bluuebunny/crossref_metadata_2025 huggingface dataset:
Inhibition of APP Trafficking by Tau Protein Does Not Increase the Generation of Amyloid‐β Peptides
Authors: Goldsbury Claire , Mocanu Maria‐Magdalena , Thies Edda , Kaether Christoph , Haass Christian , Keller Patrick , Biernat Jacek , Mandelkow Eckhard , Mandelkow Eva‐Maria
Published: May 2006

Amyloid‐β, a peptide derived from the precursor protein APP, accumulates in the brain and contributes to the neuropathology of Alzheimer's disease. Increased generation of amyloid‐β might be caused by axonal transport inhibition, via increased dwell time of APP vesicles and thereby higher probability of APP cleavage by secretase enzymes residing on the same vesicles. We tested this hypothesis using a neuronal cell culture model of inhibited axonal transport and by imaging vesicular transport of fluorescently tagged APP and β‐secretase (BACE1). Microtubule‐associated tau protein blocks vesicle traffic by inhibiting the access of motor proteins to the microtubule tracks. In neurons co‐transfected with CFP‐tau, APP‐YFP traffic into distal neurites was strongly reduced. However, this did not increase amyloid‐β levels. In singly transfected axons, APP‐YFP was transported in large tubules and vesicles moving very fast (on average 3 µm/s) and with high fluxes in the anterograde direction (on average 8.4 vesicles/min). By contrast, BACE1‐CFP movement was in smaller tubules and vesicles that were almost 2× slower (on average 1.6 µm/s) with ~18× lower fluxes (on average 0.5 vesicles/min). Two‐colour microscopy of co‐transfected axons confirmed that the two proteins were sorted into distinct carriers. The results do not support the above hypothesis. Instead, they indicate that APP is transported on vesicles distinct from the secretase components and that amyloid‐β is not generated in transit when transport is blocked by tau.
Global and Regional Geo‐strategic Implications of China's Emergence
Authors: TANAKA Akihiko
Published: May 2006

Now that China's “re‐emergence” as a world center of production is obvious, concerns about its implications are being raised throughout the world, in general, and particularly in East Asia. China's economic growth is nothing but spectacular. If all parties are rational, however, a peaceful rise for China is possible. Peaceful management of the Taiwan Strait is critical in this respect. There are two possible scenarios for the peaceful rise of China: a unilateralist China in the multipolar world of competition, and a multilateralist, postmodern China embedded in an East Asian community. It is in the interest of Japan, the United States and other countries in the international society to induce China to take the latter scenario. To realize this goal, efforts on the part of China are critical, but the efforts of other countries such as the United States and Japan are also very important.
Height Effect on Heat-Transfer Characteristics of Aluminum-Foam Heat Sinks
Authors: Shih W. H. , Chiu W. C. , Hsieh W. H.
Published: May 2006

This study investigates and demonstrates the two conflicting effects of the height on the cooling performance of aluminum-foam heat sinks, under the impinging-jet flow condition. In addition, the nonlocal thermal equilibrium phenomena are also investigated. When the H∕D (the height to diameter ratio) of the aluminum-foam heat sinks is reduced from 0.92 to 0.15, the Nusselt number of aluminum-foam heat sinks is found to first increase and then decrease. The increase in the Nusselt number is caused by the increased percentage of the cooling air reaching the top surface of the waste-heat generation block, resulting from the reduced flow resistance. The decrease in the Nusselt number is mainly caused by the reduction in the heat-transfer area between the cooling air and the solid phase of the aluminum-foam heat sink. As the porosity and pore density decrease, the Nusselt number increases and the convective heat transfer is enhanced. The correlation between the Nusselt and Reynolds numbers for each of the 15 samples studied in this work is reported. For samples with a H∕D>0.31, the temperature difference between the solid and gas phases of aluminum-foam heat sinks decreases with the increase of the distance from the heated surface. The non-local thermal equilibrium regime is observed to exist at low Reynolds number and small dimensionless height. On the other hand, for samples with a H∕D⩽0.31, the temperature difference first increases and then decreases with the increase of the distance from the heated surface; the maximum temperature difference is located at z∕H≒0.25 and is independent of the Reynolds number.
Cerebellar Activation During Copying Geometrical Shapes
Authors: Lewis Scott M. , Jerde Trenton A. , Tzagarakis Charidimos , Georgopoulos Maria-Alexandra , Tsekos Nikolaos , Amirikian Bagrat , Kim Seong-Gi , Uğurbil Kâmil , Georgopoulos Apostolos P.
Published: May 2006

We studied functional MRI activation in the cerebellum during copying 9 geometrical shapes (equilateral triangle, isosceles triangle, square, diamond, vertical trapezoid, pentagon, hexagon, circle, and vertical lemniscate). Twenty subjects were imaged during 3 consecutive 45-s periods (rest, visual presentation, and copying). First, there was a positive relation between cerebellar activation and the peak speed of individual movements. This effect was strongest in the lateral and posterior ipsilateral cerebellum but it was also present in the paramedian zones of both cerebellar hemispheres and in the vermis. A finer grain analysis of the relations between the time course of the blood oxygenation level–dependent activation and movement parameters revealed a significant relation to hand position and speed but not to acceleration. Second, there was a significant relation between the intensity of voxel activation during visual presentation and the speed of the upcoming movement. The spatial distribution of these voxels was very similar to that of the voxels activated during copying, indicating that the cerebellum might be involved in motor rehearsal, in addition to its role during movement execution. Finally, a factor analysis of the intensity of activated voxels in the ipsilateral cerebellum during copying (adjusted for the speed effect) extracted 3 shape factors. Factor 1 reflected “roundness,” factor 2 “upward pointing,” and factor 3 “pointing (up or down) and elongation.” These results link cerebellar activation to more global, spatial aspects of copying.
An Index of Topographic Normality in Rat Somatosensory Cortex: Application to a Sciatic Nerve Crush Model
Authors: Barbay Scott , Peden Eric K. , Falchook Gerald , Nudo Randolph J.
Published: May 2006

Previous studies have demonstrated that peripheral denervation of the skin is reflected in the CNS as a reorganization of somatotopic representations. In cases in which peripheral nerve regeneration occurs there is a gradual reactivation of cortex by novel receptive fields that is reversed as regenerated nerves reestablish connections with the original skin surface. Functional recovery appears to depend on the pattern in which somatotopic organization in the cortex is reestablished. The relationship between functional recovery and cortical topography is not precise, however, since the descriptions of postinjury representations in the cortex have been largely descriptive and not quantitative. The purpose of this study was to derive an index to quantify deviations from normal somatotopic organization in the somatosensory cortex. Multiunit recordings of cutaneous representations in the somatosensory cortex (S1) of the rat were defined using Semmes-Weinstein monofilaments to stimulate the skin over the distal hindlimb of the rat 2 and 4 months after a sciatic nerve crush. To derive a sensitive index of topography, the sciatic nerve crush was selected as the injury model since nerve regeneration following crush injuries has been reported to reinstate preinjury cortical topography. Group comparisons were made with an intact control group. The results show that there were subtle, but significant differences in topography between rats with a regenerated sciatic nerve and normal rats. In addition, average thresholds for evoking cortical responses were higher than normal (but within normal range) 2 and 4 months after the crush. These results demonstrate that the index of topography derived for this study can reveal deviations that may not be distinguishable from normal topography when based on qualitative descriptions.
Mechanical Response Properties of A and C Primary Afferent Neurons Innervating the Rat Intracranial Dura
Authors: Levy Dan , Strassman Andrew M.
Published: May 2006

The intracranial dura receives a small-fiber sensory innervation from the trigeminal ganglion that is thought to be involved in some types of headaches, including migraine. Mechanical response properties of dural afferent neurons were examined to investigate variation across the population in the properties of threshold, slope, adaptation, and incidence of mechanosensitivity. Dural afferent neurons were recorded in the trigeminal ganglion of urethan-anesthetized rats and were identified by their constant-latency response to dural shock. Neurons were classified as fast A (>5 m/s), slow A (5 ≥ conduction velocity (CV) ≥ 1.5 m/s), or C (<1.5 m/s), based on response latency to dural shock. Mechanical receptive fields were identified by stroking or indenting the outer surface of the dura. Stimulus-response curves were obtained from responses to 2-s constant-force indenting stimuli of graded intensities delivered to the dural receptive field with a servo force-controlled mechanical stimulator. The slow A population had the highest percentage of mechanosensitive units (97%) as well as the highest slopes and the lowest thresholds. Thus by all three criteria, the slow As had the highest mechanosensitivity. Conversely, the fast A population had the lowest mechanosensitivity in that it had the lowest percentage of mechanosensitive units (66%), the lowest slopes, and the highest thresholds. The C population was intermediate with respect to all three properties but was much more similar to the slow As than to the fast As. All three fiber classes showed a negative correlation between slope and threshold. The majority of neurons showed a slowly adapting response to a maintained 2-s stimulus. Adapting neurons could be subdivided based on whether the fitted exponential curve decayed to zero or to a nonzero plateau; the latter group contained the most sensitive neurons in that they had the lowest thresholds and highest slopes. Nonadapting neurons generally had lower initial firing rates than adapting neurons. Fast A neurons exhibited greater and more rapid adaptation than slow A and C neurons. Neurons with the lowest slopes, regardless of CV, had relatively rapid adaptation. The more slowly conducting portion of the C population was distinguished from the other C neurons by a number of properties: more mechanically insensitive neurons, higher thresholds, and more nonadapting neurons. These differences in mechanical response properties may be related in part to differences in membrane currents involved in impulse generation that have been described in subpopulations of dorsal root ganglion cells.
Coincidence Detection in Pyramidal Neurons Is Tuned by Their Dendritic Branching Pattern
Authors: Schaefer Andreas T. , Larkum Matthew E. , Sakmann Bert , Roth Arnd
Published: May 2006

Neurons display a variety of complex dendritic morphologies even within the same class. We examined the relationship between dendritic arborization and the coupling between somatic and dendritic action potential (AP) initiation sites in layer 5 (L5) neocortical pyramidal neurons. Coupling was defined as the relative reduction in threshold for initiation of a dendritic calcium AP due to a coincident back-propagating AP. Simulations based on reconstructions of biocytin-filled cells showed that addition of oblique branches of the main apical dendrite in close proximity to the soma ( d < 140 μm) increases the coupling between the apical and axosomatic AP initiation zones, whereas incorporation of distal branches decreases coupling. Experimental studies on L5 pyramids in acute brain slices revealed a highly significant ( n = 28, r = 0.63, P < 0.0005) correlation: increasing the fraction of proximal oblique dendrites ( d < 140 μm), e.g., from 30 to 60% resulted on average in an increase of the coupling from approximately 35% to almost 60%. We conclude that variation in dendritic arborization may be a key determinant of variability in coupling (49 ± 17%; range 19–83%; n = 37) and is likely to outweigh the contribution made by variations in active membrane properties. Thus coincidence detection of inputs arriving from different cortical layers is strongly regulated by differences in dendritic arborization.
Effects of Electrical Stimulation of the Chorda Tympani Nerve on Taste Responses in the Nucleus of the Solitary Tract
Authors: Lemon Christian H. , Di Lorenzo Patricia M.
Published: May 2006

Despite evidence for an abundance of inhibitory synaptic processes within the taste-responsive portion of the brain stem, little is known about how these processes are activated or modulated. In this context, this study tested the hypothesis that activation of the chorda tympani nerve (CT) invokes inhibition that influences gustatory neural information processing in the rostral nucleus of the solitary tract (NTS). Stimulating electrodes were implanted in the middle ear of urethane-anesthetized rats to enable the passage of current across the CT. Electrophysiological responses to sucrose, NaCl, HCl, and quinine were recorded from single NTS neurons both individually and immediately following tetanic electrical stimulation of the CT. Additionally, NTS field responses to paired pulse stimulation of the CT were recorded. Electrical pulses delivered to the CT were found to produce a compound action potential with four components. Taste-responsive units in the NTS showed tetanus-evoked responses that varied in latency and strength. Those cells that showed strong, short latency responses to CT stimulation showed large magnitude responses to NaCl and were relatively narrowly tuned. Units with longer latencies generally responded more broadly to taste stimuli and with lower response magnitudes. Following tetanus, taste responses in 20 (43%) of the 46 units were reversibly altered in a stimulus-selective manner. Taste responses in 18 units were both enhanced and attenuated following tetanic stimulation, although attenuation was much more common. Additionally, tetanus was found to affect the temporal organization of spikes within taste responses to one stimulus in seven units (15%), four of which also showed changes in response magnitude to a different stimulus following tetanus. The influence of tetanus on taste responses was shown to be reliable and repeatable in neurons from which stimulus trials were recorded more than once. Across all units, responses to quinine were most dramatically and frequently attenuated following tetanus, while those to NaCl were least susceptible to change. NTS field responses evoked by paired pulse stimulation of the CT suggested that the initial pulse evoked an inhibitory influence in the NTS that decayed and returned to baseline by 2 s. These data are consistent with the idea that afferent input to the NTS normally activates inhibitory synaptic activity. As with other sensory systems, such inhibition may serve to facilitate contrast in the neural representation of different stimulus qualities.
Spectral Cues Explain Illusory Elevation Effects With Stereo Sounds in Cats
Authors: Tollin Daniel J. , Yin Tom C.T.
Published: May 2006

Mammals localize sound sources in azimuth based on two binaural cues, interaural differences in the time of arrival and level of the sounds at the ears. In contrast, the cue for elevation is based on patterns of the broadband power spectra at each ear that result from the direction-dependent acoustic filtering properties of the head and pinnae. Although the exact form of this “spectral shape” cue is unknown, most attention has been directed toward a prominent direction-dependent energy minimum, or “notch,” because its location in frequency, for both humans and cats, moves predictably from low to high as a source is moved from low to high elevations. However, there is little direct evidence that these spectral notches are important elevational cues in animals other than humans. Here we demonstrate a striking illusion in the localization of sounds in elevation by cats using stimulus configurations that elicit summing localization and the precedence effect that can be explained by spectral shape cues.
Circadian Entrainment to Temperature, But Not Light, in the Isolated Suprachiasmatic Nucleus
Authors: Herzog Erik D. , Huckfeldt Rachel M.
Published: May 2006

The suprachiasmatic nucleus (SCN) is the master pacemaker that drives circadian rhythms in mammalian physiology and behavior. The abilities to synchronize to daily cycles in the environment and to keep accurate time over a range of physiologic temperatures are two fundamental properties of circadian pacemakers. Recordings from a bioluminescent reporter ( Per1-luc) of Period1 gene activity in rats showed that the cultured SCN entrained to daily, 1.5°C cycles of temperature, but did not synchronize to daily light cycles. Temperature entrainment developed by 1 day after birth. Light cycles failed to affect the isolated SCN of rats aged 2 to 339 days. Entrainment to a 3-h shift in the warm-cool cycle was possible in <3 days with 3°C cycles. Importantly, Per1-luc expression in vitro was similar to that seen in vivo where peak expression occurs approximately 1 h prior to the daily increase in temperature. In addition, the firing rate of individual mouse SCN neurons continued to express near 24-h rhythms from 24–37°C. At lower temperatures, the percentage of rhythmic cells was reduced, but periodicity was temperature compensated. The results indicate that normal rhythms in brain temperature may serve to stabilize rhythmicity of the circadian system in vivo and that temperature compensation of this period is determined at the level of individual SCN cells.
Differential Impairment of Individuated Finger Movements in Humans After Damage to the Motor Cortex or the Corticospinal Tract
Authors: Lang Catherine E. , Schieber Marc H.
Published: May 2006

The purpose of this study was to quantify the long-term loss of independent finger movements in humans with lesions relatively restricted to motor cortex or corticospinal tract. We questioned whether damage to the motor cortex or corticospinal tract would permanently affect the ability to move each finger to the same degree or would affect some fingers more than others. People with pure motor hemiparesis due to ischemic cerebrovascular accident were used as our experimental sample. Pure motor hemiparetic and control subjects were tested for their ability to make cyclic flexion/extension movements of each finger independently. We recorded their finger joint motion using an instrumented glove. The fingers of control subjects and of the unaffected hands (ipsilateral to the lesion) of hemiparetic subjects moved relatively independently. The fingers of the affected hands (contralateral to the lesion) of hemiparetic subjects were differentially impaired in their ability to make independent finger movements. The independence of the thumb was normal; the independence of the index finger was slightly impaired, while the independence of the middle, ring, and little fingers was substantially impaired. The differential long-term effects of motor cortical or corticospinal damage on finger independence may result from rehabilitative training emphasizing tasks requiring independent thumb and index movements, and from a greater ability of the spared components of the neuromuscular system to control the thumb independently compared with the other four fingers.
Free Radical–Mediated Cell Damage After Experimental Status Epilepticus in Hippocampal Slice Cultures
Authors: Kovács Richard , Schuchmann Sebastian , Gabriel Siegrun , Kann Oliver , Kardos Julianna , Heinemann Uwe
Published: May 2006

Generation of free radicals may have a key role in the nerve cell damage induced by prolonged or frequently recurring convulsions (status epilepticus). Mitochondrial function may also be altered due to production of free radicals during seizures. We therefore studied changes in field potentials (fp) together with measurements of extracellular, intracellular, and intramitochondrial calcium concentration ([Ca2+]e, [Ca2+]i, and [Ca2+]m, respectively), mitochondrial membrane potential (ΔΨ), NAD(P)H auto-fluorescence, and dihydroethidium (HEt) fluorescence in hippocampal slice cultures by means of simultaneous electrophysiological and microfluorimetric measurements. As reported previously, each seizure-like event (SLE) resulted in mitochondrial depolarization associated with a delayed rise in oxidation of HEt to ethidum, presumably indicating ROS production. We show here that repeated SLEs led to a decline in intracellular and intramitochondrial Ca2+ signals despite unaltered Ca2+ influx. Also, mitochondrial depolarization and the NAD(P)H signal became smaller during recurring SLEs. By contrast, the ethidium fluorescence rises remained constant or even increased from SLE to SLE. After about 15 SLEs, activity changed to continuous afterdischarges with steady depolarization of mitochondrial membranes. Staining with a cell death marker, propidium iodide, indicated widespread cell damage after 2 h of recurring SLEs. The free radical scavenger, α-tocopherol, protected the slice cultures against this damage and also reduced the ongoing impairment of NAD(P)H production. These findings suggest involvement of reactive oxygen species (ROS) of mitochondrial origin in the epileptic cell damage and that free radical scavenging may prevent status epilepticus–induced cell loss.
Voluntary Exercise Induces a BDNF-Mediated Mechanism That Promotes Neuroplasticity
Authors: Gómez-Pinilla Fernando , Ying Zhe , Roy Roland R. , Molteni Raffaella , Edgerton V. Reggie
Published: May 2006

We have investigated potential mechanisms by which exercise can promote changes in neuronal plasticity via modulation of neurotrophins. Rodents were exposed to voluntary wheel running for 3 or 7 days, and their lumbar spinal cord and soleus muscle were assessed for changes in brain-derived neurotrophic factor (BDNF), its signal transduction receptor (trkB), and downstream effectors for the action of BDNF on synaptic plasticity. Exercise increased the expression of BDNF and its receptor, synapsin I (mRNA and phosphorylated protein), growth-associated protein (GAP-43) mRNA, and cyclic AMP response element-binding (CREB) mRNA in the lumbar spinal cord. Synapsin I, a synaptic mediator for the action of BDNF on neurotransmitter release, increased in proportion to GAP-43 and trkB mRNA levels. CREB mRNA levels increased in proportion to BDNF mRNA levels. In separate experiments, the soleus muscle was paralyzed unilaterally via intramuscular botulinum toxin type A (BTX-A) injection to determine the effects of reducing the neuromechanical output of a single muscle on the neurotrophin response to motor activity. In sedentary BTX-A-treated rats, BDNF and synapsin I mRNAs were reduced below control levels in the spinal cord and soleus muscle. Exercise did not change the BDNF mRNA levels in the spinal cord of BTX-A-treated rats but further reduced the BDNF mRNA levels in the paralyzed soleus relative to the levels in sedentary BTX-A-treated rats. Exercise also restored synapsin I to near control levels in the spinal cord. These results indicate that basal levels of neuromuscular activity are required to maintain normal levels of BDNF in the neuromuscular system and the potential for neuroplasticity.
Nitric Oxide in the Gracile Nucleus Mediates Depressor Response to Acupuncture (ST36)
Authors: Chen Shuang , Ma Sheng-Xing
Published: May 2006

The purpose of these studies was to determine the role of gracile nucleus and the effects of l-arginine-derived nitric oxide (NO) synthesis in the nucleus on the cardiovascular responses to electroacupuncture (EA) stimulation of “Zusanli” (ST36). Arterial blood pressure and heart rate were monitored during EA stimulation of ST36 following microinjections of agents into gracile nucleus. EA ST36 produced depressor and bradycardiac responses in anesthetized Sprague-Dawley rats. The cardiovascular responses to EA ST36 were blocked by bilateral microinjection of lidocaine into gracile nucleus. Microinjection of l-arginine into gracile nucleus facilitated the hypotensive and bradycardiac responses to EA ST36. The cardiovascular responses to EA ST36 were attenuated by bilateral microinjection of neuronal NO synthase (nNOS) antisense oligos into gracile nucleus. Microinjection of nNOS sense oligos into gracile nucleus did not alter the cardiovascular response to EA ST36. The results demonstrate that a blockade of neuronal conduction in the gracile nucleus inhibits the cardiovascular responses to EA ST36. The hypotensive and bradycardiac responses to EA ST36 are modified by influences of l-arginine-derived NO synthesis in the gracile nucleus. We conclude that NO plays an important role in mediating the cardiovascular responses to EA ST36 through gracile nucleus.
Membrane Potential of CA3 Hippocampal Pyramidal Cells During Postnatal Development
Authors: Tyzio Roman , Ivanov Anton , Bernard Cristophe , Holmes Gregory L. , Ben-Ari Yehezkiel , Khazipov Roustem
Published: May 2006

A depolarized resting membrane potential has long been considered to be a universal feature of immature neurons. Despite the physiological importance, the underlying mechanisms of this developmental phenomenon are poorly understood. Using perforated-patch, whole cell, and cell-attached recordings, we measured the membrane potential in CA3 pyramidal cells in hippocampal slices from postnatal rats. With gramicidin perforated-patch recordings, membrane potential was –44 ± 4 (SE) mV at postnatal days P0–P2, and it progressively shifted to –67 ± 2 mV at P13–15. A similar developmental change of the membrane potential has been also observed with conventional whole cell recordings. However, the value of the membrane potential deduced from the reversal potential of N-methyl-d-aspartate channels in cell-attached recordings did not change with age and was –77 ± 2 mV at P2 and –77 ± 2 mV at P13–14. The membrane potential measured using whole cell recordings correlated with seal and input resistance, being most depolarized in neurons with high, several gigaohms, input resistance and low seal resistance. Simulations revealed that depolarized values of the membrane potential in whole cell and perforated-patch recordings could be explained by a shunt through the seal contact between the pipette and membrane. Thus the membrane potential of CA3 pyramidal cells appears to be strongly negative at birth and does not change during postnatal development.
Taste Response Variability and Temporal Coding in the Nucleus of the Solitary Tract of the Rat
Authors: Di Lorenzo Patricia M. , Victor Jonathan D.
Published: May 2006

Theories of taste coding in the brain stem have been based on the idea that taste responses are integrated over time without regard to the temporal structure of the taste-evoked spike train. In the present experiment, the reliability of response rate across stimulus repetitions and the potential contribution of temporal coding to the discrimination of taste stimuli was examined. Taste stimuli representing the four basic taste qualities were presented repeatedly, and electrophysiological responses were recorded from single cells in the nucleus of the solitary tract (NTS) of anesthetized rats. Blocks of the four tastants were repeated for as long as the cell remained isolated. Nineteen cells were recorded with between 8 and 27 repetitions of each stimulus. Response magnitude to a given tastant varied widely within some NTS cells. This impacted the determination of both the breadth of tuning and best stimulus for a given cell. The contribution of spike timing and the pattern of interspike intervals to discrimination of taste stimuli was evaluated by an information-theoretic approach based on two families of metrics. Spike timing significantly contributed to the discrimination of taste qualities in 10 of 19 (53%) cells. This contribution was especially notable during the initial 2 s of the response. Those cells that showed the most variable firing rates in response to repetition of taste stimuli tended to show the largest contribution of temporal coding. These results suggest that, in addition to response rate, the temporal parameters of responses may convey information about taste stimuli in the NTS.
Structural Inhomogeneities Differentially Modulate Action Currents and Population Spikes Initiated in the Axon or Dendrites
Authors: López-Aguado L. , Ibarz J. M. , Varona P. , Herreras O.
Published: May 2006

Action potentials (APs) in CA1 pyramidal cells propagate in different directions along the somatodendritic axis depending on the activation mode (synaptic or axonal). We studied how the geometrical inhomogeneities along the apical shaft, soma, and initial axon modulate the transmembrane current ( I m) flow underlying APs, using model and experimental techniques. The computations obtained at the subcellular level during forward- and backpropagation were extrapolated to macroscopic level (field potentials) and compared with the basic in vivo features of the ortho- and antidromic population spike (PS) that reflects the sum total of all elementary currents from synchronously firing cells. The matching of theoretical and experimental results supports the following conclusions. Because the charge carried by axonal APs is almost entirely drained into dendrites, the soma invasion is preceded by little capacitive currents ( I cap), the ionic currents ( I ion) dominating I m and the depolarizing phase. The subsequent invasion of the tapering apical shaft is preceded, however, by significant I cap, while I ion decayed gradually. A similar pattern occurred during backpropagation of spikes synaptically initiated in the axon. On the contrary, when the AP was apically initiated, the dendritic I ion was boosted by the apical flare, it was preceded by weak I cap and spread forwardly at a slower velocity. Soma invasion is reliable once the AP reached the main apical shaft but less so distal to the primary bifurcation, where it may be upheld by concurrent synaptic activity. The decreasing internal resistance of the apical shaft guided most axial current into the soma, causing its fast charging. There, I ionbegan later in the depolarizing phase of the AP and the reduced driving force made it smaller. This, in addition to a poor temporal overlapping of somatodendritic inward currents within individual cells, built a smaller extracellular sink, i.e., a smaller PS. In both experiment and model, the antidromic (axon-initiated) PS in the soma layer is approximately 30% larger than an orthodromic (apical shaft–initiated) PS contributed by the same number of firing cells. We conclude that the dominance of capacitive or ionic current components on I m is a distinguishing feature of forward and backward APs that is predictable from the geometric inhomogeneities between conducting subregions. Correspondingly, experimental and model APs have a faster rising slope during ortho than antidromic activation. The moderate flare of the apical shaft makes forward AP conduction quite safe. This alternative trigger zone enables two different processing modes for apical inputs.
Adaptive Modification of Saccade Size Produces Correlated Changes in the Discharges of Fastigial Nucleus Neurons
Authors: Scudder Charles A. , McGee David M.
Published: May 2006

Saccade accuracy is known to be maintained by adaptive mechanisms that progressively reduce any visual error that consistently exists when the saccade ends. We used an experimental paradigm known to induce adaptation of saccade size while monitoring the neural correlates of this adaptation. In rhesus monkeys where the medial and lateral recti of one eye were surgically weakened, patching the unoperated eye and forcing the monkey to use the weakened eye induced a gradual increase in saccade size in both eyes until the viewing, weak eye almost acquired the target in one step. Subsequent patching of the weakened eye gradually reversed the situation, so that the saccades in the viewing, normal eye decreased from an initial overshooting to normal. In the caudal fastigial nuclei of unadapted monkeys, neurons typically exhibit an early burst of spikes that is correlated with the onset of contraversive saccades and a later burst of spikes that is correlated with the termination of ipsiversive saccades. Comparing the discharges of the same fastigial neurons recorded before and during adaptation, this basic pattern did not change, but some parameters of the discharges did. The most consistent changes were in the latency of the burst for ipsiversive saccades, which was positively correlated with saccade size (1.28 ms/deg), and in the number of spikes associated with contraversive saccades, which was also positively correlated (0.55 spikes/deg). The former was more important when saccade size was decreasing, and the latter was more important when saccade size was increasing. Based on current knowledge of the anatomical connections of fastigial neurons, as well as on the effects of cerebellar lesions and on recordings in other structures, we argue that these changes are appropriate for causing the associated changes in saccade size.
Long-Term Voltage-Sensitive Dye Imaging Reveals Cortical Dynamics in Behaving Monkeys
Authors: Slovin Hamutal , Arieli Amos , Hildesheim Rina , Grinvald Amiram
Published: May 2006

A novel method of chronic optical imaging based on new voltage-sensitive dyes (VSDs) was developed to facilitate the explorations of the spatial and temporal patterns underlying higher cognitive functions in the neocortex of behaving monkeys. Using this system, we were able to explore cortical dynamics, with high spatial and temporal resolution, over period of ≤1 yr from the same patch of cortex. The visual cortices of trained macaques were stained one to three times a week, and immediately after each staining session, the monkey started to perform the behavioral task, while the primary and secondary visual areas (V1 and V2) were imaged with a fast optical imaging system. Long-term repeated VSD imaging (VSDI) from the same cortical area did not disrupt the normal cortical architecture as confirmed repeatedly by optical imaging based on intrinsic signals. The spatial patterns of functional maps obtained by VSDI were essentially identical to those obtained from the same patch of cortex by imaging based on intrinsic signals. On comparing the relative amplitudes of the evoked signals and differential map obtained using these two different imaging methodologies, we found that VSDI emphasizes subthreshold activity more than imaging based on intrinsic signals, that emphasized more spiking activity. The latency of the VSD-evoked response in V1 ranged from 46 to 68 ms in the different monkeys. The amplitude of the V2 response was only 20−60% of that in V1. As expected from the anatomy, the retinotopic responses to local visual stimuli spread laterally across the cortical surface at a spreading velocity of 0.15−0.19 m/s over a larger area than that expected by the classical magnification factor, reaching its maximal anisotropic spatial extent within ∼40 ms. We correlated the observed dynamics of cortical activation patterns with the monkey's saccadic eye movements and found that due to the slow offset of the cortical response relative to its onset, there was a short period of simultaneous activation of two distinct patches of cortex following a saccade to the visual stimulus. We also found that a saccade to a small stimulus was followed by direct transient activation of a cortical region in areas of V1 and V2, located retinotopically within the saccadic trajectory.
The Mormyromast Region of the Mormyrid Electrosensory Lobe. I. Responses to Corollary Discharge and Electrosensory Stimuli
Authors: Mohr Claudia , Roberts Patrick D. , Bell Curtis C.
Published: May 2006

This is the first of two papers on the electrosensory lobe (ELL) of mormyrid electric fish. The ELL is the first stage in the central processing of electrosensory information from electroreceptors. Cells of the mormyrid ELL are affected at the time of the electric organ discharge (EOD) by two different inputs, EOD-evoked reafferent input from electroreceptors and corollary discharge input associated with the motor command that elicits the EOD. This first paper examines the intracellular responses of ELL cells to these two different inputs in the region of ELL that receives primary afferent fibers from mormyromast electroreceptors. Mormyromast electroreceptors are responsible for active electrolocation. The paper extends previous studies of the mormyrid ELL by describing the physiological responses of cell types, which had been previously identified only morphologically, including: the two types of Purkinje-like medium ganglionic cells, MG1 and MG2; the thick smooth dendrite cells; and the medium fusiform cells. In addition, two previously unrecognized cell types, the large thick smooth dendrite cell and the interzonal cell, are described both morphologically and physiologically for the first time. Finally, new information is provided on the two types of ELL efferent cells, the large ganglionic and large fusiform cells. All cell types, except for the medium fusiform cell, show nonlinear interactions between electrosensory and corollary discharge inputs. All cell types, except for the medium fusiform cell and the interzonal cell, also show plasticity of the corollary discharge response after pairing with electrosensory stimuli.
Changes of AI Receptive Fields With Sound Density
Authors: Blake David T. , Merzenich Michael M.
Published: May 2006

Primates engage in auditory behaviors under a broad range of signal-to-noise conditions. In this study, optimal linear receptive fields were measured in alert primate primary auditory cortex (A1) in response to stimuli that vary in spectrotemporal density. As density increased, A1 excitatory receptive fields systematically changed. Receptive field sensitivity, expressed as the expected change in firing rate after a tone pip onset, decreased by an order of magnitude. Spectral selectivity more than doubled. Inhibitory subfields, which were rarely recorded at low sound densities, emerged at higher sound densities. The ratio of excitatory to inhibitory population strength changed from 14.4:1 to 1.4:1. At low sound densities, the sound associated with the evocation of an action potential from an A1 neuron was broad in spectrum and time. At high sound densities, a spike-evoking sound was more likely to be a spectral or temporal edge and was narrower in time and frequency range. Receptive fields were used to predict responses to a novel high-noise-density stimulus. The predictions were highly correlated with the actual responses to the 2-s complex sound excerpt. The structure of prediction failures revealed that neurons with prominent inhibitory fields had relatively poor linear predictions. Further, the finding that stochastic variance is limiting in prediction even after averaging 150 repetitions means that high-fidelity representations of simple sounds in A1 must be distributed over at least hundreds of neurons. Auditory context alters A1 responses across multiple parameter spaces; this presents a challenge for reconstructing neural codes.
Persistent Sodium and Calcium Currents Cause Plateau Potentials in Motoneurons of Chronic Spinal Rats
Authors: Li Yunru , Bennett David J.
Published: May 2006

After chronic spinal cord injury motoneurons exhibit large plateau potentials (sustained depolarizations triggered by brief inputs) that play a primary role in the development of muscle spasms and spasticity (Bennett et al. 2001a , b ). The present study examined the voltage-gated persistent inward currents (PICs) underlying these plateaus. Adult rats were spinalized at the S2sacral spinal level and after 2 mo, when spasticity developed, intracellular recordings were made from motoneurons below the injury. For recording, the whole sacrocaudal spinal cord was removed and maintained in vitro in normal artificial cerebral spinal fluid (nACSF), without application of neuromodulators. During a slow triangular voltage-clamp command (ramp) a PIC was activated with a threshold of –54.2 ± 4.8 mV (similar to plateau threshold), with a peak current of 2.88 ± 0.95 nA and produced a pronounced negative-slope region in the V–I relation. This PIC was in part mediated by Cav1.3 L-type calcium channels because it was low threshold and significantly reduced by 10 to 20 μM nimodipine or 400 μM Cd2+. The PIC that remained during a calcium channel blockade (in Cd2+) was completely and rapidly blocked by tetrodotoxin (TTX; 0.5 to 2 μM), and thus was a TTX-sensitive persistent sodium current. This persistent sodium current was activated rapidly about 7 mV below the spike threshold (spike threshold –46.1 ± 4.5 mV), contributed approximately 1/2 of the initial peak of the total PIC, inactivated partly to contribute only approximately 1/3 of the sustained PIC (at 5 to 10 s), and deactivated rapidly with hyperpolarization (<50 ms). When TTX was added to the bath first, the nimodipine-sensitive persistent calcium current (L-type) was seen in isolation; it was slowly activated (>250 ms), had a low but variable threshold (either slightly above or below the spike threshold), contributed the other approximately 1/2 of the initial peak of the total PIC (before TTX), did not usually inactivate with time (contributed approximately two-thirds of the sustained PIC), and deactivated slowly with hyperpolarization to rest (in >300 ms). In summary, low-threshold persistent calcium (Cav1.3) and sodium currents spontaneously develop in motoneurons of chronic spinal rats and these enable large, rapidly activated plateaus that ultimately lead to spasticity.
Spatiotemporal Effects of Microstimulation in Rat Neocortex: A Parametric Study Using Multielectrode Recordings
Authors: Butovas Sergejus , Schwarz Cornelius
Published: May 2006

Using microstimulation to imprint meaningful activity patterns into intrinsically highly interconnected neuronal substrates is hampered by activation of fibers of passage leading to a spatiotemporal “blur” of activity. The focus of the present study was to characterize the shape of this blur in the neocortex to arrive at an estimate of the resolution with which signals can be transmitted by multielectrode stimulation. The horizontal spread of significant unit activity evoked by near-threshold focal electrical stimulation (charge transfer 0.8–4.8 nC) and multielectrode recording in the face representation of the primary somatosensory cortex of ketamine anesthetized rats was determined to be about 1,350 μm. The evoked activity inside this range consisted in a sequence of fast excitatory response followed by an inhibition lasting >100 ms. These 2 responses could not be separated by varying the intensity of stimulation while a slow excitatory rebound after the inhibitory response was restricted to higher stimulus intensities (>2.4 nC). Stimulation frequencies of 20 and 40 Hz evoked repetitive excitatory response standing out against a continuous background of inhibition. At 5- and 10-Hz stimulation, the inhibitory response showed a complex interaction pattern attributed to highly sublinear superposition of individual inhibitory responses. The present data help to elucidate the neuronal underpinnings of behavioral effects of microstimulation. Furthermore, they provide essential information to determine spatiotemporal constraints for purposeful multielectrode stimulation in the neocortex.
Receptive Field Properties of Unmyelinated Tactile Afferents in the Human Skin
Authors: Wessberg Johan , Olausson Håkan , Fernström Katarina Wiklund , Vallbo Åke B.
Published: May 2006

We recorded, with the microneurography technique, single-unit impulses from nine cutaneous mechanoreceptive afferents with conduction velocities in the C range and receptive fields in the hairy skin of the forearm. The units responded with high impulse rates to light touch and had low monofilament thresholds. The geography of receptive fields was explored with a scanning method: a lightweight probe with a small and rounded tip was made to scan the field area in a series of closely adjacent tracks while single-unit activity was recorded. The fields of the nine units varied considerably in size as well as complexity. The individual field consisted of one to nine small responsive spots distributed over an area of 1–35 mm2 when explored with a moving indentation of 5 mN. The fields were roughly round or oval in shape with no preferred orientation. The size of the response differed between individual sensitive spots in a field, suggesting a highly nonuniform terminal organization. The properties of the fields seem consistent with a role of tactile C afferents to provide information about pleasant touch and skin-to-skin contacts to central structures controlling emotions and affiliative behavior.
Multiple Components of Membrane Retrieval in Synaptic Terminals Revealed by Changes in Hydrostatic Pressure
Authors: Heidelberger Ruth , Zhou Zhen-Yu , Matthews Gary
Published: May 2006

Membrane retrieval following exocytosis in synaptic terminals is fast and compensatory, however, little is known about the factors that regulate or contribute to this special form of endocytosis. We used whole-terminal capacitance measurements to examine the effect of hydrostatic pressure on compensatory endocytosis in single synaptic terminals of retinal bipolar neurons. We report that a small increase in hydrostatic pressure reversibly inhibits compensatory endocytosis. Elevation in hydrostatic pressure does not block all membrane retrieval, however. A small, fast component of endocytosis persists, while a slower component is inhibited. When the hydrostatic pressure is then stepped back to a near-neutral setting, an even slower form of endocytosis is observed that restores the resting membrane capacitance to baseline. Thus even when endocytosis is temporally uncoupled from calcium entry and exocytosis, it can still be compensatory, indicating that presynaptic surface area is highly regulated. Our results suggest that at least two distinct mechanisms of membrane retrieval contribute to compensatory endocytosis. Given its dramatic inhibitory effect on membrane retrieval, we suggest that hydrostatic pressure be carefully controlled when studying endocytosis in the whole cell recording configuration.