bluuebunny/crossref_metadata_2025 huggingface dataset:
5-HT2 Receptors Promote Plateau Potentials in Turtle Spinal Motoneurons by Facilitating an L-Type Calcium Current
Authors: Perrier Jean-François , Hounsgaard Jørn
Published: May 2006

The effects of serotonin (5-HT) on intrinsic properties of spinal motoneurons were investigated with intracellular recordings in a slice preparation from adult turtles. In 55% of the cells that were recorded, addition of 5-HT to the extracellular medium promoted plateau potentials as revealed by the response to depolarizing current pulses applied through the intracellular electrode. In the remaining 45% of cells, 5-HT had an inhibitory effect. However, when tested with an applied electric field that preferentially polarizes distal dendrites, 5-HT facilitated plateau potentials in 100% of the cells. Plateau potentials were also promoted by 5-HT focally applied on a dendrite by iontophoresis. Applied near the soma, 5-HT either promoted plateau potentials or inhibited spike generation. The latter effect was accompanied by a decrease in input resistance. Voltage-clamp recordings showed that the facilitation of plateau potentials mediated by L-type Ca2+ channels was due to activation of 5-HT2 receptors. These findings show that 5-HT regulates intrinsic properties of motoneurons in opposite ways: activation of 5-HT receptors in the soma region inhibits spike generation and plateau potentials, while activation of 5-HT2 receptors in the dendrites and the soma region promotes spiking by facilitation of plateau potentials mediated by L-type Ca2+ channels.
Dipole Source Analysis of Laser-Evoked Subdural Potentials Recorded From Parasylvian Cortex in Humans
Authors: Vogel Hagen , Port John D. , Lenz Fred A. , Solaiyappan Meiyappan , Krauss Greg , Treede Rolf-Detlef
Published: May 2006

The location of the human nociceptive area(s) near the Sylvian fissure is still controversial in spite of evidence from imaging and evoked potential studies that noxious heat stimuli activate somatosensory areas in that region. Some studies have suggested the secondary somatosensory cortex (SII) on the upper bank of the Sylvian fissure posterior to the central sulcus, others the anterior insula or parietal area 7b. In this study, we applied dipole source analysis techniques to laser-evoked potentials (LEPs) that were recorded from subdural grid electrodes in three patients. As a functional marker, auditory-evoked potentials (AEPs) with a generator on the opposite bank of the Sylvian fissure were recorded from the same electrodes. The LEP global field power (GFP), a measure of spatial variance, showed a first peak at about 150 ms latency, corresponding to the latency of the N1 recorded from the scalp. In contrast to scalp recordings, the amplitude of the first GFP peak recorded from the grid was larger than the second peak (P2). This finding suggests that the generator of N1, but not that of later LEP components, was close to the subdural grids. When a regional source was fitted to the first GFP peak, its location was within the frontoparietal operculum in all patients. On average, the LEP source was 13 mm anterior, 6 mm superior, and 2 mm medial of the AEP source. This relative location also suggests a source within the frontoparietal operculum overlying the insula. At the latency of the first GFP peak, source orientation pointed inward, suggesting a generator within the inner vertical surface of the operculum. Somatotopy was assessed in one patient and was consistent with that of the projection area of the presumed nociceptive thalamic nucleus posterior part of the ventromedial nucleus, but differed from that of SII. These findings suggest that the nociceptive area in human parasylvian cortex that is activated most rapidly by noxious heat pulses may be separate from the tactile SII area.
Nonspatial Saccade-Specific Activation in area LIP of Monkey Parietal Cortex
Authors: Dickinson A. R. , Calton J. L. , Snyder L. H.
Published: May 2006

We present evidence that neurons in the lateral intraparietal area (LIP) of monkey posterior parietal cortex (PPC) are activated by the instruction to make an eye movement, even in the complete absence of a spatial target. This study employed a visually guided motor task that dissociated the type of movement to make (saccade or reach) from the location where the movement was to be made. Using this task, animals were instructed to prepare a specific type of movement prior to knowing the spatial location of the movement target. We found that 25% of the LIP neurons recorded in two animals were activated significantly more by the instruction to prepare a saccade than by the instruction to prepare a reach. This finding indicates that LIP is involved in more than merely spatial attention and provides further evidence for nonspatial effector-specific signal processing in the dorsal stream.
Similar Electrophysiological Changes in Axotomized and Neighboring Intact Dorsal Root Ganglion Neurons
Authors: Ma Chao , Shu Yousheng , Zheng Zheng , Chen Yong , Yao Hang , Greenquist Kenneth W. , White Fletcher A. , LaMotte Robert H.
Published: May 2006

We investigated electrophysiological changes in chronically axotomized and neighboring intact dorsal root ganglion (DRG) neurons in rats after either a peripheral axotomy consisting of an L5 spinal nerve ligation (SNL) or a central axotomy produced by an L5 partial rhizotomy (PR). SNL produced lasting hyperalgesia to punctate indentation and tactile allodynia to innocuous stroking of the foot ipsilateral to the injury. PR produced ipsilateral hyperalgesia without allodynia with recovery by day 10. Intracellular recordings were obtained in vivo from the cell bodies (somata) of axotomized and intact DRG neurons, some with functionally identified peripheral receptive fields. PR produced only minor electrophysiological changes in both axotomized and intact somata in L5 DRG. In contrast, extensive changes were observed after SNL in large- and medium-sized, but not small-sized, somata of intact (L4) as well as axotomized (L5) DRG neurons. These changes included (in relation to sham values) higher input resistance, lower current and voltage thresholds, and action potentials with longer durations and slower rising and falling rates. The incidence of spontaneous activity, recorded extracellularly from dorsal root fibers in vitro, was significantly higher (in relation to sham) after SNL but not after PR, and occurred in myelinated but not unmyelinated fibers from both L4 (9.1%) and L5 (16.7%) DRGs. We hypothesize that the changes in the electrophysiological properties of axotomized and intact DRG neurons after SNL are produced by a mechanism associated with Wallerian degeneration and that the hyperexcitability of intact neurons may contribute to SNL-induced hyperalgesia and allodynia.
Organization of Ipsilateral Excitatory and Inhibitory Pathways in the Human Motor Cortex
Authors: Chen Robert , Yung Derek , Li Jie-Yuan
Published: May 2006

Motor cortex stimulation has both excitatory and inhibitory effects on ipsilateral muscles. Excitatory effects can be assessed by ipsilateral motor-evoked potentials (iMEPs). Inhibitory effects include an interruption of ipsilateral voluntary muscle activity known as the silent period (iSP) and a reduction in corticospinal excitability evoked by conditioning stimulation of the contralateral motor cortex (interhemispheric inhibition, IHI). Both iSP and IHI may be mediated by transcallosal pathways. Their relationship to the contralateral corticospinal projection and whether iSP and IHI represent the same phenomenon remain unclear. The neuronal population activated by transcranial magnetic stimulation (TMS) is highly dependent on the direction of the induced current in the brain. We examined the relationship among iMEP, iSP, IHI, and the contralateral corticospinal system by examining the effects of different stimulus intensities and current directions. Surface electromyography (EMG) was recorded from both first dorsal interosseous (FDI) muscles. The iSP in the right FDI muscle was obtained by right motor cortex stimulation during voluntary muscle contraction. IHI was examined by conditioning stimulation of the right motor cortex followed by test stimulation of the left motor cortex at interstimulus intervals (ISIs) of 2–80 ms. The induced current directions tested in the right motor cortex were anterior medial (AM), posterior medial (PM), posterior lateral, and anterior lateral (AL). Contralateral MEPs (cMEPs) had the lowest threshold with the AM direction and the shortest latency with the PM direction. iMEPs were present in 8 of 10 subjects. Both iMEP and IHI did not show significant directional preference. iSP was observed in all subjects with the highest threshold for the AL direction and the longest duration for the AM direction. cMEP, iSP, and IHI all increased with stimulus intensity up to ∼75% stimulator output. Target muscle activation decreased IHI at 8-ms ISI but had little effect on IHI at 40-ms ISI. iSP and IHI at 8-ms ISI did not correlate at any stimulus intensities and current directions tested, and factor analysis showed that they are explained by different factors. However, active IHI at 40-ms ISI was explained by the same factor as iSP. The different directional preference for cMEP compared with iMEP and IHI suggests that these ipsilateral effects are mediated by populations of cortical neurons that are different from those activating the corticospinal neurons. iSP and IHI do not represent the same phenomenon and should be considered complementary measures of ipsilateral inhibition.
Early Development of Voltage-Gated Ion Currents and Firing Properties in Neurons of the Mouse Cerebral Cortex
Authors: Picken Bahrey Heidi L. , Moody William J.
Published: May 2006

Voltage- and current-clamp recordings were made from acute slices of mouse cerebral cortex from embryonic day 14 to postnatal day 17. We targeted cells in the migratory population of the embryonic intermediate zone (IZ) and in deep layers of embryonic and postnatal cortical plate (CP). IZ neurons maintain fairly consistent properties through the embryonic period, all expressing high-input resistance, inward Na+currents and outward K+currents, and none showing any hyperpolarization-activated currents. In CP neurons, several changes in physiological properties occur in the late embryonic and early postnatal period: inward Na+current density is strongly upregulated while outward K+current density remains almost unchanged, input resistance drops dramatically, and a hyperpolarization-activated current resembling Ihappears. As a result of these changes, the action potential becomes larger, shorter in duration, and its threshold shifts to more negative potentials. In addition, CP cells become capable of firing repetitively and an increasing fraction show spontaneous action potentials. This coordinated development of ion channel properties may help to time the occurrence of developmentally relevant spontaneous activity in the immature cortex.
From Following Edges to Pursuing Objects
Authors: Masson Guillaume S. , Stone Leland S.
Published: May 2006

Primates can generate accurate, smooth eye-movement responses to moving target objects of arbitrary shape and size, even in the presence of complex backgrounds and/or the extraneous motion of non-target objects. Most previous studies of pursuit have simply used a spot moving over a featureless background as the target and have thus neglected critical issues associated with the general problem of recovering object motion. Visual psychophysicists and theoreticians have shown that, for arbitrary objects with multiple features at multiple orientations, object-motion estimation for perception is a complex, multi-staged, time-consuming process. To examine the temporal evolution of the motion signal driving pursuit, we recorded the tracking eye movements of human observers to moving line-figure diamonds. We found that pursuit is initially biased in the direction of the vector average of the motions of the diamond's line segments and gradually converges to the true object-motion direction with a time constant of approximately 90 ms. Furthermore, transient blanking of the target during steady-state pursuit induces a decrease in tracking speed, which, unlike pursuit initiation, is subsequently corrected without an initial direction bias. These results are inconsistent with current models in which pursuit is driven by retinal-slip error correction. They demonstrate that pursuit models must be revised to include a more complete visual afferent pathway, which computes, and to some extent latches on to, an accurate estimate of object direction over the first hundred milliseconds or so of motion.
Electrophysiological Changes in Adult Rat Dorsal Horn Neurons After Neonatal Peripheral Inflammation
Authors: Peng Yuan Bo , Ling Qing Dong , Ruda M. A. , Kenshalo Daniel R.
Published: May 2006

Neonatal peripheral inflammation has been shown to produce profound anatomical changes in the dorsal horn of adult rats. In this study, we explored whether parallel physiological changes exist. Neonatal rats were injected with complete Freund's adjuvant (CFA) into the left hind paw. At 8–10 wk of age, single dorsal horn neurons were recorded in response to graded intensities of mechanical stimuli delivered to the receptive field. In addition, cord dorsum potentials, produced by electrical stimuli delivered to the left sciatic nerve at 2.5× threshold, were recorded bilaterally from L2 to S3. There were significant increases in background activity and responses to brush and pinch in neonatal rats that were treated with CFA, as compared with control rats. Further analysis showed similar significant changes when dorsal horn neurons were categorized into wide dynamic range (WDR), high-threshold (HT), and low-threshold (LT) groups. The receptive field was significantly larger in neonatally treated rats as compared with control rats. Additionally, there was a significant increase in the response to a 49°C heat stimulus in neonatally treated rats as compared with control rats. There was also a trend for the amplitudes of N1, N2, and P waves of the cord dorsum potential to increase and latencies to decrease in neonatally treated rats, but no significant differences were detected between different levels of the spinal cord (L2 to S3). These data further support the notion that anatomical and physiological plasticity changes occurred in the spinal cord following early neonatal CFA treatment.
Reduced Inhibition and Sensitivity to Neurosteroids in Hippocampus of Mice Lacking the GABAAReceptor δ Subunit
Authors: Spigelman Igor , Li Zhiwei , Liang Jing , Cagetti Elisabetta , Samzadeh Sepideh , Mihalek Robert M. , Homanics Gregg E. , Olsen Richard W.
Published: May 2006

The δ subunit of the γ-aminobutyric acid (A) receptor (GABAAR) is expressed postnatally mostly in the cerebellum, thalamus, and dentate gyrus. Previous studies in mice with a targeted disruption of the δ subunit revealed a considerable attenuation of behavioral responses to neuroactive steroids but not to other neuromodulatory drugs. Here we show that δ subunit loss leads to a concomitant reduction in hippocampal α4 subunit levels. These changes were accompanied by faster decay of evoked inhibitory postsynaptic potentials (IPSPs) in dentate granule neurons of –/– mutants (decay τ = 25 ms) compared with +/+ controls (τ = 50 ms). Furthermore, the GABAAR-mediated miniature inhibitory postsynaptic currents (mIPSCs) also decayed faster in δ-mutants (τ = 6.3 ms) than controls (τ = 7.2 ms) and had decreased frequency (controls, 10.5 Hz; mutants, 6.6 Hz). Prolongation of mIPSCs by the neuroactive steroid anesthetic, alphaxalone (1–10 μM), was smaller in δ-mutants (at 10 μM, 65% increase) compared with +/+ littermates (308% increase). In competition binding experiments, alphaxalone (0.03–1 μM) modulation of [35S]t-butylbicyclophosphorothionate binding was reduced in δ-mutant brain homogenates, indicating that the decreased alphaxalone effects on mIPSCs were due to changes in the GABAAR protein. Faster decay of evoked IPSPs and mIPSCs in δ-mutants suggests presence of the δ subunit at both synaptic and extrasynaptic GABAARs. Decreased synaptic and extrasynaptic inhibition likely contributes to the pro-epileptic phenotype of δ-mutants. Reduced neurosteroid sensitivity might also contribute to seizure susceptibility. While the simplest explanation is that δ subunit-containing GABAARs represent the actual target of neurosteroids, it is possible that the behavioral and physiological sensitivity to neuroactive steroids is indirectly altered in the δ –/– mice.
Protein Synthesis Inhibition Blocks the Late-Phase LTP of C-Fiber Evoked Field Potentials in Rat Spinal Dorsal Horn
Authors: Hu Neng-Wei , Zhang Hong-Mei , Hu Xiao-Dong , Li Ming-Tao , Zhang Tong , Zhou Li-Jun , Liu Xian-Guo
Published: May 2006

Previous studies have demonstrated that in the hippocampus the maintenance of long-term potentiation (LTP) requires de novo protein synthesis. To investigate the role of protein synthesis in the maintenance of LTP of C-fiber evoked field potentials in spinal dorsal horn, which may be relevant to hyperalgesia, protein synthesis inhibitor (either cycloheximide or anisomycin) was applied locally to the recording segments of spinal cord in anesthetized rats, 30 min prior to tetanic stimulation to the sciatic nerve. We found that both cycloheximide and anisomycin selectively inhibited late-phase maintenance of the spinal LTP but affected neither LTP induction nor baseline responses of C-fiber evoked field potentials. In the presence of cycloheximide, LTP of C-fiber evoked field potentials was 281.5 ± 16.5% ( n = 6) of baseline 1 h after tetanic stimulation and the potentiation significantly decreased to 235.5 ± 18.5% at 145 min after tetanic stimulation ( P< 0.05). Afterward, LTP of C-fiber evoked field potentials decreased continuously and at 270 min after tetanic stimulation reached 130.8 ± 18.0%, which was no longer different from baseline ( P > 0.05). Spinal application of anisomycin at 30 min before tetanic stimulation yielded similar results ( n = 6). These results suggest that protein synthesis may be crucial for the late-phase maintenance of LTP of C-fiber evoked field potentials in spinal dorsal horn.
How Do Infants Adapt to Loading of the Limb During the Swing Phase of Stepping?
Authors: Lam Tania , Wolstenholme Claire , Yang Jaynie F.
Published: May 2006

Previous results from this laboratory have shown that human infants (<12 mo old) respond appropriately to transient changes in sensory input during stepping. We examined how infants adapted to a more enduring change in sensory input by applying load to one limb during stepping. A small weight (500–900 g) was strapped around the lower leg of infants aged 3–11 mo. Stepping with the weight on was recorded on the treadmill for a period of 0.5–3 min. The weight was then quickly detached during stepping, and the immediate response to unexpected loss of the weight recorded. Three-segment dynamic analysis of leg motion was used to estimate hip, knee, and ankle torques during swing in the sagittal plane. All infants adapted to the additional load on the leg by immediately increasing the generation of hip and knee flexor muscle torques. When the weight was removed, 7 of the 22 infants tested exhibited an after-effect (high stepping) in the first step after removal of the weight. The after-effect was manifested as an increase in toe trajectory height and hip flexion and coincided with higher hip flexor muscle torque in early swing. In an additional series of control experiments using seven infants, after-effects were shown to be unrelated to a sudden change in cutaneous input with removal of the weight. The presence of an after-effect indicates that some infants made an enduring adaptation to their stepping pattern that is revealed with the unexpected removal of the weight.
Positive Proprioceptive Feedback Elicited By Isometric Contractions of Ankle Flexors on Pretibial Motoneurons in Cats
Authors: Brizzi L. , Ting L. H. , Zytnicki D.
Published: May 2006

Pretibial flexor motoneurons were recorded intracellularly in anesthetized cats during unfused isometric contractions of a subpopulation of motor units from either tibialis anterior (TA) or extensor digitorum longus (EDL) muscles. The contractions elicited excitatory postsynaptic potentials in 23 of 28 pretibial flexor motoneurons. No effect was observed in the remaining motoneurons. In control experiments, the effects of electrical stimulation of afferents within the TA nerve were investigated to help identify afferents responsible for the contraction-induced positive feedback. This feedback was ascribed to actions of Ia fibers because the pattern of the contraction-induced excitatory potentials was consistent with the known pattern of Ia discharge; in control experiments, electrical stimulation of group I fibers elicited only monosynaptic excitatory potentials; and the distribution of both the contraction-induced positive feedback among motor nuclei as well as the electrically evoked Ia excitatory monosynaptic potentials were restricted to homonymous and synergic motoneurons. Observation of the Ia contraction-induced positive feedback was facilitated by the absence of Ib autogenic inhibition. This contraction-induced Ia excitatory feedback in ankle flexors might either reinforce Ia-induced reflexes when these muscles are lengthened or help to lift the leg over an obstacle.
Dopamine Modulates Synaptic Transmission Between Rat Olfactory Bulb Neurons in Culture
Authors: Davila Nestor G. , Blakemore Laura J. , Trombley Paul Q.
Published: May 2006

The glomerular layer of the olfactory bulb (OB) contains synaptic connections between olfactory sensory neurons and OB neurons as well as connections among OB neurons. A subpopulation of external tufted cells and periglomerular cells (juxtaglomerular neurons) expresses dopamine, and recent reports suggest that dopamine can inhibit olfactory sensory neuron activation of OB neurons. In this study, whole cell electrophysiological and primary culture techniques were employed to characterize the neuromodulatory properties of dopamine on glutamatergic transmission between rat OB mitral/tufted (M/T) cells and interneurons. Immunocytochemical analysis confirmed the expression of tyrosine hydroxylase, the rate-limiting enzyme for dopamine synthesis, in a subpopulation of cultured neurons. D2 receptor immunoreactivity was also observed in cultured M/T cells. Dopamine reduced spontaneous excitatory synaptic events recorded in interneurons. Although the D1 receptor agonist SKF38393 and the D2 receptor agonist bromocriptine mesylate mimicked this effect, evoked excitatory postsynaptic potentials (EPSPs) recorded from monosynaptically coupled neuron pairs were attenuated by dopamine and bromocriptine but not by SKF38393 . Neither glutamate-evoked currents nor the membrane resistance of the postsynaptic interneuron were affected by dopamine. However, evoked calcium channel currents in the presynaptic M/T cell were diminished during the application of either dopamine or bromocriptine, but not SKF38393 . Dopamine suppressed calcium channel currents even after nifedipine blockade of L-type channels, suggesting that inhibition of the dihydropyridine-resistant high-voltage activated calcium channels implicated in transmitter release may mediate dopamine's effects on spontaneous and evoked synaptic transmission. Together, these data suggest that dopamine inhibits excitatory neurotransmission between M/T cells and interneurons via a presynaptic mechanism.
Dimethyl Disulfide Exerts Insecticidal Neurotoxicity Through Mitochondrial Dysfunction and Activation of Insect KATPChannels
Authors: Dugravot Sébastien , Grolleau Françoise , Macherel David , Rochetaing Annie , Hue Bernard , Stankiewicz Maria , Huignard Jacques , Lapied Bruno
Published: May 2006

The plant-derived insecticides have introduced a new concept in insecticide research. In response to insect attacks, some plants can release volatile sulfur compounds such as dimethyl disulfide (DMDS) in the atmosphere, which are lethal for the generalist insects. We demonstrate that DMDS induced an uncommon complex neurotoxic activity. The studies of in vivo toxicity of DMDS in three insect species and mice indicated a highest bioactivity for insects. Although DMDS did not alter the electrophysiological properties of the cockroach Periplaneta americana giant axon, it affected the synaptic transmission at the presynaptic level resulting in an inhibition of the neurotransmitter release. Whole cell patch-clamp experiments performed on cockroach cultured dorsal unpaired median (DUM) neurons revealed a dose-dependent hyperpolarization induced by DMDS associated with a decrease in the input resistance and the disappearance of action potentials. The hyperpolarization was inhibited by glibenclamide and tolbutamide, and was dependent on intracellular ATP concentration, demonstrating a neurotoxicity via the activation of KATPchannels. Finally, the same effects observed with oligomycin, 2,4-dinitrophenol, and KCN together with the studies of DMDS toxicity on isolated mitochondria confirmed an unusual action occurring through an inhibition of the mitochondrial respiratory chain complex IV (cytochrome oxydase). This DMDS-induced inhibition of complex IV subsequently decreased the intracellular ATP concentration, which thereby activated neuronal KATPchannels mediating membrane hyperpolarization and reduction of neuronal activity.
Perceived Horizontal Body Position in Healthy and Paraplegic Subjects: Effect of Centrifugation
Authors: Jarchow T. , Wirz M. , Haslwanter T. , Dietz V. , Straumann D.
Published: May 2006

The perception of body position is mainly mediated by otolith information and visual cues. It has been shown, however, that proprioceptive sources are also involved. To distinguish between the contributions of the vestibular and nonvisual extra-vestibular information to graviception, we tested the effects of a stimulus that leaves the vestibular input unchanged but modifies the information from sense organs located more caudal along the trunk. This was achieved by bringing subjects into a horizontal ear-down position and rotating them around an earth-vertical axis that coincided with the interaural axis. In this paradigm, through centrifugal force, the stimulation of the vestibular and the putative extravestibular graviceptive organs in the body becomes dissociated. Healthy subjects ( n = 14) and paraplegic patients with lesions between T4 and T8 ( n = 7) adjusted themselves to the perceived horizontal right-ear down body position under two conditions: one with constant velocity rotation (ROT, velocity =120°/s) around the earth-vertical axis of the turntable, and one without rotation (BASE). Among healthy subjects, the individual differences between BASE and ROT varied widely in both the feet-up or feet-down direction. In contrast, adjustments in paraplegic patients during ROT were always in the feet-down direction compared with BASE. A model with two extravestibular graviceptive sensors could explain our results: one sensor is located rostral to T4, and the other is caudal to T8. A load on the rostral graviceptor is interpreted as a tilt of the body in the feet-up direction and shifts the adjustments of perceived body position feet-down; a load on the caudal receptor is interpreted as a tilt in the feet-down direction and shifts the perceived body position feet-up. During ROT, healthy subjects solve the discrepant inputs of both extravestibular graviceptors in a highly variable manner, while paraplegic subjects show less variability because they are restricted to only the rostral graviceptor.
mGluR1, But Not mGluR5, Mediates Depolarization of Spinal Cord Neurons by Blocking a Leak Current
Authors: Kettunen Petronella , Hess Dietmar , Manira Abdeljabbar El
Published: May 2006

The modulation of neuronal excitability by group I metabotropic glutamate receptors (mGluRs) was studied in isolated lamprey spinal cord. At resting potential, application of the group I mGluR agonist ( R,S)-3,5-dihydroxyphenylglycine (DHPG) slightly depolarized the cells. However, at depolarized membrane potentials, this agonist induced repetitive firing. When Na+channels were blocked by TTX, DHPG induced a slight depolarization at rest that increased in amplitude as the neurons were held at more depolarized membrane potentials. In voltage-clamp conditions, DHPG application induced an inward current associated with a decrease in membrane conductance when cells were held at –40 mV. At resting membrane potential, no significant change in the current was induced by DHPG, although a decrease in membrane conductance was seen. The conductance blocked by DHPG corresponded to a leak current, since DHPG had no effect on the voltagegated current elicited by a voltage step from –60 to –40 mV, when leak currents were subtracted. The leak current blocked by DHPG is mediated by fluxes of both K+and Na+. The subtype of group I mGluR mediating the block of the leak current was characterized using specific antagonists for mGluR1 and mGluR5. The inhibition of the leak current was blocked by the mGluR1 antagonist LY 367385 but not by the mGluR5 antagonist 2-methyl-6-(phenylethynyl)pyridine (MPEP). The DHPG-induced blockage of the leak current required phospholipase C (PLC)-activation and release of Ca2+from internal stores as the effect of DHPG was suppressed by the PLC-blocker U-73122 and after depletion of intracellular Ca2+pools by thapsigargin. Our results thus show that mGluR1 activation depolarizes spinal neurons by inhibiting a leak current. This will boost membrane depolarization and result in an increase in the excitability of spinal cord neurons, which could contribute to the modulation of the activity of the spinal locomotor network.
Three-Dimensional Ocular Kinematics During Eccentric Rotations: Evidence for Functional Rather Than Mechanical Constraints
Authors: Angelaki Dora E.
Published: May 2006

Previous studies have reported that the translational vestibuloocular reflex (TVOR) follows a three-dimensional (3D) kinematic behavior that is more similar to visually guided eye movements, like pursuit, rather than the rotational VOR (RVOR). Accordingly, TVOR rotation axes tilted with eye position toward an eye-fixed reference frame rather than staying relatively fixed in the head like in the RVOR. This difference arises because, contrary to the RVOR where peripheral image stability is functionally important, the TVOR like pursuit and saccades cares to stabilize images on the fovea. During most natural head and body movements, both VORs are simultaneously activated. In the present study, we have investigated in rhesus monkeys the 3D kinematics of the combined VOR during yaw rotation about eccentric axes. The experiments were motivated by and quantitatively compared with the predictions of two distinct hypotheses. According to the first (fixed-rule) hypothesis, an eye-position-dependent torsion is computed downstream of a site for RVOR/TVOR convergence, and the combined VOR axis would tilt through an angle that is proportional to gaze angle and independent of the relative RVOR/TVOR contributions to the total eye movement. This hypothesis would be consistent with the recently postulated mechanical constraints imposed by extraocular muscle pulleys. According to the second (image-stabilization) hypothesis, an eye-position-dependent torsion is computed separately for the RVOR and the TVOR components, implying a processing that takes place upstream of a site for RVOR/TVOR convergence. The latter hypothesis is based on the functional requirement that the 3D kinematics of the combined VOR should be governed by the need to keep images stable on the fovea with slip on the peripheral retina being dependent on the different functional goals of the two VORs. In contrast to the fixed-rule hypothesis, the data demonstrated a variable eye-position-dependent torsion for the combined VOR that was different for synergistic versus antagonistic RVOR/TVOR interactions. Furthermore, not only were the eye-velocity tilt slopes of the combined VOR as much as 10 times larger than what would be expected based on extraocular muscle pulley location, but also eye velocity during antagonistic RVOR/TVOR combinations often tilted opposite to gaze. These results are qualitatively and quantitatively consistent with the image-stabilization hypothesis, suggesting that the eye-position-dependent torsion is computed separately for the RVOR and the TVOR and that the 3D kinematics of the combined VOR are dependent on functional rather than mechanical constraints.
Distinct Firing Properties of Higher Order Thalamic Relay Neurons
Authors: Li Jianli , Bickford Martha E. , Guido William
Published: May 2006

It has been proposed that the thalamus is composed of at least two types of nuclei. First-order relay nuclei transmit signals from the periphery to the cortex while higher order nuclei may route information from one cortical area to another. Although much is known about the functional properties of relay neurons in first-order nuclei, little is known about relay neurons belonging to higher-order nuclei. We investigated the electrophysiological properties of relay cells in a higher-order thalamic nucleus using in vitro intracellular recordings from thalamic slices of the rat's lateral posterior nucleus (LPN). We found neurons of the LPN possess many of the same membrane properties as first-order relay neurons. These included low-threshold calcium spikes ( IT) and burst firing, a mixed cation conductance ( IH) that prevented membrane hyperpolarization, and a transient K+ conductance that delayed spike firing ( IA). The repetitive firing characteristics of LPN neurons were more distinct. One group of cells, located in the more caudal regions of the LPN responded to depolarizing current pulses with a train of action potentials or in a regular spiking (RS) mode. This form of firing showed a steep but highly linear increase in firing frequency with increasing levels of membrane depolarization. Another group of cells, located in the more rostral regions of the LPN, responded to depolarizing current pulses with clusters of high-frequency bursts or in a clustered spiking (CS) mode. The overall firing frequency rose nonlinearly with membrane depolarization, but the frequency of a given burst remained relatively constant. The caudal LPN receives input from the superior colliculus, whereas the rostral LPN receives input from layers V and VI of the visual cortex. Thus the RS and CS cells may be driven by subcortical and cortical inputs respectively, and the distinct temporal properties of their response modes may be a necessary component of the LPN circuitry.
Suppression of Class I and II Histone Deacetylases Blunts Pressure-Overload Cardiac Hypertrophy
Authors: Kong Yongli , Tannous Paul , Lu Guangrong , Berenji Kambeez , Rothermel Beverly A. , Olson Eric N. , Hill Joseph A.
Published: May 2006

Background—

Recent work has demonstrated the importance of chromatin remodeling, especially histone acetylation, in the control of gene expression in the heart. In cell culture models of cardiac hypertrophy, pharmacological suppression of histone deacetylases (HDACs) can either blunt or amplify cell growth. Thus, HDAC inhibitors hold promise as potential therapeutic agents in hypertrophic heart disease.

Methods and Results—

In the present investigation, we studied 2 broad-spectrum HDAC inhibitors in a physiologically relevant banding model of hypertrophy, observing dose-responsive suppression of ventricular growth that was well tolerated in terms of both clinical outcome and cardiac performance measures. In both short-term (3-week) and long-term (9-week) trials, cardiomyocyte growth was blocked by HDAC inhibition, with no evidence of cell death or apoptosis. Fibrotic change was diminished in hearts treated with HDAC inhibitors, and collagen synthesis in isolated cardiac fibroblasts was blocked. Preservation of systolic function in the setting of blunted hypertrophic growth was documented by echocardiography and by invasive pressure measurements. The hypertrophy-associated switch of adult and fetal isoforms of myosin heavy chain expression was attenuated, which likely contributed to the observed preservation of systolic function in HDAC inhibitor–treated hearts.

Conclusions—

Together, these data suggest that HDAC inhibition is a viable therapeutic strategy that holds promise in the treatment of load-induced heart disease.
Company Incentives and Tools for Promoting Telecommuting
Authors: Robèrt Markus , Börjesson Maria
Published: May 2006

The aim of this article is to identify company and employee benefits from telecommuting. Telecommuting implies that a large proportion of the company's office space is unoccupied. To use this efficiently, flexible offices could be introduced in which the employees do not have their own office but use any desk in an open office space. In addition, if telecommuting implies reductions in office space in which employees donate the use of their homes—rent free—to the employer, it is quite fair for the employer to consider returning some of that savings to the telecommuters in compensation for the use of their homes. The results indicate that employees are in fact sensitive to the monetary compensation and that company benefits could be obtained.
Violating Equality in Social Dilemmas: Emotional and Retributive Reactions as a Function of Trust, Attribution, and Honesty
Authors: Stouten Jeroen , De Cremer David , van Dijk Eric
Published: May 2006

In social dilemmas, equality is an important coordination rule. When equality is violated, people seek explanations. In Experiment 1, the authors assessed dispositional trust and found that especially high trusters were affected by the given explanation. High trusters reacted less negatively to external than internal explanations. Experiment 2, using a manipulation of trust in others, revealed a similar pattern across a wider range of negative emotions. In Experiment 3, the authors only induced high trust and showed that when the external explanation turned out to be a lie, emotional and retributive reactions became more negative. Moreover, attribution information did not influence reactions when participants realized that the information was dishonest.
Democracy and the Environment on the Internet
Authors: Zavestoski Stephen , Shulman Stuart , Schlosberg David
Published: May 2006

We hypothesize that recent uses of the Internet as a public-participation mechanism in the United States fail to overcome the adversarial culture that characterizes the American regulatory process. Although the Internet has the potential to facilitate deliberative processes that could result in more widespread public involvement, greater transparency in government processes, and a more satisfied citizenry, we argue that efforts to implement Internet-based public participation have overlaid existing problematic government processes without fully harnessing the transformative power of information technologies. Public comments submitted in two United States Department of Agriculture (USDA) rulemaking processes—the National Organic Program’s organic standard and the Forest Service’s Roadless Area Conservation Rule—compose our data. We conclude that the Internet provides an arena for playing out three types of conflicts that have long plagued environmental decision-making processes: conflicts over trust of federal agencies, the use of science, and the role of public values.
Marital Conflict, Parent-Child Relations, and Youth Maladjustment
Authors: Gerard Jean M. , Krishnakumar Ambika , Buehler Cheryl
Published: May 2006

Contemporaneous and longitudinal associations among marital conflict, parentchild relationship quality, and youth maladjustment were examined using data from the National Survey of Families and Households.Analyses were based on 551 married families with a child age 5 to 11 years at Wave 1. The concurrent association between marital conflict and youth externalizing problems at both waves was mediated completely at Wave 1 and partially at Wave 2 by harsh discipline and parent-youth conflict. The concurrent association between marital conflict and internalizing problems at both waves was mediated partially through parent-youth conflict. Longitudinal mediating effects were detected through stable marital conflict over 5 years and through its connection with parent-youth conflict. Findings delineate areas of specificity and stability in marital conflict processes as children transition from middle childhood through adolescence.
Surgical Anatomy of the Triceps Brachii Tendon
Authors: Madsen Michael , Marx Robert G. , Millett Peter J. , Rodeo Scott A. , Sperling John W. , Warren Russell F.
Published: May 2006

Background

The triceps tendon has been described as a single unit with contribution from each of the 3 heads of the muscle. An observation at the time of surgical repair of a triceps tendon injury led to an anatomical study to further define the anatomy of this tendon as it inserts on the olecranon.

Hypothesis

The medial head of the triceps has a tendon that is distinct from, and deep to, the common tendon of the long and lateral heads.

Study Design

Descriptive laboratory study and case report.

Methods

Eight cadaveric elbows were dissected to examine the triceps tendon. None of the specimens had any evidence of prior injury or surgery to the elbow. All specimens were fresh-frozen and stored at–4°C until they were thawed for use. Skin and subcutaneous tissue were removed, and the tendon of each head of the triceps was explored from the muscle to its bony insertion.

Results

In all 8 specimens, on gross inspection, the medial head had a separate insertion deep to the common insertion of the lateral and long heads. The muscle of the medial head extended further distally than did the long and lateral heads. The medial head was muscular to its deep insertion, with a small amount of tendon blended with the muscle distally. Histologic analysis demonstrated that the tendon of the medial head and that of the other 2 heads are confluent distally at their olecranon insertion.

Conclusion

The medial head of the triceps has a tendon that is distinct from, and deep to, the common tendon of the long and lateral heads on gross inspection. Histologic studies show the insertion of these 2 tendons is confluent.

Clinical Relevance

This anatomy has important implications for surgical repair of these tendon injuries. Rupture of the deep triceps insertion alone can occur and lead to weakness of elbow extension with the elbow flexed beyond 90°. Triceps strength should be tested with the elbow fully flexed when injury to the tendinous insertion is suspected.
Differentially profiling the low-expression transcriptomes of human hepatoma using a novel SSH/microarray approach
Authors: Pan Yi-Shin , Lee Yun-Shien , Lee Yung-Lin , Lee Wei-Chen , Hsieh Sen-Yung
Published: May 2006

Background

The main limitation in performing genome-wide gene-expression profiling is the assay of low-expression genes. Approaches with high throughput and high sensitivity for assaying low-expression transcripts are urgently needed for functional genomic studies. Combination of the suppressive subtractive hybridization (SSH) and cDNA microarray techniques using the subtracted cDNA clones as probes printed on chips has greatly improved the efficiency for fishing out the differentially expressed clones and has been used before. However, it remains tedious and inefficient sequencing works for identifying genes including the great number of redundancy in the subtracted amplicons, and sacrifices the original advantages of high sensitivity of SSH in profiling low-expression transcriptomes.

Results

We modified the previous combination of SSH and microarray methods by directly using the subtracted amplicons as targets to hybridize the pre-made cDNA microarrays (named as "SSH/microarray"). mRNA prepared from three pairs of hepatoma and non-hepatoma liver tissues was subjected to the SSH/microarray assays, as well as directly to regular cDNA microarray assays for comparison. As compared to the original SSH and microarray combination assays, the modified SSH/microarray assays allowed for much easier inspection of the subtraction efficiency and identification of genes in the subtracted amplicons without tedious and inefficient sequencing work. On the other hand, 5015 of the 9376 genes originally filtered out by the regular cDNA microarray assays because of low expression became analyzable by the SSH/microarray assays. Moreover, the SSH/microarray assays detected about ten times more (701 vs. 69) HCC differentially expressed genes (at least a two-fold difference and P < 0.01), particularly for those with rare transcripts, than did the regular cDNA microarray assays. The differential expression was validated in 9 randomly selected genes in 18 pairs of hepatoma/non-hepatoma liver tissues using quantitative RT-PCR. The SSH/microarray approaches resulted in identifying many differentially expressed genes implicated in the regulation of cell cycle, cell death, signal transduction and cell morphogenesis, suggesting the involvement of multi-biological processes in hepato-carcinogenesis.

Conclusion

The modified SSH/microarray approach is a simple but high-sensitive and high-efficient tool for differentially profiling the low-expression transcriptomes. It is most adequate for applying to functional genomic studies.
Protease nexin-1 expression is altered in human breast cancer
Authors: Candia Britny J , Hines William C , Heaphy Christopher M , Griffith Jeffrey K , Orlando Robert A
Published: May 2006

Background

Urokinase-type Plasminogen Activator (uPA), a serine protease, plays a pivotal role in human breast cancer metastasis by mediating the degradation of extracellular matrix proteins and promoting cell motility. In more advanced breast cancers, uPA activity is significantly up regulated and serves as a prognostic indicator of poor patient outcome. Classically, regulation of uPA activity, especially in breast cancers, is thought to be mediated by Type 1 Plasminogen Activator Inhibitor (PAI-1). However, we have recently found that a lesser known natural inhibitor of uPA, Protease Nexin 1 (PN-1), is expressed in normal human mammary tissue. Based on this observation, we investigated if PN-1 is also expressed in human breast cancers where it may contribute to the regulation of uPA and participate in the development of a metastatic phenotype.

Results

Using quantitative real-time PCR analysis, we measured PN-1 mRNA expression in tissues obtained from 26 human breast tumor biopsies and compared these values with those obtained from 10 normal breast tissue samples. Since both PAI-1 and uPA expression levels are known to be elevated in metastatic breast cancer, we also measured their levels in our 26 tumor samples for direct comparison with PN-1 expression. We found that PN-1 expression was elevated over that found in normal mammary tissue; an increase of 1.5- to 3.5-fold in 21 of 26 human breast tumors examined. As anticipated, both PAI-1 and uPA mRNA levels were significantly higher in the majority of breast tumors; 19 of 26 tumors for PAI-1 and 22 of 26 tumors for uPA. A quantile box plot of these data demonstrates that the elevated PN-1 expression in breast tumor tissues directly correlates with the increased expression levels found for PAI-1 and uPA.

Conclusion

The fact that PN-1 expression is elevated in human breast cancer, and that its increased expression is directly correlated with increases measured for PAI-1 and uPA, suggests that PN-1 may contribute to the regulation of uPA-mediate tumor cell motility and metastatic spread.