conditions, asynchrony, termed large-amplitude irregular activity, and synchrony, termed theta. During the spontaneous cycling between these two field states, the effect of four levels of intracellular depolarizing and hyperpolarizing constant current injections on the amplitude and phase of membrane potential oscillations (MPOs) and the rate and pattern of cell discharges was assessed. Labeled CA1 pyramidal cells and bistratified cells met the criteria for classification as phasic theta-on cells and labeled CA1 pyramidal layer basket cells, mossy hilar cells, and granule cells met the criteria for classification as phasic theta-off cells. MPOs were recorded in CA1 pyramidal cells, CA1 layer basket cells, mossy interneurons, and granule cells only during theta field activity, their onset in theta-on cells signaled by a depolarizing shift of 5–10 mV and in theta-off cells by a hyperpolarizing shift of 5–10 mV, in membrane potential. The effect of current injections in phasic theta-on and theta-off cells during the theta field condition revealed that MPO amplitude was voltage dependent and frequency was voltage independent. There were no phase changes observed in phasic theta-on cells during current injections; however, amplitude analysis revealed an inverted U-shaped curve asymmetrically distributed around the average value of the membrane potential occurring during the spontaneous theta (no current) control condition. The occurrence and rate of rhythmical cell discharges in CA1 pyramidal phasic theta-on cells during the theta condition was precisely controlled within a critical range of membrane potential values from approximately −57 to −68 mV, corresponding to a range of MPO amplitudes of ∼4–7 mV. Outside the critical range, rhythmic cell discharges were abolished. Membrane potential oscillations in CA1 pyramidal layer basket cells underwent an approximate 180° phase reversal when the membrane potential was depolarized above −65 mV. The occurrence and rate of rhythmic cell discharges in CA1 pyramidal layer basket cell phasic theta-off cells during the theta condition was precisely controlled within a critical range of membrane potential values from approximately −62 to −60 mV, corresponding to a range of MPO amplitudes of ∼7–7.5 mV. Outside the critical range, cell discharges were absent or occurred singly.
Cortex Controls Multisensory Depression in Superior Colliculus
Authors: Jiang Wan , Stein Barry E.
Published: May 2006

Multisensory depression is a fundamental index of multisensory integration in superior colliculus (SC) neurons. It is initiated when one sensory stimulus (auditory) located outside its modality-specific receptive field degrades or eliminates the neuron's responses to another sensory stimulus (visual) presented within its modality-specific receptive field. The present experiments demonstrate that the capacity of SC neurons to engage in multisensory depression is strongly dependent on influences from two cortical areas (the anterior ectosylvian and rostral lateral suprasylvian sulci). When these cortices are deactivated, the ability of SC neurons to synthesize visual-auditory inputs in this way is compromised; multisensory responses are disinhibited, becoming more vigorous and in some cases indistinguishable from responses to the visual stimulus alone. Although obtaining a more robust multisensory SC response when cortex is nonfunctional than when it is functional may seem paradoxical, these data may help explain previous observations that the loss of these cortical influences permits visual orientation behavior in the presence of a normally disruptive auditory stimulus.
Differential Spatial Organization of Otolith Signals in Frog Vestibular Nuclei
Authors: Straka Hans , Holler Stefan , Goto Fumiyuki , Kolb Florian P. , Gilland Edwin
Published: May 2006

Activation maps of pre- and postsynaptic field potential components evoked by separate electrical stimulation of utricular, lagenar, and saccular nerve branches in the isolated frog hindbrain were recorded within a stereotactic outline of the vestibular nuclei. Utricular and lagenar nerve-evoked activation maps overlapped strongly in the lateral and descending vestibular nuclei, whereas lagenar amplitudes were greater in the superior vestibular nucleus. In contrast, the saccular nerve-evoked activation map coincided largely with the dorsal nucleus and the adjacent dorsal part of the lateral vestibular nucleus, corroborating a major auditory and lesser vestibular function of the frog saccule. The stereotactic position of individual second-order otolith neurons matched the distribution of the corresponding otolith nerve-evoked activation maps. Furthermore, particular types of second-order utricular and lagenar neurons were clustered with particular types of second-order canal neurons in a topology that anatomically mirrored the preferred convergence pattern of afferent otolith and canal signals in second-order vestibular neurons. Similarities in the spatial organization of functionally equivalent types of second-order otolith and canal neurons between frog and other vertebrates indicated conservation of a common topographical organization principle. However, the absence of a precise afferent sensory topography combined with the presence of spatially segregated groups of particular second-order vestibular neurons suggests that the vestibular circuitry is organized as a premotor map rather than an organotypical sensory map. Moreover, the conserved segmental location of individual vestibular neuronal phenotypes shows linkage of individual components of vestibulomotor pathways with the underlying genetically specified rhombomeric framework.
Mammalian Retinal Bipolar Cells Express Inwardly Rectifying K+ Currents (IKir) With a Different Distribution Than That of Ih
Authors: Ma Yu-Ping , Cui Jinjuan , Hu Hui-Juan , Pan Zhuo-Hua
Published: May 2006

Retinal bipolar cells comprise multiple subtypes that are well known for the diversity of their physiological properties. We investigated the properties and functional roles of the hyperpolarization-activated currents in mammalian retinal bipolar cells using whole cell patch-clamp recording techniques. We report that bipolar cells express inwardly rectifying K+ currents ( IKir) in addition to the hyperpolarization-activated cationic currents ( Ih) previously reported. Furthermore, these two currents are differentially expressed among different subtypes of bipolar cells. One group of cone bipolar cells in particular displayed mainly IKir. A second group of cone bipolar cells displayed both currents but with a much larger Ih. Rod bipolar cells, on the other hand, showed primarily Ih. Moreover, we showed that IKir and Ih differentially influence the voltage responses of bipolar cells: Ih facilitates and/or accelerates the membrane potential rebound, whereas IKir counteracts or prevents such rebound. The findings of the expression of IKir and the differential expression of Ih and IKir in bipolar cells may provide new insights into an understanding of the physiological properties of bipolar cells.
Changes in Reciprocal Inhibition Across the Ankle Joint With Changes in External Load and Pedaling Rate During Bicycling
Authors: Pyndt H. S. , Laursen M. , Nielsen J. B.
Published: May 2006

The purpose of this study was to investigate the role of reciprocal inhibition in the regulation of antagonistic ankle muscles during bicycling. A total of 20 subjects participated in the study. Reciprocal inhibition was induced by stimulation of the peroneal nerve (PN) at 1.2 times threshold for the M-response in the tibialis anterior muscle (TA) and recorded as a depression of the rectified soleus (SOL) EMG. Recordings were made during tonic plantar flexion and during bicycling on an ergometer bicycle. During tonic contraction, the amount of inhibition in the SOL EMG was linearly correlated to the amount of background EMG. This linear relation was used to calculate the expected amount of reciprocal inhibition at corresponding EMG levels during bicycling. During the early phase of down-stroke of bicycling at 60 revolutions per minute (RPM) and an external load of 1.0 kg, the amount of recorded reciprocal inhibition was significantly smaller than that calculated from the linear relation during tonic contraction. In nine subjects, the SOL H-reflex was used to evaluate the amount of inhibition. At a short conditioning test interval (2–3 ms), the PN stimulation depressed the SOL H-reflex when the subjects were at rest. This short latency inhibition was absent during downstroke, but appeared during upstroke just prior to and during TA activation. A positive linear relation was found between the level of SOL background EMG in early downstroke and the external load (0.5–2.5 kg) as well as the rate of pedaling (30–90 RPM at 1.0 kg external load). The amount of inhibition in the SOL EMG when expressed as a percentage of the background EMG activity decreased significantly with increasing load. During increased pedaling rate, a similar decrease was seen, but it did not reach a statistically significant level. The data illustrate that reciprocal inhibition of the soleus muscle is modulated during bicycling being small in downstroke when the SOL muscle is active and large in upstroke where the muscle is inactive and its antagonist becomes active. The depression of the inhibition in relation to increased load and pedaling rate likely reflects the need of reducing inhibition of the SOL motoneurons to ensure a sufficient activation of the muscle.
Functional Interaction of Auxiliary Subunits and Synaptic Proteins With CaV1.3 May Impart Hair Cell Ca2+Current Properties
Authors: Song Haitao , Nie Liping , Rodriguez-Contreras Adrian , Sheng Zu-Hang , Yamoah Ebenezer N.
Published: May 2006

We assessed the functional determinants of the properties of L-type Ca2+ currents in hair cells by co-expressing the pore-forming CaV1.3α1subunit with the auxiliary subunits β1A and/or α2δ. Because Ca2+channels in hair cells are poised to interact with synaptic proteins, we also co-expressed the CaV1.3α1 subunit with syntaxin, vesicle-associated membrane protein (VAMP), and synaptosome associated protein of 25 kDa (SNAP25). Expression of the CaV1.3α1 subunit in human embryonic kidney cells (HEK 293) produced a dihydropyridine (DHP)-sensitive Ca2+ current (peak current density −2.0 ± 0.2 pA/pF; n = 11). Co-expression with β1A and α2δsubunits enhanced the magnitude of the current (peak current density: CaV1.3α1 + β1A = −4.3 ± 0.8 pA/pF, n = 10; CaV1.3α1 + β1A + α2δ = −4.1 ± 0.6 pA/pF, n = 9) and produced a leftward shift of approximately 9 mV in the voltage-dependent activation of the currents. Furthermore, co-expression of CaV1.3α1 with syntaxin/VAMP/SNAP resulted in at least a twofold increase in the peak current density (−4.7 ± 0.2 pA/pF; n = 11) and reduced the extent of inactivation of the Ca2+currents. Botulinum toxin, an inhibitor of syntaxin, accelerated the inactivation profile of Ca2+ currents in hair cells. Immunocytochemical data also indicated that the Ca2+ channels and syntaxin are co-localized in hair cells, suggesting there is functional interaction of the CaV1.3α1 with auxiliary subunits and synaptic proteins, that may contribute to the distinct properties of the DHP-sensitive channels in hair cells.
Neuron-Specific Response Characteristics Predict the Magnitude of Multisensory Integration
Authors: Perrault Thomas J. , Vaughan J. William , Stein Barry E. , Wallace Mark T.
Published: May 2006

Multisensory neurons in the superior colliculus (SC) typically respond to combinations of stimuli from multiple modalities with enhancements and/or depressions in their activity. Although such changes in response have been shown to follow a predictive set of integrative principles, these principles fail to completely account for the full range of interactions seen throughout the SC population. In an effort to better define this variability, we sought to determine if there were additional features of the neuronal response profile that were predictive of the magnitude of the multisensory interaction. To do this, we recorded from 109 visual-auditory SC neurons while systematically manipulating stimulus intensity. Along with the previously described roles of space, time, and stimulus effectiveness, two features of a neuron's response profile were found to offer predictive value as to the magnitude of the multisensory interaction: spontaneous activity and the level of sensory responsiveness. Multisensory neurons with little or no spontaneous activity and weak sensory responses had the capacity to exhibit large response enhancements. Conversely, neurons with modest spontaneous activity and robust sensory responses exhibited relatively small response enhancements. Together, these results provide a better view into multisensory integration, and suggest substantial heterogeneity in the integrative characteristics of the multisensory SC population.
Corticofugal Modulation on Both on andoff Responses in the Nonlemniscal Auditory Thalamus of the Guinea Pig
Authors: He Jufang
Published: May 2006

Corticofugal modulation on both on andoff responses in various nuclei in the medial geniculate body (MGB) was examined by locally activating the auditory cortex and looking for effects on the neuronal responses to acoustic stimuli. In contrast with a major corticofugal facilitatory effect on theon neurons in the lemniscal nucleus of the MGB of the guinea pigs, of 132 on neurons tested in three conditions with cortical activation through each of three implanted electrodes, the majority of the tested conditions (319/396) that were sampled from the nonlemniscal nuclei of the MGB received inhibitory modulation from the activated cortex. This inhibitory effect was >50% for 99 cases while the auditory cortex was activated. Most of the offand on-off MGB neurons (44/54) showed a facilitatory effect of 111.4 ± 99.9%, and three showed a small inhibitory effect of 25.7 ± 5.8% on their off responses. Thirty neurons in the border region between the lemniscal and nonlemniscal MGB showed mainly facilitatory corticofugal effects on both on andoff responses. Meanwhile, cortical stimulation induced almost exclusive inhibitory effects on the on response and facilitatory effects on the off response in the MGcm. It is suggested that the off response is produced as a disinhibition from the inhibitory input of the auditory stimulus. The present results provide a possible explanation for selective gating of the auditory information through the lemniscal MGB while switching off other unwanted sensory signals and the interference from the limbic system, leaving the other auditory cortex prepared to process only the auditory signal.
Neural Pathways Between Sacrocaudal Afferents and Lumbar Pattern Generators in Neonatal Rats
Authors: Strauss I. , Lev-Tov A.
Published: May 2006

Projections of sacrocaudal afferents (SCA) onto lumbar pattern generators were studied in isolated spinal cords of neonatal rats. A locomotor-like pattern could be produced by SCA stimulation in the majority of the preparations. The SCA-induced lumbar rhythm was abolished after blocking synaptic transmission in the sacrococcygeal (SC) cord by bathing its segments in a low-calcium, high-magnesium artificial cerebrospinal fluid and restored when the synaptic block was alleviated by local application of calcium onto specific SC segments prior to SCA stimulation. Thus the SCA evoked lumbar rhythm involves synaptic activation of relay neurons in the SC cord. Functional activation of these relays depends on non– N-methyl-d-aspartate (NMDA) receptors because the lumbar rhythm was abolished when the non-NMDA receptor antagonist CNQX was added to the SC cord. By contrast, pharmacological block of the rhythmicity in the SC cord by specific antagonists of NMDA receptors and α1 and α2 adrenoceptors did not impair the SCA-induced lumbar rhythm. Midsagittal splitting experiments of parts of the SC and lumbar cord revealed that crossed and uncrossed ascending/propriospinal pathways are coactivated by SCA stimulation. We suggest that these pathways ascend onto the thoracolumbar cord through the lateral, ventrolateral, and ventral funiculi, because a complete block of the lumbar rhythm could only be obtained with a bilateral interruption of all of these funiculi. The relevance of our findings to the neural control of the rhythmogenic networks in the spinal cord is discussed.
Genetic Evidence for a Role of CREB in Sustained Cortical Arousal
Authors: Graves Laurel A. , Hellman Kevin , Veasey Sigrid , Blendy Julie A. , Pack Allan I. , Abel Ted
Published: May 2006

The cyclic AMP-response element binding protein (CREB) is an activity-dependent transcription factor important for synaptic plasticity and memory storage. Levels of phosphorylated CREB within the cortex are higher in waking than in sleep, suggesting that CREB plays a role in sleep/wake regulation in mammals. We tested the hypothesis that CREB is critical for sleep/wake regulation by examining behavioral state parameters in mice lacking the α and Δ isoforms of CREB. Over 24 h, time spent awake was significantly decreased in CREB αΔ mutant mice by approximately 100 min, and time spent in nonrapid eye movement sleep (NREM) sleep was increased correspondingly. Wake and REM sleep periods were shorter in CREB αΔ mice, and CREB αΔ mice had decreased levels of θ-activity during wake and REM sleep, consistent with an impairment in the ability to maintain an activated electroencephalogram. These results suggest that the CREB protein contributes to the mechanisms by which wakefulness is maintained and demonstrate that specific genetic alterations in species as diverse as Drosophila and mice produce similar phenotypes in arousal and wakefulness.
Enhanced Adenosine A2A Receptor Facilitation of Synaptic Transmission in the Hippocampus of Aged Rats
Authors: Rebola Nelson , Sebastião Ana M. , de Mendonça Alexandre , Oliveira Catarina R. , Ribeiro J. A. , Cunha Rodrigo A.
Published: May 2006

Adenosine either inhibits or facilitates synaptic transmission through A1 or A2A receptors, respectively. Since A2A receptor density increases in the limbic cortex of aged (24 mo) compared with young adult rats (2 mo), we tested if A2A receptor modulation of synaptic transmission was also increased in aged rats. The A2A receptor agonist, CGS21680 (10 nM), caused a larger facilitation of the field excitatory postsynaptic potential (fEPSP) slope in hippocampal slices of aged (38%) than in young rats (19%), an effect prevented by the A2A receptor antagonist, ZM241385 (20 nM). In contrast to young rats, where CGS21680 facilitation of fEPSPs is prevented by the protein kinase C inhibitor, chelerythrine (6 μM), but not by the protein kinase A inhibitor, H-89 (1 μM), the CGS21680 -induced facilitation of fEPSP slope in aged rats was prevented by H-89 (1 μM) but not by chelerythrine (6 μM). Also, in contrast to the β–receptor agonist, isoproterenol (30 μM), CGS21680 (100–1,000 nM) enhanced cAMP levels in hippocampal nerve terminals of aged but not young rats. Finally, we observed a significant increase of both the binding density of [3H]CGS 21680 and the [3H]ZM241385 as well as of the anti-A2A receptor immunoreactivity in hippocampal nerve terminal membranes from aged compared with young rats. This shows that A2A receptor-mediated facilitation of hippocampal synaptic transmission is larger in aged than young rats due to increased A2A receptor density in nerve terminals and to the modified transducing system operated by A2A receptors, from a protein kinase C mediated control of A1 receptors into a direct protein kinase A dependent facilitation of synaptic transmission.
Angiotensin II Activates a Nitric-Oxide-Driven Inhibitory Feedback in the Rat Paraventricular Nucleus
Authors: Latchford Kevin J. , Ferguson Alastair V.
Published: May 2006

The hypothalamic paraventricular nucleus (PVN) has been shown to play major obligatory roles in autonomic and neuroendocrine regulation. Angiotensin II (ANG) acts as a neurotransmitter regulating the excitability of magnocellular neurons in this nucleus. We report here that ANG also activates a nitric-oxide-mediated negative feedback loop in the PVN that acts to regulate the functional output of magnocellular neurons. Thus in addition to its depolarizing actions on magnocellular neurons, ANG application results in an increase in the frequency of inhibitory postsynaptic potentials in a population of these neurons without effect on the amplitude of these events. ANG was also without significant effect on the mean frequency or amplitude of mini synaptic currents analyzed in voltage-clamp experiments. This increase in inhibitory input after ANG can be abolished by the nitric oxide synthase inhibitor Nω-nitro-l-arginine methylester, demonstrating a requisite role for nitric oxide in the activation of this pathway. The depolarization of magnocellular neurons that show increased inhibitory postsynaptic potential (IPSP) frequency in response to ANG is significantly smaller than that observed in neurons in which IPSPs frequency was unaffected (3.2 ± 1.1 vs. 8.0 ± 0.5mV, P < 0.05). Correspondingly, after nitric oxide synthase inhibition, the depolarizing effects of ANG on magnocellular neurons are augmented (2.0 ± 0.7 vs. 6.7 ± 0.7mV, P < 0.05). The depolarization was also enhanced in the presence of the GABAergic antagonist bicuculline (1.9 ± 1.2 vs. 11.9 ± 2.3, P < 0.001). These data demonstrate that there exists within the PVN an intrinsic negative feedback loop that modulates neuronal excitability in response to peptidergic excitation.
Control Strategies Correcting Inaccurately Programmed Fingertip Forces: Model Predictions Derived From Human Behavior
Authors: Fagergren Anders , Ekeberg Örjan , Forssberg Hans
Published: May 2006

When picking up a familiar object between the index finger and the thumb, the motor commands are predetermined by the CNS to correspond to the frictional demand of the finger-object contact area. If the friction is less than expected, the object will start to slip out of the hand, giving rise to unexpected sensory information. Here we study the correction strategies of the motor system in response to an unexpected frictional demand. The motor commands to the mononeuron pool are estimated by a novel technique combining behavioral recordings and neuromuscular modelling.

We first propose a mathematical model incorporating muscles, hand mechanics, and the action of lifting an object. A simple control system sends motor commands to and receives sensory signals from the model. We identify three factors influencing the efficiency of the correction: the time development of the motor command, the delay between the onset of the grip and load forces (GF-LF-delay), and how fast the lift is performed. A sensitivity analysis describes how these factors affect the ability to prevent or stop slipping and suggests an efficient control strategy that prepares and corrects for an altered frictional condition.

We then analyzed fingertip grip and load forces (GF and LF) and position data from 200 lifts made by five healthy subjects. The friction was occasionally reduced, forcing an increase of the GF to prevent the object being dropped. The data were then analyzed by feeding it through the inverted model. This provided an estimate of the motor commands to the motoneuron pool.

As suggested by the sensitivity analysis the GF-LF-delay was indeed used by the subjects to prevent slip. In agreement with recordings from neurons in the primary motor cortex of the monkey, a sharp burst in the estimated GF motor command (NGF) efficiently arrested any slip. The estimated motor commands indicate a control system that uses a small set of corrective commands, which together with the GF-LF-delay form efficient correction strategies. The selection of a strategy depends on the amount of tactile information reporting unexpected friction and how long it takes to arrive. We believe that this technique of estimating the motor commands behind the fingertip forces during a precision grip lift can provide a powerful tool for the investigation of the central control of the motor system.
Modest Gaze-Related Discharge Modulation in Monkey Dorsal Premotor Cortex During a Reaching Task Performed With Free Fixation
Authors: Cisek Paul , Kalaska John F.
Published: May 2006

Recent studies have shown that gaze angle modulates reach-related neural activity in many cortical areas, including the dorsal premotor cortex (PMd), when gaze direction is experimentally controlled by lengthy periods of imposed fixation. We looked for gaze-related modulation in PMd during the brief fixations that occur when a monkey is allowed to look around freely without experimentally imposed gaze control while performing a center-out delayed arm-reaching task. During the course of the instructed-delay period, we found significant effects of gaze angle in 27–51% of PMd cells. However, for 90–95% of cells, these effects accounted for <20% of the observed discharge variance. The effect of gaze was significantly weaker than the effect of reach-related variables. In particular, cell activity during the delay period was more strongly related to the intended movement expressed in arm-related coordinates than in gaze-related coordinates. Under the same experimental conditions, many cells in medial parietal cortex exhibited much stronger gaze-related modulation and expressed intended movement in gaze-related coordinates. In summary, gaze direction-related modulation of cell activity is indeed expressed in PMd during the brief fixations that occur in natural oculomotor behavior, but its overall effect on cell activity is modest.
The distribution and evolutionary history of the PRP8 intein
Authors: Butler Margaret I , Gray Jeremy , Goodwin Timothy JD , Poulter Russell TM
Published: May 2006

Background

We recently described a mini-intein in the PRP8 gene of a strain of the basidiomycete Cryptococcus neoformans, an important fungal pathogen of humans. This was the second described intein in the nuclear genome of any eukaryote; the first nuclear encoded intein was found in the VMA gene of several saccharomycete yeasts. The evolution of eukaryote inteins is not well understood. In this report we describe additional PRP8 inteins (bringing the total of these to over 20). We compare and contrast the phylogenetic distribution and evolutionary history of the PRP8 intein and the saccharomycete VMA intein, in order to derive a broader understanding of eukaryote intein evolution. It has been suggested that eukaryote inteins undergo horizontal transfer and the present analysis explores this proposal.

Results

In total, 22 PRP8 inteins have been detected in species from three different orders of euascomycetes, including Aspergillus nidulans and Aspergillus fumigatus (Eurotiales), Paracoccidiodes brasiliensis, Uncinocarpus reesii and Histoplasma capsulatum (Onygales) and Botrytis cinerea (Helotiales). These inteins are all at the same site in the PRP8 sequence as the original Cryptococcus neoformans intein. Some of the PRP8 inteins contain apparently intact homing endonuclease domains and are thus potentially mobile, while some lack the region corresponding to the homing endonuclease and are thus mini-inteins. In contrast, no mini-inteins have been reported in the VMA gene of yeast. There are several examples of pairs of closely related species where one species carries the PRP8 intein while the intein is absent from the other species. Bio-informatic and phylogenetic analyses suggest that many of the ascomycete PRP8 homing endonucleases are active. This contrasts with the VMA homing endonucleases, most of which are inactive.

Conclusion

PRP8 inteins are widespread in the euascomycetes (Pezizomycota) and apparently their homing endonucleases are active. There is no evidence for horizontal transfer within the euascomycetes. This suggests that the intein is of ancient origin and has been vertically transmitted amongst the euascomycetes. It is possible that horizontal transfer has occurred between the euascomycetes and members of the basidiomycete genus Cryptococcus.