bluuebunny/crossref_metadata_2025 huggingface dataset:
Risk taking by Eurasian lynx (Lynx lynx) in a human‐dominated landscape: effects of sex and reproductive status
Authors: Bunnefeld N. , Linnell J. D. C. , Odden J. , Van Duijn M. A. J. , Andersen R.
Published: May 2006

This study aimed to test how the sex and reproductive status of Eurasian lynx influenced their use of ‘attractive sinks’– habitats with high prey density and high mortality risks. Locations of 24 Eurasian lynxLynx lynxwere obtained by radio‐telemetry in a mixed forest and agricultural habitat in south‐eastern Norway. Roe deer, the major food source of lynx in the study area, occurred at higher densities closer to areas of human activity and infrastructure. Proximity of lynx locations to human activity and infrastructure was used as a risk index because the most common causes of death among Scandinavian lynx were of anthropogenic origin. This study shows that distances from lynx locations to human activity were significantly greater for females with newborn kittens than for males, but this decreased with kitten age. The data suggest that this response to human activity is influenced by the reproductive strategies of males and females, and might explain male‐biased human‐induced mortality in this study and in carnivores more generally.
A Social Decision Analysis of the Earthquake Safety Problem: The Case of Existing Los Angeles Buildings
Authors: Sarin Rakesh Kumar
Published: May 2006

In this paper we propose a framework for conducting a decision analysis for a societal problem such as earthquake safety. The application deals with the formulation and evaluation of alternative policies for the seismic safety problem faced by the city of Los Angeles with regard to its old masonry buildings. A social decision analysis compares the costs and benefits of the alternative policies from the viewpoints of the impacted constituents. The emphasis is on identifying acceptable policy that considers the interests of the impacted constituents and provides incentives for their cooperation. Alternatives ranging from strict regulation to free market are examined. In order to evaluate the trade‐offs between additional cost and savings in lives, a direct willingness‐to‐pay and an economic approach, based on property value differential, are used. Recommendations range from strict regulation for the residential and critical buildings (schools, hospitals, fire stations, etc.) to simply informing the occupants (in the case of commercial and industrial buildings) of the risks involved.
Mandatory Belt Use and Driver Risk Taking
Authors: Lund Adrian K. , Zador Paul
Published: May 2006

A study of driver behavior before and after a mandatory seat belt use law in Newfoundland found that the benefits of such legislation are not reduced by riskier driving, as has been suggested by some theorists. On average, belt use in Newfoundland increased from 16% of drivers before the law to 77% after the law. At the same time, the quality of driving changed very little when compared to control groups of Nova Scotia drivers, who were not subject to the law and whose belt use rates did not change. In only one situation did Newfoundland drivers differ from the control group in Nova Scotia: after the belt law, drivers in Newfoundland became relatively more cautious (slower) in their speeds on four‐lane expressways. These data confirm the results of earlier less controlled studies that also found no changes in driving behavior following nonvoluntary changes in occupant protection. Since the “risk‐compensation” hypothesis predicts such changes, it seems to have no merit in explaining changes in fatalities and injuries after occupant protection legislation.
A 12 year prospective study of circulatory disease among Danish shift workers
Authors: Tüchsen F , Hannerz H , Burr H
Published: May 2006

Background:Previous studies of the risk of heart disease after shift work reached different estimates and review authors disagree about the validity of some of the studies. A cross sectional study showed that shift workers had a higher prevalence of nearly every unfavourable work environment factor investigated. Conflicts at work and low decision latitude were more frequent among shift workers, and all-day walking or standing work and part-time jobs were more often found among female shift workers.

Objectives:To estimate the risk of circulatory disease in a prospective follow up of a representative sample of gainfully employed Danes, considering known or suspected confounding factors.

Methods:A cohort of 5517 people who were gainfully employed in 1990 were followed up for all hospital treatments due to circulatory diseases (390–458, ICD-8; I00–I99, ICD-10) from 1991 to 2002 inclusive. A log linear Poisson regression model was applied to control confounding factors and calculate the relative risk for 927 men and women working nights, evenings, or other non-day shifts compared to 4579 day workers.

Results:Non-day workers compared to day workers had a relative risk (RR) for all circulatory diseases of 1.31 (95% CI 1.06–1.63). Without control for BMI and smoking, the RR estimate was 1.33 (95% CI 1.07–1.65). For a subgroup of workers with at least three years’ seniority, the RR was 1.40 (95% CI 1.09–1.81). The population based aetiological fraction of shift work was estimated to 5%.

Conclusion:This study adds to a growing body of evidence suggesting that shift work carries an excess risk of circulatory diseases.
Effects of Orexin (Hypocretin) on GIRK Channels
Authors: Hoang Q. V. , Bajic D. , Yanagisawa M. , Nakajima S. , Nakajima Y.
Published: May 2006

Orexins (hypocretins) are recently discovered excitatory transmitters implicated in arousal and sleep. Yet, their ionic and signal transduction mechanisms have not been fully clarified. Here we show that orexins suppress G-protein–coupled inward rectifier (GIRK) channel activity, and this suppression is likely to lead to neuronal excitation. Cultured neurons from the locus coeruleus (LC) and the nucleus tuberomammillaris (TM) were used, as well as HEK293A cells transfected with GIRK1 and 2, either human orexin receptor type 1 (OX1R) or type 2 (OX2R), mu opioid receptor and GFP cDNAs. In GTPγS-loaded cells, orexin A (OXA, 3 μM) inhibited GIRK currents that had previously been activated by somatostatin (in LC cells), nociceptin (TM cells), or the mu opioid agonist DAMGO (HEK cells). In guanosine triphosphate (GTP)–loaded HEK cells, in which GIRK currents were not preactivated, OXA induced a biphasic response through both types of orexin receptors: an initial current increase and a subsequent decrease to below resting levels. Current–voltage (I–V) relationships revealed that both the OXA-induced and suppressed currents are inwardly rectifying with reversal potentials around E K. The OXA-induced initial current was partially pertussis toxin (PTX) sensitive and partially PTX insensitive, whereas the OXA-suppressed current was PTX insensitive. These data suggest that orexin receptors couple with more than one type of G-protein, including PTX-sensitive (such as Gi/o) and PTX-insensitive (such as Gq/11) G-proteins. The modulation of GIRK channels by orexins may be one of the cellular mechanisms for the regulation of brain nuclei (e.g., LC and TM) that are crucial for arousal, sleep, and appetite.
Development of GABAAReceptor-Mediated Inhibitory Postsynaptic Currents in Hippocampus
Authors: Banks Matthew I. , Hardie Jason B. , Pearce Robert A.
Published: May 2006

Hippocampal CA1 pyramidal cells receive two kinetic classes of GABAAreceptor-mediated inhibition: slow dendritic inhibitory postsynaptic currents (GABAA,slowIPSCs) and fast perisomatic (GABAA,fast) IPSCs. These two classes of IPSCs are likely generated by two distinct groups of interneurons, and we have previously shown that the kinetics of the IPSCs have important functional consequences for generating synchronous firing patterns. Here, we studied developmental changes in the properties of GABAA,fastand GABAA,slowspontaneous, miniature, and evoked IPSCs (sIPSCs, mIPSCs, and eIPSCs, respectively) using whole cell voltage-clamp recordings in brain slices from animals aged P10–P35. We found that the rate of GABAA,slowsIPSCs increased by over 70-fold between P11 and P35 (from 0.0017 to 0.12 s−1). Over this same age range, we observed a >3.5-fold increase in the maximal amplitude of GABAA,sloweIPSCs evoked by stratum lacunosum-moleculare (SL-M) stimuli. However, the rate and amplitude of GABAA,slowmIPSCs remained unchanged between P10 and P30, suggesting that the properties of GABAA,slowsynapses remained stable over this age range, and that the increase in sIPSC rate and in eIPSC amplitude was due to increased excitability or excitation of GABAA,slowinterneurons. This hypothesis was tested using bath application of norepinephrine (NE), which we found at low concentrations (1 μM) selectively increased the rate of GABAA,slowsIPSCs while leaving GABAA,fastsIPSCs unchanged. This effect was observed in animals as young as P13 and was blocked by coapplication of tetrodotoxin, suggesting that NE was acting to increase the spontaneous firing rate of GABAA,slowinterneurons and consistent with our hypothesis that developmental changes in GABAA,slowIPSCs are due to changes in presynaptic excitability. In contrast to the changes we observed in GABAA,slowIPSCs, the properties of GABAA,fastsIPSCs remained largely constant between P11 and P35, whereas the rate, amplitude, and kinetics of GABAA,fastmIPSCs showed significant changes between P10 and P30, suggesting counterbalancing changes in action potential-dependent GABAA,fastsIPSCs. These observations suggest differential developmental regulation of the firing properties of GABAA,fastand GABAA,slowinterneurons in CA1 between P10 and P35.
Reaching to Grasp With a Multi-Jointed Arm. I. Computational Model
Authors: Torres Elizabeth B. , Zipser David
Published: May 2006

The generation of goal-directed movements requires the solution of many difficult computational problems. Among these are transformations from extrinsic to intrinsic reference frames, specifying solution paths, removing under-specification due to excess degrees of freedom and path multiplicity, constraint satisfaction, and error correction. There are no current motor-control computational models that address these issues in the context of realistic arm movement with redundant degrees of freedom. In this paper, we conjecture there is a geometric stage between sensory input and physical execution. The geometric stage determines movement trajectories independently of forces. It uses a gradient technique that relies on the metric of the space of postures to resolve endpoint path selection, posture-change specification, error correction, and multiple constraint satisfaction on-line without preplanning. The model is instantiated in an arm with seven degrees of freedom that moves in three-dimensional space. Simulated orientation-matching movements are compared with actual human movement data to assess the validity of several of the model's behavioral predictions.
Role of Development in Reorganization of the SI Forelimb-Stump Representation in Fetally, Neonatally, and Adult Amputated Rats
Authors: Pluto Charles P. , Lane Richard D. , Chiaia Nicolas L. , Stojic Andrey S. , Rhoades Robert W.
Published: May 2006

Rats that sustain forelimb removal on postnatal day (P) 0 exhibit numerous multi-unit recording sites in the forelimb-stump representation of primary somatosensory cortex (SI) that also respond to hindlimb stimulation when cortical GABAA+B receptors are blocked. Most of these hindlimb inputs originate in the medial SI hindlimb representation. Although many forelimb-stump sites in these animals respond to hindlimb stimulation, very few respond to stimulation of the face (vibrissae or lower jaw), which is represented in SI just lateral to the forelimb. The lateral to medial development of SI may influence the capacity of hindlimb (but not face) inputs to “invade” the forelimb-stump region in neonatal amputees. The SI forelimb-stump was mapped in adult (>60 days) rats that had sustained amputation on embryonic day (E) 16, on P0, or during adulthood. GABA receptors were blocked and subsequent mapping revealed increases in nonstump inputs in E16 and P0 amputees: fetal amputees exhibited forelimb-stump sites responsive to face (34%), hindlimb (10%), and both (22%); neonatal amputees exhibited 10% face, 39% hindlimb, and 5% both; adult amputees exhibited 10% face, 5% hindlimb, and 0% both, with ∼80% stump-only sites. These results indicate age-dependent differences in receptive-field reorganization of the forelimb-stump representation, which may reflect the spatiotemporal development of SI. Results from cobalt chloride inactivation of the SI vibrissae region and electrolesioning of the dysgranular cortex suggest that normally suppressed vibrissae inputs to the SI forelimb-stump area originate in the SI vibrissae region and synapse in the dysgranular cortex.
Response Transformation and Receptive-Field Synthesis in the Lemniscal Trigeminothalamic Circuit
Authors: Minnery Brandon S. , Bruno Randy M. , Simons Daniel J.
Published: May 2006

To understand how the lemniscal trigeminothalamic circuit (PrV → VPM) of the rodent whisker-to-barrel pathway transforms afferent signals, we applied ramp-and-hold deflections to individual whiskers of lightly narcotized rats while recording the extracellular responses of neurons in either the ventroposterior medial (VPM) thalamic nucleus or in brain stem nucleus principalis (PrV). In PrV, only those neurons antidromically determined to project to VPM were selected for recording. We found that VPM neurons exhibited smaller response magnitudes and greater spontaneous firing rates than those of their PrV inputs, but that both populations were similarly well tuned for stimulus direction. In addition, fewer VPM (74%) than PrV neurons (93%) responded with sustained, or tonic, discharges during the plateau phase of the stimulus. Neurons in both populations responded most robustly to deflections of a single, “principal whisker” (PW), and the majority of cells in both PrV (90%) and VPM (73%) also responded to deflections of at least one adjacent whisker (AW). AW responses in both nuclei occurred on average at longer latencies and were more temporally dispersed than PW responses. Lateral inhibition, as evidenced by AW-evoked activity suppression, was rare in PrV but prevalent in VPM. In both nuclei, however, suppression was weak, with AW responses being on average excitatory. Our results suggest that the receptive-field structures and response properties of individual VPM neurons can be explained in large part by input from one or a small number of PrV neurons, but that intrathalamic mechanisms act to further transform the afferent signal.
Spectral Resolution of Monkey Primary Auditory Cortex (A1) Revealed With Two-Noise Masking
Authors: Fishman Yonatan I. , Steinschneider Mitchell
Published: May 2006

An important function of the auditory nervous system is to analyze the frequency content of environmental sounds. The neural structures involved in determining psychophysical frequency resolution remain unclear. Using a two-noise masking paradigm, the present study investigates the spectral resolution of neural populations in primary auditory cortex (A1) of awake macaques and the degree to which it matches psychophysical frequency resolution. Neural ensemble responses (auditory evoked potentials, multiunit activity, and current source density) evoked by a pulsed 60-dB SPL pure-tone signal fixed at the best frequency (BF) of the recorded neural populations were examined as a function of the frequency separation (ΔF) between the tone and two symmetrically flanking continuous 80-dB SPL, 50-Hz-wide bands of noise. ΔFs ranged from 0 to 50% of the BF, encompassing the range typically examined in psychoacoustic experiments. Responses to the signal were minimal for ΔF = 0% and progressively increased with ΔF, reaching a maximum at ΔF = 50%. Rounded exponential functions, used to model auditory filter shapes in psychoacoustic studies of frequency resolution, provided excellent fits to neural masking functions. Goodness-of-fit was greatest for response components in lamina 4 and lower lamina 3 and least for components recorded in more superficial cortical laminae. Physiological equivalent rectangular bandwidths (ERBs) increased with BF, measuring nearly 15% of the BF. These findings parallel results of psychoacoustic studies in both monkeys and humans, and thus indicate that a representation of perceptual frequency resolution is available at the level of A1.
Kinetic Analyses of Three Distinct Potassium Conductances in Ventral Cochlear Nucleus Neurons
Authors: Rothman Jason S. , Manis Paul B.
Published: May 2006

Neurons in the ventral cochlear nucleus (VCN) express three distinct K+ currents that differ in their voltage and time dependence, and in their inactivation behavior. In the present study, we quantitatively analyze the voltage-dependent kinetics of these three currents to gain further insight into how they regulate the discharge patterns of VCN neurons and to provide supporting data for the identification of their channel components. We find the transient A-type K+ current ( IA) exhibits fourth-order activation kinetics ( a4), and inactivates with one or two time constants. A second inactivation rate (leading to an a4 bc kinetic description) is required to explain its recovery from inactivation. The dendrotoxin-sensitive low-threshold K+ current ( ILT) also activates with fourth-order kinetics ( w4) but shows slower, incomplete inactivation. The high-threshold K+ current ( IHT) appears to consist of two kinetically distinct components ( n2 + p). The first component activates ∼10 mV positive to the second and has second-order kinetics. The second component activates with first-order kinetics. These two components also contribute to two kinetically distinct currents upon deactivation. The kinetic behavior of IHT was indistinguishable amongst cell types, suggesting the current is mediated by the same K+ channels amongst VCN neurons. Together these results provide a basis for more realistic modeling of VCN neurons, and provide clues regarding the molecular basis of the three K+ currents.
Accuracy of Saccades to Remembered Targets as a Function of Body Orientation in Space
Authors: Vogelstein Joshua T. , Snyder Lawrence H. , Angelaki Dora E.
Published: May 2006

A vertical asymmetry in memory-guided saccadic eye movements has been previously demonstrated in humans and in rhesus monkeys. In the upright orientation, saccades generally land several degrees above the target. The origin of this asymmetry has remained unknown. In this study, we investigated whether the asymmetry in memory saccades is dependent on body orientation in space. Thus animals performed memory saccades in four different body orientations: upright, left-side-down (LSD), right-side-down (RSD), and supine. Data in all three rhesus monkeys confirm previous observations regarding a significant upward vertical asymmetry. Saccade errors made from LSD and RSD postures were partitioned into components made along the axis of gravity and along the vertical body axis. Up/down asymmetry persisted only in body coordinates but not in gravity coordinates. However, this asymmetry was generally reduced in tilted positions. Therefore the upward bias seen in memory saccades is egocentric although orientation in space might play a modulatory role.
Characterization of Spindle Afferents in Rat Soleus Muscle Using Ramp-and-Hold and Sinusoidal Stretches
Authors: De-Doncker Laurent , Picquet Florence , Petit Julien , Falempin Maurice
Published: May 2006

The discharge properties of 51 afferents were studied in the rat soleus muscle spindles. Under deep anesthesia using a pentobarbital sodium solution (30 mg/kg), a laminectomy was performed and the right L4 and L5 dorsal and ventral roots were transected near their entry into the spinal cord. In situ, the minimal ( L min) muscle length [3 ± 0.08 (SE) cm] of the soleus was measured at full ankle extension. Unitary potentials from the L5dorsal root were recorded in response to ramp-and-hold stretches applied at 3 mm (S3) and 4 mm (S4) amplitudes and four stretch velocities (6, 10, 15, and 30 mm/s), sinusoidal stretches performed at four amplitudes (0.12, 0.25, 0.5, and 1 mm) and six stretch frequencies (0.5, 1, 2, 3, 6, and 10 Hz), and vibrations applied at 50-, 100-, and 150-Hz frequencies. These two kinds of stretches were performed at three different muscle lengths ( L min+10%, L min+15%, and L min+20%), whereas vibrations were applied at L min+20% muscle length. Conduction velocity of the fibers was calculated but did not allow to discriminate different fiber types. However, the mean conduction velocity of the first fiber group (43.3 ± 0.8 m/s) was significantly higher than that of the second fiber group (33.9 ± 0.9 m/s). Three parameters allowed to differentiate the responses of primary and secondary endings: the dynamic index (DI), the discharge during the stretch release from the ramp-and-hold stretches, and the linear range and the vibration sensitivity from sinusoidal stretches. The slope histogram of the linear regression based on the DI and the stretch velocity was clearly bimodal. Therefore the responses were separated into two groups. During the stretch release at a velocity of 3 mm/s, the first response group ( n = 26) exhibited a pause, whereas the second ( n = 25) did not. The linear range of the second ending group (0.12–1 mm) was broader than that of the first (0.12–0.25 mm). The first ending group showed a higher sensitivity to high-vibration frequencies of small amplitude than the second. In comparison with the literature, we can assert that the first and the second ending groups corresponded to the primary and secondary endings, respectively. In conclusion, our study showed that in rat soleus muscle spindles, it was possible to immediately classify the discharge of Ia and II fibers by using some parameters measured under ramp-and-hold and sinusoidal stretches.
Category-Sensitive Excitatory and Inhibitory Processes in Human Extrastriate Cortex
Authors: Allison Truett , Puce Aina , McCarthy Gregory
Published: May 2006

Single-cell recordings from the temporal lobe of monkeys viewing stimuli show that cells may be highly selective, responding for example to particular objects such as faces. However, stimulus-selective cells may be inhibited by nonpreferred stimuli. Can such inhibitory mechanisms be detected in human visual cortex? In previous recordings from the surface of human ventral extrastriate cortex, we found that specific categories of stimuli such as faces and words generate category-specific negative event-related potentials (ERPs) with a peak latency of about 200 ms (N200). Laminar recordings in animal cortex suggest that the human N200 reflects excitatory depolarizing potentials in apical dendrites of pyramidal cells. In this study we found that, at about half of word-specific N200 sites, faces generated a positive ERP (P200); conversely, at about half of face-specific sites, words generated P200s. The electrogenesis of N200 implies that P200 ERPs reflect hyperpolarizing inhibition of apical dendrites. These recordings, together with the prior animal recordings, provide strong circumstantial evidence that in human cortex populations of cells responsive to one stimulus category (such as faces) inhibit cells responsive to another category (such as words), probably by a type of lateral inhibition. Of the stimulus categories studied quantitatively, face-specific cells are maximally inhibited by words and vice versa, but other categories of stimuli may generate smaller P200s, suggesting that inhibition of category-specific cells by nonpreferred stimuli is a general feature of human extrastriate cortex involved in object recognition.
Contribution of Signals Downstream From Adaptation to Saccade Programming
Authors: Tanaka Masaki
Published: May 2006

Information about ongoing behavior is necessary for stable perception and subsequent motor planning. Although many recurrent networks are known in the motor systems, the pathways that transmit the signals for internal monitoring of behavior are not specified. The present study reports that the pathways originating from sites downstream of cerebellar adaptation provide internal signals that are used for subsequent eye-movement programming. When monkeys made two successive saccades toward the locations of previously flashed targets or initial fixation, the second saccade compensated for the adaptive changes in the primary saccade. The use of signals downstream from adaptation for saccade programming contrasts with recent findings that signals upstream from adaptation control the perceptual localization of visual stimuli presented around the time of saccade, suggesting that separate recurrent networks provide behavioral information for perception versus movement programming.
Cross Talk Between the GABAAReceptor and the Na-K-Cl Cotransporter Is Mediated by Intracellular Cl−
Authors: Schomberg Stacey L. , Bauer James , Kintner Douglas B. , Su Gui , Flemmer Andreas , Forbush Biff , Sun Dandan
Published: May 2006

It has been suggested that the GABAAreceptor-mediated depolarization in immature neurons depends on a high intracellular Cl−concentration maintained by Na-K-Cl cotransporter isoform1 (NKCC1). We previously found that activation of the GABAAreceptor led to stimulation of NKCC1. This stimulation could be a result of GABAAreceptor-mediated Cl−efflux. However, a loss of intracellular Cl−is associated with cell shrinkage, membrane depolarization, as well as a rise of intracellular Ca2+concentration ([Ca2+]i). To determine which cellular mechanism is underlying NKCC1 stimulation, we investigated changes of intracellular Cl−content, [Ca2+]i, cell volume, and NKCC1 activity following GABAAreceptor activation. The basal levels of intracellular36Cl were 0.70 ± 0.04 μmol/mg protein. The intracellular36Cl content decreased to 0.53 ± 0.03 μmol/mg protein in response to 30 μM muscimol ( P < 0.05). The loss of intracellular36Cl was blocked by 10 μM bicuculline. Muscimol triggered a rise in [Ca2+]i, but did not cause cell shrinkage. In contrast, 10–50 mM [Cl−]oor hypertonic HEPES–MEM resulted in reversible cell shrinkage ( P < 0.05). Moreover, the GABA-mediated stimulation of NKCC1 activity was not abolished either by removal of extracellular Ca2+or BAPTA-AM. An increase in phosphorylation of NKCC1 was detected under both 10 mM [Cl−]oand muscimol conditions. These results suggest that a GABA-mediated loss of intracellular Cl−, but not a subsequent rise in [Ca2+]ior shrinkage, leads to stimulation of NKCC1. This stimulation may be an important positive feedback mechanism to maintain intracellular Cl−level and GABA function in immature neurons.
Static Ocular Counterroll Is Implemented Through the 3-D Neural Integrator
Authors: Crawford J. Douglas , Tweed Douglas B. , Vilis Tutis
Published: May 2006

Static head roll about the naso-occipital axis is known to produce an opposite ocular counterroll with a gain of approximately 10%, but the purpose and neural mechanism of this response remain obscure. In theory counterroll could be maintained either by direct tonic vestibular inputs to motoneurons, or by a neurally integrated pulse, as observed in the saccade generator and vestibulo-ocular reflex. When simulated together with ocular drift related to torsional integrator failure, the direct tonic input model predicted that the pattern of drift would shift torsionally as in ordinary counterroll, but the integrated pulse model predicted that the equilibrium position of torsional drift would be unaffected by head roll. This was tested experimentally by measuring ocular counterroll in 2 monkeys after injection of muscimol into the mesencephalic interstitial nucleus of Cajal. Whereas 90° head roll produced a mean ocular counterroll of 8.5° (±0.7° SE) in control experiments, the torsional equilibrium position observed during integrator failure failed to counterroll, showing a torsional shift of only 0.3° (±0.6° SE). This result contradicted the direct tonic input model, but was consistent with models that implement counterroll by a neurally integrated pulse.
Voltage-Gated Calcium Channel Currents in Type I and Type II Hair Cells Isolated From the Rat Crista
Authors: Bao Hong , Wong Weng Hoe , Goldberg Jay M. , Eatock Ruth Anne
Published: May 2006

When studied in vitro, type I hair cells in amniote vestibular organs have a large, negatively activating K+ conductance. In type II hair cells, as in nonvestibular hair cells, outwardly rectifying K+ conductances are smaller and more positively activating. As a result, type I cells have more negative resting potentials and smaller input resistances than do type II cells; large inward currents fail to depolarize type I cells above –60 mV. In nonvestibular hair cells, afferent transmission is mediated by voltage-gated Ca2+ channels that activate positive to –60 mV. We investigated whether Ca2+ channels in type I cells activate more negatively so that quantal transmission can occur near the reported resting potentials. We used the perforated patch method to record Ca2+ channel currents from type I and type II hair cells isolated from the rat anterior crista (postnatal days 4–20). The activation range of the Ca2+ currents of type I hair cells differed only slightly from that of type II cells or nonvestibular hair cells. In 5 mM external Ca2+, currents in type I and type II cells were half-maximal at –41.1 ± 0.5 (SE) mV ( n = 10) and –37.2 ± 0.2 mV ( n = 10), respectively. In physiological external Ca2+ (1.3 mM), currents in type I cells were half-maximal at –46 ± 1 mV ( n = 8) and just 1% of maximal at –72 mV. These results lend credence to suggestions that type I cells have more positive resting potentials in vivo, possibly through K+ accumulation in the synaptic cleft or inhibition of the large K+ conductance. Ca2+ channel kinetics were also unremarkable; in both type I and type II cells, the currents activated and deactivated rapidly and inactivated only slowly and modestly even at large depolarizations. The Ca2+ current included an L-type component with relatively low sensitivity to dihydropyridine antagonists, consistent with the α subunit being CaV1.3 (α1D). Rat vestibular epithelia and ganglia were probed for L-type α-subunit expression with the reverse transcription-polymerase chain reaction. The epithelia expressed CaV1.3 and the ganglia expressed CaV1.2 (α1C).
Reduced Neuromuscular Quantal Content With Normal Synaptic Release Time Course and Depression in Canine Motor Neuron Disease
Authors: Rich Mark M. , Wang Xueyong , Cope Timothy C. , Pinter Martin J.
Published: May 2006

Hereditary canine spinal muscular atrophy is an autosomal dominant version of motor neuron disease in which motor units exhibit extensive dysfunction before motor terminal or axonal degeneration appear. We showed in a previous paper that motor endplate currents (EPCs) are reduced and that failures of nerve-evoked EPCs appear in the homozygote medial gastrocnemius (MG) muscle in which failing motor units are also found, suggesting a presynaptic deficit of ACh release. To examine this further, we performed a detailed analysis of synaptic release properties in the MG muscle of homozygotes and compared the results with data from genetically normal control animals. We found that the amplitude of miniature EPCs (mEPC) did not differ between homozygote and normal synapses, indicating that quantal content is reduced at homozygote motor terminals. Consistent with this, deconvolution analysis showed that the maximum release rates at homozygote motor terminals were significantly reduced relative to normal. This analysis also demonstrated that the time course of quantal release at homozygote synapses did not differ from normal. The extent of quantal release depression during high-frequency activation in homozygotes did not differ from normal despite the significant reduction of quantal content and maximum release rate. Surprisingly, the absolute amount of posttetanic potentiation was not decreased at homozygotes motor terminals despite the differences in quantal content. We conclude that failure of homozygote motor unit force during repetitive activity is due to a unique combination of low quantal content and normal release depression and suggest that the primary deficit in homozygote motor terminals is a reduced supply of readily releasable quanta.
Response Properties of Whisker-Associated Trigeminothalamic Neurons in Rat Nucleus Principalis
Authors: Minnery Brandon S. , Simons Daniel J.
Published: May 2006

Nucleus principalis (PrV) of the brain stem trigeminal complex mediates the processing and transfer of low-threshold mechanoreceptor input en route to the ventroposterior medial nucleus of the thalamus (VPM). In rats, this includes tactile information relayed from the large facial whiskers via primary afferent fibers originating in the trigeminal ganglion (NV). Here we describe the responses of antidromically identified VPM-projecting PrV neurons ( n = 72) to controlled ramp-and-hold deflections of whiskers. For comparison, we also recorded the responses of 64 NV neurons under identical experimental and stimulus conditions. Both PrV and NV neurons responded transiently to stimulus onset (on) and offset (off), and the majority of both populations also displayed sustained, or tonic, responses throughout the plateau phase of the stimulus (75% of NV cells and 93% of PrV cells). Averageon and off response magnitudes were similar between the two populations. In both NV and PrV, cells were highly sensitive to the direction of whisker deflection. Directional tuning was slightly but significantly greater in NV, suggesting that PrV neurons integrate inputs from NV cells differing in their preferred directions. Receptive fields of PrV neurons were typically dominated by a “principal” whisker (PW), whose evoked responses were on average threefold larger than those elicited by any given adjacent whisker (AW; n = 197). However, of the 65 PrV cells for which data from at least two AWs were obtained, most (89%) displayed statistically significanton responses to deflections of one or more AWs. AW response latencies were 2.7 ± 3.8 (SD) ms longer than those of their corresponding PWs, with an inner quartile latency difference of 1–4 ms (±25% of median). The range in latency differences suggests that some adjacent whisker responses arise within PrV itself, whereas others have a longer, multi-synaptic origin, possibly via the spinal trigeminal nucleus. Overall, our findings reveal that the stimulus features encoded by primary afferent neurons are reflected in the responses of VPM-projecting PrV neurons, and that significant convergence of information from multiple whiskers occurs at the first synaptic station in the whisker-to-barrel pathway.
Three-Dimensional Eye Position and Slow Phase Velocity in Humans With Downbeat Nystagmus
Authors: Glasauer S. , Hoshi M. , Kempermann U. , Eggert T. , Büttner U.
Published: May 2006

Downbeat nystagmus (DN), a fixation nystagmus with the fast phases directed downward, is usually caused by cerebellar lesions, but the precise etiology is not known. A disorder of the smooth-pursuit system or of central vestibular pathways has been proposed. However, both hypotheses fail to explain why DN is usually accompanied by gaze-holding nystagmus, which implies a leaky neural velocity-to-position integrator. Because three-dimensional (3-D) analysis of nystagmus slow phases provides an excellent means for testing both hypotheses, we examined 19 patients with DN during a fixation task and compared them with healthy subjects. We show that the presentation of DN patients is not uniform; they can be grouped according to their deficits: DN with vertical integrator leakage, DN with vertical and horizontal integrator leakage, and DN without integrator leakage. The 3-D analysis of the slow phases of DN patients revealed that DN is most likely neither caused by damage to central vestibular pathways carrying semicircular canal information nor by a smooth pursuit imbalance. We propose that the observed effects can be explained by partial damage of a brain stem-cerebellar loop that augments the time constant of the neural velocity to position integrators in the brain stem and neurally adjusts the orientation of Listing's plane.
Cellular Activity in the Supplementary Eye Field During Sequential Performance of Multiple Saccades
Authors: Isoda Masaki , Tanji Jun
Published: May 2006

To investigate how single neurons in the supplementary eye field (SEF) participate in sequential performance of multiple saccades, we analyzed presaccadic activity while monkeys were performing three saccades in six different orders from memory. The saccades in each sequence were separated by a fixation period and initiated from the same fixation point with intervening return saccades. We found that the majority of the presaccadic activity of the SEF neurons differed significantly depending on the numerical position of saccades in each sequence (rank order). This rank-order selectivity was found in parallel with the selectivity for the sequence of three saccades. Our data suggest a role for SEF neurons in the coding of temporally ordered saccadic eye movements.
Spontaneous Development of Synchronous Oscillatory Activity During Maturation of Cortical Networks In Vitro
Authors: Opitz Thoralf , De Lima Ana D. , Voigt Thomas
Published: May 2006

Recent studies have focused attention on mechanisms of spontaneous large-scale wavelike activity during early development of the neocortex. In this study, we describe and characterize synchronous neuronal activity that occurs in cultured cortical networks naturally without pharmacological intervention. The synchronous activity that can be detected by means of Fluo-3 fluorescence imaging starts to develop at the beginning of the second week in culture and eventually includes the entire neuronal population about 1 wk later. A synchronous increase of [Ca2+]i in the neuronal population is associated with a burst of action potentials riding on a long-lasting depolarization recorded in a single cell. It is suggested that this depolarization results directly from synaptic current, which was comprised of at least three different components mediated by AMPA, N-methyl-d-aspartate (NMDA), and GABAA receptors. We never observed a gradually depolarizing pacemaker potential and found no evidence for a change of excitability during inter-burst periods. However, we found evidence for a period of synaptic depression after bursts. Network excitability recovers gradually over seconds from this depression that can explain the episodic nature of spontaneous network activity. Using pharmacological manipulation to investigate the propagation of activity in the network, we show that synchronous network activity depends on both glutamatergic and GABAAergic neurotransmission during a brief period. Reversal potential of GABAA receptor-mediated current was found to be significantly more positive than resting membrane potential both at 1 and 2 wk in culture, suggesting depolarizing action of GABA. However, in cultures older than 2 wk, inhibition of GABAAreceptors does not result in block of synchronous network activity but in modulation of burst width and frequency.
Postsynaptic Muscarinic M1 Receptors Activate Prefrontal Cortical EEG of C57BL/6J Mouse
Authors: Douglas Christopher L. , Baghdoyan Helen A. , Lydic Ralph
Published: May 2006

Recent pharmacological studies exploring the functional roles of muscarinic cholinergic receptor (mAChR) subtypes in prefrontal cortex of C57BL/6J (B6) mouse have provided evidence for a presynaptic M2 autoreceptor. The B6 mouse was chosen for these studies because it is a genetically well-characterized model that also provides the genomic background for many genetically modified mice. In addition to increasing ACh release, one functional consequence of pharmacologically blocking the cortical M2 autoreceptor is activation of the contralateral prefrontal cortical EEG. To date, the mechanisms through which M2 autoreceptor antagonism causes cortical EEG activation have not been investigated. The present study tested the hypothesis that, in the B6 mouse, prefrontal cortical ACh activates the contralateral prefrontal EEG via postsynaptic M1 receptors. This hypothesis was tested in 15 mice using in vivo microdialysis delivery of muscarinic antagonists with simultaneous quantification of ACh release, number of 7- to 14-Hz EEG spindles, and fast Fourier transformation analysis of prefrontal EEG. Dialysis delivery of the nonsubtype selective muscarinic antagonist scopolamine (10 nM) significantly ( P = 0.01) increased ACh release. Quantitative EEG analysis showed that scopolamine did not alter contralateral prefrontal cortical EEG. To differentiate mAChR subtypes mediating pre- versus postsynaptic responses, additional experiments used muscarinic antagonists with different affinities for the five mAChR subtypes. Microdialysis delivery of 3 nM AF-DX 116, a muscarinic antagonist with relatively high affinity for the M2 and M4 subtypes, significantly ( P < 0.01) increased prefrontal cortical ACh release and activated EEG in the contralateral prefrontal cortex. EEG activation was characterized by a significant decrease in number of 7- to 14-Hz EEG spindles ( P < 0.0001) and power ( Vrms) of EEG slow waves ( P < 0.05). Microdialysis delivery of 3 nM AF-DX 116 plus 3 nM pirenzepine, a relatively selective M1 and M4 muscarinic antagonist, also significantly ( P < 0.01) increased ACh release but did not decrease the number of EEG spindles and did not change EEG slow waves. The differential EEG and ACh responses to dialysis delivery of the muscarinic antagonists support the conclusion that, in B6 mouse, postsynaptic muscarinic receptors of the M1 subtype are a primary site by which ACh activates the EEG.
Spreading Depression: Imaging and Blockade in the Rat Neocortical Brain Slice
Authors: Anderson Trent R. , Andrew R. David
Published: May 2006

Spreading depression (SD) is a profound but transient depolarization of neurons and glia that migrates across the cortical and subcortical gray at 2–5 mm/min. Under normoxic conditions, SD occurs during migraine aura where it precedes migraine pain but does not damage tissue. During stroke and head trauma, however, SD can arise repeatedly near the site of injury and may promote neuronal damage. We developed a superfused brain slice preparation that can repeatedly support robust SD during imaging and electrophysiological recording to test drugs that may block SD. Submerged rat neocortical slices were briefly exposed to artificial cerebrospinal fluid (ACSF) with KCl elevated to 26 mM. SD was evoked within 2 min, recorded in layers II/III both as a negative DC shift and as a propagating front of elevated light transmittance (LT) representing transient cell swelling in all cortical layers. An SD episode was initiated focally and could be repeatedly evoked and imaged with no damage to slices. As reported in vivo, pretreatment with one of several N-methyl-d-aspartate (NMDA) receptor antagonists blocked SD, but a non-NMDA glutamate receptor antagonist (CNQX) had no effect. NMDA receptor (NMDAR) activation does not initiate SD nor are NMDAR antagonists tolerated therapeutically so we searched for more efficacious drugs to block SD generation. Pretreatment with the sigma-one receptor (ς1R) agonists dextromethorphan (10–100 μM), carbetapentane (100 μM), or 4-IBP (30 μM) blocked SD, even when KCl exposure was extended beyond 5 min. The block was independent of NMDA receptor antagonism. Two ς1R antagonists [(+)-3PPP and BD-1063] removed this block but had no effect upon SD alone. Remarkably, the ς1R agonists also substantially reduced general cell swelling evoked by bath application of 26 mM KCl. More potent ς1R ligands that are therapeutically tolerated could prove useful in reducing SD associated with migraine and be of potential use in stroke or head trauma.
Membrane Properties Related to the Firing Behavior of Zebrafish Motoneurons
Authors: Buss Robert R. , Bourque Charles W. , Drapeau Pierre
Published: May 2006

The physiological and pharmacological properties of the motoneuron membrane and action potential were investigated in larval zebrafish using whole cell patch current-clamp recording techniques. Action potentials were eliminated in tetrodotoxin, repolarized by tetraethylammonium (TEA) and 3,4-diaminopyridine (3,4-AP)-sensitive potassium conductances, and had a cobalt-sensitive, high-threshold calcium component. Depolarizing current injection evoked a brief (approximately 10–30 ms) burst of action potentials that was terminated by strong, outwardly rectifying voltage-activated potassium and calcium-dependent conductances. In the presence of intracellular cesium ions, a prolonged plateau potential often followed brief depolarizations. During larval development (hatching to free-swimming), the resting membrane conductance increased in a population of motoneurons, which tended to reduce the apparent outward rectification of the membrane. The conductances contributing to action potential burst termination are hypothesized to play a role in patterning the synaptically driven motoneuron output in these rapidly swimming fish.
Postsynaptic Dorsal Column and Cuneate Correlations in the Raccoon: A Re-evaluation by Parallel-Cascade Analysis
Authors: French Andrew S. , Dick Susan H. , Rasmusson Douglas D.
Published: May 2006

In a previous study, we reported evidence for correlations between the firing of postsynaptic dorsal column (PSDC) neurons and cuneate neurons with overlapping receptive fields on the glabrous skin of the raccoon forepaw. The evidence was based on cross-correlation and frequency response analyses of spontaneously firing neurons. However, cross-correlation without white noise Gaussian analog inputs or Poisson distributed pulse train inputs is difficult to interpret because of the inherent convolution with the autocorrelation of the unknown input signals. While the data suggested positive correlations in the spinocuneate direction for most neuron pairs, we could not estimate the temporal characteristics of these putative connections. We have now re-analyzed these data using a parallel-cascade method to estimate the first- and second-order kernels of a Volterra series approximation to the spinocuneate system. This unbiased analysis suggests that a positive correlation occurs after about 5 ms, probably followed by a negative correlation at about 12 ms. Second-order kernels also had repeatable structure, indicating dual pathways with time separations of at least 10 ms.
Optical Analysis of Depolarization Waves in the Embryonic Brain: A Dual Network of Gap Junctions and Chemical Synapses
Authors: Momose-Sato Yoko , Miyakawa Naohisa , Mochida Hiraku , Sasaki Shinichi , Sato Katsushige
Published: May 2006

Correlated neuronal activity plays a fundamental role in the development of the CNS. Using a multiple-site optical recording technique with a voltage-sensitive dye, we previously described a novel type of depolarization wave that was evoked by cranial or spinal nerve stimulation and spread widely over the whole brain region in the chick embryo. We have now investigated developmental expression and neuronal network mechanisms of this depolarization wave by applying direct stimulation to the brain stem or upper cervical cord of E5–E11 embryos, which elicited wave activity similar to that evoked by nerve stimulation. Spatial distribution patterns of the depolarization wave changed dynamically with development, and this change appeared to be related to the regional differences in neuronal differentiation. The depolarization wave was completely eliminated by application of either gap junction blockers or an N-methyl-d-aspartate (NMDA)-receptor antagonist, indicating that functions of both gap junctions and NMDA receptors are indispensable for wave propagation. A possible interpretation of the results is that dual networks of gap junctions and chemical synaptic coupling mediate large-scale depolarization waves in the developing chick CNS.