bluuebunny/crossref_metadata_2025 huggingface dataset:
Recruitment Order of Cat Abducens Motoneurons and Internuclear Neurons
Authors: Pastor Ángel M. , González-Forero David
Published: May 2006

Abducens neurons undergo a dose-dependent synaptic blockade (either disinhibition or complete blockade) when tetanus neurotoxin (TeNT) is injected into the lateral rectus muscle at either a low (0.5) or a high dose (5 ng/kg). We studied the firing pattern and recruitment order in abducens neurons both in control and after TeNT injection. The eye position threshold for recruitment of control abducens neurons was exponentially related to the eye position and velocity sensitivities. We also found a constancy of recruitment threshold for different eye movement modalities (spontaneous, optokinetic, and vestibular). Exponential relationships were found, as well, for eye velocity sensitivity during saccades and for position and velocity sensitivities during the vestibulo-ocular reflex. Likewise, inverse relationships were found between recruitment threshold or position sensitivity with the antidromic latency in control abducens neurons. These relationships, however, did not apply following TeNT treatment. Neuronal firing after TeNT appeared either disinhibited (low dose) or depressed (high dose), but the relationships between neuronal sensitivities and recruitment still applied. However, the pattern of recruitment shifted toward the treated side as more inputs were blocked by the low- and high-dose treatments, respectively. Nonetheless, although the recruitment-to-sensitivity relationships persisted under the TeNT synaptic blockade, we conclude that synaptic inputs are determinant for establishing the recruitment threshold and recruitment spacing of abducens motoneurons and internuclear neurons.
Independent Processing of the Temporal and Ordinal Structure of Movement Sequences
Authors: Ullén Fredrik , Bengtsson Sara L.
Published: May 2006

We investigated if the temporal and ordinal structures of sequences can be represented and learned independently. In Experiment 1, subjects learned three rhythmic sequences of key presses with the right index finger: Combined consisted of nine key presses with a corresponding temporal structure of eight intervals; Temporal had the temporal structure of Combined but was performed on one key; Ordinal had the ordinal structure of Combined but an isochronous rhythm. Subjects were divided into two groups. Group 1 first learned Combined, then Temporal and Ordinal; Group 2 first learned Temporal and Ordinal, then Combined. Strong transfer effects were seen in both groups. In Group 1, having learned combined facilitated the learning of the temporal ( Temporal) or ordinal ( Ordinal) sequence alone; in Group 2, having learned Temporal and Ordinal facilitated the learning of Combined, where the two are combined. This supports that subjects had formed independent temporal and ordinal representations. In Experiment 2, we investigated if these can be learned independently. Subjects repeatedly reproduced sequences with fixed temporal and random ordinal structure; random temporal and fixed ordinal structure; and random temporal and ordinal structures. Temporal and ordinal learning was seen only in the first and second sequences, respectively. In summary, we provide evidence for the existence of independent systems for learning and representation of ordinal and temporal sequences and for implicit learning of temporal sequences. This may be important for fast learning and flexibility in motor control.
Long-Term Neuromodulatory Regulation of a Motor Pattern–Generating Network: Maintenance of Synaptic Efficacy and Oscillatory Properties
Authors: Thoby-Brisson Muriel , Simmers John
Published: May 2006

Rhythm generation by the pyloric motor network in the stomatogastric ganglion (STG) of the spiny lobster requires permissive neuromodulatory inputs from other central ganglia. When these inputs to the STG are suppressed by cutting the single, mainly afferent stomatogastric nerve (stn), pyloric neurons cease to burst and the network falls silent. However, as shown previously, if such a decentralized quiescent ganglion is maintained in organ culture, pyloric network rhythmicity returns after 3–4 days and, although slower, is similar to the motor pattern expressed when the stn is intact. Here we use current- and voltage-clamp, primarily of identified pyloric dilator (PD) neurons, to investigate changes in synaptic and cellular properties that underlie this transition in network behavior. Although the efficacy of chemical synapses between pyloric neurons decreases significantly (by ≤50%) after STG decentralization, the fundamental change leading to rhythm recovery occurs in the voltage-dependent properties of the neurons themselves. Whereas pyloric neurons, including the PD, lateral pyloric, and pyloric cell types, are unable to generate burst-producing membrane potential oscillations in the short-term absence of extrinsic modulatory inputs, in long-term decentralized ganglia, the same cells are able to oscillate spontaneously, even after experimental isolation in situ from all other elements in the pyloric network. In PD neurons this reacquisition of rhythmicity is associated with a net reduction in outward tetraethylammonium-sensitive ionic currents that include a delayed-rectifier type potassium current ( I Kd) and a calcium-dependent K+ current, I KCa. By contrast, long-term STG decentralization caused enhancement of a hyperpolarization-activated inward current that resembles I h. These results are consistent with the hypothesis that modulatory inputs sustain the modulation-dependent rhythmogenic character of the pyloric network by continuously regulating the balance of membrane conductances that underlie neuronal oscillation.
Space-Time Maps and Two-Bar Interactions of Different Classes of Direction-Selective Cells in Macaque V-1
Authors: Conway Bevil R. , Livingstone Margaret S.
Published: May 2006

We used one-dimensional sparse noise stimuli to generate first-order spatiotemporal maps and second-order two-bar interaction maps for 65 simple and 124 complex direction-selective cells in alert macaque V1. Spatial and temporal phase differences between light and dark space-time maps clearly distinguished simple and complex cell populations. Complex cells usually showed similar direction preferences to light and dark bars, but many of the directional simple cells were much more direction selective to one sign of contrast than the reverse. We show that this is predicted by a simple energy model. Some of the direction-selective simple cells showed multiple space-time-slanted subregions, but others (previously described as S1 cells) had space-time maps that looked like just one subregion of an ordinary simple cell. Both simple and complex cells showed directional interactions (nonlinearities) to pairs of flashed bars (a 2-bar apparent-motion stimulus). The space-time slant of the simple cells correlated with the optimum d X/d T (velocity) of the paired-bar interactions. Some complex cells also showed a space-time slant; the direction of the slant usually correlated with the preferred direction of motion, but the degree of slant correlated with the inferred velocity tuning only when measured by a weighted-centroid calculation. Principal components analysis of the simple-cell space-time maps yielded one fast temporally biphasic component and a slower temporally monophasic component. We saw no consistent pattern for the spatial phase of the components, unlike previous reports; however, we show that principal components analysis may not distinguish between spatial offsets and phase offsets.
Postural Control in the Rabbit Maintaining Balance on the Tilting Platform
Authors: Beloozerova I. N. , Zelenin P. V. , Popova L. B. , Orlovsky G. N. , Grillner S. , Deliagina T. G.
Published: May 2006

A deviation from the dorsal-side-up body posture in quadrupeds activates the mechanisms for postural corrections. Operation of these mechanisms was studied in the rabbit maintaining balance on a platform periodically tilted in the frontal plane. First, we characterized the kinematics and electromyographic (EMG) patterns of postural responses to tilts. It was found that a reaction to tilt includes an extension of the limbs on the side moving down and flexion on the opposite side. These limb movements are primarily due to a modulation of the activity of extensor muscles. Second, it was found that rabbits can effectively maintain the dorsal-side-up body posture when complex postural stimuli are applied, i.e., asynchronous tilts of the platforms supporting the anterior and posterior parts of the body. These data suggest that the nervous mechanisms controlling positions of these parts of the body can operate independently of each other. Third, we found that normally the somatosensory input plays a predominant role for the generation of postural responses. However, when the postural response appears insufficient to maintain balance, the vestibular input contributes considerably to activation of postural mechanisms. We also found that an asymmetry in the tonic vestibular input, caused by galvanic stimulation of the labyrinths, can affect the stabilized body orientation while the magnitude of postural responses to tilts remains unchanged. Fourth, we found that the mechanisms for postural corrections respond only to tilts that exceed a certain (threshold) value.
Modulation of Striatal Single Units by Expected Reward: A Spiny Neuron Model Displaying Dopamine-Induced Bistability
Authors: Gruber Aaron J. , Solla Sara A. , Surmeier D. James , Houk James C.
Published: May 2006

Single-unit activity in the neostriatum of awake monkeys shows a marked dependence on expected reward. Responses to visual cues differ when animals expect primary reinforcements, such as juice rewards, in comparison to secondary reinforcements, such as tones. The mechanism of this reward-dependent modulation has not been established experimentally. To assess the hypothesis that direct neuromodulatory effects of dopamine on spiny neurons can account for this modulation, we develop a computational model based on simplified representations of key ionic currents and their modulation by D1 dopamine receptor activation. This minimal model can be analyzed in detail. We find that D1-mediated increases of inward rectifying potassium and L-type calcium currents cause a bifurcation: the native up/down state behavior of the spiny neuron model becomes truly bistable, which modulates the peak firing rate and the duration of the up state and introduces a dependence of the response on the past state history. These generic consequences of dopamine neuromodulation through bistability can account for both reward-dependent enhancement and suppression of spiny neuron single-unit responses to visual cues. We validate the model by simulating responses to visual targets in a memory-guided saccade task; our results are in close agreement with the main features of the experimental data. Our model provides a conceptual framework for understanding the functional significance of the short-term neuromodulatory actions of dopamine on signal processing in the striatum.
An Unfolded Map of the Cerebellar Dentate Nucleus and its Projections to the Cerebral Cortex
Authors: Dum Richard P. , Strick Peter L.
Published: May 2006

We have used retrograde transneuronal transport of neurotropic viruses to examine the organization of the projections from the dentate nucleus of the cerebellum to “motor” and “nonmotor” areas of the cerebral cortex. To perform this analysis we created an unfolded map of the dentate. Plotting the results from current and prior experiments on this unfolded map revealed important features about the topography of function in the dentate. We found that the projections to the primary motor and premotor areas of the cerebral cortex originated from dorsal portions of the dentate. In contrast, projections to prefrontal and posterior parietal areas of cortex originated from ventral portions of the dentate. Thus the dentate contains anatomically separate and functionally distinct motor and nonmotor domains.
Prediction of Muscle Activity by Populations of Sequentially Recorded Primary Motor Cortex Neurons
Authors: Morrow M. M. , Miller L. E.
Published: May 2006

We have adopted an analysis that produces a post hoc prediction of the time course of electromyogram (EMG) activity from the discharge of ensembles of neurons recorded sequentially from the primary motor cortex (M1) of a monkey. Over several recording sessions, we collected data from 50 M1 neurons and several distal forelimb muscles during a stereotyped precision grip task. Ensemble averages were constructed from 5 to 10 trials for each neuron and EMG signal. We used multiple linear regression on randomly chosen subsets of these neurons to find the best fit between the neuronal and EMG data. The fixed delay between neuronal and EMG signals that yielded the largest coefficient of determination ( R 2) between predicted and actual EMG was 50 ms. R 2 averaged 0.83 for ensembles composed of 15 neurons. If, instead, each neuronal signal was delayed by the time of its peak cross-correlation with the EMG signal, R 2 increased to 0.88. Using all 50 neurons, R 2 under these conditions averaged nearly 0.97. A similar analysis was conducted with signals recorded during both a power grip and a precision grip task. Quality of the fit dropped dramatically when parameters from the precision grip for a given set of neurons were used to fit data recorded during the power grip. However, when a single set of regression parameters was used to fit a combination of the two tasks, the quality of the fits decreased by <10% from that of a single task.
Neural Model for Physiological Responses to Frequency and Amplitude Transitions Uncovers Topographical Order in the Auditory Cortex
Authors: Fishbach Alon , Yeshurun Yehezkel , Nelken Israel
Published: May 2006

We characterize primary auditory cortex (AI) units using a neural model for the detection of frequency and amplitude transitions. The model is a generalization of a model for the detection of amplitude transition. A set of neurons, tuned in the spectrotemporal domain, is created by means of neural delays and frequency filtering. The sensitivity of the model to frequency and amplitude transitions is achieved by applying a 2-dimensional rotatable receptive field to the set of spectrotemporally tuned neurons. We evaluated the model using data recorded in AI of anesthetized ferrets. We show that the model is able to fit the responses of AI units to variety of stimuli, including single tones, delayed 2-tone stimuli and various frequency-modulated tones, using only a small number of parameters. Furthermore, we show that the topographical order in maps of the model parameters is higher than in maps created from response indices extracted directly from the responses to any single stimulus. These results suggest a possible ordered organization of a simple rotatable spectrotemporal receptive field in the mammalian AI.
ASIC3 and ASIC1 Mediate FMRFamide-Related Peptide Enhancement of H+-Gated Currents in Cultured Dorsal Root Ganglion Neurons
Authors: Xie Jinghui , Price Margaret P. , Wemmie John A. , Askwith Candice C. , Welsh Michael J.
Published: May 2006

The acid-sensing ion channels (ASICs) form cation channels that are transiently activated by extracellular protons. They are expressed in dorsal root ganglia (DRG) neurons and in the periphery where they play a function in nociception and mechanosensation. Previous studies showed that FMRFamide and related peptides potentiate H+-gated currents. To better understand this potentiation, we examined the effect of FMRFamide-related peptides on DRG neurons from wild-type mice and animals missing individual ASIC subunits. We found that FMRFamide and FRRFamide potentiated H+-gated currents of wild-type DRG in a dose-dependent manner. They increased current amplitude and slowed desensitization following a proton stimulus. Deletion of ASIC3 attenuated the response to FMRFamide-related peptides, whereas the loss of ASIC1 increased the response. The loss of ASIC2 had no effect on FMRFamide-dependent enhancement of H+-gated currents. These data suggest that FMRFamide-related peptides modulate DRG H+-gated currents through an effect on both ASIC1 and ASIC3 and that ASIC3 plays the major role. The recent discovery of RFamide-related peptides (RFRP) in mammals suggested that they might also modulate H+-gated current. We found that RFRP-1 slowed desensitization of H+-gated DRG currents, whereas RFRP-2 increased the peak amplitude. COS-7 cells heterologously expressing ASIC1 or ASIC3 showed similar effects. These results suggest that FMRFamide-related peptides, including the newly identified RFRPs, modulate H+-gated DRG currents through ASIC1 and ASIC3. The presence of several ASIC subunits, the diversity of FMRFamide-related peptides, and the distinct effects on H+-gated currents suggest the possibility of substantial complexity in modulation of current in DRG sensory neurons.
Elevated Free Calcium Levels in the Subretinal Space Elevate the Absolute Dark-Adapted Threshold in Hypopigmented Mice
Authors: Lavallee C. R. , Chalifoux J. R. , Moosally A. J. , Balkema G. W.
Published: May 2006

Abundant evidence spanning 25 years demonstrates that hypopigmentation is associated with sensory abnormalities manifested most clearly as elevated absolute dark-adapted thresholds in hypopigmented mice. Here we show that when ocular melanin is increased in the himalayan mouse via α-melanocyte stimulating hormone (α-MSH) injections, dark-adapted thresholds drop in proportion to the change in ocular melanin. We further measured free calcium concentration with calcium-sensitive microelectrodes in both albino and black mouse retinal eyecups in living subjects. The recordings were done in anesthetized animals as the defect is not present in isolated retinas or in the superfused eye preparation. A double-barreled electrode—pCa and Vref—was used to simultaneously record the calcium concentration and the electroretinogram (ERG) at each of many depths as the electrode was driven through the retina. The position of the electrode was confirmed with ERG and 1,1′-dioctadecyl-3, 3,3′,3′-tetramethylindocarbocyanine perchlorate electrode tract reconstruction. Dark-adapted albinos ( n = 6) had 1.4 ± 0.015 mM calcium in the subretinal space compared with 0.80 ± 0.025 mM in black mice ( n = 6). The results of these experiments are consistent with the hypothesis that ocular hypopigmentation causes elevated calcium levels in the subretinal space that in turn mimic light adaptation in hypopigmented mice.
Response of the Respiratory Network of Mice to Hyperthermia
Authors: Tryba Andrew K. , Ramirez Jan-Marino
Published: May 2006

Most mammals modulate respiratory frequency (RF) to dissipate heat (i.e., panting) and avoid heat stroke during hyperthermic conditions. During hyperthermia, the RF of intact mammals increases and then declines or ceases (apnea). It has been proposed that this RF modulation depends on the presence of higher brain structures such as the hypothalamus. However, the direct effects of hyperthermia on the respiratory neural network have not been examined. To address this issue, the respiratory neural network [i.e., ventral respiratory group (VRG)] was isolated in a brain stem preparation taken from the medulla of mice (P0 –P6). Integrated population activity, predominated by inspiratory neurons, was recorded extracellularly from VRG neurons. The bath temperature was then heated from 30 to 40°C, resulting in a biphasic frequency response in VRG activity. Following an initial six- to sevenfold increase and subsequent decline, fictive RF was maintained at a frequency that was higher than baseline frequency; at 40°C, the RF was maintained at about two to four times that at 30°C. The inspiratory burst amplitude and duration were significantly reduced during hyperthermic conditions. An increase in RF and decrease in VRG burst amplitude and duration also occurred when heating from 37 to 40°C. Fictive apnea typically occurred during cooling to the control temperature. Furthermore, changes in hypoglossal motor nucleus activity paralleled those of the VRG, suggesting that temperature modulation of the VRG is likely to have a behaviorally relevant impact on respiration. We conclude that the VRG activity itself is modulated during hyperthermia and the respiratory network is particularly sensitive to temperature changes.
Context-Dependent Anticipation of Different Task Dynamics: Rapid Recall of Appropriate Motor Skills Using Visual Cues
Authors: Krouchev Nedialko I. , Kalaska John F.
Published: May 2006

Recent studies have reported that human subjects show varying degrees of ability to use contextual cues to recall the motor skills required to compensate for different dynamic external force fields during arm movements. In particular, the subjects showed little or no ability to use color cues to adjust motor outputs in anticipation of the perturbing fields after limited periods of training that were sufficient to learn to compensate for the fields themselves. This is unexpected since humans and monkeys can use color cues to perform a wide range of visuomotor tasks. Here we show that a monkey with extensive practice compensating for viscous fields in an elbow-movement task can use associated color cues to adjust motor output in anticipation of an impending field before physically encountering it.
Role of Dendritic Spines in Action Potential Backpropagation: A Numerical Simulation Study
Authors: Tsay David , Yuste Rafael
Published: May 2006

Two remarkable aspects of pyramidal neurons are their complex dendritic morphologies and the abundant presence of spines, small structures that are the sites of excitatory input. Although the channel properties of the dendritic shaft membrane have been experimentally probed, the influence of spine properties in dendritic signaling and action potential propagation remains unclear. To explore this we have performed multi-compartmental numerical simulations investigating the degree of consistency between experimental data on dendritic channel densities and backpropagation behavior, as well as the necessity and degree of influence of excitable spines. Our results indicate that measured densities of Na+ channels in dendritic shafts cannot support effective backpropagation observed in apical dendrites due to suprathreshold inactivation. We demonstrate as a potential solution that Na+ channels in spines at higher densities than those measured in the dendritic shaft can support extensive backpropagation. In addition, clustering of Na+ channels in spines appears to enhance their effect due to their unique morphology. Finally, we show that changes in spine morphology significantly influence backpropagation efficacy. These results suggest that, by clustering sodium channels, spines may serve to control backpropagation.
Integrins Regulate NMDA Receptor-Mediated Synaptic Currents
Authors: Lin Bin , Arai Amy C. , Lynch Gary , Gall Christine M.
Published: May 2006

Synapses contain high concentrations of integrins, adhesion receptors known to influence the operation of neighboring transmembrane proteins. Evidence that integrins are important for consolidation of long-term potentiation suggests that these adhesion proteins may modulate activities of synaptic glutamate receptors. The present study provides a first test of the possibility that integrins modulate synaptic N-methyl-d-aspartate (NMDA)-type glutamate receptor activities. Excitatory postsynaptic currents (EPSCs) were recorded with whole cell clamp from hippocampal slices in which AMPA-type glutamate receptors and GABAAreceptors were pharmacologically blocked. Microperfusion of the peptide integrin ligand gly-arg-gly-asp-ser-pro (GRGDSP) caused an approximately twofold increase in the amplitude and duration of NMDA receptor-gated synaptic currents. Control peptides had no effect. Paired-pulse facilitation was unchanged, indicating that the ligand did not modify neurotransmitter release probabilities. Infusion of the Src kinase antagonist PP2 but not the control drug 4-amino-7-phenylpyrazolo[3,4-d]pyrimidine eliminated the enhancing effect of GRGDSP. Integrins regulate Src kinases that are known to phosphorylate NMDA receptors. It is concluded that integrins act through this route to exert potent modulatory effects on the operation of NMDA receptors.
Human Brain Activation During Sustained and Intermittent Submaximal Fatigue Muscle Contractions: An fMRI Study
Authors: Liu Jing Z. , Shan Zu Y. , Zhang Lu D. , Sahgal Vinod , Brown Robert W. , Yue Guang H.
Published: May 2006

During prolonged submaximal muscle contractions, electromyographic (EMG) signals typically increase as a result of increasing motor unit activities to compensate for fatigue-induced force loss in the muscle. It is thought that cortical signals driving the muscle to higher activation levels also increases, but this has never been experimentally demonstrated. The purpose of this study was to quantify brain activation during submaximal fatigue muscle contractions using functional magnetic resonance imaging (fMRI). Twelve volunteers performed a sustained handgrip contraction for 225 s and 320 intermittent handgrip contractions (∼960 s) at 30% maximal level while their brain was imaged. For the sustained contraction, EMG signals of the finger flexor muscles increased linearly while the target force was maintained. The fMRI-measured cortical activities in the contralateral sensorimotor cortex increased sharply during the first 150 s, then plateaued during the last 75 s. For the intermittent contractions, the EMG signals increased during the first 660 s and then began to decline, while the handgrip force also showed a sign of decrease despite maximal effort to maintain the force. The fMRI signal of the contralateral sensorimotor area showed a linear rise for most part of the task and plateaued at the end. For both the tasks, the fMRI signals in the ipsilateral sensorimotor cortex, prefrontal cortex, cingulate gyrus, supplementary motor area, and cerebellum exhibited steady increases. These results showed that the brain increased its output to reinforce the muscle for the continuation of the performance and possibly to process additional sensory information.
Neural Coding of Spatial Phase in V1 of the Macaque Monkey
Authors: Aronov Dmitriy , Reich Daniel S. , Mechler Ferenc , Victor Jonathan D.
Published: May 2006

We examine the responses of single neurons and pairs of neurons, simultaneously recorded with a single tetrode in the primary visual cortex of the anesthetized macaque monkey, to transient presentations of stationary gratings of varying spatial phase. Such simultaneously recorded neurons tended to have similar tuning to the phase of the grating. To determine the response features that reliably discriminate these stimuli, we use the metric-space approach extended to pairs of neurons. We find that paying attention to the times of individual spikes, at a resolution of ∼30 ms, and keeping track of which neuron fires which spike rather than just the summed local activity contribute substantially to phase coding. The contribution is both quantitative (increasing the fidelity of phase coding) and qualitative (enabling a 2-dimensional “response space” that corresponds to the spatial phase cycle). We use a novel approach, the extraction of “temporal profiles” from the metric space analysis, to interpret and compare temporal coding across neurons. Temporal profiles were remarkably consistent across a large subset of neurons. This consistency indicates that simple mechanisms (e.g., comparing the size of the transient and sustained components of the response) allow the temporal contribution to phase coding to be decoded.
A Biophysical Model of Nonlinear Dynamics Underlying Plateau Potentials and Calcium Spikes in Purkinje Cell Dendrites
Authors: Genet Stéphane , Delord Bruno
Published: May 2006

Computational capabilities of Purkinje cells (PCs) are central to the cerebellum function. Information originating from the whole nervous system converges on their dendrites, and their axon is the sole output of the cerebellar cortex. PC dendrites respond to weak synaptic activation with long-lasting, low-amplitude plateau potentials, but stronger synaptic activation can generate fast, large amplitude calcium spikes. Pharmacological data have suggested the involvement of only the P-type of Ca channels in both of these electric responses. However, the mechanism allowing this Ca current to underlie responses with such different dynamics is still unclear. This mechanism was explored by constraining a biophysical model with electrophysiological, Ca-imaging, and single ion channel data. A model is presented here incorporating a simplified description of [Ca]i regulation and three ionic currents: 1) the P-type Ca current, 2) a delayed-rectifier K current, and 3) a generic class of K channels activating sharply in the sub-threshold voltage range. This model sustains fast spikes and long-lasting plateaus terminating spontaneously with recovery of the resting potential. Small depolarizing, tonic inputs turn plateaus into a stable membrane state and endow the dendrite with bistability properties. With larger tonic inputs, the plateau remains the unique equilibrium state, showing long traces of transient inhibitory inputs that are called “valley potentials” because their dynamics mirrors that of inverted, finite-duration plateaus. Analyzing the slow subsystem obtained by assuming instantaneous activation of the delayed-rectifier reveals that the time course of plateaus and valleys is controlled by the slow [Ca]i dynamics, which arises from the high Ca-buffering capacity of PCs. A bifurcation analysis shows that tonic currents modulate sub-threshold dynamics by displacing the resting state along a hysteresis region edged by two saddle-node bifurcations; these bifurcations mark transitions from finite-duration plateaus to bistability and from bistability to valley potentials, respectively. This low-dimensionality model may be introduced into large-scale models to explore the role of PC dendrite computations in the functional capabilities of the cerebellum.
Development of Inward Rectification and Control of Membrane Excitability in Mesencephalic V Neurons
Authors: Tanaka Susumu , Wu Nanping , Hsaio Chie-Fang , Turman Jack , Chandler Scott H.
Published: May 2006

The present study was performed to assess the postnatal development and functional roles of inward rectifying currents in rat mesencephalic trigeminal (Mes V) neurons, which are involved in the genesis and control of oral-motor activities. Whole cell voltage-clamp recordings obtained from Mes V neurons in brain stem slices identified fast ( I KIR) and slow ( I h) inward rectifying currents, which were specifically blocked by BaCl2 (300–500 μM) or 4-( N-ethyl- N-phenylamino)-1,2-dimethyl-6-(methylamino) pyrimidinium chloride (ZD 7288, 10 μM), respectively. The whole cell current density for these channels increased between postnatal days 2 to 12 (P2-P12), and the time courses for I h activation and deactivation were each well described by two time constants. Application of ZD 7288 produced membrane hyperpolarization in the majority of cells and prolonged afterhyperpolarization repolarization. Additionally, in the presence of ZD 7288, spike frequency was decreased and adaptation was more pronounced. Interestingly, these neurons exhibited a voltage-dependent membrane resonance (<10 Hz) that was prominent around resting potential and more negative to rest and was blocked by ZD 7288. These results suggest that I hcontributes to stabilizing resting membrane potential and controlling cell excitability. The presence of I himparts the neuron with the unique property of low-frequency membrane resonance; the ability to discriminate between synaptic inputs based on frequency content.
Gabor Analysis of Auditory Midbrain Receptive Fields: Spectro-Temporal and Binaural Composition
Authors: Qiu Anqi , Schreiner Christoph E. , Escabí Monty A.
Published: May 2006

The spectro-temporal receptive field (STRF) is a model representation of the excitatory and inhibitory integration area of auditory neurons. Recently it has been used to study spectral and temporal aspects of monaural integration in auditory centers. Here we report the properties of monaural STRFs and the relationship between ipsi- and contralateral inputs to neurons of the central nucleus of cat inferior colliculus (ICC) of cats. First, we use an optimal singular-value decomposition method to approximate auditory STRFs as a sum of time-frequency separable Gabor functions. This procedure extracts nine physiologically meaningful parameters. The STRFs of ∼60% of collicular neurons are well described by a time-frequency separable Gabor STRF model, whereas the remaining neurons exhibited obliquely oriented or multiple excitatory/inhibitory subfields that require a nonseparable Gabor fitting procedure. Parametric analysis reveals distinct spectro-temporal tradeoffs in receptive field size and modulation filtering resolution. Comparisons between an identical model used to study spatio-temporal integration areas of visual neurons further shows that auditory and visual STRFs share numerous structural properties. We then use the Gabor STRF model to compare quantitatively receptive field properties of contra- and ipsilateral inputs to the ICC. We show that most interaural STRF parameters are highly correlated bilaterally. However, the spectral and temporal phases of ipsi- and contralateral STRFs often differ significantly. This suggests that activity originating from each ear share various spectro-temporal response properties such as their temporal delay, bandwidth, and center frequency but have shifted or interleaved patterns of excitation and inhibition. These differences in converging monaural receptive fields expand binaural processing capacity beyond interaural time and intensity aspects and may enable colliculus neurons to detect disparities in the spectro-temporal composition of the binaural input.
Discharge of Saccade-Related Superior Colliculus Neurons During Saccades Accompanied by Vergence
Authors: Walton Mark M. G. , Mays Lawrence E.
Published: May 2006

It has long been believed that the superior colliculus (SC) is involved in the production of saccades but plays no role in the generation of vergence eye movements. However, results from several recent studies suggest that it may be worthwhile to examine the role of the SC in saccade-vergence interactions. Specifically, the available literature suggests two questions: do saccade-related neurons in SC have three-dimensional movement fields and is the slowing of saccades by vergence attributable, in part, to changes in the level of activity in SC? Single-unit data were recorded from 51 saccade-related neurons in rhesus monkey SC during saccades without vergence, saccades accompanied by convergence, and saccades accompanied by divergence. Most cells (78% for convergence, 86% for divergence) showed a significant reduction in peak spike density when the saccade was accompanied by vergence. A minority of cells (16% for convergence, 2% for divergence) increased their firing rate for saccades accompanied by vergence. Three cells were found that discharged in association with saccades, vergence, and the combination of the two. There were no cells that exhibited the pattern of discharge that would be expected of a cell tuned for saccades with divergence. Thus the present results do not support the hypothesis that saccade-related SC neurons are, as a rule, tuned in three dimensions. Small, but significant, differences in firing rate were often found for saccades without vergence at near and far distances. Approximately half of the cells showed a significant relationship between spike activity and saccade velocity, but the correlations tended to be very weak. This suggests that the decreased neuronal activity of SC neurons has only a limited effect on saccade velocity. For some cells, the movement field shifted for saccades with vergence. These shifts were highly variable from one cell to another.
Spindle Model Responsive to Mixed Fusimotor Inputs and Testable Predictions of β Feedback Effects
Authors: Maltenfort Mitchell G. , Burke R. E.
Published: May 2006

Skeletofusimotor (β) motoneurons innervate both extrafusal muscle units and muscle fibers within muscle spindle stretch receptors. By receiving excitation from group Ia muscle spindle afferents and driving the muscle spindle afferents that excite them, they form a positive feedback loop of unknown function. To study it, we developed a computationally efficient model of group Ia afferent behavior, capable of responding to multiple fusimotor inputs, that matched experimental data. This spindle model was then incorporated into a simulation of group Ia feedback during ramp/hold and triangular stretches with and without closure of the β loop, assuming that γ and β fusimotor drives of the same type (static or dynamic) have identical effects on spindle afferent firing. The effects of β feedback were implemented by driving a fusimotor input with a delayed and filtered fraction of the spindle afferent output. During triangular stretches, feedback through static β motoneurons enhanced Ia afferent firing during shortening of the spindle. In contrast, closure of a dynamic β loop increased Ia firing during lengthening. The strength of β feedback, estimated as a “loop gain” was comparable to experimental estimates. The loop gain increased with velocity and amplitude of stretch but decreased with increased superimposed γ fusimotor rates. The strongest loop gains were seen when the β loop and the γ bias were of different types (static vs. dynamic).
Evidence for the Involvement of the Posterior Parietal Cortex in Coordination of Fingertip Forces for Grasp Stability in Manipulation
Authors: Ehrsson H. Henrik , Fagergren Anders , Johansson Roland S. , Forssberg Hans
Published: May 2006

Grasp stability during object manipulation is achieved by the grip forces applied normal to the grasped surfaces increasing and decreasing in phase with increases and decreases of destabilizing load forces applied tangential to the grasped surfaces. This force coordination requires that the CNS anticipates the grip forces that match the requirements imposed by the self-generated load forces. Here, we use functional MRI (fMRI) to study neural correlates of the grip-load force coordination in a grip-load force task in which six healthy humans attempted to lift an immovable test object held between the tips of the right index finger and thumb. The recorded brain activity was compared with the brain activity obtained in two control tasks in which the same pair of digits generated forces with similar time courses and magnitudes; i.e., a grip force task where the subjects only pinched the object and did not apply load forces, and a load force task, in which the subjects applied vertical forces to the object without generating grip forces. Thus neither the load force task nor the grip force task involved coordinated grip-load forces, but together they involved the same grip force and load force output. We found that the grip-load force task was specifically associated with activation of a section of the right intraparietal cortex, which is the first evidence for involvement of the posterior parietal cortex in the sensorimotor control of coordinated grip and load forces in manipulation. We suggest that this area might represents a node in the network of cortical and subcortical regions that implement anticipatory control of fingertip forces for grasp stability.
Excitatory Effects of Hypocretin-1 (Orexin-A) in the Trigeminal Motor Nucleus Are Reversed by NMDA Antagonism
Authors: Peever John H. , Lai Yuan-Yang , Siegel Jerome M.
Published: May 2006

Hypocretin-1 and -2 (Hcrt-1 and -2, also called orexin-A and -B) are newly identified neuropeptides synthesized by hypothalamic neurons. Defects in the Hcrt system underlie the sleep disorder narcolepsy, which is characterized by sleep fragmentation and the involuntary loss of muscle tone called cataplexy. Hcrt neurons project to multiple brain regions including cranial and spinal motor nuclei. In vitro studies suggest that Hcrt application can modulate presynaptic glutamate release. Together these observations suggest that Hcrt can affect motor output and that glutamatergic processes may be involved. We addressed these issues in decerebrate cats by applying Hcrt-1 and -2 into the trigeminal motor nucleus to determine whether these ligands alter masseter muscle activity and by pretreating the trigeminal motor nucleus with a N-methyl-d-aspartate (NMDA) antagonist to determine if glutamatergic pathways are involved in the transduction of the Hcrt signal. We found that Hcrt-1 and -2 microinjections into the trigeminal motor nucleus increased ipsilateral masseter muscle tone in a dose-dependent manner. We also found that Hcrt application into the hypoglossal motor nucleus increases genioglossus muscle activity. Pretreatment with a NMDA antagonist (d-(−)-2-amino-phosphonovaleric acid) abolished the excitatory response of the masseter muscle to Hcrt-1 application; however, pretreatment with methysergide, a serotonin antagonist had no effect. These studies are the first to demonstrate that Hcrt causes the excitation of motoneurons and that functional NMDA receptors are required for this response. We suggest that Hcrt regulates motor control processes and that this regulation is mediated by glutamate release in the trigeminal motor nucleus.
Aβ25–35-Induced Depression of Long-Term Potentiation in Area CA1 In Vivo and In Vitro Is Attenuated by Verapamil
Authors: Freir D. B. , Costello D. A. , Herron C. E.
Published: May 2006

The effect of intracerebroventricular (icv) injection of Aβ25–35 and/or intraperitoneal (ip) application of the L-type calcium channel (VDCC) blockers verapamil or diltiazem were examined in vivo. To by-pass possible systemic actions of these agents, their effects on long-term potentiation (LTP) in the CA1 region of the in vitro hippocampal slice preparation were also examined. Application of Aβ25–35 (10 nmol in 5 μl, icv) significantly impaired LTP in vivo, as did IP injection of verapamil (1 or 10 mg/kg) or diltiazem (1 or 10 mg/kg). In the in vitro slice preparation, LTP was also depressed by prior application of Aβ25–35 (500 nmol), verapamil (20 μM), or diltiazem (50 μM). Combined application of Aβ25–35 and verapamil in either the in vivo or in vitro preparation resulted in a significant reversal of the LTP depression observed in the presence of either agent alone. However, co-application of diltiazem and Aβ25–35 failed to attenuate the depression of LTP observed in the presence of either agent alone in vivo or in vitro. Since LTP is a cellular correlate of memory and Aβ is known to be involved in Alzheimer's disease (AD), these results indicate that verapamil, a phenylalkylamine, may be useful in the treatment of cognitive deficits associated with AD.
Changes in Segmental and Motor Cortical Output With Contralateral Muscle Contractions and Altered Sensory Inputs in Humans
Authors: Hortobágyi Tibor , Taylor Janet L. , Petersen Nicolas T. , Russell Gabrielle , Gandevia Simon C.
Published: May 2006

Motor or sensory activity in one arm can affect the other arm. We tested the hypothesis that a voluntary contraction can affect the motor pathway to the contralateral homologous muscle and investigated whether alterations in sensory input might mediate such effects. Responses to transcranial magnetic stimulation [motor-evoked potentials (MEPs)], stimulation of the descending tracts [cervicomedullary MEPs (CMEPs)], and peripheral nerve stimulation (H-reflex) were recorded from the relaxed right flexor carpi radialis (FCR), while the left arm underwent unilateral interventions (5 s duration) that included voluntary contraction, muscle contraction evoked through percutaneous stimulation, tendon vibration, and cutaneous and mixed nerve stimulation. During moderate to strong voluntary wrist flexion on the left, MEPs in the right FCR increased, CMEPs were unaffected, and the H-reflex was depressed. These results are consistent with an increase in excitability of the motor cortex, no effect on the motoneuron pool, and presynaptic inhibition of Ia afferents. In contrast, percutaneous muscle stimulation facilitated both MEPs and the H-reflex. However, muscle contraction produced by a combination of voluntary effort and electrical stimulation also reduced the contralateral H-reflex. After voluntary contractions, the H-reflex remained depressed for 35 s, but after stimulationevoked contractions, it rapidly returned to baseline. Under both conditions, MEPs recovered rapidly. After voluntary contractions, CMEPs were also depressed for approximately 10 s despite their lack of change during contractions. Wrist tendon vibration (100 Hz) did not affect, and 20-Hz median nerve stimulation or forearm medial cutaneous nerve stimulation mildly facilitated, the H-reflex without affecting MEPs. Voluntary wrist extension, similarly to wrist flexion, increased MEPs and depressed H-reflexes. However, ankle dorsiflexion facilitated the H-reflex akin to the Jendrassik maneuver. These data suggest that a unilateral voluntary muscle contraction has contralateral effects at both cortical and segmental levels and that the segmental effects are not replicated by stimulated muscle contraction or by input from muscle spindles or non-nociceptive cutaneous afferents.
A Slow Fraction of Mg2+ Unblock of NMDA Receptors Limits Their Contribution to Spike Generation in Cortical Pyramidal Neurons
Authors: Vargas-Caballero Mariana , Robinson Hugh P. C.
Published: May 2006

The timing of voltage-dependent removal of Mg2+block of N-methyl-d-aspartate receptors (NMDARs) is potentially critical for determining their nonlinear contribution to excitability. Here, we measure the kinetics of NMDAR unblock in nucleated patch and whole cell recordings of rat cortical pyramidal neurons during depolarizing voltage steps. At room temperature, the unblock showed a very fast component (τ < 1 ms) and a slower component (τ = 14–23 ms in nucleated patches). The slow component accounted for half of the current at +40 mV and its amplitude and time constant showed some voltage dependence. Blocking with hyperpolarization was very fast (τ < 200 μs). Voltage-clamp with action potential waveforms, at both room temperature and at 33°C, showed that the rising phase of single fast action potentials unblocks far less NMDAR current than expected from the stationary voltage dependence, while a large amplitude of current is uncovered during the upstroke of slow calcium action potentials. The repolarization of fast sodium action potentials uncovers an NMDAR tail current, much bigger than the stationary level of current.
Evidence for Object Permanence in the Smooth-Pursuit Eye Movements of Monkeys
Authors: Churchland Mark M. , Chou I-Han , Lisberger Stephen G.
Published: May 2006

We recorded the smooth-pursuit eye movements of monkeys in response to targets that were extinguished (blinked) for 200 ms in mid-trajectory. Eye velocity declined considerably during the target blinks, even when the blinks were completely predictable in time and space. Eye velocity declined whether blinks were presented during steady-state pursuit of a constant-velocity target, during initiation of pursuit before target velocity was reached, or during eye accelerations induced by a change in target velocity. When a physical occluder covered the trajectory of the target during blinks, creating the impression that the target moved behind it, the decline in eye velocity was reduced or abolished. If the target was occluded once the eye had reached target velocity, pursuit was only slightly poorer than normal, uninterrupted pursuit. In contrast, if the target was occluded during the initiation of pursuit, while the eye was accelerating toward target velocity, pursuit during occlusion was very different from normal pursuit. Eye velocity remained relatively stable during target occlusion, showing much less acceleration than normal pursuit and much less of a decline than was produced by a target blink. Anticipatory or predictive eye acceleration was typically observed just prior to the reappearance of the target. Computer simulations show that these results are best understood by assuming that a mechanism of eye-velocity memory remains engaged during target occlusion but is disengaged during target blinks.