bluuebunny/crossref_metadata_2025 huggingface dataset:
Postural Control in the Lamprey: A Study With a Neuro-Mechanical Model
Authors: Zelenin P. V. , Deliagina T. G. , Grillner S. , Orlovsky G. N.
Published: December 2017

The swimming lamprey normally maintains the dorsal-side-up orientation due to activity of the postural control system driven by vestibular organs. Commands for postural corrections are transmitted from the brain stem to the spinal cord mainly by the reticulospinal (RS) pathways. As shown in previous studies, RS neurons are activated by contralateral roll tilt, they exhibit a strong dynamic response, but much weaker static response. Here we test a hypothesis that decoding of these commands in the spinal cord is based on the subtraction of signals in the left and right RS pathways. In this study, we used a neuro-mechanical model. An intact lamprey was mounted on a platform that restrained its postural activity but allowed lateral locomotor undulations to occur. The activity in the left and right RS pathways was recorded by implanted electrodes. These natural biological signals were then used to control an electrical motor rotating the animal around its longitudinal axis toward the stronger signal. It was found that this “hybrid” system automatically stabilized a normal orientation of the lamprey in the gravitational field. The system compensated for large postural disturbances (lateral tilt up to ±180°) due to wide angular zones of the gravitational sensitivity of RS neurons. In the nonswimming lamprey, activity of RS neurons and their vestibular responses were considerably reduced, and the system was not able to stabilize the normal orientation. However, the balance could be restored by imposing small oscillations on the lamprey, which elicited additional activation of the vestibular organs. This finding indicates that head oscillations caused by locomotor movements may contribute to postural stabilization. In addition to postural stabilization, the neuro-mechanical model reproduced a number of postural effects characteristic of the lamprey: 1) unilateral eye illumination elicited a lateral tilt (“dorsal light response”) due to a shift of the equilibrium point in the vestibular-driven postural network; 2) removal of one labyrinth resulted in a loss of postural control due to an induced left-right asymmetry in the vestibulo-reticulospinal reflexes, which 3) could be compensated for by asymmetrical visual input. The main conclusion of the present study is that natural supraspinal commands for postural corrections in the roll plane can be effectively decoded on the basis of subtraction of the effects of signals delivered by the left and right RS pathways. Possible mechanisms for this transformation are discussed.
Changes in the Responses of Purkinje Cells in the Floccular Complex of Monkeys After Motor Learning in Smooth Pursuit Eye Movements
Authors: Kahlon Maninder , Lisberger Stephen G.
Published: December 2017

We followed simple- and complex-spike firing of Purkinje cells (PCs) in the floccular complex of the cerebellum through learned modifications of the pursuit eye movements of two monkeys. Learning was induced by double steps of target speed in which initially stationary targets move at a “learning” speed for 100 ms and then change to either a higher or lower speed in the same direction. In randomly interleaved control trials, targets moved at the learning speed in the opposite direction. When the learning direction was theon direction for simple-spike responses, learning was associated with statistically significant changes in simple-spike firing for 10 of 32 PCs. Of the 10 PCs that showed significant expressions of learning, 8 showed changes in simple-spike output in the expected direction: increased or decreased firing when eye acceleration increased or decreased through learning. There were no statistically significant changes in simple-spike responses or eye acceleration during pursuit in the control direction. When the learning direction was in the off direction for simple-spike responses, none of 15 PCs showed significant correlates of learning. Although changes in simple-spike firing were recorded in only a subset of PCs, analysis of the population response showed that the same relationship between population firing and eye acceleration obtained before and after learning. Thus learning is associated with changes that render the modified population response appropriate to drive the changed behavior. To analyze complex-spike firing during learning we correlated complex-spike firing in the second, third, and fourth 100 ms after the onset of target motion with the retinal image motion in the previous 100 ms. Data were largely consistent with previous evidence that image motion drives complex spikes with a direction selectivity opposite that for simple spikes. Comparison of complex-spike responses at different times after the onset of control and learning target motions in the learning direction implied that complex spikes could guide learning during decreases but not increases in eye acceleration. Learning caused increases or decreases in the sensitivity of complex spikes to image motion in parallel with changes in eye acceleration. Complex-spike responses were similar in all PCs, including many in which learning did not modify simple-spike responses. Our data do not disprove current theories of cerebellar learning but suggest that these theories would have to be modified to account for simple- and complex-spike firing of floccular Purkinje cells reported here.
Visual and Tactile Information About Object-Curvature Control Fingertip Forces and Grasp Kinematics in Human Dexterous Manipulation
Authors: Jenmalm Per , Dahlstedt Seth , Johansson Roland S.
Published: December 2017

Most objects that we manipulate have curved surfaces. We have analyzed how subjects during a prototypical manipulatory task use visual and tactile sensory information for adapting fingertip actions to changes in object curvature. Subjects grasped an elongated object at one end using a precision grip and lifted it while instructed to keep it level. The principal load of the grasp was tangential torque due to the location of the center of mass of the object in relation to the horizontal grip axis joining the centers of the opposing grasp surfaces. The curvature strongly influenced the grip forces required to prevent rotational slips. Likewise the curvature influenced the rotational yield of the grasp that developed under the tangential torque load due to the viscoelastic properties of the fingertip pulps. Subjects scaled the grip forces parametrically with object curvature for grasp stability. Moreover in a curvature-dependent manner, subjects twisted the grasp around the grip axis by a radial flexion of the wrist to keep the desired object orientation despite the rotational yield. To adapt these fingertip actions to object curvature, subjects could use both vision and tactile sensibility integrated with predictive control. During combined blindfolding and digital anesthesia, however, the motor output failed to predict the consequences of the prevailing curvature. Subjects used vision to identify the curvature for efficient feedforward retrieval of grip force requirements before executing the motor commands. Digital anesthesia caused little impairment of grip force control when subjects had vision available, but the adaptation of the twist became delayed. Visual cues about the form of the grasp surface obtained before contact was used to scale the grip force, whereas the scaling of the twist depended on visual cues related to object movement. Thus subjects apparently relied on different visuomotor mechanisms for adaptation of grip force and grasp kinematics. In contrast, blindfolded subjects used tactile cues about the prevailing curvature obtained after contact with the object for feedforward adaptation of both grip force and twist. We conclude that humans use both vision and tactile sensibility for feedforward parametric adaptation of grip forces and grasp kinematics to object curvature. Normal control of the twist action, however, requires digital afferent input, and different visuomotor mechanisms support the control of the grasp twist and the grip force. This differential use of vision may have a bearing to the two-stream model of human visual processing.
Convergence of Multimodal Sensory Input Onto Higher-Level Neurons of the Crayfish Olfactory Pathway
Authors: Mellon DeForest
Published: December 2017

Intracellular electrophysiological studies of lateral protocerebral interneurons (LPIs) in the crayfish Procambarus clarkii have revealed convergence of multimodal sensory information onto these higher-level cells of the crustacean central olfactory pathway. Antennular stimulation by odors or electrical shocks generates excitatory-inhibitory sequences in some LPIs as does electrical or hydrodynamic stimulation of the antennae. Photic stimulation of the ipsilateral compound eye generates excitatory responses in LPIs, usually in the form of trains of impulse bursts that are timed to the peaks of the spontaneous oscillatory activity that characterizes these neurons. Focal electrical stimulation of the olfactory lobe, the termination point of antennular afferent input, or the accessory lobe, where higher-level visual and tactile inputs converge, also generates brief excitation and a delayed, prolonged inhibition in LPIs. Both phases of this activity are thought to be transmitted to the lateral protocerebrum via deutocerebral projection neurons, which have extensive dendritic arborizations in the olfactory lobe and the accessory lobe. The excitatory pathway is thought to synapse directly with target LPIs, whereas the inhibitory pathway is probably indirect and mediated through GABAergic interneurons within the lateral protocerebrum. There is evidence that both presynaptic and postsynaptic inhibition suppress activity in LPIs. Preliminary observations suggest that a small cluster of neurons adjacent to the hemi-ellipsoid body are inhibitory to LPI activity. Multimodal inhibitory and excitatory modulation of LPI activity may play a part in the contextual identification of odors in the crayfish olfactory system.
Context-Specific Adaptation of the Vertical Vestibuloocular Reflex With Regard to Gravity
Authors: Yakushin Sergei B. , Raphan Theodore , Cohen Bernard
Published: December 2017

We determined whether head position with regard to gravity is an important context for angular vestibuloocular reflex (aVOR) gain adaptation. Vertical aVOR gains were adapted with monkeys upright or on side by rotating the animals about an interaural axis in phase or out of phase with the visual surround for 4 h. When aVOR gains were adapted with monkeys upright, gain changes were symmetrical when tested in either on-side position (23 ± 7%; mean ± SD). After on-side adaptation, however, gain changes were always larger when animals were tested in the same on-side position in which they were adapted. Gain changes were 43 ± 16% with ipsilateral side down and 9 ± 8% with contralateral side down. The context-specific effects of head position on vertical aVOR gain were the same whether the gain was increased or decreased. The data indicate that vertical aVOR gain changes are stored in the context of the head orientation in which changes were induced. This association could be an important context for expressing the adapted state of the aVOR gain during vertical head movement.
Vertical Divergence and Counterroll Eye Movements Evoked by Whole-Body Position Steps About the Roll Axis of the Head in Humans
Authors: Kori A. A. , Schmid-Priscoveanu A. , Straumann D.
Published: December 2017

In healthy human subjects, a head tilt about its roll axis evokes a dynamic counterroll that is mediated by both semicircular canal and otolith stimulation, and a static counterroll that is mediated by otolith stimulation only. The vertical ocular divergence associated with the static counterroll too is otolith-mediated. A previous study has shown that, in humans, there is also a vertical divergence during dynamic head roll, but this report was not conclusive on whether this response was mediated by the semicircular canals only or whether the otoliths made a significant contribution. To clarify this issue, we applied torsional whole-body position steps (amplitude 10°, peak acceleration of 90°/s2, duration 650 ms) about the earth-vertical (supine body position) and earth-horizontal (upright body position) axis to healthy human subjects who were monocularly fixating a straight-ahead target. Eye movements were recorded binocularly with dual search coils in three dimensions. The dynamic parameters were determined 120 ms after the beginning of the turntable movement, i.e., before the first fast phase of nystagmus. The static parameters were measured 4 s after the beginning of the turntable movement. The dynamic gain of the counterroll was larger in upright (average gain: 0.48 ± 0.10 SD) than in supine (0.36 ± 0.10) position. The static gain of the counterroll in the upright position (0.21 ± 0.06) was smaller than the dynamic gain. Divergent eye movements (intorting eye hypertropic) evoked during the dynamic phase were not significantly different between supine (average vergence velocity: 0.87 ± 0.51°/s) and upright (0.84 ± 0.64°/s) positions. The static vertical divergence in upright position was 0.32 ± 0.14°. The results indicate that the dynamic vertical divergence in contrast to the dynamic ocular counterroll is not enhanced by otolith input. These results can be explained through the different patterns of connectivity between semicircular canals and utricles to the eye muscles. Alternatively, we hypothesize that the small dynamic vertical divergence represents the remaining vertical error necessary to drive an adaptive control mechanism that normally maintains a vertical eye alignment.
Contributions of the Reticulospinal System to the Postural Adjustments Occurring During Voluntary Gait Modifications
Authors: Prentice Stephen D. , Drew Trevor
Published: December 2017

To test the hypothesis that reticulospinal neurons (RSNs) are involved in the formation of the dynamic postural adjustments that accompany visually triggered, voluntary modifications of limb trajectory during locomotion, we recorded the activity of 400 cells (183 RSNs; 217 unidentified reticular cells) in the pontomedullary reticular formation (PMRF) during a locomotor task in which intact cats were required to step over an obstacle attached to a moving treadmill belt. Approximately one half of the RSNs (97/183, 53%) showed significant changes in cell activity as the cat stepped over the obstacle; most of these cells exhibited either single (26/97, 26.8%) or multiple (63/97, 65.0%) increases of activity. There was a range of discharge patterns that varied in the number, timing, and sequencing of the bursts of modified activity, although individual bursts in different cells tended to occur at similar phases of the gait cycle. Most modified cells, regardless of the number of bursts of increased discharge, or of the discharge activity of the cell during unobstructed, control, locomotion, discharged during the passage of the lead forelimb over the obstacle. Thus, 86.9% of the modified cells increased their discharge when the forelimb ipsilateral to the recording site was the first to pass over the obstacle, and 72.2% when the contralateral limb was the first. Approximately one quarter of the RSNs increased their discharge during the passage of each of the four limbs over the obstacle in both the lead (27.1%) and trail (27.9%) conditions. In general, in any one cell, the number and relative sequencing of the subsequent bursts (with respect to the lead forelimb) was maintained during both lead and trail conditions. Patterns of activity observed in unidentified cells were very similar to the RSN activity despite the diverse population of cells this unidentified group may represent. We suggest that the increased discharge that we observed in these reticular neurons reflects the integration of afferent activity from several sources, including the motor cortex, and that this increased discharge signals the timing and the relative magnitude of the postural patterns that accompany the voluntary gait modification. However, based on the characteristics of the patterns of neuronal activity in these cells, we further suggest that while individual RSNs probably contribute to the selection of different patterns of postural activity, the ultimate expression of the postural response may be determined by the excitability of the locomotor circuits within the spinal cord.
Processing of Shape Defined by Disparity in Monkey Inferior Temporal Cortex
Authors: Tanaka Hiroki , Uka Takanori , Yoshiyama Kenji , Kato Makoto , Fujita Ichiro
Published: December 2017

Neurons in the monkey inferior temporal cortex (IT) have been shown to respond to shapes defined by luminance, texture, or motion. In the present study, we determined whether IT neurons respond to shapes defined solely by binocular disparity, and if so, whether signals of disparity and other visual cues to define shape converge on single IT neurons. We recorded extracellular activity from IT neurons while monkeys performed a fixation task. Among the neurons that responded to at least one of eight random-dot stereograms (RDSs) containing different disparity-defined shapes, 21% varied their responses to different RDSs. Responses of most of the neurons were positively correlated between two sets of RDSs, which consisted of different dot patterns but defined the same set of eight shapes, whereas responses to RDSs and their monocular images were not correlated. This indicates that the response modulation for the eight RDSs reflects selectivity for shapes (or their component contours) defined by disparity, although responses were also affected by dot patterns per se. Among the neurons that showed selectivity for shapes defined by luminance or disparity, 44% were activated by both cues. Responses of these neurons to luminance-defined shapes and those to disparity-defined shapes were often positively correlated to each other. Furthermore the stimulus rank, which was determined by the magnitude of responses to shapes, generally matched between these cues. The same held true between disparity and texture cues. The results suggest that the signals of disparity, luminance, and texture cues to define the shapes converge on a population of single IT neurons to produce the selectivity for shapes.
Pontine Gustatory Activity Is Altered by Electrical Stimulation in the Central Nucleus of the Amygdala
Authors: Lundy Robert F. , Norgren Ralph
Published: December 2017

Visceral signals and experience modulate the responses of brain stem neurons to gustatory stimuli. Both behavioral and anatomical evidence suggests that this modulation may involve descending input from the forebrain. The present study investigates the centrifugal control of gustatory neural activity in the parabrachial nucleus (PBN). Extracellular responses were recorded from 51 single PBN neurons during application of sucrose, NaCl, NaCl mixed with amiloride, citric acid, and QHCl with or without concurrent electrical stimulation in the ipsilateral central nucleus of the amygdala (CeA). Based on the sapid stimulus that evoked the greatest discharge, 3 neurons were classified as sucrose-best, 32 as NaCl-best, and 16 as citric acid-best. In most of the neurons sampled, response rates to an effective stimulus were either inhibited or unchanged during electrical stimulation of the CeA. Stimulation in the CeA was without effect in two sucrose-best neurons, nine NaCl-best neurons, and one citric acid-best neuron. Suppression was evident in 1 sucrose-best neuron, 18 NaCl-best neurons, and 15 citric acid-best neurons. In NaCl-best neurons inhibited by CeA stimulation, the magnitude of the effect was similar for spontaneous activity and responses to the five taste stimuli. Nonetheless, the inhibitory modulation of gustatory sensitivity increased the relative effectiveness of NaCl resulting in narrower chemical selectivity. For citric acid–best neurons, the magnitude of inhibition produced by CeA activation increased with an increase in stimulus effectiveness. The responses to citric acid were inhibited significantly more than the responses to all other stimuli with the exception of NaCl mixed with amiloride. The overall effect was to change these CA-best neurons to CA/NaCl-best neurons. In a smaller subset of NaCl-best neurons ( n = 5), CeA stimulation augmented the responsiveness to NaCl but was without effect on the other stimuli or on baseline activity. It appears that electrical stimulation in the CeA modulates response intensity, as well as the type of gustatory information that is transmitted in a subset of NaCl-best neurons. These findings provide an additional link between the amygdala and the PBN in the control of NaCl intake, modulating the response and the chemical selectivity of an amiloride-sensitive Na+-detecting input pathway.
Coriolis-Force-Induced Trajectory and Endpoint Deviations in the Reaching Movements of Labyrinthine-Defective Subjects
Authors: DiZio Paul , Lackner James R.
Published: December 2017

When reaching movements are made during passive constant velocity body rotation, inertial Coriolis accelerations are generated that displace both movement paths and endpoints in their direction. These findings directly contradict equilibrium point theories of movement control. However, it has been argued that these movement errors relate to subjects sensing their body rotation through continuing vestibular activity and making corrective movements. In the present study, we evaluated the reaching movements of five labyrinthine-defective subjects (lacking both semicircular canal and otolith function) who cannot sense passive body rotation in the dark and five age-matched, normal control subjects. Each pointed 40 times in complete darkness to the location of a just extinguished visual target before, during, and after constant velocity rotation at 10 rpm in the center of a fully enclosed slow rotation room. All subjects, including the normal controls, always felt completely stationary when making their movements. During rotation, both groups initially showed large deviations of their movement paths and endpoints in the direction of the transient Coriolis forces generated by their movements. With additional per-rotation movements, both groups showed complete adaptation of movement curvature (restoration of straight-line reaches) during rotation. The labyrinthine-defective subjects, however, failed to regain fully accurate movement endpoints after 40 reaches, unlike the control subjects who did so within 11 reaches. Postrotation, both groups' movements initially had mirror image curvatures to their initial per-rotation reaches; the endpoint aftereffects were significantly different from prerotation baseline for the control subjects but not for the labyrinthine-defective subjects reflecting the smaller amount of endpoint adaptation they achieved during rotation. The labyrinthine-defective subjects' movements had significantly lower peak velocity, higher peak elevation, lower terminal velocity, and a more vertical touchdown than those of the control subjects. Thus the way their reaches terminated denied them the somatosensory contact cues necessary for full endpoint adaptation. These findings fully contradict equilibrium point theories of movement control. They emphasize the importance of contact cues in adaptive movement control and indicate that movement errors generated by Coriolis perturbations of limb movements reveal characteristics of motor planning and adaptation in both healthy and clinical populations.
Biophysical Properties, Pharmacology, and Modulation of Human, Neuronal L-Type (α1D, CaV1.3) Voltage-Dependent Calcium Currents
Authors: Bell D. C. , Butcher A. J. , Berrow N. S. , Page K. M. , Brust P. F. , Nesterova A. , Stauderman K. A. , Seabrook G. R. , Nürnberg B. , Dolphin A. C.
Published: December 2017

Voltage-dependent calcium channels (VDCCs) are multimeric complexes composed of a pore-forming α1subunit together with several accessory subunits, including α2δ, β, and, in some cases, γ subunits. A family of VDCCs known as the L-type channels are formed specifically from α1S(skeletal muscle), α1C(in heart and brain), α1D(mainly in brain, heart, and endocrine tissue), and α1F(retina). Neuroendocrine L-type currents have a significant role in the control of neurosecretion and can be inhibited by GTP-binding (G-) proteins. However, the subunit composition of the VDCCs underlying these G-protein–regulated neuroendocrine L-type currents is unknown. To investigate the biophysical and pharmacological properties and role of G-protein modulation of α1Dcalcium channels, we have examined calcium channel currents formed by the human neuronal L-type α1Dsubunit, co-expressed with α2δ-1 and β3a, stably expressed in a human embryonic kidney (HEK) 293 cell line, using whole cell and perforated patch-clamp techniques. The α1D-expressing cell line exhibited L-type currents with typical characteristics. The currents were high-voltage activated (peak at +20 mV in 20 mM Ba2+) and showed little inactivation in external Ba2+, while displaying rapid inactivation kinetics in external Ca2+. The L-type currents were inhibited by the 1,4 dihydropyridine (DHP) antagonists nifedipine and nicardipine and were enhanced by the DHP agonist BayK S-(−)8644. However, α1DL-type currents were not modulated by activation of a number of G-protein pathways. Activation of endogenous somatostatin receptor subtype 2 (sst2) by somatostatin-14 or activation of transiently transfected rat D2 dopamine receptors (rD2long) by quinpirole had no effect. Direct activation of G-proteins by the nonhydrolyzable GTP analogue, guanosine 5′-0-(3-thiotriphospate) also had no effect on the α1Dcurrents. In contrast, in the same system, N-type currents, formed from transiently transfected α1B/α2δ-1/β3, showed strong G-protein–mediated inhibition. Furthermore, the I–II loop from the α1Dclone, expressed as a glutathione-S-transferase (GST) fusion protein, did not bind Gβγ, unlike the α1BI–II loop fusion protein. These data show that the biophysical and pharmacological properties of recombinant human α1DL-type currents are similar to α1Ccurrents, and these currents are also resistant to modulation by Gi/o-linked G-protein–coupled receptors.
Modulation by Extracellular pH of Low- and High-Voltage-Activated Calcium Currents of Rat Thalamic Relay Neurons
Authors: Shah Mukesch Johannes , Meis Susanne , Munsch Thomas , Pape Hans-Christian
Published: December 2017

The effects of changes in the extracellular pH (pHo) on low-voltage- (LVA) and high-voltage- (HVA) activated calcium currents of acutely isolated relay neurons of the ventrobasal thalamic complex (VB) were examined using the whole cell patch-clamp technique. Modest extracellular alkalinization (pH 7.3 to 7.7) reversibly enlarged LVA calcium currents by 18.6 ± 3.2% (mean ± SE, n = 6), whereas extracellular acidification (pH 7.3 to 6.9) decreased the current by 24.8 ± 3.1% ( n = 9). Normalized current amplitudes ( I/ I 7.3) fitted as a function of pHo revealed an apparent pKa of 6.9. Both, half-maximal activation voltage and steady-state inactivation were significantly shifted to more negative voltages by 2–4 mV on extracellular alkalinization and to more positive voltages by 2–3 mV on extracellular acidification, respectively. Recovery from inactivation of LVA calcium currents was not significantly affected by changes in pHo. In contrast, HVA calcium currents were less sensitive to changes in pHo. Although extracellular alkalinization increased maximal HVA current by 6.0 ± 2.0% ( n = 7) and extracellular acidification decreased it by 11.9 ± 0.02% ( n = 11), both activation and steady-state inactivation were only marginally affected by the moderate changes in pHo used in the present study. The results show that calcium currents of thalamic relay neurons exhibit different pHo sensitivity. Therefore activity-related extracellular pH transients might selectively modulate certain aspects of the electrogenic behavior of thalamic relay neurons.
Damping Actions of the Neuromuscular System With Inertial Loads: Human Flexor Pollicis Longus Muscle
Authors: Lin David C. , Rymer W. Zev
Published: December 2017

Our previous work in an animal model showed that neuromuscular damping properties help maintain limb posture by effectively dissipating mechanical energy arising from disturbances. The purpose of this study was to determine whether similar damping properties were expressed in intact, normal human muscles. To review briefly, when the reflexively active soleus muscle in a decerebrate cat is coupled to an inertial load, application of a force impulse to the load results in lightly damped oscillations. By calculating the logarithmic decrement in muscle velocity following the impulse (the decrement being related to the amount of energy dissipated from the inertia), we found that damping increased with oscillation amplitude, a nonlinear property. This nonlinearity represents an automatic compensation for larger perturbations. Our findings in parallel experiments on the interphalangeal joint of the human thumb were that the long thumb flexor, the flexor pollicis longus (FPL), displayed mechanical and reflex behavior closely comparable to that reported earlier for the cat soleus, despite differences in architectural and metabolic properties between these muscles. Specifically, by selecting experimental trials that did not include voluntary interventions, we observed amplitude-dependent differences in damping in which larger amplitude movements elicited larger damping than did smaller movements. In addition, even after accounting for amplitude-dependent differences in damping, damping was found to be larger in later cycles than in the first cycle. This nonlinearity indicates that both mechanical properties of muscle and reflex mechanisms are dependent on prior movement history. We propose that this history-dependent behavior arises from the effects of prior movement on stretch reflex gain, and these effects are mediated primarily via changes in muscle spindle properties. Recordings of electromyographic activity from the FPL, during the first and second cycles of oscillation supported this postulate of a reduced reflex gain following prior motion. The functional significance of these nonlinear damping properties is that during the initial muscle stretch, the stiffness is high, which helps to preserve the initial position (although at the expense of promoting oscillation). Subsequently, the ensuing increase in damping helps suppress continuing oscillation. This sequence of varying mechanical properties is broadly analogous to the features of a predictive, or feed-forward controller, designed to produce a response that initially maintains position, and subsequently dampens oscillations. These results show that the intrinsic properties of muscle and spinal reflexes automatically provide a complex time-varying response, appropriate for maintenance of stable limb posture.
Neonatal Deafferentation Does Not Alter Membrane Properties of Trigeminal Nucleus Principalis Neurons
Authors: Lo Fu-Sun , Erzurumlu Reha S.
Published: December 2017

In the brain stem trigeminal complex of rats and mice, presynaptic afferent arbors and postsynaptic target cells form discrete modules (“barrelettes”), the arrangement of which duplicates the patterned distribution of whiskers and sinus hairs on the ipsilateral snout. Within the barrelette region of the nucleus principalis of the trigeminal nerve (PrV), neurons participating in barrelettes and those with dendritic spans covering multiple barrelettes (interbarrelette neurons) can be identified by their morphological and electrophysiological characteristics as early as postnatal day 1. Barrelette cells have focal dendritic processes, are characterized by a transient K+ conductance ( I A), whereas interbarrelette cells with larger soma and extensive dendritic fields characteristically exhibit low-threshold T-type Ca2+ spikes (LTS). In this study, we surveyed membrane properties of barrelette and interbarrelette neurons during and after consolidation of barrelettes in the PrV and effects of peripheral deafferentation on these properties. During postnatal development (PND1–13), there were no changes in the resting potential, composition of active conductances and Na+ spikes of both barrelette and interbarrelette cells. The only notable changes were a decline in input resistance and a slight increase in the amplitude of LTS. The infraorbital (IO) branch of the trigeminal nerve provides the sole afferent input source to the whisker pad. IO nerve transection at birth abolishes barrelette formation as well as whisker-related neuronal patterns all the way to the neocortex. Surprisingly this procedure had no effect on membrane properties of PrV neurons. The results of the present study demonstrate that distinct membrane properties of barrelette and interbarrelette cells are maintained even in the absence of input from the whiskers during the critical period of pattern formation.
Hypoglycemia Enhances Ionotropic But Reduces Metabotropic Glutamate Responses in Substantia Nigra Dopaminergic Neurons
Authors: Marinelli Silvia , Federici Mauro , Giacomini Patrizia , Bernardi Giorgio , Mercuri Nicola B.
Published: December 2017

It is widely accepted that energy deprivation causes a neuronal death that is mainly determined by an increase in the extracellular level of glutamate. Consequently an excessive membrane depolarization and a rise in the intracellular concentration of sodium and calcium are produced. In spite of this scenario, the function of excitatory and inhibitory amino acids during an episode of energy failure has not been studied yet at a cellular level. In a model of cerebral hypoglycemia in the rat substantia nigra pars compacta, we measured neuronal responses to excitatory amino acid agonists. Under single-electrode voltage-clamp mode at −60 mV, the application of the ionotropic glutamate receptor agonists N-methyl-d-aspartate, α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid, kainate, and the metabotropic group I agonist (S)-3,5-dihydroxyphenilglycine (DHPG) produced reversible inward currents in the dopaminergic cells. In addition, an outward current was caused by the superfusion of the metabotropic GABAB agonist baclofen. Glucose deprivation enhanced the inward responses caused by each ionotropic glutamate agonist. In contrast, hypoglycemia depressed the DHPG-induced inward current and the baclofen-induced outward current. These effects of hypoglycemia were reversible. To test whether a failure of the Na+/K+ ATPase pump could account for the modification of the agonist-induced currents during hypoglycemia, we treated the midbrain slices with strophanthidin (1–3 μM). Strophanthidin enhanced the inward currents caused by glutamate agonists. However, it did not modify the GABAB-induced outward current. Our data suggest that glucose deprivation enhances the inward current caused by the stimulation of ionotropic glutamate receptors while it dampens the responses caused by the activation of metabotropic receptors. Thus a substantial component of the augmented neuronal response to glutamate, during energy deprivation, is very likely due to the failure of Na+ and Ca2+ extrusion and might ultimately favor excitotoxic processes in the dopaminergic cells.
Spontaneous and Stimulus-Evoked Intrinsic Optical Signals in Primary Auditory Cortex of the Cat
Authors: Spitzer Matthew W. , Calford Michael B. , Clarey Janine C. , Pettigrew John D. , Roe Anna W.
Published: December 2017

Spontaneous and tone-evoked changes in light reflectance were recorded from primary auditory cortex (A1) of anesthetized cats (barbiturate induction, ketamine maintenance). Spontaneous 0.1-Hz oscillations of reflectance of 540- and 690-nm light were recorded in quiet. Stimulation with tone pips evoked localized reflectance decreases at 540 nm in 3/10 cats. The distribution of patches “activated” by tones of different frequencies reflected the known tonotopic organization of auditory cortex. Stimulus-evoked reflectance changes at 690 nm were observed in 9/10 cats but lacked stimulus-dependent topography. In two experiments, stimulus-evoked optical signals at 540 nm were compared with multiunit responses to the same stimuli recorded at multiple sites. A significant correlation ( P < 0.05) between magnitude of reflectance decrease and multiunit response strength was evident in only one of five stimulus conditions in each experiment. There was no significant correlation when data were pooled across all stimulus conditions in either experiment. In one experiment, the spatial distribution of activated patches, evident in records of spontaneous activity at 540 nm, was similar to that of patches activated by tonal stimuli. These results suggest that local cerebral blood volume changes reflect the gross tonotopic organization of A1 but are not restricted to the sites of spiking neurons.
Distinct Roles of CaMKII and PKA in Regulation of Firing Patterns and K+Currents inDrosophilaNeurons
Authors: Yao Wei-Dong , Wu Chun-Fang
Published: December 2017

The Ca2+/calmodulin-dependent protein kinase II (CaMKII) and the cAMP-dependent protein kinase A (PKA) cascades have been implicated in neural mechanisms underlying learning and memory as supported by mutational analyses of the two enzymes in Drosophila. While there is mounting evidence for their roles in synaptic plasticity, less attention has been directed toward their regulation of neuronal membrane excitability and spike information coding. Here we report genetic and pharmacological analyses of the roles of PKA and CaMKII in the firing patterns and underlying K+currents in cultured Drosophilacentral neurons. Genetic perturbation of the catalytic subunit of PKA ( DC0) did not alter the action potential duration but disrupted the frequency coding of spike-train responses to constant current injection in a subpopulation of neurons. In contrast, selective inhibition of CaMKII by the expression of an inhibitory peptide in ala transformants prolonged the spike duration but did not affect the spike frequency coding. Enhanced membrane excitability, indicated by spontaneous bursts of spikes, was observed in CaMKII-inhibited but not in PKA-diminished neurons. In wild-type neurons, the spike train firing patterns were highly reproducible under consistent stimulus conditions. However, disruption of either of these kinase pathways led to variable firing patterns in response to identical current stimuli delivered at a low frequency. Such variability in spike duration and frequency coding may impose problems for precision in signal processing in these protein kinase learning mutants. Pharmacological analyses of mutations that affect specific K+channel subunits demonstrated distinct effects of PKA and CaMKII in modulation of the kinetics and amplitude of different K+currents. The results suggest that PKA modulates Shaker A-type currents, whereas CaMKII modulates Shal-A type currents plus delayed rectifier Shab currents. Thus differential regulation of K+channels may influence the signal handling capability of neurons. This study provides support for the notion that, in addition to synaptic mechanisms, modulations in spike activity patterns may represent an important mechanism for learning and memory that should be explored more fully.
Prefrontal Cortex Neurons Reflecting Reports of a Visual Illusion
Authors: Lebedev Mikhail A. , Douglass Diana K. , Moody Sohie Lee , Wise Steven P.
Published: December 2017

When a small, focally attended visual stimulus and a larger background frame shift location at the same time, the frame's new location can affect spatial perception. For horizontal displacements on the order of 1–2°, when the frame moves more than the attended stimulus, human subjects may perceive that the attended stimulus has shifted to the right or left when it has not done so. However, that misapprehension does not disable accurate eye movements to the same stimulus. We trained a rhesus monkey to report the direction that an attended stimulus had shifted by making an eye movement to one of the two report targets. Then, using conditions that induce displacement illusions in human subjects, we tested the hypothesis that neuronal activity in the prefrontal cortex (PF) would reflect the displacement directions reported by the monkey, even when they conflicted with the actual displacement, if any, of the attended stimulus. We also predicted that these cells would have directional selectivity for movements used to make those reports, but not for similar eye movements made to fixate the attended stimulus. A population of PF neurons showed the predicted properties, which could not be accounted for on the basis of either eye-movement or frame-shift parameters. This activity, termed report-related, began approximately 150 ms before the onset of the reporting saccade. Another population of PF neurons showed greater directional selectivity for saccadic eye movements made to fixate the attended stimulus than for similar saccades made to report its displacement. In view of the evidence that PF functions to integrate inputs and actions occurring at different times and places, the present findings support the idea that such integration involves movements to acquire response targets, directly, as well as actions guided by less direct response rules, such as perceptual reports.
Responses and Afferent Pathways of Superficial and Deeper C1–C2 Spinal Cells to Intrapericardial Algogenic Chemicals in Rats
Authors: Qin Chao , Chandler Margaret J. , Miller Kenneth E. , Foreman Robert D.
Published: December 2017

Electrical stimulation of vagal afferents or cardiopulmonary sympathetic afferent fibers excites C1–C2spinal neurons. The purposes of this study were to compare the responses of superficial (depth <0.35 mm) and deeper C1–C2 spinal neurons to noxious chemical stimulation of cardiac afferents and determine the relative contribution of vagal and sympathetic afferent pathways for transmission of noxious cardiac afferent input to C1–C2 neurons. Extracellular potentials of single C1–C2 neurons were recorded in pentobarbital anesthetized and paralyzed male rats. A catheter was placed in the pericardial sac to administer a mixture of algogenic chemicals (0.2 ml) that contained adenosine (10− 3 M), bradykinin, histamine, serotonin, and prostaglandin E2(10− 5 M each). Intrapericardial chemicals changed the activity of 20/106 (19%) C1–C2 spinal neurons in the superficial laminae, whereas 76/147 (52%) deeper neurons responded to cardiac noxious input ( P < 0.01). Of 96 neurons responsive to cardiac inputs, 48 (50%) were excited (E), 41 (43%) were inhibited (I), and 7 were excited/inhibited (E-I) by intrapericardial chemicals. E or I neurons responsive to intrapericardial chemicals were subdivided into two groups: short-lasting (SL) and long-lasting (LL) response patterns. In superficial gray matter, excitatory responses to cardiac inputs were more likely to be LL-E than SL-E neurons. Mechanical stimulation of the somatic field from the head, neck, and shoulder areas excited 85 of 95 (89%) C1–C2 spinal neurons that responded to intrapericardial chemicals; 31 neurons were classified as wide dynamic range, 49 were high threshold, 5 responded only to joint movement, and no neuron was classified as low threshold. For superficial neurons, 53% had small somatic fields and 21% had bilateral fields. In contrast, 31% of the deeper neurons had small somatic fields and 46% had bilateral fields. Ipsilateral cervical vagotomy interrupted cardiac noxious input to 8/30 (6 E, 2 I) neurons; sequential transection of the contralateral cervical vagus nerve (bilateral vagotomy) eliminated the responses to intrapericardial chemicals in 4/22 (3 E, 1 I) neurons. Spinal transection at C6–C7 segments to interrupt effects of sympathetic afferent input abolished responses to cardiac input in 10/10 (7 E, 3 I) neurons that still responded after bilateral vagotomy. Results of this study support the concept that C1–C2 superficial and deeper spinal neurons play a role in integrating cardiac noxious inputs that travel in both the cervical vagal and/or thoracic sympathetic afferent nerves.
Response Properties of Mechanoreceptors and Nociceptors in Mouse Glabrous Skin: An In Vivo Study
Authors: Cain David M. , Khasabov Sergey G. , Simone Donald A.
Published: December 2017

The increasing use of transgenic mice for the study of pain mechanisms necessitates comprehensive understanding of the murine somatosensory system. Using an in vivo mouse preparation, we studied response properties of tibial nerve afferent fibers innervating glabrous skin. Recordings were obtained from 225 fibers identified by mechanical stimulation of the skin. Of these, 106 were classed as Aβ mechanoreceptors, 51 as Aδ fibers, and 68 as C fibers. Aβ mechanoreceptors had a mean conduction velocity of 22.2 ± 0.7 (SE) m/s (13.8–40.0 m/s) and a median mechanical threshold of 2.1 mN (0.4–56.6 mN) and were subclassed as rapidly adapting (RA, n = 75) or slowly adapting (SA, n = 31) based on responses to constant force mechanical stimuli. Conduction velocities ranged from 1.4 to 13.6 m/s (mean 7.1 ± 0.6 m/s) for Aδ fibers and 0.21 to 1.3 m/s (0.7 ± 0.1 m/s) for C fibers. Median mechanical thresholds were 10.4 and 24.4 mN for Aδ and C fibers, respectively. Responses of Aδ and C fibers evoked by heat (35–51°C) and by cold (28 to −12°C) stimuli were determined. Mean response thresholds of Aδ fibers were 42.0 ± 3.1°C for heat and 7.6 ± 3.8°C for cold, whereas mean response thresholds of C fibers were 40.3 ± 0.4°C for heat and 10.1 ± 1.9°C for cold. Responses evoked by heat and cold stimuli increased monotonically with stimulus intensity. Although only 12% of tested Aδ fibers were heat sensitive, 50% responded to cold. Only one Aδ nociceptor responded to both heat and cold stimuli. In addition, 40% of Aδ fibers were only mechanosensitive since they responded neither to heat nor to cold stimuli. Thermal stimuli evoked responses from the majority of C fibers: 82% were heat sensitive, while 77% of C fibers were excited by cold, and 68% were excited by both heat and cold stimuli. Only 11% of C fibers were insensitive to heat and/or cold. This in vivo study provides an analysis of mouse primary afferent fibers innervating glabrous skin including new information on encoding of noxious thermal stimuli within the peripheral somatosensory system of the mouse. These results will be useful for future comparative studies with transgenic mice.