bluuebunny/crossref_metadata_2025 huggingface dataset:
Contribution of Cutaneous Inputs From the Hindpaw to the Control of Locomotion. II. Spinal Cats
Authors: Bouyer L.J.G. , Rossignol S.
Published: May 2006

The goal of these experiments was to define the contribution of hindpaw cutaneous inputs in the expression of spinal locomotion in cats. In 3 cats, some ( n = 1) or all ( n = 2) cutaneous nerves were cut bilaterally at ankle level before spinalization. This denervation caused small deficits that were gradually compensated as reported in the companion study. After spinalization, the completely denervated cats never recovered plantar foot placement or weight bearing of the hindquarters despite more than 35 days of treadmill training. Although normal electromyographic rhythmic activity developed at the hip and knee, ankle flexors and extensors were abnormally coactivated during stance. In contrast, the partially denervated cat regained foot placement and weight support 15 days after spinalization. However, after completing the denervation, foot placement and weight bearing were lost as in previous cats. In a 4th cat, spinalization was performed before denervation and the cutaneous nerves were cut sequentially in the right hindlimb only. Rapid locomotor adaptation occurred after cutting the deep peroneal, saphenous, and sural nerves. Later, cutting the superficial peroneal nerve produced paw drag, which was compensated within 8 days. On cutting the last cutaneous nerve (tibial), plantar foot placement was lost despite another 71 days of training. On the one hand, these experiments show that some cutaneous inputs are necessary for appropriate plantar foot placement and weight bearing of the hindquarters during spinal locomotion and, on the other hand, that locomotor compensation to partial cutaneous denervation after spinalization reveals important adaptive capacities of the spinal cord.
Heterogeneous Actions of Serotonin on Interneurons in Rat Visual Cortex
Authors: Xiang Zixiu , Prince David A.
Published: May 2006

The effects of serotonin (5-HT) on excitability of two cortical interneuronal subtypes, fast-spiking (FS) and low threshold spike (LTS) cells, and on spontaneous inhibitory postsynaptic currents (sIPSCs) in layer V pyramidal cells were studied in rat visual cortical slices using whole-cell recording techniques. Twenty-two of 28 FS and 26 of 35 LTS interneurons responded to local application of 5-HT. In the group of responsive neurons, 5-HT elicited an inward current in 50% of FS cells and 15% of LTS cells, an outward current was evoked in 41% of FS cells and 81% of LTS cells, and an inward current followed by an outward current in 9% of FS cells and 4% LTS cells. The inward and outward currents were blocked by a 5-HT3receptor antagonist, tropisetron, and a 5-HT1Areceptor antagonist, NAN-190, respectively. The 5-HT–induced inward and outward currents were both associated with an increase in membrane conductance. The estimated reversal potential was more positive than −40 mV for the inward current and close to the calculated K+equilibrium potential for the outward current. The 5-HT application caused an increase, a decrease, or an increase followed by a decrease in the frequency of sIPSCs in pyramidal cells. The 5-HT3receptor agonist 1-( m-chlorophenyl) biguanide increased the frequency of larger and fast-rising sIPSCs, whereas the 5-HT1Areceptor agonist (±)8-hydroxydipropylaminotetralin hydrobromide elicited opposite effects and decreased the frequency of large events. These data indicate that serotonergic activation imposes complex actions on cortical inhibitory networks, which may lead to changes in cortical information processing.
Imaging Neuronal Activity During Zebrafish Behavior With a Genetically Encoded Calcium Indicator
Authors: Higashijima Shin-ichi , Masino Mark A. , Mandel Gail , Fetcho Joseph R.
Published: May 2006

Genetically encoded calcium indicators, such as cameleon, have offered the promise of noninvasively monitoring activity of neurons, but no one has demonstrated whether these indicators can report calcium transients in neurons of behaving vertebrates. We show that cameleon can be expressed at high levels in sensory and spinal cord neurons in zebrafish by using neural-specific promoters in both transient expression experiments and in a stable transgenic line. Using standard confocal microscopy, calcium transients in identified motoneurons and spinal interneurons could be detected during escape behaviors produced by a touch on the head of the fish. Small movements of the restrained fish during the behavior did not represent a major problem for analyzing the calcium responses because of the ratiometric nature of cameleon. We conclude that cameleon can be used to noninvasively study the activity of neurons in an intact, behaving vertebrate. The ability to introduce an indicator genetically allows for studies of the functional roles of local interneurons that cannot easily be monitored with other approaches. Transgenic lines such as the one we generated can also be crossed into mutant lines of fish to study both structural and functional consequences of the mutations.
Spatial Memory Following Shifts of Gaze. I. Saccades to Memorized World-Fixed and Gaze-Fixed Targets
Authors: Baker Justin T. , Harper Timothy M. , Snyder Lawrence H.
Published: May 2006

During a shift of gaze, an object can move along with gaze or stay fixed in the world. To examine the effect of an object's reference frame on spatial working memory, we trained monkeys to memorize locations of visual stimuli as either fixed in the world or fixed to gaze. Each trial consisted of an initial reference frame instruction, followed by a peripheral visual flash, a memory-period gaze shift, and finally a memory-guided saccade to the location consistent with the instructed reference frame. The memory-period gaze shift was either rapid (a saccade) or slow (smooth pursuit or whole body rotation). This design allowed a comparison of memory-guided saccade performance under various conditions. Our data indicate that after a rotation or smooth-pursuit eye movement, saccades to memorized world-fixed targets are more variable than saccades to memorized gaze-fixed targets. In contrast, memory-guided saccades to world- and gaze-fixed targets are equally variable following a visually guided saccade. Across all conditions, accuracy, latency, and main sequence characteristics of memory-guided saccades are not influenced by the target's reference frame. Memory-guided saccades are, however, more accurate after fast compared with slow gaze shifts. These results are most consistent with an eye-centered representational system for storing the spatial locations of memorized objects but suggest that the visual system may engage different mechanisms to update the stored signal depending on how gaze is shifted.
Learned Dynamics of Reaching Movements Generalize From Dominant to Nondominant Arm
Authors: Criscimagna-Hemminger Sarah E. , Donchin Opher , Gazzaniga Michael S. , Shadmehr Reza
Published: May 2006

Accurate performance of reaching movements depends on adaptable neural circuitry that learns to predict forces and compensate for limb dynamics. In earlier experiments, we quantified generalization from training at one arm position to another position. The generalization patterns suggested that neural elements learning to predict forces coded a limb's state in an intrinsic, muscle-like coordinate system. Here, we test the sensitivity of these elements to the other arm by quantifying inter-arm generalization. We considered two possible coordinate systems: an intrinsic (joint) representation should generalize with mirror symmetry reflecting the joint's symmetry and an extrinsic representation should preserve the task's structure in extrinsic coordinates. Both coordinate systems of generalization were compared with a naı̈ve control group. We tested transfer in right-handed subjects both from dominant to nondominant arm (D→ND) and vice versa (ND→D). This led to a 2 × 3 experimental design matrix: transfer direction (D→ND/ND→D) by coordinate system (extrinsic, intrinsic, control). Generalization occurred only from dominant to nondominant arm and only in extrinsic coordinates. To assess the dependence of generalization on callosal inter-hemispheric communication, we tested commissurotomy patient JW. JWshowed generalization from dominant to nondominant arm in extrinsic coordinates. The results suggest that when the dominant right arm is used in learning dynamics, the information could be represented in the left hemisphere with neural elements tuned to both the right arm and the left arm. In contrast, learning with the nondominant arm seems to rely on the elements in the nondominant hemisphere tuned only to movements of that arm.
Encoding of Compressive Stress During Indentation by Group III and IV Muscle Mechano-Nociceptors in Rat Gracilis Muscle
Authors: Ge Weiqing , Khalsa Partap S.
Published: May 2006

The mechanical state encoded by group III and IV muscle afferents, putative mechano-nociceptors, during indentation was examined using an isolated muscle-nerve preparation in a rat model. Gracilis muscle and its intact innervation were surgically removed from the medial thigh of the rat hindlimb and placed in a dish containing rodent synthetic interstitial fluid. The tendons of the muscle were coupled to an apparatus that could stretch and apply compression to the muscle. Using a standard teased-nerve preparation, the neural responses of single mechanically sensitive group III or IV afferents were identified. Afferents were classified as mechano-nociceptors on the basis of their graded response to noxious levels of compressive stress (or strain) as well as, in some cases, their polymodal response to noxious thermal stimuli. Mechano-nociceptors ( n = 13) were stimulated using controlled compressive stress (10–30 kPa) or strain (40–80%) while simultaneously measuring displacement and force by compressing the muscle between a flat cylinder and a hard platform. Linear regression was used to evaluate the relationships between neural response and mechanical stress, force, strain, and displacement. The mean neural response (threshold: 1.1 ± 0.4 kPa; sensitivity: 0.5 ± 0.1 Hz/kPa; means ± SE) was significantly and substantially more highly correlated with compressive stress than force, strain, or displacement. The data from this study support the hypothesis that muscle nociceptors stimulated by indentation encode compressive stress rather than force, strain, or displacement.
Use of Knockout Mice Reveals Involvement of M2-Muscarinic Receptors in Control of the Kinetics of Acetylcholine Release
Authors: Slutsky I. , Wess J. , Gomeza J. , Dudel J. , Parnas I. , Parnas H.
Published: May 2006

We have previously suggested that presynaptic M2-muscarinic receptors (M2R) are involved in the control of the time course of evoked acetylcholine release in the frog neuromuscular junction. The availability of knockout mice lacking functional M2R (M2-KO) enabled us to address this issue in a more direct way. Using the phrenic diaphragm preparation, we show that in wild-type (WT) mice experimental manipulations known to affect Ca2+entry and removal, greatly affected the amount of acetylcholine released (quantal content). However, the time course of release remained unaltered under all these experimental treatments. On the other hand, in the M2-KO mice, similar experimental treatments affected both the quantal content and the time course of release. In general, a larger quantal content was accompanied by a longer duration of release. Similarly, the rise time of the postsynaptic current produced by axon stimulation was sensitive to changes in [Ca2+]oor [Mg2+]oin M2-KO mice but not in WT mice. Measurements of Ca2+currents revealed that the shorter rise time of the postsynaptic current seen in high [Mg2+]oin M2-KO mice was not produced by a shorter wave of the presynaptic Ca2+current. These results support our earlier findings and provide direct evidence for the major role that presynaptic M2-muscarinic receptors play in the control of the time course of evoked acetylcholine release under physiological conditions.
Effect of Chronic Stress on Synaptic Currents in Rat Hippocampal Dentate Gyrus Neurons
Authors: Karst Henk , Joëls Marian
Published: May 2006

We investigated the effect of chronic stress on synaptic responses of rat dentate granule cells to perforant path stimulation. Rats were subjected for 3 wk to unpredictable stressors twice daily or to control handling. One day after the last stressor, hippocampal slices were prepared and synaptic responses were determined with whole-cell recording. At that time, adrenal weight was found to be increased and thymus weight as well as gain in body weight were decreased in the stressed versus control animals, indicative of corticosterone hypersecretion during the stress period. In slices from rats with basal corticosteroid levels (at the circadian trough, under rest), no effect of prior stress exposure was observed on synaptic responses. However, synaptic responses of dentate granule cells from chronically stressed and control rats were differently affected by in vitro activation of glucocorticoid receptors, i.e., 1–4 h after administration of 100 nM corticosterone for 20 min. Thus the maximal response to synaptic activation of dentate cells at holding potential of −70 mV [when N-methyl-d-aspartate (NMDA) receptors are blocked by magnesium] was significantly enhanced after corticosterone administration in chronically stressed but not in control animals. In accordance, the amplitude of α-amino-3-hydroxy-5-methylisolazole-4-propionic acid (AMPA) but not of NMDA receptor-mediated currents was increased by corticosterone in stressed rats, over the entire voltage range. Corticosterone treatment also decreased the time to peak of AMPA currents, but this effect did not depend on prior stress exposure. The data indicate that following chronic stress exposure synaptic excitation of dentate granule cells may be enhanced when corticosterone levels rise. This enhanced synaptic flow could contribute to enhanced excitation of projection areas of the dentate gyrus, most notably the CA3 hippocampal region.
Relative Contributions of Balance and Voluntary Leg-Coordination Deficits to Cerebellar Gait Ataxia
Authors: Morton Susanne M. , Bastian Amy J.
Published: May 2006

Different cerebellar regions participate in balance control and voluntary limb coordination, both of which might be important for normal bipedal walking. We wanted to determine the relative contributions of balance versus leg-coordination deficits to cerebellar gait ataxia in humans. We studied 20 subjects with cerebellar damage and 20 control subjects performing three tasks: a lateral weight-shifting task to measure balance, a visually guided stepping task to measure leg- coordination, and walking. We recorded three-dimensional joint position data during all tasks and center of pressure coordinates during weight-shifting. Each cerebellar subject was categorized as having no detectable deficits, a balance deficit only, a leg-placement deficit only, or both deficits. We then determined the walking abnormalities associated with each of these categories. Five of 10 measures of gait ataxia were abnormal in cerebellar subjects with a balance deficit, but only 1 was abnormal in cerebellar subjects with a leg-placement deficit. Furthermore, subjects with a balance deficit performed worse than subjects with a leg-placement deficit on 9 of the 10 gait measures. Finally, performance on the balance task, but not the leg-placement task, explained a significant proportion of the variance in walking speed for the entire cerebellar group. We conclude that balance deficits are more closely related to cerebellar gait ataxia than leg-placement deficits. Our findings are consistent with animal literature, which has suggested that cerebellar control of balance and gait are interrelated, and dissociable from cerebellar control of voluntary, visually guided limb movements.
Response Properties of TMJ Units in Superficial Laminae at the Spinomedullary Junction of Female Rats Vary Over the Estrous Cycle
Authors: Okamoto K. , Hirata H. , Takeshita S. , Bereiter D. A.
Published: May 2006

Neurons responsive to stimulation of the temporomandibular joint (TMJ) region were recorded from superficial laminae at the trigeminal subnucleus caudalis/upper cervical cord (Vc/C2) junction region of cycling female rats under barbiturate anesthesia. To determine if receptive field (RF) properties or sensitivity to algesic chemicals of TMJ units vary over the estrous cycle, animals were selected from proestrous (high estrogen) or early diestrous (low estrogen) stages. More than 90% of TMJ units from each group received convergent nociceptive input [wide dynamic range (WDR) or nociceptive specific (NS)-like] from facial skin. The cutaneous high-threshold RF areas of WDR units from proestrous rats were 30% larger than diestrous units, while RF areas of NS units were similar. Bradykinin (BK, 0.1–10 μM) injection into the TMJ region excited a high percentage of units (>80% of total) from both groups in a dose-related manner. However, BK-evoked response magnitude ( R mag, +140%) and duration (+64%) were greater for proestrous than diestrous units. Both WDR and NS-like TMJ units of proestrous females displayed enhanced BK-evoked R mag values and response duration. Glutamate or mustard oil excitation of TMJ units was not affected by stage of the estrous cycle. Several TMJ units from proestrous and diestrous females were activated antidromically from the contralateral posterior thalamus, indicating that projection and nonprojection units were included in the sample population. These results were consistent with the hypothesis that factors related to stage of the estrous cycle modify the processing of deep craniofacial inputs by superficial dorsal horn neurons at the spinomedullary junction, a key region for the initial integration of sensory signals from the TMJ.
Model of Song Selectivity and Sequence Generation in Area HVc of the Songbird
Authors: Drew Patrick J. , Abbott L. F.
Published: May 2006

In songbirds, nucleus HVc plays a key role in the generation of the syllable sequences that make up a song. Auditory responses of neurons in HVc are selective for single syllables and for combinations of syllables occurring in temporal sequences corresponding to those in the bird's own song. We present a model of HVc that produces syllable- and temporal-combination-selective responses on the basis of input from recorded bird songs filtered through spectral temporal receptive fields similar to those measured in field L, a primary auditory area. Normalization of the field L outputs, similar to that proposed in models of visual processing, plays an important role in the generation of syllable-selective responses in the model. For temporal-combination-selective responses, N-methyl-d-aspartate (NMDA) conductances provide a memory that allows inhibitory neurons to gate responses to a final syllable in a sequence on the basis of responses to earlier syllables. When the same network that produces temporal-combination-selective responses is excited by a nonspecific timing signal, it generates a similar pattern of output as it does in response to auditory song input. Thus the same model network can perform both sensory and motor functions.
Neuronal Activity Related to the Visual Representation of Arm Movements in the Lateral Cerebellar Cortex
Authors: Liu Xuguang , Robertson Edwin , Miall R. Christopher
Published: May 2006

Testing the hypothesis that the lateral cerebellum forms a sensory representation of arm movements, we investigated cortical neuronal activity in two monkeys performing visually guided step-tracking movements with a manipulandum. A virtual target and cursor image were viewed co-planar with the manipulandum. In the normal task, manipulandum and cursor moved in the same direction; in the mirror task, the cursor was left-right reversed. In one monkey, 70- and 200-ms time delays were introduced on cursor movement. Significant task-related activity was recorded in 31 cells in one animal and 142 cells in the second: 10.2% increased activity before arm movements onset, 77.1% during arm movement, and 12.7% after the new position was reached. To test for neural representation of the visual outcome of movement, firing rate modulation was compared in normal and mirror step-tracking. Most task-related neurons (68%) showed no significant directional modulation. Of 70 directionally sensitive cells, almost one-half ( n = 34, 48%) modulated firing with a consistent cursor movement direction, many fewer responding to the manipulandum direction ( n = 9, 13%). For those “cursor-related” cells tested with delayed cursor movement, increased activity onset was time-locked to arm movement and not cursor movement, but activation duration was extended by an amount similar to the applied delay. Hence, activity returned to baseline about when the delayed cursor reached the target. We conclude that many cells in the lateral cerebellar cortex signaled the direction of cursor movement during active step-tracking. Such a predictive representation of the arm movement could be used in the guidance of visuo-motor actions.
Synchronization in Monkey Motor Cortex During a Precision Grip Task. II. Effect of Oscillatory Activity on Corticospinal Output
Authors: Baker Stuart N. , Pinches Elizabeth M. , Lemon Roger N.
Published: May 2006

Recordings from primary motor cortex (M1) during periods of steady contraction show oscillatory activity; these oscillations are coherent with the activity of contralateral muscles. We investigated synchronization of corticospinal output neurons with the oscillations, which could provide the pathway for their transmission to the spinal motoneurons. One hundred seventy-six antidromically identified pyramidal tract neurons (PTNs) were recorded from M1 in three macaque monkeys trained to perform a precision grip task. Local field potentials (LFP) were simultaneously recorded. All analysis was confined to the hold period of the task, where our previous work has shown that there is the strongest oscillatory activity. Coherence was calculated between LFP and PTN discharge. Significant coherence was seen in three bands, with frequencies of 10–14, 17–31, and 34–44 Hz. Coherence values were low, with the majority of PTN–LFP coherences having a peak lower than 0.05. The phase of coherence was approximately −π/2 radians for each band (with LFP polarity defined as negative upward), although there was some dispersion of phase across the population of PTNs. Coherence was also calculated between pairs of PTNs that had been simultaneously recorded. Where there was significant coherence, it was also generally smaller than 0.05. The phase of PTN–PTN coherence clustered around zero radians. A computer model was constructed to assist the interpretation of the experimental results. It simulated an integrate-and-fire neuron responding to synaptic inputs. A fraction of the synaptic inputs was synchronized with a simulated LFP; the remainder were uncorrelated with it. The model showed that coherence between the LFP and the output spike train considerably underestimated the fraction of synchronized inputs. Additionally, for a given fraction of synchronized inputs, coherence was smaller for high- compared with low-frequency bins. Cell discharge rate also influenced the spike–LFP coherence: coherence was higher for simulations in which the cell discharged at a faster rate. Thus although levels of PTN–LFP coherence seen experimentally were low, a considerable proportion of the input to the PTN must be synchronized with the global oscillatory activity recorded by the LFP. The low LFP–PTN coherences do however indicate that cortical oscillations are transmitted with only low fidelity in the discharge of a single PTN. Using further computer simulations, it was demonstrated that a small population of PTNs could encode the cortical oscillatory signal effectively, since the action of averaging across the population improves the signal:noise ratio. The oscillations will therefore be effectively transmitted to spinal motoneurons, and this has important consequences for the possible role of oscillations in motor control of the hand.
A Temporally Asymmetric Hebbian Rule Governing Plasticity in the Human Motor Cortex
Authors: Wolters Alexander , Sandbrink Friedhelm , Schlottmann Antje , Kunesch Erwin , Stefan Katja , Cohen Leonardo G. , Benecke Reiner , Classen Joseph
Published: May 2006

Synaptic plasticity is conspicuously dependent on the temporal order of the pre- and postsynaptic activity. Human motor cortical excitability can be increased by a paired associative stimulation (PAS) protocol. Here we show that it can also be decreased by minimally changing the interval between the two associative stimuli. Corticomotor excitability of the abductor pollicis brevis (APB) representation was tested before and after repetitively pairing of single right median nerve simulation with single pulse transcranial magnetic stimulation (TMS) delivered over the optimal site for activation of the contralateral APB. Following PAS, depression of TMS-evoked motor-evoked potentials (MEPs) was induced only when the median nerve stimulation preceded the TMS pulse by 10 ms, while enhancement of cortical excitability was induced using an interstimulus interval of 25 ms, suggesting an important role of the sequence of cortical events triggered by the two stimulation modalities. Experiments using F-wave studies and electrical brain stem stimulation indicated that the site of the plastic changes underlying the decrease of MEP amplitudes following PAS (10 ms) was within the motor cortex. MEP amplitudes remained depressed for approximately 90 min. The decrease of MEP amplitudes was blocked when PAS(10 ms) was performed under the influence of dextromethorphan, an N-methyl-d-aspartate-receptor antagonist, or nimodipine, an L-type voltage-gated calcium-channel antagonist. The physiological profile of the depression of human motor cortical excitability following PAS(10 ms) suggests long-term depression of synaptic efficacy to be involved. Together with earlier findings, this study suggests that strict temporal Hebbian rules govern the induction of long-term potentiation/long-term depression-like phenomena in vivo in the human primary motor cortex.
Stretch Responses of Cutaneous RA Afferent Neurons in Mouse Hairy Skin
Authors: Del Prete Zaccaria , Baker Stephen P. , Grigg Peter
Published: May 2006

Rapidly adapting (RA), stretch-sensitive neurons were recorded in vitro, using an isolated preparation of skin and nerve from mouse hindlimb. The skin was stretched uniaxially using a pseudo-Gaussian noise stimulus. Loads and displacements were recorded as were spike responses of single RA afferent neurons. The goal was to determine what components of the mechanical stimulus were associated with spike responses. The association between stimuli and spike responses was measured using multiple logistic regression. Spike responses were strongly associated with the rate of change of stress and weakly associated with the rate of change of strain and with stress. There was no association between spike responses and strain. There were significant memory effects associated with each variable, and memory effects differed for each variable. The maximal effect of the rate of change of stress was observed 8–12 ms prior to a spike.
Vanilloid Receptors in Hearing: Altered Cochlear Sensitivity by Vanilloids and Expression of TRPV1 in the Organ of Corti
Authors: Zheng Jiefu , Dai Chunfu , Steyger Peter S. , Kim Youngki , Vass Zoltan , Ren Tianying , Nuttall Alfred L.
Published: May 2006

Capsaicin, the vanilloid that selectively activates vanilloid receptors (VRs) on sensory neurons for noxious perception, has been reported to increase cochlear blood flow (CBF). VR-related receptors have also been found in the inner ear. This study aims to address the question as to whether VRs exist in the organ of Corti and play a role in cochlear physiology. Capsaicin or the more potent VR agonist, resiniferatoxin (RTX), was infused into the scala tympani of guinea pig cochlea, and their effects on cochlear sensitivity were investigated. Capsaicin (20 μM) elevated the threshold of auditory nerve compound action potential and reduced the magnitude of cochlear microphonic and electrically evoked otoacoustic emissions. These effects were reversible and could be blocked by a competitive antagonist, capsazepine. Application of 2 μM RTX resulted in cochlear sensitivity alterations similar to that by capsaicin, which could also be blocked by capsazepine. A desensitization phenomenon was observed in the case of prolonged perfusion with either capsaicin or RTX. Brief increase of CBF by capsaicin was confirmed, and the endocochlear potential was not decreased. Basilar membrane velocity (BM) growth functions near the best frequency and BM tuning were altered by capsaicin. Immunohistochemistry study revealed the presence of vanilloid receptor type 1 of the transient receptor potential channel family in the hair cells and supporting cells of the organ of Corti and the spiral ganglion cells of the cochlea. The results indicate that the main action of capsaicin is on outer hair cells and suggest that VRs in the cochlea play a role in cochlear homeostasis.
Role of Intracortical Inhibition in Selective Hand Muscle Activation
Authors: Stinear Cathy M. , Byblow Winston D.
Published: May 2006

Previous studies have shown that intracortical inhibition (ICI) plays an important role in shaping the output from primary motor cortex (M1). This study explored the muscle specificity and temporal modulation of ICI during the performance of a phasic index finger flexion task. Fifteen subjects were asked to rest their dominant hand on a computer mouse and depress the mouse button using their index finger in time with a 1-Hz auditory metronome, while keeping the rest of their hand as relaxed as possible. Responses to single- and paired-pulse transcranial magnetic stimulation were recorded from the first dorsal interosseous (FDI) and abductor pollicis brevis (APB) muscles while subjects were at rest and during “on” and “off” phases of the task. For FDI during the on phase, motor evoked potential (MEP) amplitude and pretrigger EMG increased and ICI decreased, as expected. This pattern of modulation was also observed for APB in seven subjects. The remaining eight subjects demonstrated a decrease in MEP amplitude and increase in ICI for APB during the on phase. This was associated with significantly less APB activation during the on phase. These findings suggest that an increase in ICI and decrease in corticospinal excitability can prevent unwanted muscle activation in a muscle-specific, temporally modulated manner.
Learning and Adaptation in a Recurrent Model of V1 Orientation Selectivity
Authors: Teich Andrew F. , Qian Ning
Published: May 2006

Learning and adaptation in the domain of orientation processing are among the most studied topics in the literature. However, little effort has been devoted to explaining the diverse array of experimental findings via a physiologically based model. We have started to address this issue in the framework of the recurrent model of V1 orientation selectivity and found that reported changes in V1 orientation tuning curves after learning and adaptation can both be explained with the model. Specifically, the sharpening of orientation tuning curves near the trained orientation after learning can be accounted for by slightly reducing net excitatory connections to cells around the trained orientation, while the broadening and peak shift of the tuning curves after adaptation can be reproduced by appropriately scaling down both excitation and inhibition around the adapted orientation. In addition, we investigated the perceptual consequences of the tuning curve changes induced by learning and adaptation using signal detection theory. We found that in the case of learning, the physiological changes can account for the psychophysical data well. In the case of adaptation, however, there is a clear discrepancy between the psychophysical data from alert human subjects and the physiological data from anesthetized animals. Instead, human adaptation studies can be better accounted for by the learning data from behaving animals. Our work suggests that adaptation in behaving subjects may be viewed as a short-term form of learning.
Altered Excitability of Intestinal Neurons in Primary Culture Caused by Acute Oxidative Stress
Authors: Vogalis Fivos , Harvey John R.
Published: May 2006

Neurons were isolated from the intestine of guinea pigs and grown in primary culture for ≤15 days. Using conventional whole cell recording techniques, we demonstrated that the majority of neurons express a prolonged poststimulus afterhyperpolarization (slow AHP). These neurons also had large-amplitude (∼100 mV), broad-duration (∼2 ms) action potentials and generated a hyperpolarization activated inward current ( Ih). Application of H2O2 (0.22–8.8 mM) hyperpolarized these neurons but not those lacking slow AHPs. The H2O2-induced hyperpolarization was followed by irreversible depolarization at higher concentrations (more than ∼1 mM) of H2O2 while it was maintained after washout of submillimolar H2O2. The ionic mechanisms underlying the hyperpolarization included the suppression of Ih and the activation of an inwardly rectifying outward current, which was blocked by glybenclamide (25–50 μM) and TEA (30 mM). In addition, H2O2 suppressed the slow AHP and its underlying current. Internal perfusion of catalase and glutathione opposed the H2O2-mediated decrease in IsAHP. Our results indicate that acute oxidative stress has neuron- and conductance-specific actions in intestinal neurons that may underlie pathophysiological conditions.
Properties of Exocytotic Response in Vertebrate Photoreceptors
Authors: Kreft M. , Križaj D. , Grilc S. , Zorec R.
Published: May 2006

Synaptic transmission at the photoreceptor synapse is characterized by continuous release of glutamate in darkness. Release is regulated by the intracellular calcium concentration ([Ca2+]i). We here examined the physiological properties of exocytosis in tiger salamander ( Ambystoma tigrinum) retinal rods and cones. Patch-clamp capacitance measurements were used to monitor exocytosis elicited by a rapid and uniform increase in [Ca2+]i by photolysis of the caged Ca2+ compound NP-EGTA. The amplitude of flash-induced increases in membrane capacitance (Cm) varied monotonically with [Ca2+]i beyond approximately 15 μM. The following two types of kinetic responses in Cm were recorded in both rods and cones: 1) a single exponential rise (39% of cells) or 2) a double-exponential rise (61%). Average rate constants of rapid and slow exocytotic responses were 420 ± 168 and 7.85 ± 5.02 s–1, respectively. The rate constant for the single exponential exocytotic response was 17.5 ± 12.4 s–1, not significantly different from that of the slow exocytotic response. Beyond the threshold [Ca2+]i of approximately 15 μM, the average amplitude of rapid, slow, and single Cm response were 0.84 ± 0.35, 0.82 ± 0.20, and 0.70 ± 0.23 pF, respectively. Antibodies against synaptotagmin I, a vesicle protein associated with fast exocytosis, strongly stained the synaptic terminal of isolated photoreceptors, suggesting the presence of fusion-competent vesicles. Our results confirm that photoreceptors possess a large rapidly releasable pool activated by a low-affinity Ca2+ sensor whose kinetic and calcium-dependent properties are similar to those reported in retinal bipolar cells and cochlear hair cells.
Differentiation of Visceral and Cutaneous Pain in the Human Brain
Authors: Strigo Irina A. , Duncan Gary H. , Boivin Michel , Bushnell M. Catherine
Published: May 2006

The widespread convergence of information from visceral, cutaneous, and muscle tissues onto CNS neurons invites the question of how to identify pain as being from the viscera. Despite referral of visceral pain to cutaneous areas, individuals regularly distinguish cutaneous and visceral pain and commonly have contrasting behavioral reactions to each. Our study addresses this dilemma by directly comparing human neural processing of intensity-equated visceral and cutaneous pain. Seven subjects underwent fMRI scanning during visceral and cutaneous pain produced by balloon distention of the distal esophagus and contact heat on the midline chest. Stimulus intensities producing nonpainful and painful sensations, interleaved with rest periods, were presented in each functional run. Analyses compared painful to nonpainful conditions. A similar neural network, including secondary somatosensory and parietal cortices, thalamus, basal ganglia, and cerebellum, was activated by visceral and cutaneous painful stimuli. However, cutaneous pain evoked higher activation bilaterally in the anterior insular cortex. Further, cutaneous but not esophageal pain activated ventrolateral prefrontal cortex, despite higher affective scores for visceral pain. Visceral but not cutaneous pain activated bilateral inferior primary somatosensory cortex, bilateral primary motor cortex, and a more anterior locus within anterior cingulate cortex. Our results reveal a common cortical network subserving cutaneous and visceral pain that could underlie similarities in the pain experience. However, we also observed differential activation patterns within insular, primary somatosensory, motor, and prefrontal cortices that may account for the ability to distinguish visceral and cutaneous pain as well as the differential emotional, autonomic and motor responses associated with these different sensations.
Muscarinic and Nicotinic ACh Receptor Activation Differentially Mobilize Ca2+in Rat Intracardiac Ganglion Neurons
Authors: Beker Friederike , Weber Martin , Fink Rainer H. A. , Adams David J.
Published: May 2006

The origin of intracellular Ca2+concentration ([Ca2+]i) transients stimulated by nicotinic (nAChR) and muscarinic (mAChR) receptor activation was investigated in fura-2-loaded neonatal rat intracardiac neurons. ACh evoked [Ca2+]iincreases that were reduced to ∼60% of control in the presence of either atropine (1 μM) or mecamylamine (3 μM) and to <20% in the presence of both antagonists. Removal of external Ca2+reduced ACh-induced responses to 58% of control, which was unchanged in the presence of mecamylamine but reduced to 5% of control by atropine. The nAChR-induced [Ca2+]iresponse was reduced to 50% by 10 μM ryanodine, whereas the mAChR-induced response was unaffected by ryanodine, suggesting that Ca2+release from ryanodine-sensitive Ca2+stores may only contribute to the nAChR-induced [Ca2+]iresponses. Perforated-patch whole cell recording at –60 mV shows that the rise in [Ca2+]iis concomitant with slow outward currents on mAChR activation and with rapid inward currents after nAChR activation. In conclusion, different signaling pathways mediate the rise in [Ca2+]iand membrane currents evoked by ACh binding to nicotinic and muscarinic receptors in rat intracardiac neurons.
Relation Between Bicarbonate Concentration and Voltage Dependence of Sodium Currents in Freshly Isolated CA1 Neurons of the Rat
Authors: Bruehl C. , Witte O. W.
Published: May 2006

It recently has been shown that whole cell calcium and sodium currents are modulated by CO2/HCO[Formula: see text]-buffered saline. While the bicarbonate ion, but not CO2, has been proven to modulate calcium currents, this information is lacking for sodium currents. Furthermore, it is not known whether the strength of modulation dependents on the bicarbonate concentration or whether it is an all-or-nothing phenomenon. To answer these questions, we used the whole cell voltage-clamp technique on freshly isolated hippocampal CA1 neurons from the rat. A voltage step from −130 to −20 mV elicited a sodium current with an amplitude of −5.1 ± 0.5 nA (mean ± SE, n = 17) when cells were superfused with HEPES-buffered saline. The amplitude of this current increased during a subsequent superfusion with solutions containing increasing amounts of bicarbonate and CO2(%CO2/mM HCO[Formula: see text]: 2.5/5.6; 5.0/18; 10/37), with a maximal increment in 10% CO2/37 mM HCO[Formula: see text] of −6.9 ± 0.8 nA. The increase in amplitude was associated with a linear negative shift (slope: −0.7 mV/mM HCO[Formula: see text]) of the potential of half-maximal activation (Δ V h,a: −19.4 ± 1.8 mV in 10% CO2) but not with an alteration in the maximal conductance ( g max: HEPES: 203.1 ± 21.0 nS and 10% CO2/37 mM HCO[Formula: see text]: 207.3 ± 21.3 nS). In addition, the potential of half-maximal inactivation ( V h,i) shifted to more negative potentials (slope: −0.6 mV/mM HCO[Formula: see text]) with increasing amounts of bicarbonate and CO2 (HEPES: −53.6 ± 11.8 mV; 10% CO2/37 mM HCO[Formula: see text]: −69.8 ± 2.1 mV), making the amplitude of the current highly sensitive for small potential changes at resting membrane potential. The same negative shift in voltage dependence arose when cells were exposed to solutions with different amounts of bicarbonate (5.6; 18; 26 mM) but constant CO2(5%) with slope rates of −0.5 mV/mM HCO[Formula: see text] for V h,a and −0.5 mV/mM HCO[Formula: see text] for V h,i. Again, there was no correlation between bicarbonate concentration and the size of g max. When currents were evoked in solutions containing a constant concentration (18 mM) of bicarbonate but different amounts of CO2 (2.5; 5.0 10%), no significant changes have been observed. The present data demonstrate that bicarbonate ions, and not CO2, modulate voltage-gated sodium currents in a concentration-dependent manner. Because the amplitude of the sodium current becomes highly sensitive to membrane potential changes concomitant with increased bicarbonate amounts, this may be critical for the excitability of the neuronal network in situations (like metabolic acidosis, respiratoric alkalosis and hypercapnia) in which the concentration of this ion can alter.
New Corticocuneate Cellular Mechanisms Underlying the Modulation of Cutaneous Ascending Transmission in Anesthetized Cats
Authors: Aguilar Juan , Rivadulla Casto , Soto Cristina , Canedo Antonio
Published: May 2006

The ascending cutaneous transmission through the middle cuneate nucleus is subject to cortico-feedback modulation. This work studied the intracuneate cellular mechanisms underlying the corticocuneate influence. Single unit extracellular records combined with iontophoresis showed that the corticocuneate input activates cuneo-lemniscal (CL) and noncuneo-lemniscal (nCL) cells via N-methyl-d-aspartate (NMDA) and non-NMDA receptors as shown by the decrease of the cortical-induced activation on ejection of CNQX and APV, either alone or in combination. These results were confirmed by in vivo intracellular recordings. Two subgroups of nCL cells were distinguished according to their sensitivity to iontophoretic ejection of glycine and its antagonist, strychnine. Finally, the corticalevoked activation of CL cells was decreased by GABA and increased by glycine acting at a strychnine-sensitive site, indicating that glycine indirectly affects the cuneo-lemniscal transmission. A model is proposed whereby the cortex influences CL cells through three different mechanisms, producing 1) activation via non-NMDA and NMDA receptors, 2) inhibition through GABAergic nCLs, and 3) disinhibition via serial glycinergic-GABAergic nCL cells. These corticocuneate feedback effects serve to potentiate the activity of CL cells topographically aligned through direct activation and disinhibition, while inhibiting, via GABAergic cells, other CL neurons not topographically aligned.
Testing Quantitative Models of Binocular Disparity Selectivity in Primary Visual Cortex
Authors: Read Jenny C. A. , Cumming Bruce G.
Published: May 2006

Disparity-selective neurons in striate cortex (V1) probably implement the initial processing that supports binocular vision. Recently, much progress has been made in understanding the computations that these neurons perform on retinal inputs. The binocular energy model has been highly successful in providing a simple theory of these computations. A key feature of the energy model is that it is linear until after inputs from the two eyes are combined. Recently, however, a modified version of the energy model, incorporating threshold nonlinearities before binocular combination, has been proposed to account for the weaker disparity tuning observed with anticorrelated stimuli. In this study, we present new data needed for a critical assessment of these two models. We compare two key predictions of the models with responses of disparity-selective neurons recorded from V1 of awake fixating monkeys. We find that the original energy model, and a family of generalizations retaining linear binocular combination, are quantitatively inconsistent with the response of V1 neurons. In contrast, the modified version incorporating threshold nonlinearities can explain both sets of observations. We conclude that the energy model can be reconciled with experimental observations by adding a threshold before binocular combination. This gives us the clearest picture yet of the computation being carried out by disparity-selective V1 neurons.
Ocular Motor Responses to Abrupt Interaural Head Translation in Normal Humans
Authors: Ramat Stefano , Zee David S.
Published: May 2006

We characterized the interaural translational vestibulo-ocular reflex (tVOR) in 6 normal humans to brief (∼200 ms), high-acceleration (0.4–1.4 g) stimuli, while they fixed targets at 15 or 30 cm. The latency was 19 ± 5 ms at 15-cm and 20 ± 12 ms at 30-cm viewing. The gain was quantified using the ratio of actual to ideal behavior. The median position gain (at time of peak head velocity) was 0.38 and 0.37, and the median velocity gain, 0.52 and 0.62, at 15- and 30-cm viewing, respectively. These results suggest the tVOR scales proportionally at these viewing distances. Likewise, at both viewing distances, peak eye velocity scaled linearly with peak head velocity and gain was independent of peak head acceleration. A saccade commonly occurred in the compensatory direction, with a greater latency (165 vs. 145 ms) and lesser amplitude (1.8 vs. 3.2 deg) at 30- than 15-cm viewing. Even with saccades, the overall gain at the end of head movement was still considerably undercompensatory (medians 0.68 and 0.77 at 15- and 30-cm viewing). Monocular viewing was also assessed at 15-cm viewing. In 4 of 6 subjects, gains were the same as during binocular viewing and scaled closely with vergence angle. In sum the low tVOR gain and scaling of the response with viewing distance and head velocity extend previous results to higher acceleration stimuli. tVOR latency (∼20 ms) was lower than previously reported. Saccades are an integral part of the tVOR, and also scale with viewing distance.