bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of Hyperbaric Oxygen Treatment on Nitric Oxide and Oxygen Free Radicals in Rat Brain
Authors: Elayan Ikram M. , Axley Milton J. , Prasad Paruchuri V. , Ahlers Stephen T. , Auker Charles R.
Published: December 2017

Oxygen (O2) at high pressures acts as a neurotoxic agent leading to convulsions. The mechanism of this neurotoxicity is not known; however, oxygen free radicals and nitric oxide (NO) have been suggested as contributors. This study was designed to follow the formation of oxygen free radicals and NO in the rat brain under hyperbaric oxygen (HBO) conditions using in vivo microdialysis. Male Sprague-Dawley rats were exposed to 100% O2at a pressure of 3 atm absolute for 2 h. The formation of 2,3-dihydroxybenzoic acid (2,3-DHBA) as a result of perfusing sodium salicylate was followed as an indicator for the formation of hydroxyl radicals. 2,3-DHBA levels in hippocampal and striatal dialysates of animals exposed to HBO conditions were not significantly different from controls. However, rats treated under the same conditions showed a six- and fourfold increase in nitrite/nitrate, break down products of NO decomposition, in hippocampal and striatal dialysates, respectively. This increase was completely blocked by the nitric oxide synthase (NOS) inhibitor l-nitroarginine methyl ester (l-NAME). Using neuronal NOS, we determined the NOS O2Kmto be 158 ± 28 (SD) mmHg, a value which suggests that production of NO by NOS would increase approximately four- to fivefold under hyperbaric O2conditions, closely matching the measured increase in vivo. The increase in NO levels may be partially responsible for some of the detrimental effects of HBO conditions.
Modulation of H Reflex of Pretibial Muscles and Reciprocal Ia Inhibition of Soleus Muscle During Voluntary Teeth Clenching in Humans
Authors: Takada Yoshiyuki , Miyahara Takao , Tanaka Tatsuya , Ohyama Takashi , Nakamura Yoshio
Published: December 2017

A previous study has demonstrated that the soleus H reflex is facilitated in association with voluntary teeth clenching in proportion with biting force in humans. The present study tried to elucidate the functional significance of this facilitation of the soleus H reflex, by examining 1) whether the facilitation of the H reflex is reciprocal or nonreciprocal between the ankle extensors and flexors and 2) whether the reciprocal Ia inhibition of crural muscles is facilitated or depressed in association with voluntary teeth clenching. The H reflex of the pretibial muscles was evoked by stimulation of the common peroneal nerve in seven healthy subjects with no oral dysfunction. The pretibial H reflex was facilitated in association with voluntary teeth clenching in a force-dependent manner. The facilitation started preceding the onset of electromyographic activity of the masseter muscle. Stimulation of the common peroneal nerve at low intensities subthreshold for evoking the M wave of the pretibial muscles inhibited the soleus H reflex after a short latency corresponding with a disynaptic inhibition, indicating that the reciprocal Ia inhibition was depressed in association with voluntary teeth clenching. Thus, the present study has shown that voluntary teeth clenching evokes a nonreciprocal facilitation of ankle extensor and flexor muscles and attenuated reciprocal Ia inhibition from the pretibial muscles to the soleus muscle. It is concluded that voluntary teeth clenching contributes to improve stability of stance rather than smoothness of movements.
Protein Kinase A Mediates the Modulation of the Slow Ca2+-Dependent K+Current,IsAHP, by the Neuropeptides CRF, VIP, and CGRP in Hippocampal Pyramidal Neurons
Authors: Haug Trude , Storm Johan F.
Published: December 2017

We have studied modulation of the slow Ca2+-activated K+current ( IsAHP) in CA1 hippocampal pyramidal neurons by three peptide transmitters: corticotropin releasing factor (CRF, also called corticotropin releasing hormone, CRH), vasoactive intestinal peptide (VIP), and calcitonin gene–related peptide (CGRP). These peptides are known to be expressed in interneurons. Using whole cell voltage clamp in hippocampal slices from young rats, in the presence of tetrodotoxin (TTX, 0.5 μM) and tetraethylammonium (TEA, 5 mM), IsAHPwas measured after a brief depolarizing voltage step eliciting inward Ca2+current. Each of the peptides CRF (100–250 nM), VIP (400 nM), and CGRP (1 μM) significantly reduced the amplitude of IsAHP. Thus the IsAHPamplitude was reduced to 22% by 100 nM CRF, to 17% by 250 nM CRF, to 22% by 400 nM VIP, and to 40% by 1 μM CGRP. We found no consistent concomitant changes in the Ca2+current or in the time course of IsAHPfor any of the three peptides, suggesting that the suppression of IsAHPwas not secondary to a general suppression of Ca2+channel activity. Because each of these peptides is known to activate the cyclic AMP (cAMP) cascade in various cell types, and IsAHPis known to be suppressed by cAMP via the cAMP-dependent protein kinase (PKA), we tested whether the effects on IsAHPby CRF, VIP, and CGRP are mediated by PKA. Intracellular application of the PKA-inhibitor Rp-cAMPS significantly reduced the suppression of IsAHPby CRF, VIP, and CGRP. Thus with 1 mM Rp-cAMPS in the recording pipette, the average suppression of IsAHPwas reduced from 78 to 26% for 100 nM CRF, from 83 to 32% for 250 nM CRF, from 78 to 30% for 400 nM VIP, and from 60 to 7% for 1 μM CGRP. We conclude that CRF, VIP, and CGRP suppress the slow Ca2+-activated K+current, IsAHP, in CA1 hippocampal pyramidal neurons by activating the cAMP-dependent protein kinase, PKA. Together with the monoamine transmitters norepinephrine, serotonin, histamine, and dopamine, these peptide transmitters all converge on the cAMP cascade modulating IsAHP.
Differences in Control of Limb Dynamics During Dominant and Nondominant Arm Reaching
Authors: Sainburg R. L. , Kalakanis D.
Published: December 2017

This study compares the coordination patterns employed for the left and right arms during rapid targeted reaching movements. Six right-handed subjects reached to each of three targets, designed to elicit progressively greater amplitude interaction torques at the elbow joint. All targets required the same elbow excursion (20°), but different shoulder excursions (5, 10, and 15°, respectively). Movements were restricted to the shoulder and elbow and supported on a horizontal plane by a frictionless air-jet system. Subjects received visual feedback only of the final hand position with respect to the start and target locations. For motivation, points were awarded based on final position accuracy for movements completed within an interval of 400–600 ms. For all subjects, the right and left hands showed a similar time course of improvement in final position accuracy over repeated trials. After task adaptation, final position accuracy was similar for both hands; however, the hand trajectories and joint coordination patterns during the movements were systematically different. Right hand paths showed medial to lateral curvatures that were consistent in magnitude for all target directions, whereas the left hand paths had lateral to medial curvatures that increased in magnitude across the three target directions. Inverse dynamic analysis revealed substantial differences in the coordination of muscle and intersegmental torques for the left and right arms. Although left elbow muscle torque contributed largely to elbow acceleration, right arm coordination was characterized by a proximal control strategy, in which movement of both joints was primarily driven by the effects of shoulder muscles. In addition, right hand path direction changes were independent of elbow interaction torque impulse, indicating skillful coordination of muscle actions with intersegmental dynamics. In contrast, left hand path direction changes varied directly with elbow interaction torque impulse. These findings strongly suggest that distinct neural control mechanisms are employed for dominant and non dominant arm movements. However, whether interlimb differences in neural strategies are a consequence of asymmetric use of the two arms, or vice versa, is not yet understood. The implications for neural organization of voluntary movement control are discussed.
Input of Anterior and Posterior Semicircular Canal Interneurons Encoding Head-Velocity to the Dorsal Y Group of the Vestibular Nuclei
Authors: Blazquez Pablo , Partsalis Agis , Gerrits Nicolaas M. , Highstein Stephen M.
Published: December 2017

Neurons in the Y group of the vestibular nuclei are activated disynaptically from the ipsilateral VIIIth nerve and polysynaptically from the contralateral nerve. The ipsilateral anterior and posterior semicircular canals project to the Y group via interneurons in the vestibular nuclei. Candidate interneurons located in the rostrolateral corner of the superior (SVN) and in the caudal medial (MVN) vestibular nuclei were retrogradely labeled by the iontophoretic injection of biocytin into the Y group. The physiology of these interneurons named Y-group projecting neurons (YPNs) was studied in the SVN. SVN-YPNs were activated antidromically by electric pulse stimulation in the Y group. The properties of SVN-YPNs are distinct from those of SVN flocculus projecting neurons (FPNs). Namely, YPNs have a lower resting rate than FPNs, have more irregular interspike intervals, show a different phase and gain during the vestibuloocular reflex, and are located differentially within the SVN. After the injection of biocytin into the Y group, the locations of Purkinje cells that project to the Y group were confined to the vertical zones of the flocculus and ventral paraflocculus. However, mossy fibers originating in the Y group terminate in both the vertical and horizontal zones of the flocculus and ventral paraflocculus as well as in the ipsilateral nodulus.
Equilibrium Potential of GABAA Current and Implications for Rebound Burst Firing in Rat Subthalamic Neurons In Vitro
Authors: Bevan Mark D. , Wilson Charles J. , Bolam J. Paul , Magill Peter J.
Published: December 2017

Reciprocally connected glutamatergic subthalamic and GABAergic globus pallidus neurons have recently been proposed to act as a generator of low-frequency oscillatory activity in Parkinson's disease. To determine whether GABAA receptor-mediated synaptic potentials could theoretically generate rebound burst firing in subthalamic neurons, a feature that is central to the proposed oscillatory mechanism, we determined the equilibrium potential of GABAA current ( E GABAA ) and the degree of hyperpolarization required for rebound firing using perforated-patch recording. In the majority of neurons that fired rebounds, E GABAA was equal to or more hyperpolarized than the hyperpolarization required for rebound burst firing. These data suggest that synchronous activity of pallidal inputs could underlie rhythmic bursting activity of subthalamic neurons in Parkinson's disease.
Vestibular Signals in the Parasolitary Nucleus
Authors: Barmack N. H. , Yakhnitsa V.
Published: December 2017

Vestibular primary afferents project to secondary vestibular neurons located in the vestibular complex. Vestibular primary afferents also project to the uvula-nodulus of the cerebellum where they terminate on granule cells. In this report we describe the physiological properties of neurons in a “new” vestibular nucleus, the parasolitary nucleus (Psol). This nucleus consists of 2,300 GABAergic neurons that project onto the ipsilateral inferior olive (β-nucleus and dorsomedial cell column) as well as the nucleus reticularis gigantocellularis. These olivary neurons are the exclusive source of vestibularly modulated climbing fiber inputs to the cerebellum. We recorded the activity of Psol neurons during natural vestibular stimulation in anesthetized rabbits. The rabbits were placed in a three-axis rate table at the center of a large sphere, permitting vestibular and optokinetic stimulation. We recorded from 74 neurons in the Psol and from 23 neurons in the regions bordering Psol. The activity of 72/74 Psol neurons and 4/23 non-Psol neurons was modulated by vestibular stimulation in either the pitch or roll planes but not the horizontal plane. Psol neurons responded in phase with ipsilateral side-down head position or velocity during sinusoidal stimulation. Approximately 80% of the recorded Psol neurons responded to static roll-tilt. The optimal response planes of evoked vestibular responses were inferred from measurement of null planes. Optimal response planes usually were aligned with the anatomical orientation of one of the two ipsilateral vertical semicircular canals. The frequency dependence of null plane measurements indicated a convergence of vestibular information from otoliths and semicircular canals. None of the recorded neurons evinced optokinetic sensitivity. These results are consistent with the view that Psol neurons provide the vestibular signals to the inferior olive that eventually reached the cerebellum in the form of modulated climbing fiber discharges. These signals provide information about spatial orientation about the longitudinal axis.
Reflex Responses Induced by Tooth Unloading
Authors: Türker Kemal S. , Jenkins Melissa
Published: December 2017

The reflex response of the masseter muscle to the rapid unloading of a single maxillary incisor tooth was studied. Unloading of a static force of 2 N in the horizontal direction resulted in a short-latency excitation, inhibition, and long-latency excitation of masseter muscle activity occurring at latencies of approximately 13, 20, and 40 ms, respectively, with a corresponding change in bite force occurring slightly later in each case. Following the blocking of periodontal input by the injection of local anesthetic around the stimulated tooth, inhibitory responses were abolished. Therefore, it is concluded that the observed masseteric inhibition was caused by the unloading of periodontal mechanoreceptors and thus that these receptors may contribute to the jaw unloading reflex.
Important Role of Reverse Na+-Ca2+Exchange in Spinal Cord White Matter Injury at Physiological Temperature
Authors: Li Shuxin , Jiang Qiubo , Stys Peter K.
Published: December 2017

Spinal cord injury is a devastating condition in which most of the clinical disability results from dysfunction of white matter tracts. Excessive cellular Ca2+ accumulation is a common phenomenon after anoxia/ischemia or mechanical trauma to white matter, leading to irreversible injury because of overactivation of multiple Ca2+-dependent biochemical pathways. In the present study, we examined the role of Na+-Ca2+ exchange, a ubiquitous Ca2+ transport mechanism, in anoxic and traumatic injury to rat spinal dorsal columns in vitro. Excised tissue was maintained in a recording chamber at 37°C and injured by exposure to an anoxic atmosphere for 60 min or locally compressed with a force of 2 g for 15 s. Mean compound action potential amplitude recovered to ≈25% of control after anoxia and to ≈30% after trauma. Inhibitors of Na+-Ca2+ exchange (50 μM bepridil or 10 μM KB-R7943) improved functional recovery to ≈60% after anoxia and ≈70% after traumatic compression. These inhibitors also prevented the increase in calpain-mediated spectrin breakdown products induced by anoxia. We conclude that, at physiological temperature, reverse Na+-Ca2+exchange plays an important role in cellular Ca2+ overload and irreversible damage after anoxic and traumatic injury to dorsal column white matter tracts.
Discharge Properties of Neurons in the Rostral Superior Colliculus of the Monkey During Smooth-Pursuit Eye Movements
Authors: Krauzlis Richard J. , Basso Michele A. , Wurtz Robert H.
Published: December 2017

The intermediate and deep layers of the monkey superior colliculus (SC) comprise a retinotopically organized map for eye movements. The rostral end of this map, corresponding to the representation of the fovea, contains neurons that have been referred to as “fixation cells” because they discharge tonically during active fixation and pause during the generation of most saccades. These neurons also possess movement fields and are most active for targets close to the fixation point. Because the parafoveal locations encoded by these neurons are also important for guiding pursuit eye movements, we studied these neurons in two monkeys as they generated smooth pursuit. We found that fixation cells exhibit the same directional preferences during pursuit as during small saccades—they increase their discharge during movements toward the contralateral side and decrease their discharge during movements toward the ipsilateral side. This pursuit-related activity could be observed during saccade-free pursuit and was not predictive of small saccades that often accompanied pursuit. When we plotted the discharge rate from individual neurons during pursuit as a function of the position error associated with the moving target, we found tuning curves with peaks within a few degrees contralateral of the fovea. We compared these pursuit-related tuning curves from each neuron to the tuning curves for a saccade task from which we separately measured the visual, delay, and peri-saccadic activity. We found the highest and most consistent correlation with the delay activity recorded while the monkey viewed parafoveal stimuli during fixation. The directional preferences exhibited during pursuit can therefore be attributed to the tuning of these neurons for contralateral locations near the fovea. These results support the idea that fixation cells are the rostral extension of the buildup neurons found in the more caudal colliculus and that their activity conveys information about the size of the mismatch between a parafoveal stimulus and the currently foveated location. Because the generation of pursuit requires a break from fixation, the pursuit-related activity indicates that these neurons are not strictly involved with maintaining fixation. Conversely, because activity during the delay period was found for many neurons even when no eye movement was made, these neurons are also not obligatorily related to the generation of a movement. Thus the tonic activity of these rostral neurons provides a potential position-error signal rather than a motor command—a principle that may be applicable to buildup neurons elsewhere in the SC.
Effects of Inhibitory Timing on Contrast Enhancement in Auditory Circuits in Crickets (Teleogryllus oceanicus)
Authors: Faulkes Zen , Pollack Gerald S.
Published: December 2017

In crickets ( Teleogryllus oceanicus), the paired auditory interneuron Omega Neuron 1 (ON1) responds to sounds with frequencies in the range from 3 to 40 kHz. The neuron is tuned to frequencies similar to that of conspecific songs (4.5 kHz), but its latency is longest for these same frequencies by a margin of 5–10 ms. Each ON1 is strongly excited by input from the ipsilateral ear and inhibits contralateral auditory neurons that are excited by the contralateral ear, including the interneurons ascending neurons 1 and 2 (AN1 and AN2). We investigated the functional consequences of ON1's long latency to cricket-like sound and the resulting delay in inhibition of AN1 and AN2. Using dichotic stimuli, we controlled the timing of contralateral inhibition of the ANs relative to their excitation by ipsilateral stimuli. Advancing the stimulus to the ear driving ON1 relative to that driving the ANs “subtracted” ON1's additional latency to 4.5 kHz. This had little effect on the spike counts of AN1 and AN2. The response latencies of these neurons, however, increased markedly. This is because in the absence of a delay in ON1's response, inhibition arrived at AN1 and AN2 early enough to abolish the first spikes in their responses. This also increased the variability of AN1 latency. This suggests that one possible function of the delay in ON1's response may be to protect the precise timing of the onset of response in the contralateral AN1, thus preserving interaural difference in response latency as a reliable potential cue for sound localization. Hyperpolarizing ON1 removed all detectable contralateral inhibition of AN1 and AN2, suggesting that ON1 is the main, if not the only, source of contralateral inhibition.
Diversity of Channels Involved in Ca2+Activation of K+Channels During the Prolonged AHP in Guinea-Pig Sympathetic Neurons
Authors: Martínez-Pinna Juan , Davies Philip J. , McLachlan Elspeth M.
Published: December 2017

The types of Ca2+-dependent K+channel involved in the prolonged afterhyperpolarization (AHP) in a subgroup of sympathetic neurons have been investigated in guinea pig celiac ganglia in vitro. The conductance underlying the prolonged AHP (gKCa2) was reduced to a variable extent in 100 nM apamin, an antagonist of SK-type Ca2+-dependent K+channels, and by about 55% in 20 nM iberiotoxin, an antagonist of BK-type Ca2+-dependent K+channels. The reductions in gKCa2 amplitude by apamin and iberiotoxin were not additive, and a resistant component with an amplitude of nearly 50% of control remained. These data imply that, as well as apamin- and iberiotoxin-sensitive channels, other unknown Ca2+-dependent K+channels participate in gKCa2. The resistant component of gKCa2 was not abolished by 0.5–10 mM tetraethylammonium, 1 mM 4-aminopyridine, or 5 mM glibenclamide. We also investigated which voltage-gated channels admitted Ca2+for the generation of gKCa2. Blockade of Ca2+entry through L-type Ca2+channels has previously been shown to reduce gKCa2 by about 40%. Blockade of N-type Ca2+channels (with 100 nM ω-conotoxin GVIA) and P-type Ca2+channels (with 40 nM ω-agatoxin IVA) each reduced the amplitude of gKCa2 by about 35%. Thus Ca2+influx through multiple types of voltage-gated Ca2+channel can activate the intracellular mechanisms that generate gKCa2. The slow time course of gKCa2 may be explained if activation of multiple K+channels results from Ca2+influx triggering a kinetically invariant release of Ca2+from intracellular stores located close to the membrane.
Neuronal Activity in Macaque Supplementary Eye Field During Planning of Saccades in Response to Pattern and Spatial Cues
Authors: Olson Carl R. , Gettner Sonya N. , Ventura Valérie , Carta Roberto , Kass Robert E.
Published: December 2017

The aim of this study was to determine whether neuronal activity in the macaque supplementary eye field (SEF) is influenced by the rule used for saccadic target selection. Two monkeys were trained to perform a variant of the memory-guided saccade task in which any of four visible dots (rightward, upward, leftward, and downward) could be the target. On each trial, the cue identifying the target was either a spot flashed in superimposition on the target (spatial condition) or a foveally presented digitized image associated with the target (pattern condition). Trials conforming to the two conditions were interleaved randomly. On recording from 439 SEF neurons, we found that two aspects of neuronal activity were influenced by the nature of the cue. 1) Activity reflecting the direction of the impending response developed more rapidly following spatial than following pattern cues. 2) Activity throughout the delay period tended to be higher following pattern than following spatial cues. We consider these findings in relation to the possible involvement of the SEF in processes underlying attention, arousal, response-selection, and motor preparation.
Tactile Discrimination of Gaps by Slowly Adapting Afferents: Effects of Population Parameters and Anisotropy in the Fingerpad
Authors: Wheat Heather E. , Goodwin Antony W.
Published: December 2017

The aim of this study was to determine the acuity of the peripheral tactile system for gaps and to determine how stimulus orientation may impact on this. We quantified the ability of humans to discriminate small differences in gap width using a forced-choice task. Stimuli were presented passively to the distal fingerpad in a region where the skin ridges all run approximately in the same direction. Two standard gap widths were used (2 and 2.9 mm), and the comparison gap widths were larger than the standard gaps. With the gap axis parallel to the skin ridges, the average difference limen was approximately 0.2 mm for both standards. We examined the effect of stimulus orientation by asking subjects to discriminate between a smooth surface and a grating (ridge width, 1.5 mm; groove width, 0.75 mm). They were able to discriminate the two surfaces when the axis of the grooves was parallel to the skin ridges, but performance was below threshold in the orthogonal orientation. The underlying neural mechanisms were investigated using the gap stimuli to activate single slowly adapting type I mechanoreceptive afferents (SAIs) innervating the fingerpads of anesthetized monkeys. The edges of the gap produced response peaks, and the gap resulted in a trough in the receptive field profiles. The response magnitude at the peaks was greater, and at the troughs was smaller, for larger gap widths and also when the axis of the gap was parallel to the skin ridges as compared with the orthogonal orientation. Simulated SAI population responses showed that response profiles were distorted by variation in afferent sensitivity and by neural noise. Using signal detection theory, based on a neural measure of the gaps computed over the active population, the acuity of the SAIs under realistic population conditions was compared with human performance. These analyses showed how parameters like afferent sensitivity, the pattern and density of innervation, and noise impact on performance and why their impact is different for the two stimulus orientations investigated. The greatest limitation was imposed by noise that is independent of response magnitude, and this effect was greater for stimuli oriented orthogonal to the skin ridges than for the parallel orientation.
Precise Spatiotemporal Repeating Patterns in Monkey Primary and Supplementary Motor Areas Occur at Chance Levels
Authors: Baker Stuart N. , Lemon Roger N.
Published: December 2017

Precise spatiotemporal patterns in neural discharge are a possible mechanism for information encoding in the brain. Previous studies have found that such patterns repeat and appear to relate to key behavioral events. Whether these patterns occur above chance levels remains controversial. To address this question, we have made simultaneous recordings from between two and nine neurons in the primary motor cortex and supplementary motor area of three monkeys while they performed a precision grip task. Out of a total of 67 neurons, 46 were antidromically identified as pyramidal tract neurons. Sections of recordings 60 s long were searched for patterns involving three or more spikes that repeated at least twice. The allowed jitter for pattern repetition was 3 ms, and the pattern length was limited to 192 ms. In all 11 recordings analyzed, large numbers of repeating patterns were found. To assess the expected chance level of patterns, “surrogate” datasets were generated. These had the same moment-by-moment modulation in firing rate as the experimental spike trains, and matched their interspike interval distribution, but did not preserve the precise timing of individual spikes. The number of repeating patterns in 10 randomly generated surrogates was used to form 99% confidence limits on the repeating pattern count expected by chance. There was close agreement between these confidence limits and the number of patterns seen in the experimental data. Analysis of high complexity patterns was carried out in four long recordings (mean duration 23.2 min, mean number of neurons simultaneously recorded 7.5). This analysis logged only patterns composed of a larger number (7–11) of spikes. The number of patterns seen in the surrogate datasets showed a small but significant excess over those seen in the original experimental data; this is discussed in the context of surrogate generation. The occurrence of repeating patterns in the experimental data were strongly associated with particular phases of the precision grip task; however, a similar task dependence was seen for the surrogate data. When a repeating pattern was used as a template to find inexact matches, in which up to half of the component spikes could be missing, similar numbers of matches were found in experimental and surrogate data, and the time of occurrence of such matches showed the same task dependence. We conclude that the existence of precise repeating patterns in our data are not due to cortical mechanisms that favor this form of coding, since as many, if not more, patterns are produced by spike trains constructed only to modulate their firing rate in the same way as the experimental data, and to match the interspike interval histograms. The task dependence of pattern occurrence is explicable as an artifact of the modulation of neural firing rate. The consequences for theories of temporal coding in the cortex are discussed.
Atonia-Related Regions in the Rodent Pons and Medulla
Authors: Hajnik T. , Lai Y. Y. , Siegel J. M.
Published: December 2017

Electrical stimulation of circumscribed areas of the pontine and medullary reticular formation inhibits muscle tone in cats. In this report, we present an analysis of the anatomical distribution of atonia-inducing stimulation sites in the brain stem of the rat. Muscle atonia could be elicited by electrical stimulation of the nuclei reticularis pontis oralis and caudalis in the pons as well as the nuclei gigantocellularis, gigantocellularis alpha, gigantocellularis ventralis, and paragigantocellularis dorsalis in the medulla of decerebrate rats. This inhibitory effect on muscle tone was a function of the intensity and frequency of the electrical stimulation. Average latencies of muscle-tone suppressions elicited by electrical stimulation of the pontine reticular formation were 11.02 ± 2.54 and 20.49 ± 3.39 (SD) ms in the neck and in the hindlimb muscles, respectively. Following medullary stimulation, these latencies were 11.29 ± 2.44 ms in the neck and 18.87 ± 2.64 ms in the hindlimb muscles. Microinjection of N-methyl-d-aspartate (NMDA, 7 mM/0.1 μl) agonists into the pontine and medullary inhibitory sites produced muscle-tone facilitation, whereas quisqualate (10 mM/0.1 μl) injection induced an inhibition of muscle tone. NMDA-induced muscle tone change had a latency of 31.8 ± 35.3 s from the pons and 10.5 ± 0.7 s from the medulla and a duration of 146.7 ± 95.2 s from the pons and 55.5 ± 40.4 s from the medulla. The latency of quisqualate (QU)-induced reduction of neck muscle tone was 30.1 ± 37.9 s after pontine and 39.5 ± 21.8 s after medullary injection. The duration of muscle-tone suppression induced by QU injection into the pons and medulla was 111.5 ± 119.2 and 169.2 ± 145.3 s. Smaller rats (8 wk old) had a higher percentage of sites producing muscle-tone inhibition than larger rats (16 wk old), indicating an age-related change in the function of brain stem inhibitory systems. The anatomical distribution of atonia-related sites in the rat has both similarities and differences with the distribution found in the cat, which can be explained by the distinct anatomical organization of the brain stem in these two species.
Substance P Preferentially Inhibits Large Conductance Nicotinic ACh Receptor Channels in Rat Intracardiac Ganglion Neurons
Authors: Cuevas Javier , Adams David J.
Published: December 2017

The effects of substance P (SP) on nicotinic acetylcholine (ACh)-evoked currents were investigated in parasympathetic neurons dissociated from neonatal rat intracardiac ganglia using standard whole cell, perforated patch, and outside-out recording configurations of the patch-clamp technique. Focal application of SP onto the soma reversibly decreased the peak amplitude of the ACh-evoked current with half-maximal inhibition occurring at 45 μM and complete block at 300 μM SP. Whole cell current-voltage ( I-V) relationships obtained in the absence and presence of SP indicate that the block of ACh-evoked currents by SP is voltage independent. The rate of decay of ACh-evoked currents was increased sixfold in the presence of SP (100 μM), suggesting that SP may increase the rate of receptor desensitization. SP-induced inhibition of ACh-evoked currents was observed following cell dialysis and in the presence of either 1 mM 8-Br-cAMP, a membrane-permeant cAMP analogue, 5 μM H-7, a protein kinase C inhibitor, or 2 mM intracellular AMP-PNP, a nonhydrolyzable ATP analogue. These data suggest that a diffusible cytosolic second messenger is unlikely to mediate SP inhibition of neuronal nicotinic ACh receptor (nAChR) channels. Activation of nAChR channels in outside-out membrane patches by either ACh (3 μM) or cytisine (3 μM) indicates the presence of at least three distinct conductances (20, 35, and 47 pS) in rat intracardiac neurons. In the presence of 3 μM SP, the large conductance nAChR channels are preferentially inhibited. The open probabilities of the large conductance classes activated by either ACh or cytisine were reversibly decreased by 10- to 30-fold in the presence of SP. The single-channel conductances were unchanged, and mean apparent channel open times for the large conductance nAChR channels only were slightly decreased by SP. Given that individual parasympathetic neurons of rat intracardiac ganglia express a heterogeneous population of nAChR subunits represented by the different conductance levels, SP appears to preferentially inhibit those combinations of nAChR subunits that form the large conductance nAChR channels. Since ACh is the principal neurotransmitter of extrinsic (vagal) innervation of the mammalian heart, SP may play an important role in modulating autonomic control of the heart.
Spatial Distribution of Contextual Interactions in Primary Visual Cortex and in Visual Perception
Authors: Kapadia Mitesh K. , Westheimer Gerald , Gilbert Charles D.
Published: December 2017

To examine the role of primary visual cortex in visuospatial integration, we studied the spatial arrangement of contextual interactions in the response properties of neurons in primary visual cortex of alert monkeys and in human perception. We found a spatial segregation of opposing contextual interactions. At the level of cortical neurons, excitatory interactions were located along the ends of receptive fields, while inhibitory interactions were strongest along the orthogonal axis. Parallel psychophysical studies in human observers showed opposing contextual interactions surrounding a target line with a similar spatial distribution. The results suggest that V1 neurons can participate in multiple perceptual processes via spatially segregated and functionally distinct components of their receptive fields.
Ocular Pursuit Responses to Repeated, Single-Cycle Sinusoids Reveal Behavior Compatible With Predictive Pursuit
Authors: Barnes G. R. , Barnes D. M. , Chakraborti S. R.
Published: December 2017

The link between anticipatory smooth eye movements and prediction in sinusoidal pursuit was investigated by presentation of series of identical, single-cycle, sinusoidal target motion stimuli. Stimuli occurred at randomized intervals (1.2–2.8 s) but were preceded by an audio warning cue 480 ms before each presentation. Cycle period ( T) varied from 0.64 to 2.56 s and target displacement from 4 to 20° in separate series. For T ≤ 1.28 s, responses to the first stimulus of each series exhibited a time delay across the whole cycle (mean = 121 ms for T = 0.8 s). But, in the second and subsequent (steady-state) presentations, anticipatory movements, proportional to target velocity, were made and time delay was significantly reduced (mean = 43 ms for T = 0.8 s). Steady-state time delays were comparable to those evoked during continuous sinusoidal pursuit and less than pursuit reaction time. Even when subjects did not follow the target in the first presentation, they responded to the second presentation with reduced time delay. Throughout the experiments, three types of catch trial ( A–C) were introduced. In A, the target failed to appear as expected after the warning cue. Anticipatory smooth movements were initiated, reaching a peak velocity proportional to prior target velocity around 200 ms after expected target onset. In B, the target stopped midway through the cycle. Even if the target remained on and was stationary, the eye movement continued to be driven away from the stationary target with a velocity similar to that of prior responses, reaching a peak velocity that was again proportional to expected target velocity after ≥205 ms. In C, the amplitude of the single sinusoid was unexpectedly increased or decreased. When it decreased, eye velocity throughout the first half-cycle of the response was close to that executed in response to prior stimuli of higher velocity and did not return to an appropriate level for 382–549 ms. Conversely, when amplitude increased, eye velocity remained inappropriately low for the first half-cycle. Results of A and C indicate that subjects are able to use velocity information stored from prior presentations to initiate an oculomotor drive that predominates over visual feedback for the first half-cycle. Results of Bindicate that the second part of the cycle is also preprogrammed because it continued despite efforts to suppress it by fixation. The results suggest that initial retinal velocity error information can be sampled, stored, and subsequently replayed as a bi-directional anticipatory pattern of movement that reduces temporal delay and could account for predictive control during sinusoidal pursuit.
Electrophysiological Properties of Avian Basal Ganglia Neurons Recorded In Vitro
Authors: Farries Michael A. , Perkel David J.
Published: December 2017

The forebrains of mammals and birds appear quite different in their gross morphology, making it difficult to identify homologies between them and to assess how far they have diverged in organization. Nevertheless one set of forebrain structures, the basal ganglia, has been successfully compared in mammals and birds. Anatomical, histochemical, and molecular data have identified the avian homologues of the mammalian basal ganglia and indicate that they are very similar in organization, suggesting that they perform similar functions in the two classes. However, the physiological properties of the avian basal ganglia have not been studied, and these properties are critical for inferring functional similarity. We have used a zebra finch brain slice preparation to characterize the intrinsic physiological properties of neurons in the avian basal ganglia, particularly in the input structure of the basal ganglia, the striatum. We found that avian striatum contains a cell type that closely resembles the medium spiny neuron, the principal cell type of mammalian striatum. Avian striatum also contains a rare cell type that is very similar to an interneuron class found in mammalian striatum, the low-threshold spike cell. On the other hand, we found an aspiny, fast-firing cell type in avian striatum that is distinct from all known classes of mammalian striatal neuron. These neurons usually fired spontaneously at 10 Hz or more and were capable of sustained firing at very high rates when injected with depolarizing current. The existence of this cell type represents an important difference between avian striatum and mammalian dorsal striatum. Our data support the general idea that the organization and functional properties of the basal ganglia have been largely conserved in mammals and birds, but they imply that avian striatum is not identical to mammalian dorsal striatum.
Dynamic Synchronization Between Multiple Cortical Motor Areas and Muscle Activity in Phasic Voluntary Movements
Authors: Feige Bernd , Aertsen Ad , Kristeva-Feige Rumyana
Published: December 2017

To study the functional role of synchronized neuronal activity in the human motor system, we simultaneously recorded cortical activity by high-resolution electroencephalography (EEG) and electromyographic (EMG) activity of the activated muscle during a phasic voluntary movement in seven healthy subjects. Here, we present evidence for dynamic beta-range (16–28 Hz) synchronization between cortical activity and muscle activity, starting after termination of the movement. In the same time range, increased tonic activity in the activated muscle was found. During the movement execution a low-frequency (2–14 Hz) synchronization was found. Using a novel analysis, phase-reference analysis, we were able to extract the EMG-coherent EEG maps for both, low- and high-frequency beta range synchronization. The electrical source reconstruction of the EMG-coherent EEG maps was performed with respect to the individual brain morphology from magnetic resonance imaging (MRI) using a distributed source model (cortical current density analysis) and a realistic head model. The generators of the beta-range synchronization were not only located in the primary motor area, but also in premotor areas. The generators of the low-frequency synchronization were also located in the primary motor and in premotor areas, but with additional participation of the medial premotor area. These findings suggest that the dynamic beta-range synchronization between multiple cortical areas and activated muscles reflects the transition of the collective motor network into a new equilibrium state, possibly related to higher demands on attention, while the low-frequency synchronization is related to the movement execution.
Cerebellar Posterior Interpositus Nucleus as an Enhancer of Classically Conditioned Eyelid Responses in Alert Cats
Authors: Gruart A. , Guillazo-Blanch G. , Fernández-Mas R. , Jiménez-Díaz L. , Delgado-García J. M.
Published: December 2017

Cerebellar posterior interpositus neurons were recorded in cats during delayed and trace conditioning of eyeblinks. Type A neurons increased their firing in the time interval between conditioned and unconditioned stimulus presentations for both paradigms, while type B neurons decreased it. The discharge of different type A neurons recorded across successive conditioning sessions increased, with slopes of 0.061–0.078 spikes/s/trial. Both types of neurons modified their firing several trials in advance of the appearance of eyelid conditioned responses, but for each conditioned stimulus presentation their response started after conditioned response onset. Interpositus microstimulation evoked eyelid responses similar in amplitude and profiles to conditioned responses, and microinjection of muscimol decreased conditioned response amplitude. It is proposed that the interpositus nucleus is an enhancer, but not the initiator, of eyelid conditioned responses.
Freshly Isolated Astrocytes From Rat Hippocampus Show Two Distinct Current Patterns and Different [K+]oUptake Capabilities
Authors: Zhou Min , Kimelberg Harold K.
Published: December 2017

Whether astrocytes predominantly express ohmic K+ channels in vivo, and how expression of different K+ channels affects [K+]ohomeostasis in the CNS have been long-standing questions for how astrocytes function. In the present study, we have addressed some of these questions in glial fibrillary acidic protein [GFAP(+)], freshly isolated astrocytes (FIAs) from CA1 and CA3 regions of P7–15 rat hippocampus. As isolated, these astrocytes were uncoupled allowing a higher resolution of electrophysiological study. FIAs showed two distinct ion current profiles, with neither showing a purely linear I-V relationship. One population of astrocytes had a combined expression of outward potassium currents ( I Ka, I Kd) and inward sodium currents ( I Na). We term these outwardly rectifying astrocytes (ORA). Another population of astrocytes is characterized by a relatively symmetric potassium current pattern, comprising outward I Kdr, I Ka, and abundant inward potassium currents ( I Kin), and a larger membrane capacitance ( C m ) and more negative resting membrane potential (RMP) than ORAs. We term these variably rectifying astrocytes (VRA). The I Kin in 70% of the VRAs was essentially insensitive to Cs+, while I Kin in the remaining 30% of VRAs was sensitive. The I Ka of VRAs was most sensitive to 4-aminopyridine (4-AP), while I Kdr of ORAs was more sensitive to tetraethylammonium (TEA). ORAs and VRAs occurred approximately equally in FIAs isolated from the CA1 region (52% ORAs versus 48% VRAs), but ORAs were enriched in FIAs isolated from the CA3 region (71% ORAs versus 29% VRAs), suggesting an anatomical segregation of these two types of astrocytes within the hippocampus. VRAs, but not ORAs, showed robust inward currents in response to an increase in extracellular K+ from 5 to 10 mM. As VRAs showed a similar current pattern and other passive membrane properties (e.g., RMP, R in) to “passive astrocytes”in situ (i.e., these showing linear I-V curves), such passive astrocytes possibly represent VRAs influenced by extensive gap-junction coupling in situ. Thus, our data suggest that, at least in CA1 and CA3 regions from P7–15 rats, there are two classes of GFAP(+) astrocytes which possess different K+ currents. Only VRAs seem suited to uptake of extracellular K+ via I Kin channels at physiological membrane potentials and increases of [K+]o. ORAs show abundant outward potassium currents with more depolarized RMP. Thus VRAs and ORAs may cooperate in vivo for uptake and release of K+, respectively.
Roles of High-Voltage–Activated Calcium Channel Subtypes in a Vertebrate Spinal Locomotor Network
Authors: Büschges A. , Wikström M. A. , Grillner S. , El Manira A.
Published: December 2017

Lamprey spinal cord neurons possess N-, L-, and P/Q-type high-voltage–activated (HVA) calcium channels. We have analyzed the role of the different HVA calcium channels subtypes in the overall functioning of the spinal locomotor network by monitoring the influence of their specific agonists and antagonists on synaptic transmission and on N-methyl-d-aspartate (NMDA)–elicited fictive locomotion. The N-type calcium channel blocker ω-conotoxin GVIA (ω-CgTx) depressed synaptic transmission from excitatory and inhibitory interneurons. Blocking L-type and P/Q-type calcium channels with nimodipine and ω-agatoxin, respectively, did not affect synaptic transmission. Application of ω-CgTx initially decreased the frequency of the locomotor rhythm, increased the burst duration, and subsequently increased the coefficient of variation and disrupted the motor pattern. These effects were accompanied by a depression of the synaptic drive between neurons in the locomotor network. Blockade of L-type channels by nimodipine also decreased the frequency and increased the duration of the locomotor bursts. Conversely, potentiation of L-type channels increased the frequency of the locomotor activity and decreased the duration of the ventral root bursts. In contrast to blockade of N-type channels, blockade or potentiation of L-type calcium channels had no effect on the stability of the locomotor pattern. The P/Q-type calcium channel blocker ω-agatoxin IVA had little effect on the locomotor frequency or burst duration. The results indicate that rhythm generation in the spinal locomotor network of the lamprey relies on calcium influx through L-type and N-type calcium channels.