bluuebunny/crossref_metadata_2025 huggingface dataset:
Using Response Models to Estimate Channel Capacity for Neuronal Classification of Stationary Visual Stimuli Using Temporal Coding
Authors: Wiener Matthew C. , Richmond Barry J.
Published: December 2017

Both spike count and temporal modulation are known to carry information about which of a set of stimuli elicited a response; but how much information temporal modulation adds remains a subject of debate. This question usually is addressed by examining the results of a particular experiment that depend on the specific stimuli used. Developing a response model allows us to ask how much more information is carried by the best use of response strength and temporal modulation together (that is, the channel capacity using a code incorporating both) than by the best use of spike count alone (the channel capacity using the spike count code). This replaces dependence on a particular data set with dependence on the accuracy of the model. The model is constructed by finding statistical rules obeyed by all the observed responses and assuming that responses to stimuli not presented in our experiments obey the same rules. We assume that all responses within the observed dynamic range, even if not elicited by a stimulus in our experiment, could be elicited by some stimulus. The model used here is based on principal component analysis and includes both response strength and a coarse (±10 ms) representation of temporal modulation. Temporal modulation at finer time scales carries little information about the identity of stationary visual stimuli (although it may carry information about stimulus motion or change), and we present evidence that, given its variability, it should not be expected to do so. The model makes use of a linear relation between the logarithms of mean and variance of responses, similar to the widely seen relation between mean and variance of spike count. Responses are modeled using truncated Gaussian distributions. The amount of stimulus-related information carried by spike count in our data are 0.35 and 0.31 bits in primary visual and inferior temporal cortices, respectively, rising to 0.52 and 0.37 bits for the two-principal-component code. The response model estimates that the channel capacity is 1.1 and 1.4 bits, respectively, using the spike count only, rising to 2.0 and 2.2 bits using two principal components. Thus using this representation of temporal modulation is nearly equivalent to adding a second independent cell using the spike count code. This is much more than estimated using transmitted information but far less than would be expected if all degrees of freedom provided by the individual spike times carried independent information.
Regulation of Action Potential Size and Excitability in Substantia Nigra Compacta Neurons: Sensitivity to 4-Aminopyridine
Authors: Nedergaard S.
Published: December 2017

Slow, pacemaker-like firing is due to intrinsic membrane properties in substantia nigra compacta (SNc) neurons in vitro. How these properties interact with afferent synaptic inputs is not fully understood. In this study, intracellular recordings from SNc neurons in brain slices showed that spontaneous action potentials (APs) were attenuated when generated from lower than normal threshold. Such APs were blocked by 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) and could be related to non– N-methyl-d-aspartate (NMDA) receptor–mediated spontaneous excitatory postsynaptic potentials (EPSPs). The AP attenuation was reproduced by stimulus-evoked EPSPs and by current injections to the soma. APs evoked from holding potentials between −40 and −60 mV were reduced in width by Cd2+(0.2 mM). Tetraethylammonium chloride (TEA, 10 mM) or 4-aminopyridine (4-AP, 5 mM) increased the AP width. However, at more negative holding potentials, Cd2+and TEA were inefficacious, whereas 4-AP enlarged the AP, partly via induction of a Cd2+-sensitive component. A monophasic afterhyperpolarization (AHP), following attenuated APs, was little affected by either Cd2+or TEA, but inhibited by 4-AP, which induced an additional, slow component, sensitive to Cd2+or apamin (100 nM). The AP delay showed a discontinuous relation to the amplitude or slope of the injected current (delay shift), which was sensitive to low doses of 4-AP (0.05 mM). The initial time window before the delay shift was longer than the rise time of EPSPs. It is suggested that a 4-AP–sensitive current prevents or postpones discharge during slow depolarization's, but allows direct excitation by fast EPSPs. Fast excitation leads to AP attenuation, primarily due to strong activation of 4-AP–sensitive current. This seems to cause inhibition of the Ca2+current during the AP and reduction of Ca2+-dependent K+currents. Together, these properties are likely to influence the excitability and the local, somatodendritic effects of the AP, in a manner that discriminates between firing induced by the intrinsic pacemaker mechanism and fast synaptic potentials.
Computational Model of the Serotonergic Modulation of Sensory Neurons inAplysia
Authors: Baxter Douglas A. , Canavier Carmen C. , Clark John W. , Byrne John H.
Published: December 2017

Serotonergic modulation of the sensory neurons that mediate the gill- and tail-withdrawal reflexes of Aplysia is a useful model system for studies of neuronal plasticity that contributes to learning and memory. The effects of serotonin (5-HT) are mediated, in part, via two protein kinases (protein kinase A, PKA, and protein kinase C, PKC), which in turn, modulate at least four membrane currents, including a S (“serotonin-sensitive”) K+current ( IK,S), a steeply voltage-dependent K+current ( IK-V), a slow component of the Ca2+-activated K+current ( IK,Ca-S), and a L-type Ca2+current ( ICa-L). The present study investigated how the modulation of these currents altered the spike duration and excitability of sensory neurons and examined the relative contributions of PKA- and PKC-mediated effects to the actions of 5-HT. A Hodgkin-Huxley type model was developed that described the ionic conductances in the somata of sensory neurons. The descriptions of these currents and their modulation were based largely on voltage-clamp data from sensory neurons. Simulations were preformed with the program SNNAP (Simulator for Neural Networks and Action Potentials). The model was sufficient to replicate empirical data that describes the membrane currents, action potential waveform and excitability as well as their modulation by application of 5-HT, increased levels of adenosine cyclic monophosphate or application of active phorbol esters. In the model, modulation of IK-Vby PKC played a dominate role in 5-HT-induced spike broadening, whereas the concurrent modulation of IK,Sand IK,Ca-Sby PKA primarily accounted for 5-HT-induced increases in excitability. Finally, simulations indicated that a PKC-induced increase in excitability resulted from decreases of IK,Sand IK,Ca-S, which was likely the indirect result of cross-talk between the PKC and PKA systems. The results provide several predictions that warrant additional experimental investigation and illustrate the importance of considering indirect as well as direct effects of modulatory agents on the modulation of membrane currents.
Activation of Serotonin Receptors Modulates Synaptic Transmission in Rat Cerebral Cortex
Authors: Zhou Fu-Ming , Hablitz John J.
Published: December 2017

The cerebral cortex receives an extensive serotonergic (5-hydroxytryptamine, 5-HT) input. Immunohistochemical studies suggest that inhibitory neurons are the main target of 5-HT innervation. In vivo extracellular recordings have shown that 5-HT generally inhibited cortical pyramidal neurons, whereas in vitro studies have shown an excitatory action. To determine the cellular mechanisms underlying the diverse actions of 5-HT in the cortex, we examined its effects on cortical inhibitory interneurons and pyramidal neurons. We found that 5-HT, through activation of 5-HT2A receptors, induced a massive enhancement of spontaneous inhibitory postsynaptic currents (sIPSCs) in pyramidal neurons, lasting for ∼6 min. In interneurons, this 5-HT-induced enhancement of sIPSCs was much weaker. Activation of 5-HT2Areceptors also increased spontaneous excitatory postsynaptic currents (sEPSCs) in pyramidal neurons. This response desensitized less and at a slower rate. In contrast, 5-HT slightly decreased evoked IPSCs (eIPSCs) and eEPSCs. In addition, 5-HT via 5-HT3 receptors evoked a large and rapidly desensitizing inward current in a subset of interneurons and induced a transient enhancement of sIPSCs. Our results suggest that 5-HT has widespread effects on both interneurons and pyramidal neurons and that a short pulse of 5-HT is likely to induce inhibition whereas the prolonged presence of 5-HT may result in excitation.
Nicotine Modulates Evoked GABAergic Transmission in the Brain
Authors: Zhu Ping Jun , Chiappinelli Vincent A.
Published: December 2017

The effects of nicotine on evoked GABAergic synaptic transmission were examined using whole cell recordings from neurons of the lateral spiriform nucleus in embryonic chick brain slices. All synaptic activities were abolished by the GABAA receptor antagonist, bicuculline (20 μM). Under voltage-clamp with KCl-filled pipettes (holding potential −70 mV), nicotine (0.1–1.0 μM) increased the frequency of spontaneous GABAergic currents in a dose-dependent manner. Nicotine enhanced electrically evoked GABAergic transmission only at relatively low concentrations of 50–100 nM (but not 25 nM), which approximate the concentrations of nicotine in the blood produced by cigarette smoking. At higher concentrations nicotine had either no effect (0.25 μM) or diminished (0.5–1.0 μM) evoked GABAergic neurotransmission. Nicotine had no significant effect on the postsynaptic current induced by exogenous GABA (30–50 μM). These data imply that nicotine levels attained in smokers are sufficient to enhance evoked GABAergic transmission in the brain, and that this effect is most likely mediated through activation of presynaptic nicotinic receptors.
Attributes of Quiet Stance in the Chronic Spinal Cat
Authors: Fung Joyce , Macpherson Jane M.
Published: December 2017

Standing is a dynamic task that requires antigravity support of the body mass and active regulation of the position of the body center of mass. This study examined the extent to which the chronic spinal cat can maintain postural orientation during stance and adapt to changes in stance distance (fore-hindpaw separation). Intact cats adapt to changes in stance distance by maintaining a constant horizontal orientation of the trunk and changing orientation of the limbs, while keeping intralimb geometry constant and aligning the ground reaction forces closely with the limb axes. Postural adaptation was compared in four cats before and after spinalization at the T6level, in terms of the forces exerted by each paw against the support, body geometry (kinematics) and electromyographic (EMG) activity recorded from chronic, indwelling electrodes, as well as the computed net torques in the fore and hindlimbs. Five fore-hindpaw distances spanning the preferred distance were tested before spinalization, with a total range of 20 cm from the shortest to the longest stance. After spinalization, the cats were trained on a daily basis to stand on the force platform, and all four cats were able to support their full body weight. Three of the four cats could adapt to changes in stance distance, but the range was smaller and biased toward the shorter distances. The fourth cat could stand only at one stance distance, which was 8 cm shorter than the preferred distance before spinalization. All cats shifted their center of pressure closer to the forelimbs after spinalization, but the amount of shift could largely be accounted for by the weight loss in the hindquarters. The three cats that could adapt to changes in stance distance used a similar strategy as the intact cat by constraining the trunk and changing orientation of the limb axes in close relation with the forces exerted by each limb. However, different postures in the fore- and hindlimbs were adopted, particularly at the scapula (more extended) and pelvis (tipped more anteriorly). Other changes from control included a redistribution of net extensor torque across the joints of the forelimb and of the hindlimb. We concluded that the general form of body axis orientation is relatively conserved in the spinal cat, suggesting that the lumbosacral spinal circuitry includes rudimentary set points for hindlimb geometry. Both mechanical and neural elements can contribute toward maintaining body geometry through stiffness regulation and spinal reflexes.
Activity of the Brain Stem Omnipause Neurons During Saccades Perturbed by Stimulation of the Primate Superior Colliculus
Authors: Gandhi Neeraj J. , Keller Edward L.
Published: December 2017

Stimulation of the rostral ∼2 mm of the superior colliculus (SC) during a large, visual target-initiated saccade produces a spatial deviation of the ongoing saccade and then stops it in midflight. After the termination of the stimulation, the saccade resumes and ends near the location of the flashed target. The density of collicular projections to the omnipause neuron (OPN) region is greatest from the rostral SC and decreases gradually for the more caudal regions. It has been hypothesized that the microstimulation excites the OPNs through these direct connections, and the reactivation of OPNs, which are normally silent during saccades, stops the initial component in midflight by gating off the saccadic burst generator. Two predictions emerge from this hypothesis: 1) for microstimulation triggered on the onset of large saccades, the time from stimulation onset to resumption of OPN discharge should decrease as the stimulation site is moved rostral and 2) the lead time from reactivation of OPNs to the end of the initial saccade on stimulation trials should be equal to the lead time of pause end with respect to the end of control saccades. We tested this hypothesis by recording OPN activity during saccades perturbed by stimulation of the rostral ∼2 mm of the SC. The distance of the stimulation site from the most rostral extent of the SC and the time of reactivation with respect to stimulation onset were not significantly correlated. The mean lead of reactivation of OPNs relative to the end of the initial component of perturbed saccades (6.5 ms) was significantly less than the mean lead with respect to the end of control (9.6 ms) and resumed saccades (10.4 ms). These results do not support the notion that the excitatory input from SC neurons—in particular, the fixation neurons in the rostral SC—provide the major signal to reactivate OPNs and end saccades. An alternative, conceptual model to explain the temporal sequence of events induced by stimulation of the SC during large saccades is presented. Other OPN activity parameters also were measured and compared for control and stimulation conditions. The onset of pause with respect to resumed saccade onset was larger and more variable than the onset of pause with respect to control saccades, whereas pause end with respect to the end of resumed and control saccades was similar. The reactivated discharge of OPNs during the period between the end of the initial and the onset of the resumed saccades was at least as strong as that following control movements. This latter observation is interpreted in terms of the resettable neural integrator hypothesis.
In Vivo Calcium Accumulation in Presynaptic and Postsynaptic Dendrites of Visual Interneurons
Authors: Dürr Volker , Egelhaaf Martin
Published: December 2017

In this comparative in vivo study of dendritic calcium accumulation, we describe the time course and spatial integration properties of two classes of visual interneurons in the lobula plate of the blowfly. Calcium accumulation was measured during visual motion stimulation, ensuring synaptic activation of the neurons within their natural spatial and temporal operating range. The compared cell classes, centrifugal horizontal (CH) and horizontal system (HS) cells, are known to receive retinotopic input of similar direction selectivity, but to differ in morphology, biophysics, presence of dendrodendritic synapses, and computational task. 1) The time course of motion-induced calcium accumulation was highly invariant with respect to stimulus parameters such as pattern contrast and size. In HS cells, the rise of [Ca2+]i can be described by a single exponential with a time constant of 5–6 s. The initial rise of [Ca2+]i in CH cells was much faster (τ ≈ 1 s). The decay time constant in both cell classes was estimated to be at least 3.5 times longer than the corresponding rise time constant. 2) The voltage-[Ca2+]i relationship was best described by an expansive nonlinearity in HS cells and an approximately linear relationship in CH cells. 3) Both cell classes displayed a size-dependent saturation nonlinearity of the calcium accumulation. Although in CH cells calcium saturation was indistinguishable from saturation of the membrane potential, saturation of the two response parameters differed in HS cells. 4) There was spatial overlap of the calcium signal in response to nonoverlapping visual stimuli. Both the area and the amplitude of the overlap profile was larger in CH cells than in HS cells. Thus calcium accumulation in CH cells is spatially blurred to a greater extent than in HS cells. 5) The described differences between the two cell classes may reflect the following computational tasks of these neurons: CH cells relay retinotopic information within the lobula plate via dendritic synapses with pronounced spatial low-pass filtering. HS cells are output neurons of the lobula plate, in which the slow, local calcium accumulation may be suitable for local modulatory functions.
FGF-2 Potentiates Ca2+-Dependent Inactivation of NMDA Receptor Currents in Hippocampal Neurons
Authors: Boxer Adam L. , Moreno Herman , Rudy Bernardo , Ziff Edward B.
Published: December 2017

Peptide growth factors such as the neurotrophins and fibroblast growth factors have potent effects on synaptic transmission, development, and cell survival. We report that chronic (hours) treatment with basic fibroblast growth factor (FGF-2) potentiates Ca2+-dependent N-methyl-d-aspartate (NMDA) receptor inactivation in cultured hippocampal neurons. This effect is specific for the NMDA-subtype of ionotropic glutamate receptor and FGF-2. The potentiated inactivation requires ongoing protein synthesis during growth factor treatment and the activity of protein phosphatase 2B (PP2B or calcineurin) during agonist application. These results suggest a mechanism by which FGF-2 receptor signaling may regulate neuronal survival and synaptic plasticity.
Haptic Stabilization of Posture: Changes in Arm Proprioception and Cutaneous Feedback for Different Arm Orientations
Authors: Rabin Ely , Bortolami Simone B. , DiZio Paul , Lackner James R.
Published: December 2017

Postural sway during quiet stance is attenuated by actively maintained contact of the index finger with a stationary surface, even if the level of applied force (<1 N) cannot provide mechanical stabilization. In this situation, changes in force level at the fingertip lead changes in center of foot pressure by ∼250 ms. These and related findings indicate that stimulation of the fingertip combined with proprioceptive information about the hand and arm can serve as an active sensor of body position relative to the point of contact. A geometric analysis of the relationship between hand and torso displacement during body sway led to the prediction that arm and hand proprioceptive and finger somatosensory information about body sway would be maximized with finger contact in the plane of body sway. Therefore, the most postural stabilization should be possible with such contact. To test this analysis, subjects touched a laterally versus anteriorly placed surface while in each of two stances: the heel-to-toe tandem Romberg stance that reduces medial-lateral stability and the heel-to-heel, toes-outward, knees-bent, “duck stance” that reduces fore-aft stability. Postural sway was always least with finger contact in the unstable plane: for the tandem stance, lateral fingertip contact was significantly more effective than frontal contact, and, for the duck stance, frontal contact was more effective than lateral fingertip contact. Force changes at the fingertip led changes in center of pressure of the feet by ∼250 ms for both fingertip contact locations for both test stances. These results support the geometric analysis, which showed that 1) arm joint angles change by the largest amount when fingertip contact is maintained in the plane of greatest sway, and 2) the somatosensory cues at the fingertip provide both direction and amplitude information about sway when the finger is contacting a surface in the unstable plane.
Control Strategies for the Transition From Multijoint to Single-Joint Arm Movements Studied Using a Simple Mechanical Constraint
Authors: Scheidt Robert A. , Rymer W. Zev
Published: December 2017

Changes were studied in neuromotor control that were evoked by constraining the motion of the elbow joint during planar, supported movements of the dominant arm in eight normal human subjects. Electromyograph (EMG) recordings from shoulder and arm muscles were used to determine whether the normal multijoint muscle activity patterns associated with reaching to a visual target were modified when the movement was reduced to a single-joint task, by pinning the elbow to a particular location in the planar work space. Three blocks of 150 movements each were used in the experiments. Subjects were presented with the unconstrained task in the first and third blocks with an intervening block of constrained trials. Kinematic, dynamic, and EMG measures of performance were compared across blocks. The imposition of the pin constraint caused predictable changes in kinematic performance, in that near-linear motions of the hand became curved. This was followed by changes in limb dynamic performance at the elbow. However, changes in EMG activity at the shoulder lagged the kinematic changes substantially (by about 15 trials). The gradual character of the changes in EMG timing does not support a primary role for segmental reflex action in mediating the transition between multijoint and single-joint control strategies. Furthermore, the scope and magnitude of these changes argues against the notion that human motor performance is driven by the optimization of muscle- or joint-related criteria alone. The findings are best described as reflecting the actions of a feedforward adaptive controller that has properties that are modified progressively according to the environmental state.
Nitric Oxide and Carbon Monoxide Modulate Oscillations of Olfactory Interneurons in a Terrestrial Mollusk
Authors: Gelperin A. , Flores J. , Raccuia-Behling F. , Cooke I.R.C.
Published: December 2017

Spontaneous or odor-induced oscillations in local field potential are a general feature of olfactory processing centers in a large number of vertebrate and invertebrate species. The ubiquity of such oscillations in the olfactory bulb of vertebrates and analogous structures in arthropods and mollusks suggests that oscillations are fundamental to the computations performed during processing of odor stimuli. Diffusible intercellular messengers such as nitric oxide (NO) and carbon monoxide (CO) also are associated with central olfactory structures in a wide array of species. We use the procerebral (PC) lobe of the terrestrial mollusk Limax maximus to demonstrate a role for NO and CO in the oscillatory dynamics of the PC lobe: synthesizing enzymes for NO and CO are associated with the PC lobes of Limax, application of NO to the Limax PC lobe increases the local field potential oscillation frequency, whereas block of NO synthesis slows or stops the oscillation, the bursting cells of the PC lobe that drive the field potential oscillation are driven to higher burst frequency by application of NO, the nonbursting cells of the PC lobe receive trains of inhibitory postsynaptic potentials, presumably from bursting cells, due to application of NO, and application of CO to the PC lobe by photolysis of caged CO results in an increase in oscillation frequency proportional to CO dosage.
Glutamate and GABA Activate Different Receptors and Cl− Conductances in Crab Peptide-Secretory Neurons
Authors: Duan Shumin , Cooke Ian M.
Published: December 2017

Responses to rapid application of glutamic acid (Glu) and γ-aminobutyric acid (GABA), 0.01–3 mM, were recorded by whole-cell patch clamp of cultured crab ( Cardisoma carnifex) X-organ neurons. Responses peaked within 200 ms. Both Glu and GABA currents had reversal potentials that followed the Nernst Cl− potential when [Cl−]i was varied. A Boltzmann fit to the normalized, averaged dose-response curve for Glu indicated an EC50 of 0.15 mM and a Hill coefficient of 1.05. Rapid ( t 1/2 ∼ 1 s) desensitization occurred during Glu but not GABA application that required >2 min for recovery. Desensitization was unaffected by concanavalin A or cyclothiazide. N-methyl-D-aspartate, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid, quisqualate, and kainate (to 1 mM) were ineffective, nor were Glu responses influenced by glycine (1 μM) or Mg2+ (0–26 mM). Glu effects were imitated by ibotenic acid (0.1 mM). The following support the conclusion that Glu and GABA act on different receptors: 1) responses sum; 2) desensitization to Glu or ibotenic acid did not diminish GABA responses; 3) the Cl−-channel blockers picrotoxin and niflumic acid (0.5 mM) inhibited Glu responses by ∼90 and 80% but GABA responses by ∼50 and 20%; and 4) polyvinylpyrrolydone-25 (2 mM in normal crab saline) eliminated Glu responses but left GABA responses unaltered. Thus crab secretory neurons have separate receptors responsive to Glu and to GABA, both probably ionotropic, and mediating Cl− conductance increases. In its responses and pharmacology, this crustacean Glu receptor resembles Cl−-permeable Glu receptors previously described in invertebrates and differs from cation-permeable Glu receptors of vertebrates and invertebrates.
Effect of Adaptation to Telescopic Spectacles on the Initial Human Horizontal Vestibuloocular Reflex
Authors: Crane Benjamin T. , Demer Joseph L.
Published: December 2017

Gain of the vestibuloocular reflex (VOR) not only varies with target distance and rotational axis, but can be chronically modified in response to prolonged wearing of head-mounted magnifiers. This study examined the effect of adaptation to telescopic spectacles on the variation of the VOR with changes in target distance and yaw rotational axis for head velocity transients having peak accelerations of 2,800 and 1,000°/s2. Eye and head movements were recorded with search coils in 10 subjects who underwent whole body rotations around vertical axes that were 10 cm anterior to the eyes, centered between the eyes, between the otoliths, or 20 cm posterior to the eyes. Immediately before each rotation, subjects viewed a target 15 or 500 cm distant. Lighting was extinguished immediately before and was restored after completion of each rotation. After initial rotations, subjects wore 1.9× magnification binocular telescopic spectacles during their daily activities for at least 6 h. Test spectacles were removed and measurement rotations were repeated. Of the eight subjects tolerant of adaptation to the telescopes, six demonstrated VOR gain enhancement after adaptation, while gain in two subjects was not increased. For all subjects, the earliest VOR began 7–10 ms after onset of head rotation regardless of axis eccentricity or target distance. Regardless of adaptation, VOR gain for the proximate target exceeded that for the distant target beginning at 20 ms after onset of head rotation. Adaptation increased VOR gain as measured 90–100 ms after head rotation onset by an average of 0.12 ± 0.02 (SE) for the higher head acceleration and 0.19 ± 0.02 for the lower head acceleration. After adaptation, four subjects exhibited significant increases in the canal VOR gain only, whereas two subjects exhibited significant increases in both angular and linear VOR gains. The latencies of linear and early angular target distance effects on VOR gain were unaffected by adaptation. The earliest significant change in angular VOR gain in response to adaptation occurred 50 and 68 ms after onset of the 2,800 and 1,000°/s2peak head accelerations, respectively. The latency of the adaptive increase in linear VOR gain was ∼50 ms for the peak head acceleration of 2,800°/s2, and 100 ms for the peak head acceleration of 1,000°/s2. Thus VOR gain changes and latency were consistent with modification in the angular VOR in most subjects, and additionally in the linear VOR in a minority of subjects.
Maintenance of Rat Head Direction Cell Firing During Locomotion in the Vertical Plane
Authors: Stackman Robert W. , Tullman Matthew L. , Taube Jeffrey S.
Published: December 2017

Previous studies have identified a subset of neurons in the rat anterodorsal thalamus (ADN) that encode head direction (HD) in absolute space and may be involved in navigation. These HD cells discharge selectively when the rat points its head in a specific direction (the preferred firing direction) in the horizontal plane. HD cells are typically recorded during free movement about a single horizontal surface. The current experiment examined how HD cell firing was influenced by 1) locomotion in the vertical plane and 2) locomotion on two different horizontal surfaces separated in height. Rats were trained in a cylindrical enclosure containing a single polarizing cue card attached to the cylinder wall, covering ∼100° of arc. The enclosure contained two horizontal surfaces: the cylinder floor and an annulus around the cylinder top 76 cm above the floor. A 90° vertical mesh ladder that could be affixed at any angular position on the cylinder wall allowed the rats to locomote back and forth between the two horizontal surfaces. Rats were trained to retrieve food pellets on the cylinder floor as well as climb the mesh ladder to retrieve food pellets on the annulus. HD cell activity was monitored as the rat traversed the horizontal and vertical surfaces of the apparatus. When the angular position of the mesh corresponded to the cell's preferred firing direction, the HD cells maintained their peak discharge rate as the rat climbed up the mesh, but did not fire when the rat climbed down the mesh. In contrast, when the mesh was positioned 180° opposite the preferred firing direction, HD cells did not fire when the rat climbed up the mesh, but exhibited maximal firing when the rat climbed down the mesh. When the mesh was placed 90 or 270° from the preferred firing direction, HD cells exhibited background firing rates during climbing up or down the mesh. While preferred firing directions were maintained between the two horizontal surfaces, peak firing rate increased significantly (∼30%) on the annulus as compared with the cylinder floor. These data demonstrate that HD cells continue to discharge in the vertical plane if the vertical locomotion began with the rat's orientation corresponding to the preferred firing direction. One model consistent with these data are that HD cells define the horizontal reference frame as the animal's plane of locomotion. Further, we propose that HD cell firing, as viewed within a three-dimensional coordinate system, can be characterized as the surface of a hemitorus.
Extent and Role of Multisegmental Coupling in the Lamprey Spinal Locomotor Pattern Generator
Authors: Miller William L. , Sigvardt Karen A.
Published: December 2017

Timing of oscillatory activity along the longitudinal body axis is critical for locomotion in the lamprey and other elongated animals. In the lamprey spinal locomotor central pattern generator (CPG), intersegmental coordination is thought to arise from the pattern of extensive connections made by propriospinal interneurons. However, the mechanisms responsible for intersegmental coordination remain unknown, in large part because of the difficulty in obtaining quantitative information on these multisegmental fibers. System-level experiments were performed on isolated 50-segment preparations of spinal cord of adult silver lampreys, Ichthyomyzon unicuspis, to determine the dependence of CPG performance on multisegmental coupling. Coupling was manipulated through use of an experiment chamber with movable partitions, which allowed separate application of solution to rostral, middle, and caudal regions of the spinal cord preparation. During control trials, fictive locomotion, induced by bath application ofd-glutamate in all three regions, was recorded extracellularly from ventral roots. Local synaptic activity in a variable number of middle segments was subsequently blocked with a low-Ca2+, high-Mn2+saline solution in the middle compartment, whereas conduction in axons spanning the middle segments was unaffected. Spectral analysis was used to assess the effects of blocking propriospinal coupling on intersegmental phase lag, rhythm frequency, correlation, and variability. Significant correlation and a stable phase lag between the rostral and caudal regions of the spinal cord preparation were maintained during block of as many as 16 and sometimes 20 intervening segments. However, the mean value of this rostrocaudal phase decreased with increasing number of blocked segments from the control value of approximately 1% per segment. By contrast, phase lags within the rostral and caudal end regions remained unaffected. The cycle frequency in the rostral and caudal regions decreased with the number of blocked middle segments and tended to diverge when a large number of middle segments was blocked. The variability in cycle frequency and intersegmental phase both increased with increasing number of blocked segments. In addition, a number of differences were noted in the properties of the motor output of the rostral and caudal regions of the spinal cord. The results indicate that the maximal functional length of propriospinal coupling fibers is at least 16–20 segments in I. unicuspis, whereas intersegmental phase lags are controlled at a local level and are not dependent on extended multisegmental coupling. Other possible roles for multisegmental coupling are discussed.
Cortical Activity in Precision- Versus Power-Grip Tasks: An fMRI Study
Authors: Ehrsson H. Henrik , Fagergren Anders , Jonsson Tomas , Westling Göran , Johansson Roland S. , Forssberg Hans
Published: December 2017

Most manual grips can be divided in precision and power grips on the basis of phylogenetic and functional considerations. We used functional magnetic resonance imaging to compare human brain activity during force production by the right hand when subjects used a precision grip and a power grip. During the precision-grip task, subjects applied fine grip forces between the tips of the index finger and the thumb. During the power-grip task, subjects squeezed a cylindrical object using all digits in a palmar opposition grasp. The activity recorded in the primary sensory and motor cortex contralateral to the operating hand was higher when the power grip was applied than when subjects applied force with a precision grip. In contrast, the activity in the ipsilateral ventral premotor area, the rostral cingulate motor area, and at several locations in the posterior parietal and prefrontal cortices was stronger while making the precision grip than during the power grip. The power grip was associated predominately with contralateral left-sided activity, whereas the precision-grip task involved extensive activations in both hemispheres. Thus our findings indicate that in addition to the primary motor cortex, premotor and parietal areas are important for control of fingertip forces during precision grip. Moreover, the ipsilateral hemisphere appears to be strongly engaged in the control of precision-grip tasks performed with the right hand.
Role of Pertussis Toxin–Sensitive G-Proteins in Synaptic Transmission and Plasticity at Corticostriatal Synapses
Authors: Tang Ka-Choi , Lovinger David M.
Published: December 2017

The role of pertussis toxin (PTX)–sensitive G-proteins in corticostriatal synaptic transmission and long-term synaptic depression (LTD) was examined using extracellular field potential and whole cell voltage-clamp recordings in striatal slices. High-frequency stimulation (HFS) produced LTD, defined as long-lasting decreases both in synaptically driven population spikes (PSs) measured with field potential recording and in excitatory postsynaptic currents (EPSCs) measured with whole cell recording. Striatal LTD could not be induced in slices obtained from rats that had received a unilateral intrastriatal injection of PTX. However, LTD could be induced in slices obtained from paired control slices. Furthermore, striatal LTD was prevented by pretreatment with N-ethylmaleimide (NEM), another compound that disrupts the function of PTX-sensitive G-proteins. NEM, itself, also potentiated PS and EPSC amplitudes. In addition, NEM increased the frequency and amplitude of both spontaneous and miniature EPSCs and decreased the paired-pulse facilitation ratio, suggesting that it may act on both pre- and postsynaptic sites. The findings suggest that PTX-sensitive G-proteins have multiple roles at corticostriatal synapses, including regulation of synaptic transmission at both pre- and postsynaptic sites, and a key role in striatal LTD.
Altered Regulation of Potassium and Calcium Channels by GABABand Adenosine Receptors in Hippocampal Neurons From Mice Lacking Gαo
Authors: Greif Gabriela J. , Sodickson Deborah L. , Bean Bruce P. , Neer Eva J. , Mende Ulrike
Published: December 2017

To examine the role of Goin modulation of ion channels by neurotransmitter receptors, we characterized modulation of ionic currents in hippocampal CA3 neurons from mice lacking both isoforms of Gαo. In CA3 neurons from Gαo−/−mice, 2-chloro-adenosine and the GABAB-receptor agonist baclofen activated inwardly rectifying K+currents and inhibited voltage-dependent Ca2+currents just as effectively as in Gαo+/+littermates. However, the kinetics of transmitter action were dramatically altered in Gαo−/−mice in that recovery on washout of agonist was much slower. For example, recovery from 2-chloro-adenosine inhibition of calcium current was more than fourfold slower in neurons from Gαo−/−mice [time constant of 12.0 ± 0.8 (SE) s] than in neurons from Gαo+/+mice (time constant of 2.6 ± 0.2 s). Recovery from baclofen effects was affected similarly. In neurons from control mice, effects of both baclofen and 2-chloro-adenosine on Ca2+currents and K+currents were abolished by brief exposure to external N-ethyl-maleimide (NEM). In neurons lacking Gαo, some inhibition of Ca2+currents by baclofen remained after NEM treatment, whereas baclofen activation of K+currents and both effects of 2-chloro-adenosine were abolished. These results show that modulation of Ca2+and K+currents by G protein-coupled receptors in hippocampal neurons does not have an absolute requirement for Gαo. However, modulation is changed in the absence of Gαoin having much slower recovery kinetics. A likely possibility is that the very abundant Gαois normally used but, when absent, can readily be replaced by G proteins with different properties.
Kinetic and Frequency-Domain Properties of Reflex and Conditioned Eyelid Responses in the Rabbit
Authors: Gruart Agnès , Schreurs Bernard G. , del Toro Eduardo Domínguez , Delgado-García JoséMaría
Published: December 2017

Eyelid position and the electromyographic activity of the orbicularis oculi muscle were recorded unilaterally in rabbits during reflex and conditioned blinks. Air-puff–evoked blinks consisted of a fast downward phase followed sometimes by successive downward sags. The reopening phase had a much longer duration and slower peak velocity. Onset latency, maximum amplitude, peak velocity, and rise time of reflex blinks depended on the intensity and duration of the air puff–evoking stimulus. A flashlight focused on the eye also evoked reflex blinks, but not flashes of light, or tones. Both delayed and trace classical conditioning paradigms were used. For delayed conditioning, animals were presented with a 350-ms, 90-dB, 600-Hz tone, as conditioned stimulus (CS). For trace conditioning, animals were presented with a 10-ms, 1-k/cm2air puff, as CS. The unconditioned stimulus (US) consisted of a 100-ms, 3-k/cm2air puff. The stimulus interval between CS and US onsets was 250 ms. Conditioned responses (CRs) to tones were composed of downward sags that increased in number through the successive conditioning sessions. The onset latency of the CR decreased across conditioning at the same time as its maximum amplitude and its peak velocity increased, but the time-to-peak of the CR remained unaltered. The topography of CRs evoked by short, weak air puffs as the CS showed three different components: the alpha response to the CS, the CR, and the reflex response to the US. Through conditioning, CRs showed a decrease in onset latency, and an increase in maximum amplitude and peak velocity. The time-to-peak of the CR remained unchanged. A power spectrum analysis of reflex and conditioned blink acceleration profiles showed a significant ≈8-Hz oscillation within a broadband of frequencies between 4 and 15 Hz. Nose and mandible movements presented power spectrum profiles different from those characterizing reflex and conditioned blinks. It is concluded that eyelid reflex responses in the rabbit present significant differences from CRs in their profiles and metric properties, suggesting different neural origins, but that a common ≈8-Hz neural oscillator underlies lid motor performance. According to available data, the frequency of this putative oscillator seems to be related to the species size.
Activity of Reticulospinal Neurons During Locomotion in the Freely Behaving Lamprey
Authors: Deliagina T. G. , Zelenin P. V. , Fagerstedt P. , Grillner S. , Orlovsky G. N.
Published: December 2017

The reticulospinal (RS) system is the main descending system transmitting commands from the brain to the spinal cord in the lamprey. It is responsible for initiation of locomotion, steering, and equilibrium control. In the present study, we characterize the commands that are sent by the brain to the spinal cord in intact animals via the reticulospinal pathways during locomotion. We have developed a method for recording the activity of larger RS axons in the spinal cord in freely behaving lampreys by means of chronically implanted macroelectrodes. In this paper, the mass activity in the right and left RS pathways is described and the correlations of this activity with different aspects of locomotion are discussed. In quiescent animals, the RS neurons had a low level of activity. A mild activation of RS neurons occurred in response to different sensory stimuli. Unilateral eye illumination evoked activation of the ipsilateral RS neurons. Unilateral illumination of the tail dermal photoreceptors evoked bilateral activation of RS neurons. Water vibration also evoked bilateral activation of RS neurons. Roll tilt evoked activation of the contralateral RS neurons. With longer or more intense sensory stimulation of any modality and laterality, a sharp, massive bilateral activation of the RS system occurred, and the animal started to swim. This high activity of RS neurons and swimming could last for many seconds after termination of the stimulus. There was a positive correlation between the level of activity of RS system and the intensity of locomotion. An asymmetry in the mass activity on the left and right sides occurred during lateral turns with a 30% prevalence (on average) for the ipsilateral side. Rhythmic modulation of the activity in RS pathways, related to the locomotor cycle, often was observed, with its peak coinciding with the electromyographic (EMG) burst in the ipsilateral rostral myotomes. The pattern of vestibular response of RS neurons observed in the quiescent state, that is, activation with contralateral roll tilt, was preserved during locomotion. In addition, an inhibition of their activity with ipsilateral tilt was clearly seen. In the cases when the activity of individual neurons could be traced during swimming, it was found that rhythmic modulation of their firing rate was superimposed on their tonic firing or on their vestibular responses. In conclusion, different aspects of locomotor activity—initiation and termination, vigor of locomotion, steering and equilibrium control—are well reflected in the mass activity of the larger RS neurons.
Cannabinoid Receptor Modulation of Synapses Received by Cerebellar Purkinje Cells
Authors: Takahashi Kanji A. , Linden David J.
Published: December 2017

The high density of cannabinoid receptors in the cerebellum and the degradation of motor coordination produced by cannabinoid intoxication suggest that synaptic transmission in the cerebellum may be strongly regulated by cannabinoid receptors. Therefore the effects of exogenous cannabinoids on synapses received by Purkinje cells were investigated in rat cerebellar slices. Parallel fiber–evoked (PF) excitatory postsynaptic currents (EPSCs) were strongly inhibited by bath application of the cannabinoid receptor agonist WIN 55212-2 (5 μM, 12% of baseline EPSC amplitude). This effect was completely blocked by the cannabinoid CB1 receptor antagonist SR 141716. It is unlikely that this was the result of alterations in axonal excitability because fiber volley velocity and kinetics were unchanged and a cannabinoid-induced decrease in fiber volley amplitude was very minor (93% of baseline). WIN 55212-2 had no effect on the amplitude or frequency of spontaneously occurring miniature EPSCs (mEPSCs), suggesting that the effect of CB1 receptor activation on PF EPSCs was presynaptically expressed, but giving no evidence for modulation of release processes after Ca2+influx. EPSCs evoked by climbing fiber (CF) stimulation were less powerfully attenuated by WIN 55212-2 (5 μM, 74% of baseline). Large, action potential–dependent, spontaneously occurring inhibitory postsynaptic currents (sIPSCs) were either severely reduced in amplitude (<25% of baseline) or eliminated. Miniature IPSCs (mIPSCs) were reduced in frequency (52% of baseline) but not in amplitude, demonstrating suppression of presynaptic vesicle release processes after Ca2+ influx and suggesting an absence of postsynaptic modulation. The decrease in mIPSC frequency was not large enough to account for the decrease in sIPSC amplitude, suggesting that presynaptic voltage-gated channel modulation was also involved. Thus, while CB1 receptor activation reduced neurotransmitter release at all major classes of Purkinje cell synapses, this was not accomplished by a single molecular mechanism. At excitatory synapses, cannabinoid suppression of neurotransmitter release was mediated by modulation of voltage-gated channels in the presynaptic axon terminal. At inhibitory synapses, in addition to modulation of presynaptic voltage-gated channels, suppression of the downstream vesicle release machinery also played a large role.