bluuebunny/crossref_metadata_2025 huggingface dataset:
Two Neuropeptides Colocalized in a Command-Like Neuron Use Distinct Mechanisms to Enhance Its Fast Synaptic Connection
Authors: Koh H.-Y. , Vilim F. S. , Jing J. , Weiss K. R.
Published: May 2006

In many neurons more than one peptide is colocalized with a classical neurotransmitter. The functional consequence of such an arrangement has been rarely investigated. Here, within the feeding circuit of Aplysia, we investigate at a single synapse the actions of two modulatory neuropeptides that are present in a cholinergic interneuron. In combination with previous work, our study shows that the command-like neuron for feeding, CBI-2, contains two neuropeptides, feeding circuit activating peptide (FCAP) and cerebral peptide 2 (CP2). Previous studies showed that high-frequency prestimulation or repeated stimulation of CBI-2 increases the size of CBI-2 to B61/62 excitatory postsynaptic potentials (EPSPs) and shortens the latency of firing of neuron B61/62 in response to CBI-2 stimulation. We find that both FCAP and CP2 mimic these two effects. The variance method of quantal analysis indicates that FCAP increases the calculated quantal size ( q) and CP2 increases the calculated quantal content ( m) of EPSPs. Since the PSP amplitude represents the product of q and m, the joint action of the two peptides is expected to be cooperative. This observation suggests a possible functional implication for multiple neuropeptides colocalized with a classical neurotransmitter in one neuron.
Pentobarbital Depressant Effects Are Independent of GABA Receptors in Auditory Thalamic Neurons
Authors: Wan Xiang , Puil Ernest
Published: May 2006

Pentobarbital, a general anesthetic, has received extensive study for its ability to potentiate inhibition at GABAAsubtype of receptors for GABA. Using whole cell current-clamp techniques and bath applications, we determined the effects of pentobarbital and GABA receptor antagonists on the membrane properties and tonic or burst firing of medial geniculate neurons in thalamic slices. Pentobarbital (0.01–200 μM) induced depressant effects in 50 of 66 neurons (76%). Pentobarbital hyperpolarized neurons by a mean of 3 mV and decreased the number of action potentials in tonic firing, evoked by current pulse injection from near the resting potential. Pentobarbital also decreased burst firing or low threshold Ca2+-spikes, evoked by current pulse injection into neurons at potentials hyperpolarized from rest. The blockade of tonic and burst firing, as well as low threshold Ca2+-spikes, was surmountable by increasing the amplitude of input current. The GABAAreceptor antagonists, bicuculline (100 μM) and picrotoxinin (50–100 μM), did not block the depressant effects of pentobarbital (10 μM). The GABABreceptor antagonist, saclofen (200 μM), and GABACreceptor antagonist, (1,2,3,6-tetrahydropyridine-4-yl)methylphosphinate (10–50 μM), did not significantly alter the depressant effects. Pentobarbital produced excitatory effects (0.1–50 μM) on 11 neurons (17%) but had no effects on 5 neurons (7%). The excitation consisted of approximately 3 mV depolarization, increased tonic and burst firing and the rate of rise and amplitude of low threshold Ca2+spikes. These effects were associated with a increase in input resistance. In contrast, the depressant effects of pentobarbital correlated to a decreased input resistance measured with hyperpolarizing current pulse injection (IC50= 7.8 μM). Pentobarbital reduced Na+-dependent rectification on depolarization and lowered the slope resistance over a wide voltage range. Tetrodotoxin eliminated both Na+-dependent rectification and the pentobarbital-induced decrease in membrane resistance at depolarized voltages in two-thirds of the neurons. The pentobarbital-induced decrease in membrane resistance at voltages hyperpolarized from rest was not evident during co-application with Cs+, known to block the hyperpolarization-activated rectifiers. In summary, the pentobarbital acted at low concentrations to depress thalamocortical neurons. The depression resulted from decreased rectification on depolarization, which no longer boosted potentials over threshold, and an increased conductance that shunted spike generation. The depressant effects of pentobarbital did not involve known types of GABA receptor interactions.
Protracted Development of Responses to Whisker Deflection in Rat Trigeminal Ganglion Neurons
Authors: Shoykhet Michael , Shetty Pranav , Minnery Brandon S. , Simons Daniel J.
Published: May 2006

The rodent whisker-to-barrel pathway constitutes a major model system for studying experience-dependent brain development. Yet little is known about responses of neurons to whisker stimulation in young animals. Response properties of trigeminal ganglion (NV) neurons in 2-, 3-, and 4-week-old and adult rats were examined using extracellular single-unit recordings and controlled whisker stimuli. We found that the receptive field size of NV neurons is mature in 2-week-old animals while response latencies, magnitudes, and angular tuning continue to develop between 2 weeks of age and adulthood. At the earliest time recorded, NV neurons respond to stimulation of only one whisker and can be characterized as slowly or rapidly adapting (SA, RA). The proportion of SA and RA neurons remains constant during development. Consistent with known on-going myelination of NV axons, response latencies decrease with age, becoming adult-like during the third and fourth postnatal weeks for RA and SA neurons, respectively. Unexpectedly, we found that evoked response magnitudes increase several-fold during development becoming adult-like only during the fourth postnatal week. In addition, RA neurons become less selective for whisker deflection angle with age. Maturation of response magnitude and angular tuning is consistent with developmental changes in the mechanical properties of the whisker, the whisker follicle, and the surrounding tissues. The findings indicate that whisker-derived tactile inputs mature during the first postnatal month when whisker-related cortical circuits are susceptible to long-term modification by sensory experience. Thus normal developmental changes in sensory input may influence functional development of cortical circuits.
Phenytoin Protects Spinal Cord Axons and Preserves Axonal Conduction and Neurological Function in a Model of Neuroinflammation In Vivo
Authors: Lo Albert C. , Saab Carl Y. , Black Joel A. , Waxman Stephen G.
Published: May 2006

Axonal degeneration within the spinal cord contributes substantially to neurological disability in multiple sclerosis (MS). Thus neuroprotective therapies that preserve axons, so that they maintain their integrity and continue to function, might be expected to result in improved neurological outcome. Sodium channels are known to provide a route for sodium influx that can drive calcium influx, via reverse operation of the Na+/Ca2+ exchanger, after injury to axons within the CNS, and sodium channel blockers have been shown to protect CNS axons from degeneration after experimental anoxic, traumatic, and nitric oxide (NO)-induced injury. In this study, we asked whether phenytoin, which is known to block sodium channels, can protect spinal cord axons from degeneration in mice with experimental allergic encephalomyelitis (EAE), which display substantial axonal degeneration and clinical paralysis. We demonstrate that the loss of dorsal corticospinal tract (63%) and dorsal column (cuneate fasciculus; 43%) axons in EAE is significantly ameliorated (corticospinal tract: 28%; cuneate fasciculus: 17%) by treatment with phenytoin. Spinal cord compound action potentials (CAP) were significantly attenuated in untreated EAE, whereas spinal cords from phenytoin-treated EAE had robust CAPs, similar to those from phenytoin-treated control mice. Clinical scores in phenytoin-treated EAE at 28 days were significantly improved (1.5, i.e., minor righting reflex abnormalities) compared with untreated EAE (3.8, i.e., near-complete hindlimb paralysis). Our results demonstrate that phenytoin has a protective effect in vivo on spinal cord axons, preventing their degeneration, maintaining their ability to conduct action potentials, and improving clinical status in a model of neuroinflammation.
Motor Unit Firing During and After Voluntary Contractions of Human Thenar Muscles Weakened by Spinal Cord Injury
Authors: Zijdewind Inge , Thomas Christine K.
Published: May 2006

Spinal cord injury may change both the distribution and the strength of the synaptic input within a motoneuron pool and therefore alter force gradation. Here, we have studied the relative contributions of motor unit recruitment and rate modulation to force gradation during voluntary contractions of thenar muscles performed by five individuals with chronic (>1 yr) cervical spinal cord injury. Mean ± SD thenar unit firing rates were low during both steady-level 25% (8.3 ± 2.2 Hz, n = 27 units) and 100% maximal voluntary contractions (MVCs, 9.2 ± 3.1 Hz, n = 23 units). Thus modest rate modulation, or a lack of it in some units, was seen despite an average fourfold increase in integrated surface electromyographic activity and force. During ramp contractions, units were recruited at 5.7 ± 2.5 Hz, but still only reached maximal firing rates of 12.8 ± 4.9 Hz. Motor units were recruited up to 85% of the maximal force achieved (14.6 ± 5.6 N). In contrast, unit recruitment in control hand muscles is largely complete by 30% MVC. Thus, during voluntary contractions of thenar muscles weakened by cervical spinal cord injury, motor unit rate modulation was limited and recruitment occurred over a wider than usual force range. Those motor units that were stopped voluntarily had significantly lower derecruitment versus recruitment thresholds. However, 8 units (24%) continued to fire long after the signal to end the voluntary contraction at a mean frequency of 5.9 ± 0.8 Hz. The forces generated by this prolonged unit activity ranged from 0.3 to 7.2% maximum. Subjects were unable to stop this involuntary unit activity even with the help of feedback. The mechanisms that underlie this prolonged motor unit firing need to be explored further.
Dendrodendritic Inhibition and Simulated Odor Responses in a Detailed Olfactory Bulb Network Model
Authors: Davison Andrew P. , Feng Jianfeng , Brown David
Published: May 2006

In the olfactory bulb, both the spatial distribution and the temporal structure of neuronal activity appear to be important for processing odor information, but it is currently impossible to measure both of these simultaneously with high resolution and in all layers of the bulb. We have developed a biologically realistic model of the mammalian olfactory bulb, incorporating the mitral and granule cells and the dendrodendritic synapses between them, which allows us to observe the network behavior in detail. The cell models were based on previously published work. The attributes of the synapses were obtained from the literature. The pattern of synaptic connections was based on the limited experimental data in the literature on the statistics of connections between neurons in the bulb. The results of simulation experiments with electrical stimulation agree closely in most details with published experimental data. This gives confidence that the model is capturing features of network interactions in the real olfactory bulb. The model predicts that the time course of dendrodendritic inhibition is dependent on the network connectivity as well as on the intrinsic parameters of the synapses. In response to simulated odor stimulation, strongly activated mitral cells tend to suppress neighboring cells, the mitral cells readily synchronize their firing, and increasing the stimulus intensity increases the degree of synchronization. Preliminary experiments suggest that slow temporal changes in the degree of synchronization are more useful in distinguishing between very similar odorants than is the spatial distribution of mean firing rate.
Interjoint Coordination in the Stick Insect Leg-Control System: The Role of Positional Signaling
Authors: Bucher Dirk , Akay Turgay , DiCaprio Ralph A. , Büschges Ansgar
Published: May 2006

Interjoint coordination is essential for proper walking behavior in multi-jointed insect legs. We have shown previously that movement signals from the femur-tibia (FT) joint can shape motor activity of the adjacent coxa-trochanter (CT) joint in the stick insect, Carausius morosus. Here, we present data on the role of position signals from the FT-joint on activity generated in motoneurons (MNs) of the CT-joint. We show that the probability of occurrence of stance (with depression in the CT-joint) or swing movements (with levation in the CT-joint) at the start of walking sequences is influenced by the angle of the FT-joint in the resting animal. We tested the influence of FT-joint angle on pharmacologically induced rhythmic activity of CT-joint depressor (DprTr) and levator (LevTr) MNs. The burst duration, mean spike rate within bursts, and duty cycle for each MN pool were found to depend on FT position. For LevTr MNs, these parameters progressively increased as the FT-joint was moved from extension to flexion, and the opposite was true for DprTr MNs. The cycle period of CT-MN rhythmicity also depended on FT position. In addition, we sometimes observed that the motor output shifted completely to one MN pool at extreme positions, suggesting that the central rhythm-generating network for the CT-joint became locked in one phase. These results indicate that position signals from the FT-joint modulate rhythmic activity in CT-joint MNs partly by having access to central rhythm generating networks of the CT-joint.
Selectivity and Spatial Distribution of Signals From the Receptive Field Surround in Macaque V1 Neurons
Authors: Cavanaugh James R. , Bair Wyeth , Movshon J. Anthony
Published: May 2006

The responsiveness of neurons in V1 is modulated by stimuli placed outside their classical receptive fields. This nonclassical surround provides input from a larger portion of the visual scene than originally thought, permitting integration of information at early levels in the visual processing stream. Signals from the surround have been reported variously to be suppressive and facilitatory, selective and unselective. We tested the specificity of influences from the surround by studying the interactions between drifting sinusoidal gratings carefully confined to conservatively defined center and surround regions. We found that the surround influence was always suppressive when the surround grating was at the neuron's preferred orientation. Suppression tended to be stronger when the surround grating also moved in the neuron's preferred direction, rather than its opposite. When the orientation in the surround was 90° from the preferred orientation (orthogonal), suppression was weaker, and facilitation was sometimes evident. The tuning of surround signals therefore tended to match the tuning of the center, though the tuning of the surround was somewhat broader. The tuning of suppression also depended on the contrast of the center grating—when the center grating was reduced in contrast, orthogonal surround stimuli became relatively more suppressive. We also found evidence for the tuning of the surround being dependent to some degree on the stimulus used in the center—suppression was often stronger for a given center stimulus when the parameters of the surround grating matched the parameters of the center grating even when the center grating was not itself of the optimal direction or orientation. We also explored the spatial distribution of surround influence and found an orderly relationship between the orientation of grating patches presented to regions of the surround and the position of greatest suppression. When surround gratings were oriented parallel to the preferred orientation of the receptive field, suppression was strongest at the receptive field ends. When surround gratings were orthogonal, suppression was strongest on the flanks. We conclude that the surround has complex effects on responses from the classical receptive field. We suggest that the underlying mechanism of this complexity may involve interactions between relatively simple center and surround mechanisms.
Intrinsic Properties and Reflex Compensation in Reinnervated Triceps Surae Muscles of the Cat: Effect of Movement History
Authors: Huyghues-Despointes Clotilde M.J.I. , Cope Timothy C. , Nichols T. Richard
Published: May 2006

Effects of prior motion on ramp stretch responses of reflexive and areflexive muscles were measured in decerebrate cats. Soleus and gastrocnemius muscles were rendered areflexive by reinnervation a minimum of 9 mo before the terminal experiments. The introduction of a shortening phase prior to the ramp stretch increased the normalized initial stiffness of muscles and decreased the tendency to yield of the reinnervated muscles as compared with the case in which muscles contracted isometrically prior to stretch. Yielding was compensated by reflex action for all amplitudes of prior shortening in soleus and gastrocnemius muscles. The comparison of responses of untreated and reinnervated muscles indicated that the contribution of reflex action progressively declined with the amplitude of prior shortening as the extent of yielding diminished. In soleus muscle, during a variable delay period of isometric contraction interposed between shortening and lengthening force generation, initial stiffness and yielding returned to levels seen with isometric contractile history. However, these attributes recovered at different rates, suggesting that distinct processes are responsible for initial stiffness and yielding. Yielding was compensated for by reflex action regardless of the length of the interposed delay or of the amplitude of the prior shortening. These and previous findings indicate that the stretch reflex regulates muscular stiffness for a wide range of conditions. This regulation apparently arises from complementary mechanical properties of intrafusal and extrafusal muscle.
Multiwavelength Optical Intrinsic Signal Imaging of Cortical Spreading Depression
Authors: Ba Alyssa M. , Guiou Michael , Pouratian Nader , Muthialu Arpitha , Rex David E. , Cannestra Andrew F. , Chen James W. Y. , Toga Arthur W.
Published: May 2006

Cortical spreading depression (CSD) is an important disease model for migraine and cerebral ischemia. In this study, we exploit the high temporal and spatial resolution of optical imaging to characterize perfusion-dependent and -independent changes in response to CSD and to investigate the etiology of reflectance changes during CSD. In this experiment, we characterized the optical response to CSD at wavelengths that emphasize perfusion-related changes (610 and 550 nm), and we compared these results with 850 nm and blood volume data. Blood volume changes during CSD were recorded using an intravascular fluorescent dye, Texas Red dextran. We observed triphasic optical signals at 850 and 550 nm characterized by spreading waves of increased, decreased, then increased reflectance (Fig. 1 ) which expanded at a rate of approximately 3–5 mm/min. The signal at 610 nm had a similar initial phase, but the phase 2 response was slightly more complex, with a parenchymal decrease in reflectance but a vascular increase in reflectance. Reflectance values decreased in phase three. Blood volume signals were delayed relative to the optical intrinsic signals and corresponded temporally to phases 2 and 3. This is the first study to characterize optical imaging of intrinsic signal responses to CSD, in vivo, at multiple wavelengths. The data presented here suggest that changes in light scattering precede perfusion responses, the blood volume increase (phase 2) is accompanied by a reduction in deoxyhemoglobin, and the blood volume decrease (phase 3) is accompanied by an increase in deoxyhemoglobin. Previous studies have suggested the oligemia of spreading depression was a result of decreased metabolic demand. This study suggests that during the oligemic period there is a greater reduction in oxygen delivery than in demand.
Fractal Properties of Sympathetic Nerve Discharge
Authors: Das Mahasweta , Gebber Gerard L. , Barman Susan M. , Lewis Craig D.
Published: May 2006

Fano factor analysis and dispersional analysis were used to characterize time series of single and multifiber spikes recorded from the preganglionic cervical sympathetic nerve and cardiac-related slow-wave activity of the whole postganglionic sympathetic vertebral nerve (VN) in anesthetized cats. Fluctuations in spike counts and interspike intervals for single preganglionic fibers proved to be fractal (i.e., time-scale invariant), as reflected by a power law relationship between indices of the variance of these properties and the window size used to make the measurements. Importantly, random shuffling of the data eliminated the power law relationships. Fluctuations in spike counts in preganglionic multifiber activity also were fractal, as were fluctuations in the height and of the area of cardiac-related slow waves recorded from the whole postganglionic VN. These fractal fluctuations were persistent (i.e., positively correlated), as reflected by a Hurst exponent significantly >0.5. Although fluctuations in the interval between cardiac-related VN slow waves were random, those in the interval between heart beats were fractal and persistent. These results demonstrate for the first time that apparently random fluctuations in sympathetic nerve discharge are, in fact, dictated by a complex deterministic process that imparts “long-term” memory to the system. Whether such time-scale invariant behavior plays a role in generating the fractal component of heart rate variability remains to be determined.
Effects of Unilateral Vestibular Deafferentation on the Linear Vestibulo-Ocular Reflex Evoked by Impulsive Eccentric Roll Rotation
Authors: Aw S. T. , Todd M. J. , McGarvie L. A. , Migliaccio A. A. , Halmagyi G. M.
Published: May 2006

The effects of unilateral vestibular deafferentation (UVD) on the linear vestibulo-ocular reflex (LVOR) were studied by measuring three-dimensional eye movements in seven UVD subjects evoked by impulsive eccentric roll rotation while viewing an earth-fixed target at 200, 300, or 600 mm and comparing their responses to 11 normal subjects. The stimulus, a whole-body roll of approximately 1°, with the eye positioned 815 mm eccentric to the rotation axis, produced an inter-aural linear acceleration of approximately 0.5 g and a roll acceleration of approximately 360°/s2. The responses generated by the LVOR comprise horizontal eye rotations. Horizontal eye velocity at 100 ms from stimulus onset in UVD subjects was significantly lower than in normal subjects for all viewing distances, with no significant difference between ipsilesional and contralesional responses. LVOR acceleration gain, defined as the slope of actual horizontal eye velocity divided by the slope of ideal horizontal eye velocity during a 30-ms period starting 70 ms from stimulus onset, was bilaterally significantly reduced in UVD subjects at all viewing distances. Acceleration gain from all viewing distances was 1.04 ± 0.28 in normal subjects, and in UVD subjects was 0.49 ± 0.23 for ipsilesional and 0.63 ± 0.27 for contralesional acceleration. LVOR enhancement in the first 100 ms by near viewing was still present in UVD subjects. LVOR latency in UVD subjects (approximately 39 ms) was not significantly different from normal subjects (approximately 36 ms). After UVD, LVOR is bilaterally and largely symmetrically reduced, but latency remains unchanged and modulation by viewing distance is still present.
Head-Trunk Coordination During Linear Anterior-Posterior Translations
Authors: Keshner Emily A.
Published: May 2006

The purpose of this study was to evaluate the relative contributions of inputs from the vestibular system and the trunk to head-trunk coordination. Twelve healthy adults and 6 adults with diminished bilateral labyrinthine input (LD) were seated with their trunk either fixed to the seat or free to move. Subjects received 10-cm, 445-cm/s2anterior-posterior ramps and 0.35- to 4.05-Hz sum-of-sines translations while performing a mental distraction task in the dark. Kinematics of the head and trunk were derived from an Optotrak motion analysis system and a linear accelerometer placed on the head. EMG signals were collected from neck and paraspinal muscles. Data were tested for significance with multivariate ANOVA (MANOVA) and Bonferroni post hoc analyses. Initial linear and angular head acceleration directions differed in healthy subjects when the trunk was fixed or free, but did not differ in LD subjects. Peak head angular accelerations were significantly greater with the trunk fixed than when free, and were greater in LD than in control subjects. EMG response latencies did not differ when the trunk was fixed or free. Low-frequency phase responses in the healthy subjects were close to 90° and had a delayed descent as frequency increased, suggesting some neural compensation that was absent in the LD subjects. Results of this study revealed a strong initial reliance on system mechanics and on signals from segmental receptors. The vestibular system may act to damp later response components and to monitor the position of the head in space secondary to feedback from segmental proprioceptors rather than to generate the postural reactions.
Millivolt-Scale DC Shifts in the Human Scalp EEG: Evidence for a Nonneuronal Generator
Authors: Voipio Juha , Tallgren Pekka , Heinonen Erkki , Vanhatalo Sampsa , Kaila Kai
Published: May 2006

Slow shifts in the human scalp-recorded EEG, including those related to changes in brain CO2levels, have been generally assumed to result from changes in the level of tonic excitation of apical dendrites of cortical pyramidal neurons. We readdressed this issue using DC-EEG shifts elicited in healthy adult subjects by hypo- or hypercapnia. A 3-min period of hyperventilation resulted in a prompt negative shift with a rate of up to 10 μV/s at the vertex (Cz) and an extremely steep dependence (up to 100 μV/mmHg) on the end-tidal Pco2. This shift had a maximum of up to −2 mV at Cz versus the temporal derivations (T3/T4). Hyperventilation-like breathing of 5% CO2-95% O2, which does not lead to a significant hypocapnia, resulted in a near-complete block of the negative DC shift at Cz. Hypoventilation, or breathing 5% CO2in air at normal respiratory rate, induced a positive shift. The high amplitude of the voltage gradients on the scalp induced by hyperventilation is not consistent with a neuronal origin. Instead, the present data suggest that they are generated by extracortical volume currents driven by a Pco2-dependent potential difference across epithelia separating the cerebrospinal fluid and blood. Since changes in respiratory patterns and, hence, in the level of brain Pco2, are likely to occur under a number of experimental conditions in which slow EEG responses have been reported (e.g., attention shifts, preparatory states, epileptic seizures, and hypoxic episodes), the present results call for a thorough reexamination of the mechanisms underlying scalp-recorded DC-EEG responses.
Role of Myelination in the Development of a Uniform Olivocerebellar Conduction Time
Authors: Lang Eric J. , Rosenbluth Jack
Published: May 2006

Purkinje cells generate simultaneous complex spikes as a result of olivocerebellar activity. This synchronization (to within 1 ms) is thought to result from electrotonic coupling of inferior olivary neurons. However, the distance from the inferior olive (IO) varies across the cerebellar cortex. Thus signals generated simultaneously at the IO should arrive asynchronously across the cerebellar cortex, unless the length differences are compensated for. Previously, it was shown that the conduction time from the IO to the cerebellar cortex remains nearly constant at ≈4 ms in the rat, implying the existence of such compensatory mechanisms. Here, we examined the role of myelination in generating a constant olivocerebellar conduction time by investigating the latency of complex spikes evoked by IO stimulation during development in normal rats and myelin-deficient mutants. In normal rats, myelination not only reduced overall olivocerebellar conduction time, but also disproportionately reduced the conduction time to vermal lobules, which had the longest response latencies prior to myelination. The net result was a nearly uniform conduction time. In contrast, in myelin-deficient rats, conduction time differences to different parts of the cerebellum remained during the same developmental period. Thus myelination is the primary factor in generating a uniform olivocerebellar conduction time. To test the importance of a uniform conduction time for generating synchronous complex spike activity, multiple electrode recordings were obtained from normal and myelin-deficient rats. Average synchrony levels were higher in normal rats than mutants. Thus the uniform conduction time achieved through myelination of olivocerebellar fibers appears to be essential for the normal expression of complex spike synchrony.
Absence of Local Sign Withdrawal in Chronic Human Spinal Cord Injury
Authors: Schmit Brian D. , Hornby T. George , Tysseling-Mattiace Vicki M. , Benz Ela N.
Published: May 2006

Local sign withdrawal, a reflex to direct the limb away from noxious cutaneous stimuli, is thought to be indicative of a modular organization of the spinal cord. To assess the integrity of such an organization of the spinal cord in chronic human spinal cord injury (SCI), we tested the electromyogram (EMG) and joint torque responses to cutaneous stimuli applied to 6 locations of the leg in 10 SCI volunteers and 3 spinal-intact controls. The 6 locations included the medial arch of the foot, the second metatarsal, the dorsum, the region over the sural nerve at the lateral malleolus, and the anterior and posterior aspects of the lower leg. Although spinal-intact subjects demonstrated local sign withdrawal, the data from SCI subjects indicated that an invariant flexion response pattern was produced regardless of stimulus location. Ankle dorsiflexion and hip flexion were produced in all subjects at all locations and no difference in the ratio of hip:ankle torques could be detected for the 6 test locations. A windup-crossover test, employing a sequence of 6 stimuli at 1-s intervals was used to assess whether common neuronal pathways were responsible for the loss of modular organization. An additional 10 SCI volunteers were tested using stimuli in which the stimulus location was switched between the 2nd and 3rd stimulus of the test sequence. The response to the crossover stimulus more closely resembled the response to the 3rd stimulus of a windup sequence than a response without conditioning stimuli. These results indicate that increased excitability produced by windup at one stimulus site is maintained at the 2nd site. This observation suggests that deep dorsal horn neurons, typically associated with musculotopic mapping, may be reorganized in chronic spinal cord injury.
Differential Dependence of LTD on Glutamate Receptors in the Auditory Cortical Synapses of Cortical and Thalamic Inputs
Authors: Kudoh Masaharu , Sakai Masashi , Shibuki Katsuei
Published: May 2006

Pyramidal neurons in the auditory cortex (AC) receive glutamatergic inputs from the medial geniculate body (MGB inputs) and other pyramidal neurons (pyramidal inputs). We found that the induction of long-term depression (LTD) in supragranular layers was only partially suppressed by 50 μMd-(−)-2-amino-5-phosphonovalerate (APV), an antagonist of N-methyl-d-aspartate (NMDA) receptors (NMDARs), and 500 μM (+)-α-methyl-4-carboxyphenylglycine (MCPG), an antagonist of metabotropic glutamate receptors (mGluRs). However, LTD was not observed in the mixture of APV and MCPG. We hypothesized that the mixed dependence of LTD on glutamate receptors could be attributed to the heterogeneity of MGB inputs and pyramidal inputs. To test this hypothesis, the angle of slicing and other recording conditions were adjusted so that postsynaptic potentials were recorded in normal slices, but not in the slices prepared from the rats with MGB lesion. In these experiments, LTD was suppressed by MCPG alone. The conditions were adjusted to minimize the contribution of MGB inputs in field potentials. In these experiments, the induction of LTD was suppressed by APV alone. Interestingly, the induction of LTD was partially suppressed by 20 μM nifedipine, a blocker of L-type Ca2+channels, in the slices prepared from the rats with MGB lesions, but not in normal slices. These findings suggest that the induction of LTD requires activation of mGluRs in the synapses of MGB inputs and of NMDARs in the synapses of pyramidal inputs.
Interplay Between Activation of GIRK Current and Deactivation ofIhModifies Temporal Integration of Excitatory Input in CA1 Pyramidal Cells
Authors: Takigawa Tomoko , Alzheimer Christian
Published: May 2006

Trains of brief iontophoretic glutamate pulses were delivered onto the apical dendrites of CA1 pyramidal cells at variable frequencies (3–100 Hz) to examine how the activation of a G protein–activated, inwardly rectifying K+(GIRK) conductance alters the postsynaptic processing of repetitive excitatory input. Application of the GIRK channel agonist baclofen (20 μM) reduced the amplitude of individual glutamate-evoked postsynaptic potentials (GPSPs) and attenuated summation of GPSPs so that higher stimulus intensities were required to fire the cell. Notably, GIRK channel activation not only decreased GPSPs, but also suppressed the subsequent afterhyperpolarization (AHP), which arises from a transient deactivation of the hyperpolarization-activated cation current ( Ih). Voltage-clamp recordings ruled out a direct modulatory action of baclofen on Ih. GIRK channel activation alone accounts for AHP suppression, firstly because, with smaller GPSP amplitudes, fewer Ihchannels are deactivated, resulting in a diminished AHP, and secondly because, owing to its progressive increase in the hyperpolarizing direction, the GIRK conductance shunts a large portion of the remaining AHP. We provide experimental evidence that the suppression of the Ih-dependent AHP by GIRK channel activation bears particular significance on the processing of repetitive excitatory inputs at frequencies at which the deactivation kinetics of Ihexert a prominent depressing effect. In functional terms, activation of GIRK current not only produces a time-independent mitigation of incoming excitatory input, which results directly from the opening of an instantaneous K+conductance, but might also cause a time-dependent redistribution of synaptic weight within a stimulus train, which we link to an interplay with the deactivation of Ih.
Frequency-Dependent Properties of Inhibitory Synapses in the Rostral Nucleus of the Solitary Tract
Authors: Grabauskas Gintautas , Bradley Robert M.
Published: May 2006

To explore the parameters that define the characteristics of either inhibitory postsynaptic potentials (IPSP) or currents (IPSC) in the gustatory nucleus of the solitary tract (rNST), whole cell patch-clamp recordings were made in horizontal brain stem slices of newborn rats. Neurons were labeled with biocytin to confirm both their location and morphology. IPSPs or IPSCs were evoked by delivering either single, paired-pulse, or tetanic stimulus shocks (0.1-ms duration) via a bipolar stimulating electrode placed on the rNST. Pure IPSP/IPSCs were isolated by the use of glutamate receptor antagonists. For 83% of the single-stimulus-evoked IPSCs, the decay time course was fitted with two exponentials having average time constants of 38 and 181 ms, respectively, while the remainder could be fitted with one exponential of 59 ms. Paired-pulse stimulation resulted in summation of the amplitude of the conditioning and test-stimulus-evoked IPSCs. The decay time course of the test-stimulus-evoked IPSC was slower when compared to the decay time of the conditioning stimulus IPSC. Repeated stimulation resulted in an increase in the decay time of the IPSP/Cs where each consecutive stimulus contributed to prolongation of the decay time constant. Most of the IPSP/Cs resulting from a 1-s ≥ 30-Hz tetanic stimulus exhibited an S-shaped decay time course where the amplitude of the IPSP/Cs after termination of the stimulus was initially sustained before starting to decay back to the resting membrane potential. Elevation of extracellular Ca2+concentration 10 mM resulted in an increase in the amplitude and decay time of single-stimulus shock-evoked IPSP/Cs. The benzodiazepine GABAA receptor modulator diazepam increased the decay time of single-stimulus shock-evoked IPSCs. However, application of diazepam did not affect the decay time of tetanic-stimulation-evoked IPSP/Cs. These results suggest that the decay time of single-stimulus-evoked IPSCs is defined either by receptor kinetics or neurotransmitter clearance from the synaptic cleft or both, while the decay time course of the tetanic stimulus evoked IPSP/Cs is defined by neurotransmitter diffusion from the synaptic cleft. During repetitive stimulation, neurotransmitter accumulates in the synaptic cleft prolonging the decay time constant of the IPSCs. High-frequency stimulation elevates the GABA concentration in the synaptic cleft, which then oversaturates the postsynaptic receptors, and, as a consequence, after termination of the tetanic stimulus, the amplitude of IPSP/Cs is sustained resulting in an S shaped decay time course. This activity-dependent plasticity at GABAergic synapses in the rNST is potentially important in the encoding of taste responses because the dynamic range of stimulus frequencies that result in synaptic plasticity (0–70 Hz) corresponds to the breadth of frequencies that travels via afferent gustatory nerve fibers in response to taste stimuli.
Thresholds for Inducing Protective Stepping Responses to External Perturbations of Human Standing
Authors: Mille M.-L. , Rogers M. W. , Martinez K. , Hedman L. D. , Johnson M. E. , Lord S. R. , Fitzpatrick R. C.
Published: May 2006

Standing subjects were unexpectedly pulled forward to identify a threshold boundary that evokes stepping in terms of the size of the pull relative to the base of support (BoS). Performances in a range of sensorimotor tests were correlated with the threshold boundary parameters. Younger and older subjects were studied to identify age-related changes in stepping and the threshold boundaries. The threshold boundary had a forward limit (TL) that, when crossed, always made subjects step no matter how slowly they were pulled. As velocity increased, the threshold position that produced a step shifted nearer to the ankles. Eventually a pull velocity was reached above which velocity had no further effect and a position threshold (TH) was identified behind which subjects never stepped. Thus the position threshold boundary for stepping is a posterior-going sigmoidal function of perturbation velocity. Older subjects stepped more than the young (69% vs. 40% of trials). For the older subjects, TL (91% vs. 107% BoS) and TH (59% vs. 72% BoS) were closer to the ankles, and the transition between TL and TH occurred at lower velocities (96% vs. 121% BoS.s–1). Across the entire study population many sensorimotor factors were associated with TL and TH. However, these associations were not present when age was removed as a factor. Thus, although the older subjects use protective stepping more often, this cannot be attributed directly to the sensorimotor factors tested here. It can be explained by stepping as a triggered response to the perturbation event rather than later sensory input about body movement.
Nicotine Enhances the Depressive Actions of Aβ1–40 on Long-Term Potentiation in the Rat Hippocampal CA1 Region In Vivo
Authors: Freir D. B. , Herron C. E.
Published: May 2006

Hippocampal long-term potentiation (LTP) is a form of synaptic plasticity used as a cellular model of memory. Beta amyloid (Aβ) is involved in Alzheimer's disease (AD), a neurode-generative disorder leading to cognitive deficits. Nicotine is also claimed to act as a cognitive enhancer. Aβ is known to bind with high affinity to the α7-nicotinic acetylcholine receptor (nAChR). Here we have investigated the effect of intracerebroventricular (icv) injection of the endogenous peptide Aβ1–40 on LTP in area CA1 of urethananesthetized rats. We also examined the effect of Aβ12–28 (icv), which binds with high affinity to the α7-nAChR and the specific α7-nAChR antagonist methyllycaconitine (MLA) on LTP. We found that Aβ12–28 had no effect on LTP, whereas MLA depressed significantly LTP, suggesting that activation of the α7-nAChR is a requirement for LTP. Within the in vivo environment, where other factors may compete with Aβ12–28 for binding to α7-nAChR, it does not appear to modulate LTP. To determine if the depressive action of Aβ1–40 on LTP could be modulated by nicotine, these agents were also co-applied. Injection of 1 or 10 nmol Aβ1–40 caused a significant depression of LTP, whereas nicotine alone (3 mg/kg) had no effect on LTP. Co-injection of nicotine with Aβ1–40 1 h prior to LTP induction caused a further significant depression of LTP compared with Aβ1–40 alone. These results demonstrate that nicotine enhances the deficit in LTP produced by Aβ1–40. This then suggests that nicotine may exacerbate the depressive actions of Aβ on synaptic plasticity in AD.
Facilitation From Ventral Premotor Cortex of Primary Motor Cortex Outputs to Macaque Hand Muscles
Authors: Cerri G. , Shimazu H. , Maier M. A. , Lemon R. N.
Published: May 2006

We demonstrate that in the macaque monkey there is robust, short-latency facilitation by ventral premotor cortex (area F5) of motor outputs from primary motor cortex (M1) to contralateral intrinsic hand muscles. Experiments were carried out on two adult macaques under light sedation (ketamine plus medetomidine HCl). Facilitation of hand muscle electromyograms (EMG) was tested using arrays of fine intracortical microwires implanted, respectively, in the wrist/digit motor representations of F5 and M1, which were identified by previous mapping with intracortical microstimulation. Single pulses (70–200 μA) delivered to F5 microwires never evoked any EMG responses, but small responses were occasionally seen with double pulses (interval: 3 ms) at high intensity. However, both single- and double-pulse stimulation of F5 could facilitate the EMG responses evoked from M1 by single shocks. The facilitation was large (up to 4-fold with single and 12-fold with double F5 shocks) and occurred with an early onset, with significant effects at intervals of only 1–2 ms between conditioning F5 and test M1 stimuli. A number of possible pathways could be responsible for these effects, although it is argued that the most likely mechanism would be the facilitation, by cortico-cortical inputs from F5, of corticospinal I wave activity evoked from M1. This facilitatory action could be of considerable importance for the coupling of grasp-related neurons in F5 and M1 during visuomotor tasks.
Commissural Inputs to Secondary Vestibular Neurons in Alert Cats After Canal Plugs
Authors: Farrow Karl , Broussard Dianne M.
Published: May 2006

Gaze is stabilized during head movements primarily by the vestibuloocular reflex (VOR). After a unilateral canal plug, the VOR's response is reduced. Recovery of the VOR may be brought about by changes in the efficacy of brain stem synapses or by other mechanisms. We measured the responses of horizontal secondary vestibular neurons (HSNs) to stimulation of the contralateral labyrinth. HSN responses in normal alert cats were compared with those in cats that had recovered from unilateral horizontal semicircular canal (HSCC) plugs. After recovery, excitatory commissural inputs to HSNs on the plugged side elicited significantly smaller responses than in normal cats with no change in mean discharge rates. However, mean discharge rates tended to be higher after recovery for cells receiving inhibitory commissural inputs. The change in resting rate invalidates any direct comparison of inhibitory inputs. These results are interpreted in terms of possible mechanisms for recovery from unilateral vestibular loss by the VOR neural network. We conclude that after unilateral HSCC plugs, changes in brain stem excitatory synapses and/or excitability of secondary vestibular neurons may participate in the restoration of normal vestibular reflexes.
Relationships Between Skin Temperature and Temporal Summation of Heat and Cold Pain
Authors: Mauderli Andre P. , Vierck Charles J. , Cannon Richard L. , Rodrigues Anthony , Shen Chiayi
Published: May 2006

Temporal summation of heat pain during repetitive stimulation is dependent on C nociceptor activation of central N-methyl-d-aspartate (NMDA) receptor mechanisms. Moderate temporal summation is produced by sequential triangular ramps of stimulation that control skin temperature between heat pulses but do not elicit distinct first and second pain sensations. Dramatic summation of second pain is produced by repeated contact of the skin with a preheated thermode, but skin temperature between taps is not controlled by this procedure. Therefore relationships between recordings of skin temperature and psychophysical ratings of heat pain were evaluated during series of repeated skin contacts. Surface and subcutaneous recordings of skin temperatures revealed efficient thermoregulatory compensation for heat stimulation at interstimulus intervals (ISIs) ranging from 2 to 8 s. Temporal summation of heat pain was strongly influenced by the ISIs and cannot be explained by small increases in skin temperature between taps or by heat storage throughout a stimulus series. Repetitive brief contact with a precooled thermode was utilized to evaluate whether temporal summation of cold pain occurs, and if so, whether it is influenced by skin temperature. Surface and subcutaneous recordings of skin temperature revealed a sluggish thermoregulatory compensation for repetitive cold stimulation. In contrast to heat stimulation, skin temperature did not recover between cold stimuli throughout ISIs of 3–8 s. Psychophysically, repetitive cold stimulation produced an aching pain sensation that progressed gradually and radiated beyond the site of stimulation. The magnitude of aching pain was well related to skin temperature and thus appeared to be established primarily by peripheral factors.
Fast and Slow Locomotor Burst Generation in the Hemispinal Cord of the Lamprey
Authors: Cangiano Lorenzo , Grillner Sten
Published: May 2006

A fundamental question in vertebrate locomotion is whether distinct spinal networks exist that are capable of generating rhythmic output for each group of muscle synergists. In many vertebrates including the lamprey, it has been claimed that burst activity depends on reciprocal inhibition between antagonists. This question was addressed in the isolated lamprey spinal cord in which the left and right sides of each myotome display rhythmic alternating activity. We sectioned the spinal cord along the midline and tested whether rhythmic motor activity could be induced in the hemicord with bath-applied d-glutamate or N-methyl-d-aspartate (NMDA) as in the intact spinal cord or by brief trains of electrical stimuli. Fast rhythmic bursting (2–12 Hz), coordinated across ventral roots, was observed with all three methods. Furthermore, to diminish gradually the crossed glycinergic inhibition, a progressive surgical lesioning of axons crossing the midline was implemented. This resulted in a gradual increase in burst frequency, linking firmly the fast hemicord rhythm [6.6 ± 1.7 (SD) Hz] to fictive swimming in the intact cord (2.4 ± 0.7 Hz). Ipsilateral glycinergic inhibition was not required for the hemicord burst pattern generation, suggesting that an interaction between excitatory glutamatergic neurons suffices to produce the unilateral burst pattern. In NMDA, burst activity at a much lower rate (0.1–0.4 Hz) was also encountered, which required the voltage-dependent properties of NMDA receptors in contrast to the fast rhythm. Swimming is thus produced by pairs of unilateral burst generating networks with reciprocal inhibitory connections that not only ensure left/right alternation but also downregulate frequency.