bluuebunny/crossref_metadata_2025 huggingface dataset:
Hypocretin/Orexin Peptide Signaling in the Ascending Arousal System: Elevation of Intracellular Calcium in the Mouse Dorsal Raphe and Laterodorsal Tegmentum
Authors: Kohlmeier Kristi A. , Inoue Takafumi , Leonard Christopher S.
Published: March 2004

Dysfunction of the hypocretin/orexin (Hcrt/Orx) peptide system is closely linked to the sleep disorder narcolepsy, suggesting that it is also central to the normal regulation of sleep and wakefulness. Indeed, Hcrt/Orx peptides produce long-lasting excitation of arousal-related neurons, including those in the laterodorsal tegmentum (LDT) and the dorsal raphe (DR), although the mechanisms underlying these actions are not understood. Since Hcrt/Orx mobilizes intracellular calcium ([Ca2+]i) in cells transfected with orexin receptors and since receptor-mediated Ca2+transients are ubiquitous signaling mechanisms, we investigated whether Hcrt/Orx regulates [Ca2+]iin the LDT and DR. Changes in [Ca2+]iwere monitored by fluorescence changes of fura-2 AM loaded cells in young mouse brain slices. We found Hcrt/Orx (Orexin-A, 30-1,000 nM) evoked long-lasting increases in [Ca2+]iwith differing temporal profiles ranging from spiking to smooth plateaus. A fragment of Hcrt/Orx (16-33) failed to evoke changes in [Ca2+]iand changes were not blocked by TTX or ionotropic glutamate receptor antagonists, suggesting they resulted from specific activation of postsynaptic orexin receptors. Unlike orexin receptor–transfected cells, Hcrt/Orx-responses were not attenuated by depletion of Ca2+stores with cyclopiazonic acid (CPA; 3-30 μM), thapsigargin (3 μM), or ryanodine (20 μM), although store-depletion by either CPA or ryanodine blocked Ca2+mobilization by the metabotropic glutamate receptor agonist (±)-1-aminocyclopentane- trans-1,3-dicarboxylic acid ( trans-ACPD; 30 μM). In contrast, Hcrt/Orx responses were strongly attenuated by lowering extracellular Ca2+(∼20 μM) but were not inhibited by concentrations of KB-R7943 (10 μM) selective for blockade of sodium/calcium exchange. Nifedipine (10 μM), inhibited Hcrt/Orx responses but was more effective at abolishing spiking than plateau responses. Bay K 8644 (5-10 μM), an L-type calcium channel agonist, potentiated responses. Finally, responses were attenuated by inhibitors of protein kinase C (PKC) but not by inhibitors of adenylyl cyclase. Collectively, our findings indicate that Hcrt/Orx signaling in the reticular activating system involves elevation of [Ca2+]iby a PKC-involved influx of Ca2+across the plasma membrane, in part, via L-type calcium channels. Thus the physiological release of Hcrt/Orx may help regulate Ca2+-dependent processes such as gene expression and NO production in the LDT and DR in relation with behavioral state. Accordingly, the loss of Hcrt/Orx signaling in narcolepsy would be expected to disrupt calcium-dependent processes in these and other target structures.
Video-Rate Nonlinear Microscopy of Neuronal Membrane Dynamics With Genetically Encoded Probes
Authors: Roorda Robert D. , Hohl Tobias M. , Toledo-Crow Ricardo , Miesenböck Gero
Published: March 2004

Biological membranes decorated with suitable contrast agents give rise to nonlinear optical signals such as two-photon fluorescence and harmonic up-conversion when illuminated with ultra-short, high-intensity pulses of infrared laser light. Microscopic images based on these nonlinear contrasts were acquired at video or higher frame rates by scanning a focused illuminating spot rapidly across neural tissues. The scan engine relied on an acousto-optic deflector (AOD) to produce a fast horizontal raster and on corrective prisms to offset the AOD-induced dispersion of the ultra-short excitation light pulses in space and time. Two membrane-bound derivatives of the green fluorescent protein (GFP) were tested as nonlinear contrast agents. Synapto-pHluorin, a pH-sensitive GFP variant fused to a synaptic vesicle membrane protein, provided a time-resolved fluorescent read-out of neurotransmitter release at genetically specified synaptic terminals in the intact brain. Arrays of dually lipidated GFP molecules at the plasma membrane generated intense two-photon fluorescence but no detectable second-harmonic power. Comparison with second-harmonic generation by membranes stained with a synthetic styryl dye suggested that the genetically encoded chromophore arrangement lacked the orientational anisotropy and/or dipole density required for efficient coherent scattering of the incident optical field.
Tissue Resistance Changes and the Profile of Synchronized Neuronal Activity During Ictal Events in the Low-Calcium Model of Epilepsy
Authors: Fox John E. , Bikson Marom , Jefferys John G. R.
Published: March 2004

Population spikes vary in size during prolonged epileptic (“ictal”) discharges, indicating variations in neuronal synchronization. Here we investigate the role of changes in tissue electrical resistivity in this process. We used the rat hippocampal slice, low-Ca2+ model of epilepsy and measured changes in pyramidal layer extracellular resistance during the course of electrographic seizures. During each burst, population spike frequency decreased, whereas amplitude and spatial synchronization increased; after the main discharge, there could be brief secondary discharges that, in contrast with those in the primary discharge, started with high-amplitude population spikes. Mean resistivity increased from 1,231 Ω.cm immediately before the burst to a maximum of 1,507 Ω.cm during the burst. There was no significant increase during the first 0.5–1 s of the field burst, but resistance then increased (τ ∼ 5 s), reaching its peak at the end of the burst, and then decayed slowly (τ ∼ 10 s). In further experiments, we modulated the efficacy of electrical field effects by changing perfusate osmolarity. Reducing osmolarity by 40–70 mOsm increased preburst resistivity by 19%; it reduced minimum population spike frequency (×0.6–0.7) and increased both maximum population spike amplitude (×1.5–2.3) and spatial synchronization (×1.4–2.5, cross-correlation over 0.5 mm) during bursts. Increasing osmolarity by 20–40 mOsm had the opposite effects. These results suggest that, during each field burst, field effects between neurons gradually become more effective as cells swell, thereby modulating burst dynamics and facilitating the rapid synchronization of secondary discharges.
Primate Antisaccade. II. Supplementary Eye Field Neuronal Activity Predicts Correct Performance
Authors: Amador Nelly , Schlag-Rey Madeleine , Schlag John
Published: March 2004

Neuronal activities were recorded in the supplementary eye field (SEF) of 3 macaque monkeys trained to perform antisaccades pseudorandomly interleaved with prosaccades, as instructed by the shape of a central fixation point. The prosaccade goal was indicated by a peripheral stimulus flashed anywhere on the screen, whereas the antisaccade goal was an unmarked site diametrically opposite the flashed stimulus. The visual cue was given immediately after the instruction cue disappeared in the immediate-saccade task, or during the instruction period in the delayed-saccade task. The instruction cue offset was the saccade gosignal. Here we focus on 92 task-related neurons: visual, eye-movement, and instruction/fixation neurons. We found that 73% of SEF eye-movement–related neurons fired significantly more before anti-saccades than prosaccades. This finding was analyzed at 3 levels: population, single neuron, and individual trial. On individual antisaccade trials, 40 ms before saccade, the firing rate of eye-movement–related neurons was highly predictive of successful performance. A similar analysis of visual responses (40 ms astride the peak) gave less-coherent results. Fixation neurons, activated during the initial instruction period (i.e., after the instruction cue but before the stimulus) always fired more on antisaccade than on prosaccade trials. This trend, however, was statistically significant for only half of these neurons. We conclude that the SEF is critically involved in the production of antisaccades.
A Neural Network Model of Flexible Spatial Updating
Authors: White Robert L. , Snyder Lawrence H.
Published: March 2004

Neurons in many cortical areas involved in visuospatial processing represent remembered spatial information in retinotopic coordinates. During a gaze shift, the retinotopic representation of a target location that is fixed in the world (world-fixed reference frame) must be updated, whereas the representation of a target fixed relative to the center of gaze (gaze-fixed) must remain constant. To investigate how such computations might be performed, we trained a 3-layer recurrent neural network to store and update a spatial location based on a gaze perturbation signal, and to do so flexibly based on a contextual cue. The network produced an accurate readout of target position when cued to either reference frame, but was less precise when updating was performed. This output mimics the pattern of behavior seen in animals performing a similar task. We tested whether updating would preferentially use gaze position or gaze velocity signals, and found that the network strongly preferred velocity for updating world-fixed targets. Furthermore, we found that gaze position gain fields were not present when velocity signals were available for updating. These results have implications for how updating is performed in the brain.
Differential Contribution of Early Visual Areas to the Perceptual Process of Contour Processing
Authors: Schira Mark M. , Fahle Manfred , Donner Tobias H. , Kraft Antje , Brandt Stephan A.
Published: March 2004

We investigated contour processing and figure–ground detection within human retinotopic areas using event-related functional magnetic resonance imaging (fMRI) in 6 healthy and naïve subjects. A figure (6° side length) was created by a 2nd-order texture contour. An independent and demanding foveal letter-discrimination task prevented subjects from noticing this more peripheral contour stimulus. The contour subdivided our stimulus into a figure and a ground. Using localizers and retinotopic mapping stimuli we were able to subdivide each early visual area into 3 eccentricity regions corresponding to 1) the central figure, 2) the area along the contour, and 3) the background. In these subregions we investigated the hemodynamic responses to our stimuli and compared responses with or without the contour defining the figure. No contour-related blood oxygenation level–dependent modulation in early visual areas V1, V3, VP, and MT+ was found. Significant signal modulation in the contour subregions of V2v, V2d, V3a, and LO occurred. This activation pattern was different from comparable studies, which might be attributable to the letter-discrimination task reducing confounding attentional modulation. In V3a, but not in any other retinotopic area, signal modulation corresponding to the central figure could be detected. Such contextual modulation will be discussed in light of the recurrent processing hypothesis and the role of visual awareness.
Recursive Bayesian Decoding of Motor Cortical Signals by Particle Filtering
Authors: Brockwell A. E. , Rojas A. L. , Kass R. E.
Published: March 2004

The population vector (PV) algorithm and optimal linear estimation (OLE) have been used to reconstruct movement by combining signals from multiple neurons in the motor cortex. While these linear methods are effective, recursive Bayesian decoding schemes, which are nonlinear, can be more powerful when probability model assumptions are satisfied. We have implemented a recursive Bayesian algorithm for reconstructing hand movement from neurons in the motor cortex. The algorithm uses a recently developed numerical method known as “particle filtering” and follows the same general strategy as that used by Brown et al. to reconstruct the path of a foraging rat from hippocampal place cells. We investigated the method in a numerical simulation study in which neural firing rate was assumed to be positive, but otherwise a linear function of movement velocity, and preferred directions were not uniformly distributed. In terms of mean-squared error, the approach was ∼10 times more efficient than the PV algorithm and 5 times more efficient than OLE. Thus use of recursive Bayesian decoding can achieve the accuracy of the PV algorithm (or OLE) with ∼10 times (or 5 times) fewer neurons. The method was also used to reconstruct hand movement in an ellipse-drawing task from 258 cells in the ventral premotor cortex. Recursive Bayesian decoding was again more efficient than the PV and OLE methods, by factors of roughly seven and three, respectively.
Effects of Weakness on Symmetrical Bilateral Grip Force Exertion in Subjects With Hemiparesis
Authors: Bertrand Anne Martine , Mercier Catherine , Shun Priscilla Lam Wai , Bourbonnais Daniel , Desrosiers Johanne
Published: March 2004

It has been shown that, in a bilateral force-matching task, subjects presenting weakness in one limb produce a lower force in the weakened limb even though they subjectively perceive that they are exerting the same force. The aim of this study was to verify whether subjects with hemiparesis produced asymmetrical forces during a bilateral submaximal grip task and whether this asymmetry is related to weakness of the paretic limb. Fifteen subjects with hemiparesis and 15 healthy subjects were recruited. First, the maximal voluntary force was measured for each hand. Then, subjects were asked to exert equal forces with both hands simultaneously at three submaximal force levels using two dynamometers. In the bilateral task, the force ratios (paretic/nonparetic or nondominant/dominant) differed between groups. Severely weak hemiparetic subjects produced lower force ratios than mildly weak hemiparetic subjects and healthy subjects ( P < 0.000), whereas there was no difference between the force ratios produced by mildly weak hemiparetic subjects and those produced by healthy subjects. In subjects with hemiparesis, the force ratios in the bilateral task were related to the ratios of maximal voluntary forces ( R2= 0.39–0.66, P ≤ 0.013) and the presence of somatosensory impairment did not affect these relationships. These results suggest that the strategy used is to compare the intensity of the motor commands on both sides and then perform the force-matching task. The use of such a strategy by subjects who have had paresis for 1 year reflects a lack of adaptation to their weakness.
Anticipatory VOR Suppression Induced by Visual and Nonvisual Stimuli in Humans
Authors: Barnes G. R. , Paige G. D.
Published: March 2004

We compared the predictive behavior of smooth pursuit (SP) and suppression of the vestibuloocular reflex (VOR) in humans by examining anticipatory smooth eye movements, a phenomenon that arises after repeated presentations of sudden target movement preceded by an auditory warning cue. We investigated whether anticipatory smooth eye movements also occur prior to cued head motion, particularly when subjects expect interaction between the VOR and either real or imagined head-fixed targets. Subjects were presented with horizontal motion stimuli consisting of a visual target alone (SP), head motion in darkness (VOR), or head motion in the presence of a real or imagined head-fixed target (HFT and IHFT, respectively). Stimulus sequences were delivered as single cycles of a velocity sinusoid (frequency: 0.5 or 1.0 Hz) that were either cued (a sound cue 400 ms earlier) or noncued. For SP, anticipatory smooth eye movements developed over repeated trials in the cued, but not the noncued, condition. In the VOR condition, no such anticipatory eye movements were observed even when cued. In contrast, anticipatory responses were observed under cued, but not noncued, HFT and IHFT conditions, as for SP. Anticipatory HFT responses increased in proportion to the velocity of preceding stimuli. In general, anticipatory gaze responses were similar in cued SP, HFT, and IHFT conditions and were appropriate for expected target motion in space. Anticipatory responses may represent the output of a central mechanism for smooth-eye-movement generation that operates during predictive SP as well as VOR modulations that are linked with SP even in the absence of real visual targets.
Cue-Evoked Firing of Nucleus Accumbens Neurons Encodes Motivational Significance During a Discriminative Stimulus Task
Authors: Nicola Saleem M. , Yun Irene A. , Wakabayashi Ken T. , Fields Howard L.
Published: March 2004

The nucleus accumbens (NAc) has long been thought of as a limbic-motor interface. Despite behavioral and anatomical evidence in favor of this idea, little is known about how NAc neurons encode information about motivationally relevant environmental cues and use this information to affect motor action. We therefore investigated the firing of these neurons during the performance of a discriminative stimulus (DS) task using simultaneous multiple single-unit recordings in rats. In this task, two stimuli are randomly presented to the animal: a DS, which signals the availability of a sucrose reward contingent on an operant response, and a similar but nonrewarded stimulus (NS). Subpopulations of NAc neurons increased or decreased their firing in association with several distinct components of the task. In this paper, we investigate cue- and operant-responsive neurons. Neurons excited and inhibited by cues showed larger firing changes in response to the DS than the NS and larger changes when the animal made an operant response to the cue than when the animal failed to respond. Excitations during operant responding were not modulated by the information contained by the cue, whereas inhibitions during operant responding were somewhat larger if the operant response occurred during the DS and somewhat smaller if they occurred in the absence of a cue. These results are consistent with the hypothesis that the firing of subpopulations of NAc neurons encode both the predictive value of environmental stimuli and the specific motor behaviors required to respond to them.
Firing of Nucleus Accumbens Neurons During the Consummatory Phase of a Discriminative Stimulus Task Depends on Previous Reward Predictive Cues
Authors: Nicola Saleem M. , Yun Irene A. , Wakabayashi Ken T. , Fields Howard L.
Published: March 2004

The nucleus accumbens (NAc) plays an important role in both appetitive and consummatory behavior. To examine how NAc neurons encode information during reward consumption, we recorded the firing activity of rat NAc neurons during the performance of a discriminative stimulus task. In this task, the animal must make an operant response to an intermittently presented cue to obtain a sucrose reward delivered in a reward receptacle. Uncued entries to the receptacle were not rewarded. Both excitations and inhibitions during reward consumption were observed, but substantially more neurons were inhibited than excited. These excitations and inhibitions began when the animal entered the reward receptacle and ended when the animal exited the receptacle. Both excitations and inhibitions were much smaller or nonexistent when the animal made uncued entries into the reward receptacle. In one set of experiments, we randomly withheld the reward in some cued trials that would otherwise have been rewarded. Excitations and inhibitions were of similar magnitude whether or not the reward was delivered. This indicates that the sensory stimulus of reward does not drive these phasic responses; instead, the reward-associated responses may be driven by the conditioned stimuli associated with reward, or they may encode information about consummatory motor activity. Another population of NAc neurons was excited on exit from the reward receptacle. Many of these excitations persisted for tens of seconds after the receptacle exit and showed a significant inverse correlation with the rate of uncued operant responding. These findings are consistent with a contribution of NAc neurons to both reward consummatory and reward seeking behavior.
Dopamine Reduces Odor- and Elevated-K+-Induced Calcium Responses in Mouse Olfactory Receptor Neurons In Situ
Authors: Hegg Colleen C. , Lucero Mary T.
Published: March 2004

Although D2 dopamine receptors have been localized to olfactory receptor neurons (ORNs) and dopamine has been shown to modulate voltage-gated ion channels in ORNs, dopaminergic modulation of either odor responses or excitability in mammalian ORNs has not previously been demonstrated. We found that <50 μM dopamine reversibly suppresses odor-induced Ca2+transients in ORNs. Confocal laser imaging of 300-μm-thick slices of neonatal mouse olfactory epithelium loaded with the Ca2+-indicator dye fluo-4 AM revealed that dopaminergic suppression of odor responses could be blocked by the D2 dopamine receptor antagonist sulpiride (<500 μM). The dopamine-induced suppression of odor responses was completely reversed by 100 μM nifedipine, suggesting that D2 receptor activation leads to an inhibition of L-type Ca2+channels in ORNs. In addition, dopamine reversibly reduced ORN excitability as evidenced by reduced amplitude and frequency of Ca2+transients in response to elevated K+, which activates voltage-gated Ca2+channels in ORNs. As with the suppression of odor responses, the effects of dopamine on ORN excitability were blocked by the D2 dopamine receptor antagonist sulpiride (<500 μM). The observation of dopaminergic modulation of odor-induced Ca2+transients in ORNs adds to the growing body of work showing that olfactory receptor neurons can be modulated at the periphery. Dopamine concentrations in nasal mucus increase in response to noxious stimuli, and thus D2 receptor-mediated suppression of voltage-gated Ca2+channels may be a novel neuroprotective mechanism for ORNs.
Modulation of Nav1.7 and Nav1.8 Peripheral Nerve Sodium Channels by Protein Kinase A and Protein Kinase C
Authors: Vijayaragavan Kausalia , Boutjdir Mohamed , Chahine Mohamed
Published: March 2004

Voltage-gated Na+channels (VGSC) are transmembrane proteins that are essential for the initiation and propagation of action potentials in neuronal excitability. Because neurons express a mixture of Na+channel isoforms and protein kinase C (PKC) isozymes, the nature of which channel is being regulated by which PKC isozyme is not known. We showed that DRG VGSC Nav1.7 (TTX-sensitive) and Nav1.8 (TTX-resistant), expressed in Xenopus oocytes were differentially regulated by protein kinase A (PKA) and PKC isozymes using the two-electrode voltage-clamp method. PKA activation resulted in a dose-dependent potentiation of Nav1.8 currents and an attenuation of Nav1.7 currents. PKA-induced increases (Nav1.8) and decreases (Nav1.7) in peak currents were not associated with shifts in voltage-dependent activation or inactivation. The PKA-mediated increase in Nav1.8 current amplitude was prevented by chloroquine, suggesting that cell trafficking may contribute to the changes in Nav1.8 current amplitudes. A dose-dependent decrease in Nav1.7 and Nav1.8 currents was observed with the PKC activators phorbol 12-myristate, 13-acetate (PMA) and phorbol 12,13-dibutyrate. PMA induced shifts in the steady-state activation of Nav1.7 and Nav1.8 channels by 6.5 and 14 mV, respectively, in the depolarizing direction. The role of individual PKC isozymes in the regulation of Nav1.7 and Nav1.8 was determined using PKC-isozyme-specific peptide activators and inhibitors. The decrease in the Nav1.8 peak current induced by PMA was prevented by a specific ϵPKC isozyme peptide antagonist, whereas the PMA effect on Nav1.7 was prevented by ϵPKC and βIIPKC peptide inhibitors. The data showed that Nav1.7 and Nav1.8 were differentially modulated by PKA and PKC. This is the first report demonstrating a functional role for ϵPKC and βIIPKC in the regulation of Nav1.7 and Nav1.8 Na+channels. Identification of the particular PKC isozymes(s) that mediate the regulation of Na+channels is essential for understanding the molecular mechanism involved in neuronal ion channel regulation in normal and pathological conditions.
Effect of Rhythmic Arm Movement on Reflexes in the Legs: Modulation of Soleus H-Reflexes and Somatosensory Conditioning
Authors: Frigon Alain , Collins David F. , Zehr E. Paul
Published: March 2004

During locomotor tasks such as walking, running, and swimming, the arms move rhythmically with the legs. It has been suggested that connections between the cervical and lumbosacral spinal cord may mediate some of this interlimb coordination. However, it is unclear how these interlimb pathways modulate reflex excitability during movement. We hypothesized that rhythmic arm movement would alter the gain of reflex pathways in the stationary leg. Soleus H-reflexes recorded during arm cycling were compared with those recorded at similar positions with the arms stationary. Nerve stimulation was delivered with the right arm at approximately 70° shoulder flexion or 10° shoulder extension. H-reflexes were evoked alone (unconditioned) or with sural or common peroneal nerve (CP) conditioning to decrease or increase soleus IA presynaptic inhibition, respectively. Both conditioning stimuli were also delivered with no H-reflex stimulation. H-reflex amplitudes were compared at similar M-wave amplitudes and activation levels of the soleus. Arm cycling significantly reduced ( P < 0.05) unconditioned soleus H-reflexes at shoulder flexion by 21.7% and at shoulder extension by 8.8% compared with static controls. The results demonstrate a task-dependent modulation of soleus H-reflexes between arm cycling and stationary trials. Sural nerve stimulation facilitated H-reflexes at shoulder extension but not at shoulder flexion during static and cycling trials. CP nerve stimulation significantly reduced H-reflex amplitude in all conditions. Reflexes in soleus when sural and CP nerve stimulation were delivered alone, were not different between cycling and static trials; thus the task-dependent change in H reflex amplitude was not due to changes in motoneuron excitability. Therefore modulation occurred at a pre-motoneuronal level, probably by presynaptic inhibition of the IA afferent volley. Results indicate that neural networks coupling the cervical and lumbosacral spinal cord in humans are activated during rhythmic arm movement. It is proposed that activation of these networks may assist in reflex linkages between the arms and legs during locomotor tasks.
Organization of the Intermediate Gray Layer of the Superior Colliculus. I. Intrinsic Vertical Connections
Authors: Helms Matthew C. , Özen Gülden , Hall William C.
Published: March 2004

A pathway from the superficial visual layers to the intermediate premotor layers of the superior colliculus has been proposed to mediate visually guided orienting movements. In these experiments, we combined photostimulation using “caged” glutamate with in vitro whole cell patch-clamp recording to demonstrate this pathway in the rat. Photostimulation in the superficial gray and optic layers (SGS and SO, respectively) evoked synaptic responses in intermediate gray layer (SGI) cells. The responses comprised individual excitatory postsynaptic currents (EPSCs) or EPSC clusters. Blockade of these EPSCs by TTX confirmed that they were synaptically mediated. Stimulation within a column (∼500 μm diam) extending superficially from the recorded cell evoked the largest and most reliable responses, but off-axis stimuli were effective as well. The EPSCs could be evoked by stimuli 1,000 μm off-axis from the postsynaptic neuron. The dimensions of this wider region (∼2 mm diam) corresponded to those of the dendrites of superficial layer wide-field neurons. SGI neurons differed in their input from SGS and SO; neurons in the middle of the intermediate layer (SGIb) were less likely to respond to visual layer photostimulation than were those in sublayers just above and below them. However, focal stimulation within SGIa did evoke responses within SGIb, indicating that SGIb neurons may receive input from the visual layers indirectly. These results demonstrate a columnar pathway that may mediate visually guided orienting movements, but the results also reveal spatial attributes of the pathway which imply that it also plays a more complex role in visuomotor integration.
Dietary Prenatal Choline Supplementation Alters Postnatal Hippocampal Structure and Function
Authors: Li Qiang , Guo-Ross Shirley , Lewis Darrell V. , Turner Dennis , White Aaron M. , Wilson Wilkie A. , Swartzwelder H. Scott
Published: March 2004

Choline, a compound present in many foods, has recently been classified as an essential nutrient for humans. Studies with animal models indicate that the availability of choline during the prenatal period influences neural and cognitive development. Specifically, prenatal choline supplementation has been shown to enhance working memory and hippocampal long-term potentiation (LTP) in adult offspring. However, the cellular mechanisms underlying these effects remain unclear. Here we report that choline supplementation, during a 6-day gestational period, results in greater excitatory responsiveness, reduced slow afterhyperpolarizations (sAHPs), enhanced afterdepolarizing potentials (ADPs), larger somata, and greater basal dendritic arborization among hippocampal CA1 pyramidal cells studied postnatally in juvenile rats (20–25 days of age). These data indicate that dietary supplementation with a single nutrient, choline, during a brief, critical period of prenatal development, alters the structure and function of hippocampal pyramidal cells.
Hypothalamus–Brain Stem Circuitry Responsible for Vagal Efferent Signaling to the Pancreas Evoked By Hypoglycemia in Rat
Authors: Wu Xiaoyin , Gao Jun , Yan Jin , Owyang Chung , Li Ying
Published: March 2004

Circulating glucose levels significantly affect vagal neural activity, which is important in the regulation of pancreatic functions. Little is known about the mechanisms involved. This study investigates the neural pathways responsible for hypoglycemia-induced vagal efferent signaling to the pancreas and identifies the neurotransmitters involved. Vagal pancreatic efferent nerve activities were recorded in anesthetized rats. Insulin-induced hypoglycemia, a decrease of blood glucose levels from 114 ± 5 to 74 ± 6 mg dl–1, stimulated an increase in pancreatic efferent nerve firing from a basal rate of 1.1 ± 0.3 to 19 ± 3 impulses 30 s–1. In contrast, vagal primary afferent neuronal discharges recorded in the nodose ganglia were unaltered by systemic hypoglycemia. Vagal afferent rootlet section plus splanchnicotomy had no effect on hypoglycemia-induced vagal efferent firing, suggesting a central site of action. Decerebration reduced the increase in nerve firing stimulated by hypoglycemia from 21 ± 4 to 9.6 ± 2 impulses 30 s–1. Chemical ablation of the lateral hypothalamic area, but not the arcuate nucleus, inhibited pancreatic nerve firing evoked by hypoglycemia. Microinjection of the orexin-A receptor antagonist SB-334867 into the dorsal motor nucleus of the vagus (DMV) inhibited pancreatic nerve firing evoked by insulin-induced hypoglycemia by 56%. In contrast, injection of orexin-A (20 pmol) into the DMV elicited a 30-fold increase in pancreatic nerve firing. We concluded that systemic hypoglycemia stimulates pancreatic efferent nerve firing through a central mechanism. Full expression of pancreatic nerve activities during hypoglycemia requires both the forebrain and the brain stem. In addition to activating neurons in the brain stem, central neuroglucopenia activates subpopulations of neurons in the lateral hypothalamic area that contain orexin. The released orexin acts on DMV neurons to stimulate pancreatic efferent nerve activities and thus regulate pancreatic functions.
Reduced Muscle Selectivity During Individuated Finger Movements in Humans After Damage to the Motor Cortex or Corticospinal Tract
Authors: Lang Catherine E. , Schieber Marc H.
Published: March 2004

We investigated how damage to the motor cortex or corticospinal tract affects the selective activation of finger muscles in humans. We hypothesized that damage relatively restricted to the motor cortex or corticospinal tract would result in unselective muscle activations during an individuated finger movement task. People with pure motor hemiparesis attributed to ischemic cerebrovascular accident were tested. Pure motor hemiparetic and control subjects were studied making flexion/extension and then abduction/adduction finger movements. During the abduction/adduction movements, we recorded muscle activity from 3 intrinsic finger muscles: the abductor pollicis brevis, the first dorsal interosseus, and the abductor digit quinti. Each of these muscles acts as an agonist for only one of the abduction/adduction movements and might therefore be expected to be active in a highly selective manner. Motor cortex or corticospinal tract damage in people with pure motor hemiparesis reduced the selectivity of finger muscle activation during individuated abduction/adduction finger movements, resulting in reduced independence of these movements. Abduction/adduction movements showed a nonsignificant trend toward being less independent than flexion/extension movements in the affected hands of hemiparetic subjects. These changes in the selectivity of muscle activation and the consequent decrease in individuation of movement were correlated with decreased hand function. Our findings imply that, in humans, spared cerebral motor areas and descending pathways that remain might activate finger muscles, but cannot fully compensate for the highly selective control provided by the primary motor cortex and the crossed corticospinal system.
Tuning of a Basic Coordination Pattern Constructs Straight-Ahead and Curved Walking in Humans
Authors: Courtine Grégoire , Schieppati Marco
Published: March 2004

We tested the hypothesis that common principles govern the production of the locomotor patterns for both straight-ahead and curved walking. Whole body movement recordings showed that continuous curved walking implies substantial, limb-specific changes in numerous gait descriptors. Principal component analysis (PCA) was used to uncover the spatiotemporal structure of coordination among lower limb segments. PCA revealed that the same kinematic law accounted for the coordination among lower limb segments during both straight-ahead and curved walking, in both the frontal and sagittal planes: turn-related changes in the complex behavior of the inner and outer limbs were captured in limb-specific adaptive tuning of coordination patterns. PCA was also performed on a data set including all elevation angles of limb segments and trunk, thus encompassing 13 degrees of freedom. The results showed that both straight-ahead and curved walking were low dimensional, given that 3 principal components accounted for more than 90% of data variance. Furthermore, the time course of the principal components was unchanged by curved walking, thereby indicating invariant coordination patterns among all body segments during straight-ahead and curved walking. Nevertheless, limb- and turn-dependent tuning of the coordination patterns encoded the adaptations of the limb kinematics to the actual direction of the walking body. Absence of vision had no significant effect on the intersegmental coordination during either straight-ahead or curved walking. Our findings indicate that kinematic laws, probably emerging from the interaction of spinal neural networks and mechanical oscillators, subserve the production of both straight-ahead and curved walking. During locomotion, the descending command tunes basic spinal networks so as to produce the changes in amplitude and phase relationships of the spinal output, sufficient to achieve the body turn.
Lack of Monosynaptic Corticomotoneuronal EPSPs in Rats: Disynaptic EPSPs Mediated Via Reticulospinal Neurons and Polysynaptic EPSPs Via Segmental Interneurons
Authors: Alstermark B. , Ogawa J. , Isa T.
Published: March 2004

In the rat, some findings have been taken to suggest the existence of monosynaptic corticomotoneuronal (CM) connections. Because this connection is believed to be largely responsible for the ability to make independent digit movements in primates and man, it has been inferred that the monosynaptic CM connection in the rat is likewise important for skilled prehension. Comparison of intra- and extracellular recordings from forelimb motoneurons in anesthetized rats, revealed no monosynaptic CM excitatory postsynaptic potentials (EPSPs). The fastest descending excitation in forelimb motoneurons was disynaptically mediated via a corticoreticulospinal pathway and slowly conducted excitation via corticospinal fibers and segmental interneurons. The findings stress the importance of di- and trisynaptic excitatory corticofugal pathways to forelimb motoneurons in the control of skilful digit movements.
Statistical Method for Detection of Phase-Locking Episodes in Neural Oscillations
Authors: Hurtado Jose M. , Rubchinsky Leonid L. , Sigvardt Karen A.
Published: March 2004

In many networks of oscillatory neurons, synaptic interactions can promote the entrainment of units into phase-coupled groups. The detection of synchrony in experimental data, especially if the data consist of single-trial runs, can be problematic when, for example, phase entrainment is of short duration, buried in noise, or masked by amplitude fluctuations that are uncorrelated among the oscillating units. In the present study, we tackle the problem of detecting neural interactions from pairs of oscillatory signals in a narrow frequency band. To avoid the interference of amplitude fluctuations in the detection of synchrony, we extract a phase variable from the data and utilize statistical indices to measure phase locking. We use three different phase-locking indices based on coherence, entropy, and mutual information between the phase variables. Phase-locking indices are calculated over time using sliding analysis windows. By varying the duration of the analysis windows, we were able to inspect the data at different levels of temporal resolution and statistical reliability. The statistical significance of high index values was evaluated using four different surrogate data methods. We determined phase-locking indices using alternative methods for generating surrogate data and found that results are sensitive to the particular method selected. Surrogate methods that preserve the temporal structure of the individual phase time series decrease substantially the number of false positives when tested on a pair of independent signals.
Processing Deficits in Primary Visual Cortex of Amblyopic Cats
Authors: Schmidt Kerstin E. , Singer Wolf , Galuske Ralf A. W.
Published: March 2004

Early esotropic squint frequently results in permanent visual deficits in one eye, referred to as strabismic amblyopia. The neurophysiological substrate corresponding to these deficits is still a matter of investigation. Electrophysiological evidence is available for disturbed neuronal interactions in both V1 and higher cortical areas. In this study, we investigated the modulation of responses in cat V1 to gratings at different orientations and spatial frequencies (SFs; 0.1–2.0 cycles/°) with optical imaging of intrinsic signals. Maps evoked by both eyes were well modulated at most spatial frequencies. The layout of the maps resembled that of normal cats, and iso-orientation domains tended to cross adjacent ocular dominance borders preferentially at right angles. Visually evoked potentials (VEPs) were recorded at SFs ranging from 0.1 to 3.5 cycles/° and revealed a consistently weaker eye for the majority of squinting cats. At each SF, interocular differences in VEP amplitudes corresponded well with differences in orientation response and selectivity in the maps. At 0.7–1.3 cycles/°, population orientation selectivity was significantly lower for the weaker eye in cats with VEP differences compared with those with no VEP amplitude differences. In addition, the cutoff SF, above which gratings no longer induced orientation maps, was lower for the weaker eye (≥1.0 cycles/°). These data reveal a close correlation between the loss of visual acuity in amblyopia as assessed by VEPs and the modulation of neuronal activation as seen by optical imaging of intrinsic signals. Furthermore, the results indicate that amblyopia is associated with altered intracortical processing already in V1.
Nicotine Inhibits Voltage-Dependent Sodium Channels and Sensitizes Vanilloid Receptors
Authors: Liu L. , Zhu W. , Zhang Z.-S. , Yang T. , Grant A. , Oxford G. , Simon S. A.
Published: March 2004

Nicotine is an alkaloid that is used by large numbers of people. When taken into the body, it produces a myriad of physiological actions that occur primarily through the activation of neuronal nicotinic acetylcholine receptors (nAChRs). We have explored its ability to modulate TRPV1 receptors and voltage-gated sodium channels. The reason for investigating nicotine's effect on sodium channels is to obtain a better understanding of its anti-nociceptive properties. The reasons for investigating its effects on capsaicin-activated TRPV1 channels are to understand how it may modulate this channel that is involved in pain, inflammation, and gustatory physiology. Whole cell patch-clamp recordings from rat trigeminal ganglion (TG) nociceptors revealed that nicotine exhibited anesthetic properties by decreasing the number of evoked action potentials and by inhibiting tetrodotoxin-resistant sodium currents. This anesthetic property can be produced without the necessity of activating nAChRs. Nicotine also modulates TRPV1 receptors inducing a several-fold increase in capsaicin-activated currents in both TG neurons and in cells with heterologously expressed TRPV1 receptors. This sensitizing effect does not require the activation of nAChRs. Nicotine did not alter the threshold temperature (∼41°C) of heat-activated currents in TG neurons that were attributed to arise from the activation of TRPV1 receptors. In this regard, its effect on TRPV1 receptors differs from those of ethanol that has been shown to increase the capsaicin-activated current but decrease the threshold temperature. These studies document several new effects of nicotine on channels involved in nociception and indicate how they may impact physiological processes involving pain and gustation.
Spatiotemporal Evolution of Excitation and Inhibition in the Rat Barrel Cortex Investigated With Multielectrode Arrays
Authors: Wirth Corina , Lüscher Hans-R.
Published: March 2004

We investigated the spatiotemporal evolution of activity in the rat barrel cortex using multielectrode arrays (MEAs). In acute brain slices, field potentials were recorded simultaneously from 60 electrodes with high spatial and temporal resolution. This new technique allowed us to map functionally discrete barrels and to observe the interplay between the excitatory and inhibitory network. The local field potentials (LFPs) were elicited by focal electrical stimulation in layer 4 (L4). Excitation recorded in a single barrel was first confined to the stimulated barrel and subsequently spread in a columnar manner to layer 2/3 (L2/3). This excitation in L4 and lower L2/3 was followed by inhibition curtailing excitation to a short period lasting only ∼2 ms. In the uppermost layer, a long-lasting (∼10 ms), laterally spreading band of excitation remained active. Blockade of GABAA-receptors resulted in a long-lasting and diffuse activation of L4 and lower L2/3 and abolition of activation of the upper L2/3. Thus inhibition not only shaped the spatial-temporal map of excitation in L4 and lower L2/3 but also resulted indirectly in an excitatory action in the superficial layers. Stimulation in L6 revealed a feedforward inhibition to L4 and subsequently an excitatory L6-L4-L6 loop. The complex interplay between excitation and inhibition opens two spatial windows of excitation in the infra- and supragranular layers. They may prepare the L5 pyramidal neuron for associating top-down input from other cortical regions with bottom-up input from the whisker pad to generate behaviorally relevant output.
Sensorimotor Integration in the Precentral Gyrus: Polysensory Neurons and Defensive Movements
Authors: Cooke Dylan F. , Graziano Michael S. A.
Published: March 2004

The precentral gyrus of monkeys contains a polysensory zone in which the neurons respond to tactile, visual, and sometimes auditory stimuli. The tactile receptive fields of the polysensory neurons are usually on the face, arms, or upper torso, and the visual and auditory receptive fields are usually confined to the space near the tactile receptive fields, within about 30 cm of the body. Electrical stimulation of this polysensory zone, even in anesthetized animals, evokes a specific set of movements. The movements resemble those typically used to defend the body from objects that are near, approaching, or touching the skin. In the present study, to determine whether the stimulation-evoked movements represent a normal set of defensive movements, we tested whether they include a distinctive, nonsaccadic, centering movement of the eyes that occurs during defensive reactions. We report that this centering movement of the eyes is evoked by stimulation of sites in the polysensory zone. We also recorded the activity of neurons in the polysensory zone while the monkey made defensive reactions to an air puff on the face. The neurons became active during the defensive movement, and the magnitude of this activity was correlated with the magnitude of the defensive reaction. These results support the hypothesis that the polysensory zone in the precentral gyrus contributes to the control of defensive movements. More generally, the results support the view that the precentral gyrus can control movement at the level of complex sensorimotor tasks.
Neuronal Activity in Motor Cortical Areas Reflects the Sequential Context of Movement
Authors: Ben-Shaul Yoram , Drori Rotem , Asher Itay , Stark Eran , Nadasdy Zoltan , Abeles Moshe
Published: March 2004

Natural actions can be described as chains of simple elements, whereas individual motion elements are readily concatenated to generate countless movement sequences. Sequence-specific neurons have been described extensively, suggesting that the motor system may implement temporally complex motions by using such neurons to recruit lower-level movement neurons modularly. Here, we set out to investigate whether activity of movement-related neurons is independent of the sequential context of the motion. Two monkeys were trained to perform linear arm movements either individually or as components of double-segment motions. However, comparison of neuronal activity between these conditions is delicate because subtle kinematic variations generally occur within different contexts. We therefore used extensive procedures to identify the contribution of variations in motor execution to differences in neuronal activity. Yet, even after application of these procedures we find that neuronal activity in the motor cortex (PMd and M1) associated with a given motion segment differs between the two contexts. These differences appear during preparation and become even more prominent during motion execution. Interestingly, despite context-related differences on the single-neuron level, the population as a whole still allows a reliable readout of movement direction regardless of the sequential context. Thus the direction of a movement and the sequential context in which it is embedded may be simultaneously and reliably encoded by neurons in the motor cortex.