bluuebunny/crossref_metadata_2025 huggingface dataset:
Follower Neurons in Lobster (Panulirus interruptus) Pyloric Network Regulate Pacemaker Period in Complementary Ways
Authors: Weaver Adam L. , Hooper Scott L.
Published: May 2006

Distributed neural networks (ones characterized by high levels of interconnectivity among network neurons) are not well understood. Increased insight into these systems can be obtained by perturbing network activity so as to study the functions of specific neurons not only in the network's “baseline” activity but across a range of network activities. We applied this technique to study cycle period control in the rhythmic pyloric network of the lobster, Panulirus interruptus. Pyloric rhythmicity is driven by an endogenous oscillator, the Anterior Burster (AB) neuron. Two network neurons feed back onto the pacemaker, the Lateral Pyloric (LP) neuron by inhibition and the Ventricular Dilator (VD) neuron by electrical coupling. LP and VD neuron effects on pyloric cycle period can be studied across a range of periods by altering period by injecting current into the AB neuron and functionally removing (by hyperpolarization) the LP and VD neurons from the network at each period. Within a range of pacemaker periods, the LP and VD neurons regulate period in complementary ways. LP neuron removal speeds the network and VD neuron removal slows it. Outside this range, network activity is disrupted because the LP neuron cannot follow slow periods, and the VD neuron cannot follow fast periods. These neurons thus also limit, in complementary ways, normal pyloric activity to a certain period range. These data show that follower neurons in pacemaker networks can play central roles in controlling pacemaker period and suggest that in some cases specific functions can be assigned to individual network neurons.
Auditory Influences on Visual Temporal Rate Perception
Authors: Recanzone Gregg H.
Published: May 2006

Visual stimuli are known to influence the perception of auditory stimuli in spatial tasks, giving rise to the ventriloquism effect. These influences can persist in the absence of visual input following a period of exposure to spatially disparate auditory and visual stimuli, a phenomenon termed the ventriloquism aftereffect. It has been speculated that the visual dominance over audition in spatial tasks is due to the superior spatial acuity of vision compared with audition. If that is the case, then the auditory system should dominate visual perception in a manner analogous to the ventriloquism effect and aftereffect if one uses a task in which the auditory system has superior acuity. To test this prediction, the interactions of visual and auditory stimuli were measured in a temporally based task in normal human subjects. The results show that the auditory system has a pronounced influence on visual temporal rate perception. This influence was independent of the spatial location, spectral bandwidth, and intensity of the auditory stimulus. The influence was, however, strongly dependent on the disparity in temporal rate between the two stimulus modalities. Further, aftereffects were observed following approximately 20 min of exposure to temporally disparate auditory and visual stimuli. These results show that the auditory system can strongly influence visual perception and are consistent with the idea that bimodal sensory conflicts are dominated by the sensory system with the greater acuity for the stimulus parameter being discriminated.
Induction of NMDA and GABAAReceptor-Mediated Ca2+Oscillations With KCC2 mRNA Downregulation in Injured Facial Motoneurons
Authors: Toyoda Hiroki , Ohno Koji , Yamada Junko , Ikeda Masahiko , Okabe Akihito , Sato Kohji , Hashimoto Kenji , Fukuda Atsuo
Published: May 2006

To clarify the changes that occur in γ-aminobutyric acid type A (GABAA) receptor-mediated effects and contribute to alterations in the network activities after neuronal injury, we studied intracellular Ca2+concentration ([Ca2+]i) dynamics in a rat facial-nerve-transection model. In facial motoneurons, an elevation of the resting [Ca2+]i, GABA-mediated [Ca2+]itransients, enhancement of the glutamate-evoked [Ca2+]iincreases, and spontaneous [Ca2+]ioscillations were induced by axotomy. All these axotomy-induced modifications were abolished by the GABAA-receptor antagonist bicuculline and N-methyl-d-aspartate (NMDA)-receptor antagonistd(−)-2-amino-5-phosphonopentanoic acid. A downregulation of K+-Cl−cotransporter (KCC2) mRNA, an increase in intracellular Cl−concentration ([Cl−]i), and transformation of GABAergic hyperpolarization to depolarization were also induced by axotomy. We suggest that in axotomized neurons KCC2 downregulation impairs Cl−homeostasis and makes GABA act depolarizing, resulting in endogenous GABA inducing [Ca2+]ioscillations via facilitation of NMDA-receptor activation. Such GABAA-receptor-mediated [Ca2+]ioscillations may play a role in neural survival and regeneration.
Evoked Oscillations in the Thalamo-Cortical Auditory System Are Present in Anesthetized but not in Unanesthetized Rats
Authors: Cotillon-Williams Nathalie , Edeline Jean-Marc
Published: May 2006

Over the last decade, a large number of studies have characterized stimulus-evoked oscillations in the visual cortex of anesthetized and unanesthetized animals. Comparatively, only a few studies have been performed in auditory cortex. This study compared the tone-evoked oscillations detected from the same recording sites in the thalamo-cortical auditory system of unanesthetized and anesthetized rats. Simultaneous multiunit recordings were collected in auditory cortex, auditory thalamus, and the auditory sector of the reticular nucleus of restrained rats, which spontaneously shifted from waking (W) to slow-wave sleep (SWS) and paradoxical sleep (PS). Subsequently, the same recording sites were tested under pentobarbital anesthesia, then under high doses of diazepam, and finally under urethan anesthesia. Under these drugs, oscillations were detected in 54% of the recordings: one-half of them were stimulus-locked oscillations and were directly observed on peri-stimulus time histograms (PSTHs); one-half of them were non–stimulus-locked oscillations and were detected on autocorrelograms. Spontaneous oscillations were present for 17% of the recordings. During SWS, only non–stimulus-locked oscillations were observed for a small percentage of recordings (12%). This percentage did not differ significantly from the one of spontaneous oscillations obtained during SWS (8%). No oscillations were found in W and PS. Both under anesthesia and in SWS, the frequency range of the oscillations was 5–15 Hz, and there was no frequency difference between evoked and spontaneous oscillations. Although surprising, the absence of oscillations in awake animals may allow each neuron to process acoustic information independently of its neighbors and may in fact benefit auditory perception.
Direction-Selective Neurons in the Optokinetic System With Long-Lasting After-Responses
Authors: Price Nicholas S. C. , Ibbotson Michael R.
Published: May 2006

We describe the responses during and after motion of slow cells, which are a class of direction-selective neurons in the pretectal nucleus of the optic tract (NOT) of the wallaby. Neurons in the NOT respond to optic flow generated by head movements and drive compensatory optokinetic eye movements. Motion in the preferred direction produces increased firing rates in the cells, whereas motion in the opposite direction inhibits their high spontaneous activities. Neurons were stimulated with moving spatial sinusoidal gratings through a range of temporal and spatial frequencies. The slow cells were maximally stimulated at temporal frequencies <1 Hz and spatial frequencies of 0.13–1 cpd. During motion, the responses oscillate at the fundamental temporal frequency of the grating but not at higher-order harmonics. There is prolonged excitation after preferred direction motion and prolonged inhibition after anti-preferred direction motion, which are referred to as same-sign after-responses (SSARs). This is the first time that the response properties of neurons with SSARs have been reported and modeled in detail for neurons in the NOT. Slow cell responses during and after motion are modeled using an array of Reichardt-type motion detectors that include band-pass temporal prefilters. The oscillatory behavior during motion and the SSARs can be simulated accurately with the model by manipulating time constants associated with temporal filtering in the prefilters and motion detectors. The SSARs of slow cells are compared with those of previously described direction-selective neurons, which usually show transient inhibition or excitation after preferred or anti-preferred direction motion, respectively. Possible functional roles for slow cells are discussed in the context of eye movement control.
Ca2+Transient Evoked by Chemical Stimulation Is Enhanced by PGE2in Vagal Sensory Neurons: Role of cAMP/PKA Signaling Pathway
Authors: Gu Qihai , Kwong Kevin , Lee Lu-Yuan
Published: May 2006

The effect of prostaglandin E2(PGE2) on chemical stimulation-evoked calcium (Ca2+) transient was investigated in isolated vagal sensory neurons of the rat using fura-2-based ratiometric Ca2+imaging. Application of capsaicin (3 × 10−8to 10−7M; 15 s) caused a rapid surge of intracellular Ca2+concentration in small- and medium-size neurons; the response was reproducible when >10 min elapsed between two challenges and was absent in nominally Ca2+-free solution. After pretreatment with PGE2(3 × 10−7M; 5 min), the peak of this capsaicin-evoked Ca2+transient was increased by almost fourfold, and its duration was also prolonged. This augmented response to capsaicin induced by PGE2gradually declined but remained higher than control after 15-min washout. Similarly, PGE2pretreatment also markedly enhanced the Ca2+transients induced by other chemical stimulants to C neurons, such as phenylbiguanide (PBG), adenosine 5′-triphosphate (ATP), and KCl. The Ca2+transients evoked by PBG, ATP, and KCl were potentiated after the pretreatment with PGE2to 242, 204, and 163% of their control, respectively. This potentiating effect of PGE2could be mimicked by forskolin (10−6M; 5 min), an activator of adenylyl cyclase, and 8-(4-chlorophenylthio)adenosine-3′-5′-cyclic monophosphate (CPT-cAMP; 3 × 10−6M, 10 min), a membrane-permeable cAMP analogue. Furthermore, the potentiating effects of PGE2, forskolin, and CPT-cAMP were abolished by N-[2-(p-bromocinnamylamino)ethyl]-5-isoquinolinesulfonamide (H89; 10−5M; 15–20 min), a protein kinase A (PKA) inhibitor. In summary, these results show that PGE2reversibly potentiates the chemical stimuli-evoked Ca2+transients in cultured rat vagal sensory neurons, and this potentiating effect is mediated through the cyclic AMP/PKA transduction cascade.
Effects of Intrathecal Glutamatergic Drugs on Locomotion. II. NMDA and AP-5 in Intact and Late Spinal Cats
Authors: Giroux Nathalie , Chau Connie , Barbeau Hugues , Reader Tomás A. , Rossignol Serge
Published: May 2006

In a previous article, we have shown that, in cats, intrathecal injections of N-methyl-d-aspartate (NMDA) in the first few days after spinalization at T13do not induce locomotion as in many other spinal preparations. This is in contrast to alpha-2 noradrenergic receptor stimulation, which can trigger locomotion at this early stage. However, it is known that spinal cats do recover spontaneous locomotion in the absence of descending noradrenergic pathways and that the spinal pattern generator must then depend on other neurotransmitters still present in the cord such as excitatory amino acids. In the present paper, therefore we look at the effects of intrathecal NMDA, a glutamatergic agonist, and 2-amino-5-phosphonovaleric acid (AP-5), an NMDA receptor blocker, in both intact and late spinal cats. Low doses of NMDA had no major effect on the locomotor pattern in both intact and late spinal cats. Larger doses of NMDA in the chronic spinal cat initially produced an increase in the general excitability followed by more regular locomotion. AP-5 in intact cats caused a decrease in the amplitude of the flexion reflex and induced a bilateral foot drag as well as some decrease in weight support but it did not prevent locomotion. However, in late spinal cats, the same dose of AP-5 blocked locomotion completely. These results indicate that NMDA receptors may be critical for the spontaneous expression of spinal locomotion. It is proposed that the basic locomotor rhythmicity in cats is NMDA-dependent and that normally this glutamatergic mechanism is modulated by other neurotransmitters, such as 5-HT and NA.
Differential Processing of Excitation by GABAergic Gain Modulation in Canine Caudal Ventral Respiratory Group Neurons
Authors: Tonkovic-Capin V. , Stucke A. G. , Stuth E. A. , Tonkovic-Capin M. , Hopp F. A. , McCrimmon D. R. , Zuperku E. J.
Published: May 2006

The discharge frequency ( Fn) patterns of medullary respiratory premotor neurons are subject to potent tonic GABAergic gain modulation. Studies in other neuron types suggest that the synaptic input for tonic inhibition is located on the soma where it can affect total neuronal output. However, our preliminary data suggested that excitatory responses elicited by highly local application of glutamate receptor agonists are not gain modulated. In addition, modulation of the amplitude of spike afterhyperpolarizations can gain modulate neuronal output, and this mechanism is located near the spike initiation zone and/or soma. The purpose of this study was to determine if these two gain-modulating mechanisms have different functional locations on the somatodendritic membrane of bulbospinal inspiratory and expiratory neurons. Four-barrel micropipettes were used for extracellular single-neuron recording and pressure ejection of drugs in decerebrate, paralyzed, ventilated dogs. The net increases in Fndue to repeated short-duration picoejections of the glutamate receptor agonist, α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA), was quantified before and during locally induced antagonism of GABAAreceptors by bicuculline or small-conductance, calcium-activated potassium channels by apamin. The AMPA-induced net increases in Fnwere not significantly altered by BIC, although it produced large increases in the respiratory-related activity. However, the AMPA-induced net responses were amplified in accordance with the gain increase of the respiratory-related activity by apamin. These findings suggest that GABAergic gain modulation may be functionally isolated from the soma/spike initiation zone, e.g., located on a dendritic shaft. This could allow other behavioral signals requiring strong neuronal activation (e.g., coughing, sneezing, vomiting) to utilize the same neuron without being attenuated by the GABAergic modulation.
Timing of Knee-Related Spinal Neurons During Fictive Rostral Scratching in the Turtle
Authors: Stein Paul S.G. , Daniels-McQueen Susan
Published: May 2006

Knee-flexor motor activity rhythmically alternated with knee-extensor motor activity during fictive rostral scratching in the spinal turtle. A critical transition from knee-flexor motor activity to knee-extensor motor activity occurred during hip-flexor motor activity. A key feature of this transition was that the end-phases of knee-flexor motor activity were positively correlated with the start-phases of knee-extensor motor activity. We studied spinal interneurons with activities related to this transition. We previously used single-unit recording techniques to characterize a data set of descending propriospinal interneurons during rostral scratching. We focused here on a group of interneurons from this data set with start-phases (on-units) or with end-phases (off-units) near the start of knee-extensor motor activity. We showed that, for a subset of these units, the start-phases of on-units and the end-phases of off-units were positively correlated with the start-phases of knee-extensor motor activity. We present the hypothesis that some of these knee-related on- and off-units may play a role in timing knee motor activity during rostral scratching.
Three-Dimensional Eye-Head Coordination Is Implemented Downstream From the Superior Colliculus
Authors: Klier Eliana M. , Wang Hongying , Crawford J. Douglas
Published: May 2006

How the brain transforms two-dimensional visual signals into multi-dimensional motor commands, and subsequently how it constrains the redundant degrees of freedom, are fundamental problems in sensorimotor control. During fixations between gaze shifts, the redundant torsional degree of freedom is determined by various neural constraints. For example, the eye- and head-in-space are constrained by Donders' law, whereas the eye-in-head obeys Listing's law. However, where and how the brain implements these laws is not yet known. In this study, we show that eye and head movements, elicited by unilateral microstimulations of the superior colliculus (SC) in head-free monkeys, obey the same Donders' strategies observed in normal behavior (i.e., Listing's law for final eye positions and the Fick strategy for the head). Moreover, these evoked movements showed a pattern of three-dimensional eye-head coordination, consistent with normal behavior, where the eye is driven purposely out of Listing's plane during the saccade portion of the gaze shift in opposition to a subsequent torsional vestibuloocular reflex slow phase, such that the final net torsion at the end of each head-free gaze shift is zero. The required amount of saccade-related torsion was highly variable, depending on the initial position of the eye and head prior to a gaze shift and the size of the gaze shift, pointing to a neural basis of torsional control. Because these variable, context-appropriate torsional saccades were correctly elicited by fixed SC commands during head-free stimulations, this shows that the SC only encodes the horizontal and vertical components of gaze, leaving the complexity of torsional organization to downstream control systems. Thus we conclude that Listing's and Donders' laws of the eyes and head, and their three-dimensional coordination mechanisms, must be implemented after the SC.
Protein Kinase A Mediates Voltage-Dependent Facilitation of Ca2+Current in Presynaptic Hair Cells inHermissenda crassicornis
Authors: Tamse Catherine T. , Xu Yanfang , Song Haitao , Nie Liping , Yamoah Ebenezer N.
Published: May 2006

The simplest cellular model for classical conditioning in the nudibranch mollusk, Hermissenda crassicornis, involves the presynaptic hair cells and postsynaptic photoreceptors. Whereas the cellular mechanisms for postsynaptic photoreceptors have been studied extensively, the presynaptic mechanisms remain uncertain. Here, we determined the phenotype of the voltage-dependent Ca2+current in the presynaptic hair cells that may be directly involved in changes in synaptic efficacy during classical conditioning. The Ca2+current can be classified as a P-type current because its activation voltage under seawater recording conditions is approximately −30 mV, it showed slow inactivation, and it is reversibly blocked by ω-agatoxin-IVA. The steady-state activation and inactivation curves revealed a window current, and the single-channel conductance is approximately 20 pS. The P-type current was enhanced by cAMP analogs (approximately 1.3-fold), and by forskolin, an activator of adenylyl cyclase (approximately 1.25-fold). In addition, the P-type current showed voltage-dependent facilitation, which is mediated by protein kinase A (PKA). Specifically, the PKA inhibitor peptide [PKI(6–22)amide] blocked the enhancement of the Ca2+current produced by conditioning depolarization prepulses. Because neurotransmitter release is mediated by Ca2+influx via voltage-gated Ca2+channels, and because of the nonlinear relationship between the Ca2+influx and neurotransmitter release, we propose that voltage-dependent facilitation of the P-type current in hair cells would produce a robust change in synaptic efficacy.
Neural Networks for the Coordination of the Hands in Time
Authors: Ullén Fredrik , Forssberg Hans , Ehrsson H. Henrik
Published: May 2006

Without practice, bimanual movements can typically be performed either in phase or in antiphase. Complex temporal coordination, e.g., during movements at different frequencies with a noninteger ratio (polyrhythms), requires training. Here, we investigate the organization of the neural control systems for in-phase, antiphase, and polyrhythmic coordination using functional magnetic resonance imaging (fMRI). Brisk rhythmic tapping with the index fingers was used as a model behavior. We demonstrate different patterns of brain activity during in-phase and antiphase coordination. In-phase coordination was characterized by activation of the right anterior cerebellum and cingulate motor area (CMA). Antiphase coordination was accompanied by extensive fronto-parieto-temporal activations, including the supplementary motor area (SMA), the preSMA, and the bilateral inferior parietal gyri, premotor cortex, and superior temporal gyri. When contrasting polyrhythmic tapping with in-phase tapping, activity was seen in the same set of brain regions, and in the posterior cerebellum and the CMA. Antiphase and polyrhythmic coordination may thus to a large extent use common neural control circuitry. In a separate experiment, we analyzed the neural control of the rhythmic structure and the serial order of finger movements during polyrhythmic tapping. Polyrhythmic tapping was compared with an isochronous coordination pattern that retained the same serial order of finger movements as the polyrhythm. This experiment showed that the preSMA and the bilateral superior temporal gyri may be crucial for the rhythmic control of polyrhythmic tapping, while the cerebellum, the CMA, and the premotor cortices presumably are more involved in the ordinal control of the sequence of finger movements.
Raphe Magnus Neurons Respond to Noxious Colorectal Distension
Authors: Brink Thaddeus S. , Mason Peggy
Published: May 2006

First published November 13, 2002; 10.1152/jn.00825.2002. Physiological studies of neurons in raphe magnus (RM) and the adjacent nucleus reticularis magnocellularis (NRMC) have demonstrated that the response to noxious cutaneous stimulation predicts the response to opioid administration and therefore a cell's functional role in nociceptive modulation. Although visceral stimulation, like opioids, elicits antinociception, little is known about how RM and NRMC cells respond to visceral stimulation. Therefore RM and NRMC cells were tested for their responses to both colorectal distension (CRD) and noxious cutaneous heat in halothane-anesthetized rats. Less than a third of serotonergic cells responded to CRD with small increases or decreases in discharge rate. In contrast, almost two-thirds of nonserotonergic cells responded to CRD stimulation with either excitatory (35%) or inhibitory (30%) responses to CRD. The response to heat did not predict the response to CRD with nearly equal proportions of heat-excited, -inhibited, and -unaffected cells being excited, inhibited, or unaffected by CRD. The dissociation between the responses to cutaneous heat and CRD demonstrates that cell classes based on the response to noxious heat are not homogeneous and may play multiple functional roles.
Automatic Sorting for Multi-Neuronal Activity Recorded With Tetrodes in the Presence of Overlapping Spikes
Authors: Takahashi Susumu , Anzai Yuichiro , Sakurai Yoshio
Published: May 2006

Multi-neuronal recording is a powerful electrophysiological technique that has revealed much of what is known about the neuronal interactions in the brain. However, it is difficult to detect precise spike timings, especially synchronized simultaneous firings, among closely neighboring neurons recorded by one common electrode because spike waveforms overlap on the electrode when two or more neurons fire simultaneously. In addition, the non-Gaussian variability (nonstationarity) of spike waveforms, typically seen in the presence of so-called complex spikes, limits the ability to sort multi-neuronal activities into their single-neuron components. Because of these problems, the ordinary spike-sorting techniques often give inaccurate results. Our previous study has shown that independent component analysis (ICA) can solve these problems and separate single-neuron components from multi-neuronal recordings. The ICA has, however, one serious limitation that the number of separated neurons must be less than the number of electrodes. The present study combines the ICA and the efficiency of the ordinary spike-sorting technique (k-means clustering) to solve the spike-overlapping and the nonstationarity problems with no limitation on the number of single neurons to be separated. First, multi-neuronal activities are sorted into an overly large number of clusters by k-means clustering. Second, the sorted clusters are decomposed by ICA. Third, the decomposed clusters are progressively aggregated into a minimal set of putative single neurons based on similarities of basis vectors estimated by ICA. We applied the present procedure to multi-neuronal waveforms recorded with tetrodes composed of four microwires in the prefrontal cortex of awake behaving monkeys. The results demonstrate that there are functional connections among neighboring pyramidal neurons, some of which fire in a precise simultaneous manner and that precisely time-locked monosynaptic connections are working between neighboring pyramidal neurons and interneurons. Detection of these phenomena suggests that the present procedure can sort multi-neuronal activities, which include overlapping spikes and realistic non-Gaussian variability of spike waveforms, into their single-neuron components. We processed several types of synthesized data sets in this procedure and confirmed that the procedure was highly reliable and stable. The present method provides insights into the local circuit bases of excitatory and inhibitory interactions among neighboring neurons.
Corticosterone Acts Directly at the Amygdala to Alter Spinal Neuronal Activity in Response to Colorectal Distension
Authors: Qin Chao , Greenwood-Van Meerveld Beverley , Myers Dean A. , Foreman Robert D.
Published: May 2006

Administration of glucocorticoids to the amygdaloid nucleus facilitates visceromotor responses to colorectal distension in rats. The aim of this study was to determine if colorectal hypersensitivity develops through central modulation of spinal neuronal activity. Stereotaxic delivery of corticosterone ( n = 10) or cholesterol (control, n = 10) onto the dorsal margin of the amygdala was performed on male Fischer-344 rats. Seven days later, extracellular potentials of single L6-S1spinal neurons were examined for responses to colorectal distension (CRD, 20–80 mmHg, 20 s) in sodium pentobarbital anesthetized and paralyzed animals. The proportions of neurons that responded to noxious CRD in corticosterone-implanted (62/186, 33%) and cholesterol-implanted (55/163, 34%) animals were virtually identical. However, the mean excitatory response of spinal neurons to CRD in corticosterone-treated rats was significantly greater (26.7 ± 2.2 vs. 16.4 ± 1.8 imp/s, P < 0.01) and the duration was longer (37.0 ± 3.9 vs. 25.8 ± 1.5 s, P < 0.05) than in the control group. No significant differences were found in neural responses to nonnoxious and noxious mechanical stimulation of somatic fields between corticosterone-implanted and control groups. In conclusion, our data support the hypothesis that central stimulation of the amygdala by corticosterone sensitizes the lumbosacral spinal neurons that mediate visceromotor reflexes to CRD.
Effects of 4-Aminopyridine on Stretched Mammalian Spinal Cord: The Role of Potassium Channels in Axonal Conduction
Authors: Jensen Jennifer M. , Shi Riyi
Published: May 2006

Axonal conduction deficit is a major contributor to various degrees of disability after spinal cord injury. 4-aminopyridine (4-AP), a potassium channel blocker, has been shown to restore some conduction and improve neurological function in both animal and human studies. Using a double sucrosegap recording device, we have examined the effects of 4-AP on isolated guinea pig spinal cord white matter after stretch injury. At a concentration of 100 μM, 4-AP increased the amplitude of the compound action potential by 100% while 1 μM 4-AP increased it by 43%, a larger response than seen following compression injury. The length of affected tissue is suggested as a potential explanation of this differential sensitivity to 4-AP. Plastic sections taken from the injury site revealed severe myelin damage, especially in the paranodal area, which may also partially explain why 4-AP has more effect on conduction after stretch injury than compression. In addition, we have shown that while enhancing conductivity in some axons, 4-AP significantly reduced the overall responsiveness to multiple stimuli, as evidenced by increase of the refractory period in response to dual stimuli and the decreased ability to follow repetitive stimuli. This increased refractoriness may be largely attributed to residual deficits in fibers newly recruited by 4-AP treatment.
Effects of Learning on Smooth Pursuit During Transient Disappearance of a Visual Target
Authors: Madelain Laurent , Krauzlis Richard J.
Published: May 2006

Previous research has demonstrated learning in the pursuit system, but it is unclear whether these effects are the result of changes in visual or motor processing. The ability to maintain smooth pursuit during the transient disappearance of a visual target provides a way to assess pursuit properties in the absence of visual inputs. To study the long-term effects of learning on nonvisual signals for pursuit, we used an operant conditioning procedure. By providing a reinforcing auditory stimulus during periods of accurate tracking, we increased the pursuit velocity gain during target blanking from 0.59 in the baseline session to 0.89 after 8 to 10 daily sessions of training. Learning also reduced the occurrence of saccades. The learned effects generalized to untrained target velocities and persisted in the presence of a textured visual background. In a yoked-control group, the reinforcer was independent of the subjects' responses, and the velocity gain remained unchanged (from 0.6 to 0.63, respectively, before and after training). In a control group that received no reinforcer, gain increased slightly after repetition of the task (from 0.63 to 0.71, respectively, before and after training). Using a model of pursuit, we show that these effects of learning can be simulated by modifying the gain of an extra-retinal signal. Our results demonstrate that learned contingencies can increase eye velocity in the absence of visual signals and support the view that pursuit is regulated by extra-retinal signals that can undergo long-term plasticity.
Effects of Hypodynamia-Hypokinesia on the Muscle Spindle Discharges of Rat Soleus Muscle
Authors: De-Doncker Laurent , Picquet Florence , Petit Julien , Falempin Maurice
Published: May 2006

The aim of this study was to determine whether Ia and II fiber discharges of soleus muscle spindles were modified after a 14-day period of hypodynamia (absence of weight bearing) and hypokinesia (reduction of motor activity). Fifty-one and 38 afferent fibers were studied, respectively, in control and hypodynamia-hypokinesia (HH) groups. Under deep anesthesia (pentobarbital, 30 mg/kg), a L3–L6laminectomy was performed. Unitary potentials from the L5dorsal root were recorded in response to ramp-and-hold stretches applied at two stretch amplitudes (3 and 4 mm) and four stretch velocities (6, 10, 15, and 30 mm/s) and to sinusoidal stretches applied at four stretch amplitudes (0.12, 0.25, 0.5, and 1 mm) and six stretch frequencies (0.5, 1, 2, 3, 6, and 10 Hz). In both animal groups, the Ia fibers showed higher dynamic index values, smaller linear range, and higher vibration sensitivity than the II fibers. They also exhibited a pause in their discharges during the stretch release contrary to II fibers, which displayed no pause in their responses. After HH, our results showed that for both fiber types all parameters measured under ramp-and-hold stretches (except the static sensitivity) were significantly increased and under sinusoidal stretches, the vibration sensitivity increased, and the response amplitude only increased at 0.12-mm stretch amplitude. The linear range of Ia afferents was limited to 0.12 mm, whereas it was unchanged for the II fibers. After HH, the stretches could be better transmitted to the muscle spindles, probably resulting from changes in passive mechanical properties of the soleus.
Target Selection for Reaching and Saccades Share a Similar Behavioral Reference Frame in the Macaque
Authors: Scherberger Hansjörg , Goodale Melvyn A. , Andersen Richard A.
Published: May 2006

The selection of one of two visual stimuli as a target for a motor action may depend on external as well as internal variables. We examined whether the preference to select a leftward or rightward target depends on the action that is performed (eye or arm movement) and to what extent the choice is influenced by the target location. Two targets were presented at the same distance to the left and right of a fixation position and the stimulus onset asynchrony (SOA) was adjusted until both targets were selected equally often. This balanced SOA time is then a quantitative measure of selection preference. In two macaque monkeys tested, we found the balanced SOA shifted to the left side for left-arm movements and to the right side for right-arm movements. Target selection strongly depended on the horizontal target location. By varying eye, head, and trunk position, we found this dependency embedded in a head-centered behavioral reference frame for saccade targets and, somewhat counter-intuitively, for reach targets as well. Target selection for reach movements was influenced by the eye position, while saccade target selection was unaffected by the arm position. These findings suggest that the neural processes underlying target selection for a reaching movement are to a large extent independent of the coordinate frame ultimately used to make the limb movement, but are instead closely linked to the coordinate frame used to plan a saccade to that target. This similarity may be indicative of a common spatial framework for hand-eye coordination.
Prolongation of Hippocampal Miniature Inhibitory Postsynaptic Currents in Mice Lacking the GABAAReceptor α1 Subunit
Authors: Goldstein Peter A. , Elsen Frank P. , Ying Shui-Wang , Ferguson Carolyn , Homanics Gregg E. , Harrison Neil L.
Published: May 2006

GABAAreceptors (GABAA-Rs) are pentameric structures consisting of two α, two β, and one γ subunit. The α subunit influences agonist efficacy, benzodiazepine pharmacology, and kinetics of activation/deactivation. To investigate the contribution of the α1 subunit to native GABAA-Rs, we analyzed miniature inhibitory postsynaptic currents (mIPSCs) in CA1 hippocampal pyramidal cells and interneurons from wild-type (WT) and α1 subunit knock-out (α1 KO) mice. mIPSCs recorded from interneurons and pyramidal cells obtained from α1 KO mice were detected less frequently, were smaller in amplitude, and decayed more slowly than mIPSCs recorded in neurons from WT mice. The effect of zolpidem was examined in view of its reported selectivity for receptors containing the α1 subunit. In interneurons and pyramidal cells from WT mice, zolpidem significantly increased mIPSC frequency, prolonged mIPSC decay, and increased mIPSC amplitude; those effects were diminished or absent in neurons from α1 KO mice. Nonstationary fluctuation analysis of mIPSCs indicated that the zolpidem-induced increase in mIPSC amplitude was associated with an increase in the number of open receptors rather than a change in the unitary conductance of individual channels. These data indicate that the α1 subunit is present at synapses on WT interneurons and pyramidal cells, although differences in mIPSC decay times and zolpidem sensitivity suggest that the degree to which the α1 subunit is functionally expressed at synapses on CA1 interneurons may be greater than that at synapses on CA1 pyramidal cells.
Time Course and Extent of Mechanotransducer Adaptation in Mouse Utricular Hair Cells: Comparison With Frog Saccular Hair Cells
Authors: Vollrath Melissa A. , Eatock Ruth Anne
Published: May 2006

Whole cell transduction currents were recorded from hair cells in early postnatal mouse utricles in response to step deflections of the hair bundle. For displacement steps delivered by a stiff probe (1-ms rise time), half-maximal responses decayed monoexponentially with a mean time constant of 30 ms. Adaptation and other transduction properties did not vary systematically with hair cell type (I vs. II) or region (striola vs. extrastriola). Thus regional variation in the phasic properties of utricular afferents arises through other mechanisms. When bundles were deflected by a fluid jet, which delivers force steps, transduction currents decayed about 3-fold more slowly than during displacement steps. A simple model of myosin-mediated adaptation predicts such slowing through forward creep of the bundle during a force step. For a faster stiff probe (rise time 200 μs), step responses of both mouse utricular and frog saccular hair cells decayed with two exponential components, which may correspond to distinct feedback processes. For half-maximal responses, the two components had mean time constants of 5 and 45 ms (mouse) and 2 and 18 ms (frog). The fast and slow components dominated the decay of responses to small and large stimuli, respectively. Adaptation shifts the instantaneous operating range in the direction of the adapting step. In frog saccular hair cells, the operating range shift is a constant percentage of the displacement. In mouse utricular hair cells, the percentage shift increases for large displacements, extending the range of background stimuli over which adaptation can restore instantaneous sensitivity.
Changes in Na+ Channel Currents of Rat Dorsal Root Ganglion Neurons Following Axotomy and Axotomy-Induced Autotomy
Authors: Abdulla Fuad A. , Smith Peter A.
Published: May 2006

Section of rat sciatic nerve (axotomy) increases the excitability of neurons in the L4–L5 dorsal root ganglia (DRG). These changes are more pronounced in animals that exhibit a self-mutilatory behavior known as autotomy. We used whole cell recording to examine changes in the tetrodotoxin-sensitive (TTX-S) and the tetrodotoxin-resistant (TTX-R) components of sodium channel currents ( I Na) that may contribute to axotomy-induced increases in excitability. Cells were initially divided on the basis of size into “large,” “medium,” and “small” groups. TTX-S I Na predominated in “large” cells, whereas TTX-R I Napredominated in some, but not all “small cells.” “Small” cells were therefore subdivided into “small-slow” cells, which predominately exhibited TTX-R I Na and “small fast” cells that exhibited more TTX-S I Na. In contrast to results obtained in other laboratories, where slightly different experimental procedures were used, we found that axotomy increased TTX-R and/or TTX-S I Na and slowed inactivation. The effects were greatest in “small-slow” cells and least in “large” cells. The changes promoted by axotomy were expressed more clearly in animals that exhibited autotomy. Also, the presence of autotomy correlated with a shift in the properties of I Na in “large” rather than “small-slow,” putative nociceptive cells. These trends parallel previous observations on axotomy-induced increases in excitability, spike height, and spike width that are also greatest in “small” cells and least in “large” cells. In addition, the presence of autotomy correlates with an increase in excitability of “large” rather than “small” cells. Increases in TTX-R and TTX-S I Na thus coincide with axotomy-induced increases in excitability and alterations in spike shape across the whole population of sensory neurons. Injury-induced changes of this type are likely associated with the onset of chronic pain in humans.
Regulation of Neuronal Function by Choline and 4OH-GTS-21 Through α7 Nicotinic Receptors
Authors: Uteshev Vladimir V. , Meyer Edwin M. , Papke Roger L.
Published: May 2006

A unique feature of α7 nicotinic acetylcholine receptor physiology is that, under normal physiological conditions, α7 receptors are constantly perfused with their natural selective agonist, choline. Studying neurons of hypothalamic tuberomammillary (TM) nucleus, we show that choline and the selective α7 receptor agonist 4OH-GTS-21 can regulate neuronal functions directly, via activation of the native α7 receptors, and indirectly, via desensitizing those receptors or transferring them into a state “primed” for desensitization. The direct action produces depolarization and thereby increases the TM neuron spontaneous firing (SF) rate. The regulation of the spontaneous firing rate is robust in a nonphysiological range of choline concentrations >200 μM. However, modest effects persist at concentrations of choline that are likely to be attained perineuronally under some conditions (20–100 μM). At high physiological concentration levels, the indirect choline action reduces or even eliminates the responsiveness of α7 receptors and their availability to other strong cholinergic inputs. Similarly to choline, 4OH-GTS-21 increases the TM neuron spontaneous firing rate via activation of α7 receptors, and this regulation is robust in the range of clinically relevant concentrations of 4OH-GTS-21. We conclude that factors that regulate choline accumulation in the brain and in experimental slices such as choline uptake, hydrolysis of ACh, membrane phosphatidylcholine catabolism, and solution perfusion rate influence α7 nAChR neuronal and synaptic functions, especially under pathological conditions such as stroke, seizures, Alzheimer's disease, and head trauma, when the choline concentration in the CSF is expected to rise.
Circle-Drawing Movements at Different Speeds: Role of Inertial Anisotropy
Authors: Pfann Kerstin D. , Corcos Daniel M. , Moore Charity G. , Hasan Ziaul
Published: May 2006

This study investigated the role of inertial anisotropy at the hand in causing distortions in movement. Subjects drew circles in the horizontal plane at four locations in the workspace at three instructed paces using elbow and shoulder movements. Specifically, we tested two hypotheses, which we would expect if the anisotropy of inertia were not completely accounted for by the CNS when generating circle-drawing movements: 1) speed will affect the circularity of figures, with faster movements associated with greater elongation into an oval shape, irrespective of workspace location for configurations with a similar angle between the forearm and upper arm. 2) The elongation of the circle at fast speeds will be in the direction of least inertia. The results showed that despite individual differences in the speed dependence of the relative motions at the elbow and the shoulder, the circularity decreased (distortion increased) with increased speed, and workspace location had no effect on circularity. We also found that the elongation of the circles at fast speeds was in a direction close to but significantly different from the direction of least inertia for three workspace locations and was in the direction of least inertia for the fourth location. We suggest that the elongation results from lack of full accounting by the CNS of the anisotropy of viscosity and inertia.
Ca2+ Ions Block and Permeate Serotonin 5-HT3 Receptor Channels in Rat Hippocampal Interneurons
Authors: van Hooft Johannes A. , Wadman Wytse J.
Published: May 2006

The serotonin 5-HT3receptor native to rat hippocampal CA1 stratum radiatum interneurons is blocked by Ca2+ ions in a dose- and voltage-dependent manner, which is reflected by a region of negative slope conductance in the I-V curve. The steep dependence on the extracellular Ca2+concentration suggests that the channel contains more than one binding site for Ca2+. A three barrier-two site model, based on Eyring rate theory, was used to describe the I-Vcurves. When extra- and intracellular K+ and Cs+ were substituted with Na+, the I-V curves were accurately fit by the model, unlike the I-V curves recorded under standard ionic conditions. This suggests that the K+ and Cs+ permeabilities are small compared with that of Na+. The distribution of the energy barriers and binding sites for Ca2+ and Na+ showed that the binding sites are located at approximately the 13′ and the –4′ position in the ion channel. The model predicts that at large hyperpolarized membrane potentials (more negative than −120 mV), the fractional Ca2+ current amounts to approximately 1% of the total ion current. However, at physiologically relevant membrane potentials, the fractional Ca2+ current is smaller (<0.1%) and the relative Ca2+permeability ( P Ca/ P Na) is estimated to be 0.10 at –60 mV.
Ca2+Clearance at Growth Cones Produced by Crayfish Motor Axons in an Explant Culture
Authors: Rumpal Nidhi , Lnenicka Gregory A.
Published: May 2006

Intracellular free Ca2+concentration ([Ca2+]i) plays an important role in the regulation of growth cone (GC) motility; however, the mechanisms responsible for clearing Ca2+from GCs have not been examined. We studied the Ca2+-clearance mechanisms in GCs produced by crayfish tonic and phasic motor axons by measuring the decay of [Ca2+]iafter a high [K+] depolarizing pulse using fura-2AM. Tonic motor axons regenerating in explant cultures develop GCs with more rapid Ca2+clearance than GCs from phasic axons. When Na/Ca exchange was blocked by replacing external Na+with N-methyl-d-glucamine (NMG), [Ca2+]idecay was delayed in both tonic and phasic GCs. Tonic GCs appear to have higher Na/Ca exchange activity than phasic ones since reversal of Na/Ca exchange by lowering external Na+caused a greater increase in [Ca2+]ifor tonic than phasic GCs. Application of the mitochondrial inhibitors, Antimycin A1 (1 μM) and CCCP (10 μM), demonstrated that mitochondrial Ca2+uptake/release was more prominent in phasic than tonic GCs. When both Na/Ca exchange and mitochondria were inhibited, the plasma membrane Ca2+ATPase was effective in extruding Ca2+from tonic, but not phasic GCs. We conclude that Na/Ca exchange plays a prominent role in extruding large Ca2+loads from both tonic and phasic GCs. High Na/Ca exchange activity in tonic GCs contributes to the rapid decay of [Ca2+]iin these GCs; low rates of Ca2+extrusion plus the release of Ca2+from mitochondria prolongs the decay of [Ca2+]iin the phasic GCs.
Windup of Flexion Reflexes in Chronic Human Spinal Cord Injury: A Marker for Neuronal Plateau Potentials?
Authors: Hornby T. G. , Rymer W. Z. , Benz E. N. , Schmit B. D.
Published: May 2006

The physiological basis of flexion spasms in individuals after spinal cord injury (SCI) may involve alterations in the properties of spinal neurons in the flexion reflex pathways. We hypothesize that these changes would be manifested as progressive increases in reflex response with repetitive stimulus application (i.e., “windup”) of the flexion reflexes. We investigated the windup of flexion reflex responses in 12 individuals with complete chronic SCI. Flexion reflexes were triggered using trains of electrical stimulation of plantar skin at variable intensities and inter-stimulus intervals. For threshold and suprathreshold stimulation, windup of both peak ankle and hip flexion torques and of integrated tibialis anterior electromyographic activity was observed consistently in all patients at inter-stimulus intervals ≤3 s. For subthreshold stimuli, facilitation of reflexes occurred only at intervals ≤1 s. Similarly, the latency of flexion reflexes decreased significantly at intervals ≤1 s. Patients that were receiving anti-spasticity medications (e.g., baclofen) had surprisingly larger windup of reflex responses than those who did not take such medications, although this difference may be related to differences of spasm frequency between the groups of subjects. The results indicate that the increase in spinal neuronal excitability following a train of electrical stimuli lasts for ≤3 s, similar to previous studies of nociceptive processing. Such long-lasting increases in flexion reflex responses suggest that cellular mechanisms such as plateau potentials in spinal motoneurons, interneurons, or both, may partially mediate spinal cord hyperexcitability in the absence of descending modulatory input.