bluuebunny/crossref_metadata_2025 huggingface dataset:
A Two-State Stochastic Model of REM Sleep Architecture in the Rat
Authors: Gregory Gavin G. , Cabeza Rafael
Published: May 2006

Rapid eye movement (REM) sleep is a recurring state throughout the sleeping period. Based on the examination of 45 sleep records of 3-mo-old male rats during the middle of the light phase, a stochastic model is proposed for the sequence X 1, Y 2, X 2, Y 2, . . . of REM sleep durations X and inter-REM sleep waiting times Y experienced by a rat during a sleeping period. In our model the probability distribution of any variable in the sequence, given the past, is allowed to depend on only the immediately previous variable. The conditional distributions f( yi ‖ xi ) and g( x i+1 ‖ yi ) do not depend on the index i. It is shown that the marginal distributions tend to stationarity. Aggregations of the data on a discrete time scale suggest that the conditional distributions be formulated as two-component mixtures. These component distributions are modeled as Poisson and their means are called the means of short and long waiting time and the means of short and long REM sleep duration. Associated with each mean is a probability weight. Parametric forms are given to the means and probability weights. The model estimated by maximum likelihood shows a good fit to data of the 3-mo-old rats. The model fit to a smaller data set obtained from rats aged 15–22 mo shows a significant shortening of the means for both short and long REM sleep bout durations compared with the means of the 3-mo-old rats. Neuronal correlates for the behavior of the model are discussed in the context of the reciprocal interaction model of REM sleep regulation.
Vibration-Induced Changes in EMG During Human Locomotion
Authors: Verschueren Sabine M. P. , Swinnen Stephan P. , Desloovere Kaat , Duysens Jacques
Published: May 2006

The present study was set up to examine the contribution of Ia afferent input in the generation of electromyographic (EMG) activity. Subjects walked blindfolded along a walkway while tendon vibration was applied continuously to a leg muscle. The effects of vibration were measured on mean EMG activity in stance and swing phase. The results show that vibration of the quadriceps femoris (Q) at the knee and of biceps femoris (BF) at the knee enhanced the EMG activity of these muscles and this occurred mainly in the stance phase of walking. These results suggest involvement of Ia afferent input of Q and BF in EMG activation during stance. In contrast, vibration of muscles at the ankle and hip had no significant effect on burst amplitude. Additionally, the onset time of tibialis anterior was measured to look at timing of phase transitions. Only vibration of quadriceps femoris resulted in an earlier onset of tibialis anterior within the gait cycle, suggesting involvement of these Ia afferents in the triggering of phase transitions. In conclusion, the results of the present study suggest involvement of Ia afferent input in the control of muscle activity during locomotion in humans. A limited role in timing of phase transitions is proposed as well.
Modulation of Rat Corticohippocampal Synaptic Activity by High Pressure and Extracellular Calcium: Single and Frequency Responses
Authors: Talpalar Adolfo E. , Grossman Yoram
Published: May 2006

High pressure (>1.5 MPa) induces a series of disturbances of the nervous system that are generically termed high-pressure nervous syndrome (HPNS). HPNS is characterized by motor and cognitive impairments. The neocortex and the hippocampus are presumably involved in this last disorder. The medial perforant path (MPP) synapse onto the granule cells of the dentate gyrus is the main connection between these structures. We have studied high-pressure (HP) effects on single and frequency response of this synapse. Since effects of HP on various synapses were mimicked by reducing [Ca2+]o, results under these conditions were compared. Medial perforant path-evoked field excitatory postsynaptic potentials (fEPSPs) were recorded from granule cells in rat brain slices. Slices were exposed to high pressure of helium (0.1–10.1 MPa) at 30°C. HP depressed single fEPSPs by 35 and 55% at 5.1 and 10.1 MPa, respectively, and increased paired-pulse facilitation (PPF) at 10- to 40-ms inter-stimulus intervals. Frequency-dependent depression (FDD) was enhanced by HP during trains of stimuli at 50 but not at 25 Hz. Depression of single fEPSPs by reduction of [Ca2+]o from 2 mM control to 1 mM at normal pressure was equivalent to the effect of 10.1 MPa at control [Ca2+]o. However, this low [Ca2+]o induced greater enhancement of PPF, and in contrast, turned FDD at 25–50 Hz into frequency-dependent potentiation. These results suggest that HP depresses single synaptic release by reducing Ca2+ entry, whereas slowing of synaptic frequency response is independent of Ca2+. These findings increase our understanding of HPNS experienced by deep divers.
Handedness: Dominant Arm Advantages in Control of Limb Dynamics
Authors: Bagesteiro Leia B. , Sainburg Robert L.
Published: May 2006

Recent findings from our laboratory suggest that a major factor distinguishing dominant from nondominant arm performance is the ability by which the effects of intersegmental dynamics are controlled by the CNS. These studies indicated that the dominant arm reliably used more torque-efficient patterns for movements made with similar speeds and accuracy than nondominant arm movements. Whereas, nondominant hand-path curvatures systematically varied with the amplitude of the interaction torques transferred between the segments of the moving limb, dominant hand-path curvatures did not. However, our previous studies did not distinguish whether dominant arm coordination advantages emerged from more effective control of dynamic factors or were simply a secondary effect of planning different kinematics. The purpose of this study was to further investigate interlimb differences in coordination through analysis of inverse dynamics and electromyography recorded during the performance of reaching movements. By controlling the amplitude of intersegmental dynamics in the current study, we were able to assess whether systematic differences in torque-efficiency exist, even when differences in hand-path shape were minimal. Subject's arms were supported in the horizontal plane by a frictionless air-jet system and were constrained to movements about the shoulder and elbow joints. Two targets were designed, such that the interaction torques elicited at the elbow were either large or small. Our results showed that the former produced large differences in hand-path curvature, whereas the latter did not. Additionally, the movements with small differences in hand-path kinematics showed substantial differences in torque patterns and corresponding EMG profiles which implied a more torque-efficient strategy for the dominant arm. In view of these findings we propose that distinct neural control mechanisms are employed for dominant and nondominant arm movements.
Modulation of Glutamatergic Transmission by Bergmann Glial Cells in Rat Cerebellum In Situ
Authors: Bordey Angélique , Sontheimer Harald
Published: May 2006

We obtained patch-clamp recordings from neuron-glial cell pairs in cerebellar brain slices to examine the contribution of glutamate (Glu) uptake by Bergmann glial cells to shaping excitatory postsynaptic currents (EPSCs) at the parallel fiber to Purkinje cell synapse. We show that electrical stimulation of parallel fibers not only activates EPSCs in Purkinje cells but also activates inward currents in antigenically identified Bergmann glial cells that invest Purkinje cell synapse with their processes. The inward current is partially due to 6-cyano-7-nitroquinoxalene-2,3-dione (CNQX)- and 2-amino-5-phosphonopentanoic acid (AP5)-sensitive ionotropic Glu receptors, but ≥70% of the current was mediated byd,l-threo-beta-hydroxyaspartate (THA)-sensitive Glu transporters. Glu inward currents were completely and reversibly inhibited by depolarization of Bergmann glial cells to positive membrane potentials allowing biophysical inhibition of Glu uptake into a single glial cell. Inhibition of Glu transport into Bergmann glial cells by voltage-clamping the cell to depolarized potentials caused a reversible increase in spontaneous EPSC frequency in the Purkinje cell. This increase could also be achieved by pharmacological inhibition of Glu transport with the Glu transport inhibitor THA, suggesting that inhibition of Glu uptake into Bergmann glial cells is responsible for the modulation of postsynaptic EPSCs. THA modulation of spontaneous EPSCs could only be observed in the absence of TTX, suggesting primarily a presynaptic effect. Taken together these data suggest that glial Glu uptake can profoundly affect excitatory transmission in the cerebellum, most likely by regulating presynaptic glutamate release.
Neural Circuits Subserving the Retrieval and Maintenance of Abstract Rules
Authors: Bunge Silvia A. , Kahn Itamar , Wallis Jonathan D. , Miller Earl K. , Wagner Anthony D.
Published: May 2006

Behavior is often governed by abstract rules or instructions for behavior that can be abstracted from one context and applied to another. Prefrontal cortex (PFC) is thought to be important for representing rules, although the contributions of ventrolateral (VLPFC) and dorsolateral (DLPFC) regions remain under-specified. In the present study, event-related fMRI was used to examine abstract rule representation in humans. Prior to scanning, subjects learned to associate unfamiliar shapes and nonwords with particular rules. During each fMRI trial, presentation of one of these cues was followed by a delay and then by sample and probe stimuli. Match and non-match rules required subjects to indicate whether or not the sample and probe matched; go rules required subjects to make a response that was not contingent on the sample/probe relation. Left VLPFC, parietal cortex, and pre-SMA exhibited sensitivity to rule type during the cue and delay periods. Delay-period activation in these regions, but not DLPFC, was greater when subjects had to maintain response contingencies (match, non-match) relative to when the cue signaled a specific response (go). In contrast, left middle temporal cortex exhibited rule sensitivity during the cue but not delay period. These results support the hypothesis that VLPFC interacts with temporal cortex to retrieve semantic information associated with a cue and with parietal cortex to retrieve and maintain relevant response contingencies across delays. Future investigations of cross-regional interactions will enable full assessment of this account. Collectively, these results demonstrate that multiple, neurally separable processes are recruited during abstract rule representation.
Spatial Representation of Predictive Motor Learning
Authors: Witney Alice G. , Wolpert Daniel M.
Published: May 2006

A key feature of skilled motor behavior is the ability of the CNS to predict the consequences of its actions. Such prediction occurs when one hand pulls on an object held in the other hand; the restraining hand generates an anticipatory increase in grip force, thereby preventing the object from slipping. When manipulating a novel object, the CNS adapts its predictive response to ensure that predictions are accurately tuned to the dynamics of the object. Here we examine whether learning to predict the consequences of an action on a novel object is restricted to the actions performed during manipulation or generalizes to novel actions. A bimanual task in which subjects held an object in each hand and the relationship between actions on one object and the motion of the other could be computer controlled from trial-to-trial was used. In four conditions we varied the spatial relationship between the direction of force subjects applied to the left-hand object and the consequent direction of motion of an object held in their right hand, which subjects were required to restrain. The results show that predictive learning was local to the direction of forces experienced during learning and that the magnitude of predictive responses was greatly reduced for novel directions of action of the left hand. The pattern of generalization shows that the representation of predictive learning is spatially local and can be approximated as having a spatially narrow Gaussian basis function.
Oblique Effect: A Neural Basis in the Visual Cortex
Authors: Li Baowang , Peterson Matthew R. , Freeman Ralph D.
Published: May 2006

The details of oriented visual stimuli are better resolved when they are horizontal or vertical rather than oblique. This “oblique effect” has been confirmed in numerous behavioral studies in humans and to some extent in animals. However, investigations of its neural basis have produced mixed and inconclusive results, presumably due in part to limited sample sizes. We have used a database to analyze a population of 4,418 cells in the cat's striate cortex to determine possible differences as a function of orientation. We find that both the numbers of cells and the widths of orientation tuning vary as a function of preferred orientation. Specifically, more cells prefer horizontal and vertical orientations compared with oblique angles. The largest population of cells is activated by orientations close to horizontal. In addition, orientation tuning widths are most narrow for cells preferring horizontal orientations. These findings are most prominent for simple cells tuned to high spatial frequencies. Complex cells and simple cells tuned to low spatial frequencies do not exhibit these anisotropies. For a subset of simple cells from our population ( n = 104), we examined the relative contributions of linear and nonlinear mechanisms in shaping orientation tuning curves. We find that linear contributions alone do not account for the narrower tuning widths at horizontal orientations. By modeling simple cells as linear filters followed by static expansive nonlinearities, our analysis indicates that horizontally tuned cells have a greater nonlinear component than those tuned to other orientations. This suggests that intracortical mechanisms play a major role in shaping the oblique effect.
Angiotensin AT1-Receptors Depolarize Neonatal Spinal Motoneurons and Other Ventral Horn Neurons Via Two Different Conductances
Authors: Oz Murat , Renaud Leo P.
Published: May 2006

Angiotensin receptors are highly expressed in neonatal spinal cord. To identify their influence on neuronal excitability, we used patch-clamp recordings in spinal cord slices to assess responses of neonatal rat (5–12 days) ventral horn neurons to bath-applied angiotensin II (ANG II; 1 μM). In 14/34 identified motoneurons tested under current clamp, ANG II induced a slowly rising and prolonged membrane depolarization, blockable with Losartan ( n = 5) and (Sar1, Val5, Ala8)-ANG II (Saralasin, n = 4) but not PD123319 (1 μM each; n = 4). Under voltage clamp ( V H −65 mV), 7/22 motoneurons displayed an ANG-II-induced tetrodotoxin-resistant inward current (−128 ± 31 pA) with a similar time course, an associated reduction in membrane conductance and net current reversal at −98.8 ± 3.9 mV. Losartan-sensitive ANG II responses were also evoked in 27/78 tested ventral horn “interneurons.” By contrast with motoneurons, their ANG-II-induced inward current was smaller (−39.9 ± 5.2 pA) and analysis of their I-V plots revealed three patterns. In eight cells, membrane conductance decreased with net inward current reversing at −103.8 ± 4.1 mV. In seven cells, membrane conductance increased with net current reversing at −37.9 ± 3.6 mV. In 12 cells, I-V lines remained parallel with no reversal within the current range tested. Intracellular dialysis with GTP-γ-S significantly prolonged the ANG II effect in seven responsive interneurons and GDP-β-S significantly reduced the ANG II response in four other cells. Peak inward currents were significantly reduced in all 13 responding neurons recorded in slices incubated in pertussis toxin (5 μg/ml) for 12–18 h or in 12 neurons perfused with N-ethylmaleimide. Of 29 interneurons sensitive to pertussis toxin or N-ethylmaleimide treatment, 9 cells displayed a decrease in membrane conductance that reversed at −101.3 ± 3.8 mV. In eight cells, membrane conductance increased and reversed at −38.7 ± 3.4 mV. In 12 cells, the I-V lines remained parallel with no reversal within the current range tested, suggesting that both conductances are modulated by pertussis toxin-sensitive G proteins. These observations reveal a direct, G-protein-mediated depolarizing action of ANG II on neonatal rat ventral horn neurons. They also imply involvement of two distinct conductances that are differentially distributed among different cell types.
Local Circuit Properties Underlying Cortical Reorganization
Authors: Hickmott Peter W. , Merzenich Michael M.
Published: May 2006

Peripheral denervation has been shown to cause reorganization of the deafferented somatotopic region in primary somatosensory cortex (S1). However, the basic mechanisms that underlie reorganization are not well understood. In the experiments described in this paper, a novel in vivo/in vitro preparation of adult rat S1 was used to determine changes in local circuit properties associated with the denervation-induced plasticity of the cortical representation in rat S1. In the present studies, deafferentation of rat S1 was induced by cutting the radial and median nerves in the forelimb of adult rats, resulting in a rapid shift of the location of the forepaw/lower jaw border; the amount of the shift increased over the times assayed, through 28 days after denervation. The locations of both borders (i.e., original and reorganized) were marked with vital dyes, and slices from the marked region were used for whole-cell recording. Responses were evoked using electrical stimulation of supragranular S1 and recorded in supragranular neurons close to either the original or reorganized border. For each neuron, postsynaptic potentials (PSPs) were evoked by stimulation of fibers that crossed the border site (CB stim) and by equivalent stimulation that did not cross (NCB stim). Monosynaptic inhibitory postsynaptic potentials (IPSPs) were also examined after blocking excitatory transmission with 15 μM CNQX plus 100 μMdl-APV. The amplitudes of PSPs and IPSPs were compared between CB and NCB stimulation to quantify effects of the border sites on excitation and inhibition. Previous results using this preparation in the normal (i.e., without induced plasticity) rat S1 demonstrated that at a normal border both PSPs and IPSPs were smaller when evoked with CB stimulation than with NCB stimulation. For most durations of denervation, a similar bias (i.e., smaller responses with CB stimulation) for PSPs and IPSPs was observed at the site of the novel reorganized border, while no such bias was observed at the suppressed original border site. Thus changes in local circuit properties (excitation and inhibition) can reflect larger-scale changes in cortical organization. However, specific dissociations between these local circuit properties and the presence of the novel border at certain durations of denervation were also observed, suggesting that there are several intracortical processes contributing to cortical reorganization over time and that excitation and inhibition may contribute differentially to them.
Role of Cocontraction in Arm Movement Accuracy
Authors: Gribble Paul L. , Mullin Lucy I. , Cothros Nicholas , Mattar Andrew
Published: May 2006

Cocontraction (the simultaneous activation of antagonist muscles around a joint) provides the nervous system with a way to adapt the mechanical properties of the limb to changing task requirements—both in statics and during movement. However, relatively little is known about the conditions under which the motor system modulates limb impedance through cocontraction. The goal of this study was to test for a possible relationship between cocontraction and movement accuracy in multi-joint limb movements. The electromyographic activity of seven single- and double-joint shoulder and elbow muscles was recorded using surface electrodes while subjects performed a pointing task in a horizontal plane to targets that varied randomly in size. Movement speed was controlled by providing subjects with feedback on a trial-to-trial basis. Measures of cocontraction were estimated both during movement and during a 200-ms window immediately following movement end. We observed an inverse relationship between target size and cocontraction: as target size was reduced, cocontraction activity increased. In addition, trajectory variability decreased and endpoint accuracy improved. This suggests that, although energetically expensive, cocontraction may be a strategy used by the motor system to facilitate multi-joint arm movement accuracy. We also observed a general trend for cocontraction levels to decrease over time, supporting the idea that cocontraction and associated limb stiffness are reduced over the course of practice.
Amygdala Input Promotes Spread of Excitatory Neural Activity From Perirhinal Cortex to the Entorhinal–Hippocampal Circuit
Authors: Kajiwara Riichi , Takashima Ichiro , Mimura Yuka , Witter Menno P. , Iijima Toshio
Published: May 2006

A number of sensory modalities most likely converge in the rat perirhinal cortex. The perirhinal cortex also interconnects with the amygdala, which plays an important role in various motivational and emotional behaviors. The neural pathway from the perirhinal cortex to the entorhinal cortex is considered one of the main paths into the entorhinal–hippocampal network, which has a crucial role in memory processes. To investigate the potential associative function of the perirhinal cortex with respect to sensory and motivational stimuli and the influence of the association on the perirhinal–entorhinal–hippocampal neurocircuit, we prepared rat brain slices including the perirhinal cortex, entorhinal cortex, hippocampal formation, and amygdala. We used an optical imaging technique with a voltage-sensitive dye to analyze 1) the spatial and functional distribution of inputs from the lateral nucleus of the amygdala to the perirhinal cortex; 2) the spread of neural activity in the perirhinal cortex after layers II/III stimulation, which mimics sensory input to the perirhinal cortex; and 3) the effect of associative inputs to the perirhinal cortex from both the lateral amygdaloid nucleus and layers II/III of the perirhinal cortex on the perirhinal–entorhinal–hippocampal neurocircuit. Following stimulation in the superficial layers of the perirhinal cortex, electrical activity only propagated into the entorhinal cortex when sufficient activation occurred in the deep layers of perirhinal area 35. We observed that single stimulation of either the perirhinal cortex or amygdala did not result in sufficient neural activation of the deep layers of areas 35 to provoke activity propagation into the entorhinal cortex. However, the deep layers of area 35 were depolarized much more strongly when the two stimuli were applied simultaneously, resulting in spreading activation in the entorhinal cortex. Our observations suggest that a functional neural basis for the association of higher-order sensory inputs and emotion-related inputs exists in the perirhinal cortex and that transfer of sensory information to the entorhinal–hippocampal circuitry might be affected by the association of that information with incoming information from the amygdala.
Contrast Threshold of a Brisk-Transient Ganglion Cell In Vitro
Authors: Dhingra Narender K. , Kao Yen-Hong , Sterling Peter , Smith Robert G.
Published: May 2006

We measured the contrast threshold for mammalian brisk-transient ganglion cells in vitro. Spikes were recorded extracellularly in the intact retina (guinea pig) in response to a spot with sharp onset, flashed for 100 ms over the receptive field center. Probability density functions were constructed from spike responses to stimulus contrasts that bracketed threshold. Then an “ideal observer” (IO) compared additional trials to these probability distributions and decided, using a single-interval, two-alternative forced-choice procedure, which contrasts had most likely been presented. From these decisions we constructed neurometric functions that yielded the threshold contrast by linear interpolation. Based on the number of spikes in a response, the IO detected contrasts as low as 1% [4.2 ± 0.4% (SE); n = 35]; based on the temporal pattern of spikes, the IO detected contrasts as low as 0.8% (2.8 ± 0.2%). Contrast increments above a very low “basal contrast” were discriminated with greater sensitivity than they were detected against the background. Performance was optimal near 37°C and declined with a Q 10 of about 2, similar to that of retinal metabolism. By the method used by previous in vivo studies of brisk-transient cells, our most sensitive cells had similar thresholds. The in vitro measurements thus provide an important benchmark for comparing sensitivity of neurons upstream (cone and bipolar cell) and downstream to assess efficiency of retinal and central circuits.
A Comparison of Macaque Behavior and Superior Colliculus Neuronal Activity to Predictions From Models of Two-Choice Decisions
Authors: Ratcliff Roger , Cherian Anil , Segraves Mark
Published: May 2006

Recently, models in psychology have been shown capable of accounting for the full range of behavioral data from simple two-choice decision tasks: mean reaction times for correct and error responses, accuracy, and the reaction time distributions for correct and error responses. At the same time, recent data from neural recordings have allowed investigation of the neural systems that implement such decisions. In the experiment presented here, neural recordings were obtained from superior colliculus prelude/buildup cells in two monkeys while they performed a two-choice task that has been used in humans for testing psychological models of the decision process. The best-developed psychological model, the diffusion model, and a competing model, the Poisson counter model, were explicitly fit to the behavioral data. The pattern of activity shown in the prelude/buildup cells, including the point at which response choices were discriminated, was matched by the evidence accumulation process predicted from the diffusion model using the parameters from the fits to the behavioral data but not by the Poisson counter model. These results suggest that prelude/buildup cells in the superior colliculus, or cells in circuits in which the superior colliculus cells participate, implement a diffusion decision process or a variant of the diffusion process.
Human Frontal Eye Fields and Visual Search
Authors: Muggleton Neil G. , Juan Chi-Hung , Cowey Alan , Walsh Vincent
Published: May 2006

Recent physiological recording studies in monkeys have suggested that the frontal eye fields (FEFs) are involved in visual scene analysis even when eye movement commands are not required. We examined this proposed function of the human frontal eye fields during performance of visual search tasks in which difficulty was matched and eye movements were neither necessary nor required. Magnetic stimulation over FEF modulated performance on a conjunction search task and a simple feature search task in which the target was unpredictable from trial to trial, primarily by increasing false alarm responses. Simple feature search with a predictable target was not affected. The results establish that human FEFs are critical to visual selection, regardless of the need to generate a saccade command.
What Determines the Frequency of Fast Network Oscillations With Irregular Neural Discharges? I. Synaptic Dynamics and Excitation-Inhibition Balance
Authors: Brunel Nicolas , Wang Xiao-Jing
Published: May 2006

When the local field potential of a cortical network displays coherent fast oscillations (∼40-Hz gamma or ∼200-Hz sharp-wave ripples), the spike trains of constituent neurons are typically irregular and sparse. The dichotomy between rhythmic local field and stochastic spike trains presents a challenge to the theory of brain rhythms in the framework of coupled oscillators. Previous studies have shown that when noise is large and recurrent inhibition is strong, a coherent network rhythm can be generated while single neurons fire intermittently at low rates compared to the frequency of the oscillation. However, these studies used too simplified synaptic kinetics to allow quantitative predictions of the population rhythmic frequency. Here we show how to derive quantitatively the coherent oscillation frequency for a randomly connected network of leaky integrate-and-fire neurons with realistic synaptic parameters. In a noise-dominated interneuronal network, the oscillation frequency depends much more on the shortest synaptic time constants (delay and rise time) than on the longer synaptic decay time, and ∼200-Hz frequency can be realized with synaptic time constants taken from slice data. In a network composed of both interneurons and excitatory cells, the rhythmogenesis is a compromise between two scenarios: the fast purely interneuronal mechanism, and the slower feedback mechanism (relying on the excitatory-inhibitory loop). The properties of the rhythm are determined essentially by the ratio of time scales of excitatory and inhibitory currents and by the balance between the mean recurrent excitation and inhibition. Faster excitation than inhibition, or a higher excitation/inhibition ratio, favors the feedback loop and a much slower oscillation (typically in the gamma range).
Activity Profiles of Single Neurons in Caudal Anterior Cingulate Cortex During Trace Eyeblink Conditioning in the Rabbit
Authors: Weible Aldis P. , Weiss Craig , Disterhoft John F.
Published: May 2006

Acquisition of trace eyeblink conditioning involves the association of a conditioned stimulus (CS) with an unconditioned stimulus (US) separated by a stimulus-free trace interval. This form of conditioning is dependent upon the hippocampus and the caudal anterior cingulate cortex (AC), in addition to brain stem and cerebellar circuitry. Hippocampal involvement in trace eyeblink conditioning has been studied extensively, but the involvement of caudal AC is less well understood. In the present study, we compared neuronal responses from rabbits given either paired (trace conditioning) or unpaired (pseudoconditioning) presentations of the CS and US. Presentation of the CS elicited significant increases in neuronal activity at the onset of both trace conditioning and pseudoconditioning. A robust CS-elicited neuronal response persisted throughout the first 2 days of trace conditioning, declining gradually across subsequent training sessions. In contrast, the magnitude of the CS-elicited excitatory response during pseudoconditioning began to decline within the first 10 trials. Neurons exhibiting excitatory responses to the CS during trace conditioning also exhibited excitatory responses to the US that were significantly greater in magnitude than US-elicited responses during pseudoconditioning. CS-elicited decreases in neuronal activity became more robust over the course of trace conditioning compared to pseudoconditioning. Reductions in activity during the CS interval consistently preceded excitation in both training groups, suggesting that the CS-elicited decreases in neuronal activity may serve to increase the signal-to-noise ratio of the excitatory response to the tone. Taken together, these data suggest that the caudal AC is involved early in trace eyeblink conditioning and that maintenance of the CS-elicited excitatory response may serve to signal the salience of the tone.
Contribution of BK Ca2+-Activated K+Channels to Auditory Neurotransmission in the Guinea Pig Cochlea
Authors: Skinner Liam J. , Enée Véronique , Beurg Maryline , Jung Hak Hyun , Ryan Allen F. , Hafidi Aziz , Aran Jean-Marie , Dulon Didier
Published: May 2006

Large-conductance calcium-activated potassium (BK) channels are known to play a prominent role in the hair cell function of lower vertebrates where these channels determine electrical tuning and regulation of neurotransmitter release. Very little is known, by contrast, about the role of BK channels in the mammalian cochlea. In the current study, we perfused specific toxins in the guinea pig cochlea to characterize the role of BK channels in cochlear neurotransmission. Intracochlear perfusion of charybdotoxin (ChTX) or iberiotoxin (IbTX) reversibly reduced the compound action potential (CAP) of the auditory nerve within minutes. The cochlear microphonics (CM at f1 = 8 kHz and f2 = 9.68 kHz) and their distortion product (DPCM at 2f1–f2) were essentially not affected, suggesting that the BK specific toxins do not alter the active cochlear amplification at the outer hair cells (OHCs). We also tested the effects of these toxins on the whole cell voltage-dependent membrane current of isolated guinea pig inner hair cells (IHCs). ChTX and IbTX reversibly reduced a fast outward current (activating above –40 mV, peaking at 0 mV with a mean activation time constant τ ranging between 0.5 and 1 ms). A similar block of a fast outward current was also observed with the extracellular application of barium ions, which we believe permeate through Ca2+channels and block BK channels. In situ hybridization of Slo antisense riboprobes and immunocytochemistry demonstrated a strong expression of BK channels in IHCs and spiral ganglion and to a lesser extent in OHCs. Overall, our results clearly revealed the importance of BK channels in mammalian cochlear neurotransmission and demonstrated that at the presynaptic level, fast BK channels are a significant component of the repolarizing current of IHCs.
Mechanisms to Explain Surfactant Responses
Authors: Jobe Alan H.
Published: May 2006

Surfactant is now standard of care for infants with respiratory distress syndrome. Surfactant treatments are effective because of complex metabolic interactions between surfactant and the preterm lung. The large treatment dose functions as substrate; it is taken up by the preterm lung and is reprocessed and secreted with improved function. The components of the treatment surfactant remain in the preterm lung for days. If lung injury is avoided, then surfactant inhibition is minimized. Prenatal corticosteroids complement surfactant to further enhance lung function. The magic of surfactant therapy results from the multiple interactions between surfactant and the preterm lung.
New Synthetic Surfactant – How and When?
Authors: Curstedt Tore , Johansson Jan
Published: May 2006

Animal-derived surfactant preparations are very effective in the treatment of premature infants with respiratory distress syndrome but they are expensive to produce and supplies are limited. In order to widen the indications for surfactant treatment there is a need for synthetic preparations, which can be produced in large quantities and at a reasonable cost. However, development of clinically active synthetic surfactants has turned out to be more complicated than initially anticipated. The hydrophobic surfactant proteins, SP-B and SP-C, which are involved in the adsorption of surface-active lipids to the air-liquid interface of the alveoli and increase alveolar stability, are either too big to synthesize, structurally complex or unstable in pure form. A new generation of synthetic surfactants containing simplified phospholipid mixtures and small amounts of peptides replacing the hydrophobic proteins is currently under development and will in the near future be introduced into the market. However, more trials need to be performed before any conclusions can be drawn about the effectiveness of these synthetic surfactants in relation to natural animal-derived preparations.
Extension of the Haseman-Elston Regression Model to Longitudinal Data
Authors: Won Sungho , Elston Robert C. , Park Taesung
Published: May 2006

We propose an extension to longitudinal data of the Haseman and Elston regression method for linkage analysis. The proposed model is a mixed model having several random effects. As response variable, we investigate the sibship sample mean corrected cross-product (smHE) and the BLUP-mean corrected cross product (pmHE), comparing them with the original squared difference (oHE), the overall mean corrected cross-product (rHE), and the weighted average of the squared difference and the squared mean-corrected sum (wHE). The proposed model allows for the correlation structure of longitudinal data. Also, the model can test for gene × time interaction to discover genetic variation over time. The model was applied in an analysis of the Genetic Analysis Workshop 13 (GAW13) simulated dataset for a quantitative trait simulating systolic blood pressure. Independence models did not preserve the test sizes, while the mixed models with both family and sibpair random effects tended to preserve size well.
Kernicterus Associated with Hereditary Spherocytosis and UGT1A1 Promoter Polymorphism
Authors: Berardi Alberto , Lugli Licia , Ferrari Fabrizio , Gargano Giancarlo , D’Apolito Maria , Marrone Agnese , Iolascon Achille
Published: May 2006

Introduction: An apparent re-emergence of kernicterus has been recently reported, with some cases occurring in otherwise healthy breastfed newborn. Methods: We describe a case of kernicterus in a term Caucasian newborn. Results: An exceptional polymorphism of UGT1A1 gene promoter co-existed with asymptomatic inherited spherocytosis, due to erythroid anion exchange (band-3) deficiency. Both concurred to the development of severe neonatal hyperbilirubinaemia. Conclusion: As some cases of kernikterus remain unresolved, haemolytic diseases and bilirubin metabolism disorders should be carefully investigated in unexplained severe neonatal hyperbilirubinaemia.
Interleukin-12 Inhibits Eosinophil Degranulation and Migration but Does Not Promote Eosinophil Apoptosis
Authors: Davoine Francis , Ferland Claudine , Chakir Jamila , Lee Joo Eun , Adamko Darryl J. , Moqbel Redwan , Laviolette Michel
Published: May 2006

Background: Animal and human studies demonstrated that interleukin (IL)-12, a Th1 cytokine, reduces blood and bronchial eosinophilia, and airway hyperreactivity. According to current concepts, these effects are mediated through the release of cytokines promoting eosinophil recruitment and activation. However, the presence of IL-12 receptors on eosinophils suggests that IL-12 also acts directly on eosinophils. We postulated that IL-12 directly modulates eosinophil functions and has the capacity to regulate eosinophil degranulation, migration and survival, in vitro. Method: Effects of IL- 12 on purified human blood eosinophils were evaluated for peroxidase (EPO) release, eotaxin-induced migration through a model of basement membrane (Matrigel), and survival. Results: IL-12 inhibited 50% of PAF and secretory IgA-induced EPO release (n = 8, p < 0.001). IL-12 also reduced eotaxin-induced migration through Matrigel by 54 ±6% (n = 6, p < 0.01). These effects were not explained by an IL-12-induced impaired viability or apoptosis. Conclusion: Our results demonstrate that IL-12 directly modulates eosinophil functions without promoting apoptosis and explain, at least in part, the effects of IL-12 on eosinophils observed in in vivo studies.
Prediction of Intravenous Immunoglobulin Unresponsiveness in Patients With Kawasaki Disease
Authors: Kobayashi Tohru , Inoue Yoshinari , Takeuchi Kazuo , Okada Yasunori , Tamura Kazushi , Tomomasa Takeshi , Kobayashi Tomio , Morikawa Akihiro
Published: May 2006

Background—

In the present study, we developed models to predict unresponsiveness to intravenous immunoglobulin (IVIG) in Kawasaki disease (KD).

Methods and Results—

We reviewed clinical records of 546 consecutive KD patients (development dataset) and 204 subsequent KD patients (validation dataset). All received IVIG for treatment of KD. IVIG nonresponders were defined by fever persisting beyond 24 hours or recrudescent fever associated with KD symptoms after an afebrile period. A 7-variable logistic model was constructed, including day of illness at initial treatment, age in months, percentage of white blood cells representing neutrophils, platelet count, and serum aspartate aminotransferase, sodium, and C-reactive protein, which generated an area under the receiver-operating-characteristics curve of 0.84 and 0.90 for the development and validation datasets, respectively. Using both datasets, the 7 variables were used to generate a simple scoring model that gave an area under the receiver-operating-characteristics curve of 0.85. For a cutoff of 0.15 or more in the logistic regression model and 4 points or more in the simple scoring model, sensitivity and specificity were 86% and 67% in the logistic model and 86% and 68% in the simple scoring model. The kappa statistic is 0.67, indicating good agreement between the logistic and simple scoring models.

Conclusions—

Our predictive models showed high sensitivity and specificity in identifying IVIG nonresponders among KD patients.
An Abnormal Mitochondrial–Hypoxia Inducible Factor-1α–Kv Channel Pathway Disrupts Oxygen Sensing and Triggers Pulmonary Arterial Hypertension in Fawn Hooded Rats
Authors: Bonnet Sébastien , Michelakis Evangelos D. , Porter Christopher J. , Andrade-Navarro Miguel A. , Thébaud Bernard , Bonnet Sandra , Haromy Alois , Harry Gwyneth , Moudgil Rohit , McMurtry M. Sean , Weir E. Kenneth , Archer Stephen L.
Published: May 2006

Background—

The cause of pulmonary arterial hypertension (PAH) was investigated in humans and fawn hooded rats (FHR), a spontaneously pulmonary hypertensive strain.

Methods and Results—

Serial Doppler echocardiograms and cardiac catheterizations were performed in FHR and FHR/BN1, a consomic control that is genetically identical except for introgression of chromosome 1. PAH began after 20 weeks of age, causing death by &60 weeks. FHR/BN1 did not develop PAH. FHR pulmonary arterial smooth muscle cells (PASMCs) had a rarified reticulum of hyperpolarized mitochondria with reduced expression of electron transport chain components and superoxide dismutase-2. These mitochondrial abnormalities preceded PAH and persisted in culture. Depressed mitochondrial reactive oxygen species (ROS) production caused normoxic activation of hypoxia inducible factor (HIF-1α), which then inhibited expression of oxygen-sensitive, voltage-gated K
+
channels (eg, Kv1.5). Disruption of this mitochondrial-HIF-Kv pathway impaired oxygen sensing (reducing hypoxic pulmonary vasoconstriction, causing polycythemia), analogous to the pathophysiology of chronically hypoxic Sprague-Dawley rats. Restoring ROS (exogenous H
2
O
2
) or blocking HIF-1α activation (dominant-negative HIF-1α) restored Kv1.5 expression/function. Dichloroacetate, a mitochondrial pyruvate dehydrogenase kinase inhibitor, corrected the mitochondrial-HIF-Kv pathway in FHR-PAH and human PAH PASMCs. Oral dichloroacetate regressed FHR-PAH and polycythemia, increasing survival. Chromosome 1 genes that were dysregulated in FHRs and relevant to the mitochondria-HIF-Kv pathway included HIF-3α (an HIF-1α repressor), mitochondrial cytochrome c oxidase, and superoxide dismutase-2. Like FHRs, human PAH-PASMCs had dysmorphic, hyperpolarized mitochondria; normoxic HIF-1α activation; and reduced expression/activity of HIF-3α, cytochrome c oxidase, and superoxide dismutase-2.

Conclusions—

FHRs have a chromosome 1 abnormality that disrupts a mitochondria-ROS-HIF-Kv pathway, leading to PAH. Similar abnormalities occur in idiopathic human PAH. This study reveals an intersection between oxygen-sensing mechanisms and PAH. The mitochondria-ROS-HIF-Kv pathway offers new targets for PAH therapy.
Miraculous Images and the Sanctification of Urban Neighborhood in Post-Medieval Italy
Authors: Garnett Jane , Rosser Gervase
Published: May 2006

In Liguria, in northern Italy, religious images (usually of the Virgin Mary) dating from the medieval and early modern period continue to be the focus of local cults that create a powerful spiritual sense of neighborhood through common visual references. Their histories are often complex, at certain times involving the defense of local interests against outsiders, sometimes serving as a focal point for the reconciliation of disputes. Some local cults have been coopted by wider groupings, yet they may continue to unite individual neighborhoods. They are able to create a shared identity that ties migrants and travelers to their place of origin. The histories of such local cults reveal the creation of neighborhood identity to be an ongoing and fluctuating process, one that local people deliberately cultivate, and yet one that may simultaneously serve different groups in different ways.
From Urban Jail to Bourgeois Suburb
Authors: Davison Graeme
Published: May 2006

Early colonial Sydney was founded on convict transportation but by the 1820s was being transformed by free settlement in a developing market economy. Neighborhood relations in the town were shaped by these intersecting influences, the first dividing convict from free settler, the second dividing rich from poor. Descriptions of the town portray it as divided between a plebeian west and a respectable east, but analysis of the 1828 census reveals a more complex social geography where convicts, exconvicts, and free settlers met in individual households and neighborhoods. Court records reveal the tensions this created. The solution, for many of the urban elite, was urban planning that would create a uniform, clean, segregated, and disciplined community.
Drawing the “Color Line”
Authors: Garb Margaret
Published: May 2006

Emphasizing the importance of exclusion in the formation of urban neighborhoods, this study of early twentieth-century Chicago provides new insights into the significance of real estate markets in the development of racial segregation. Chicago's “color line” emerged from the decisions and strategies of owners, salesmen, entrepreneurs, developers, and neighborhood associations, who joined together in a concerted campaign to evermore securely link the value of properties and neighborhoods to racial identity.
Grandchildren's Perceptions of Caring for Grandparents
Authors: Fruhauf Christine A. , Jarrott Shannon E. , Allen Katherine R.
Published: May 2006

Despite the fact that caregiving related issues are well researched in the field of family gerontology, the developmental experiences of grandchildren caregivers and the meanings of their caregiving experiences have not been explored. Influenced by the lifespan perspective and a constructionism lens, interviews were conducted with 17 grandchildren (ages 21 to 29 years old) who were currently providing care for a grandparent. Grandchildren cargivers reported that filial obligation and preparing for the future were how they made sense of their role. Grandchildren experienced benefits and costs from their caregiving role and developed coping mechanisms that allowed them to be successful caregivers. Professionals should include grandchildren in established caregiver support programs to recognize the generational needs of grandchildren caregivers in their 20s.