bluuebunny/crossref_metadata_2025 huggingface dataset:
Inhibition of Backpropagating Action Potentials in Mitral Cell Secondary Dendrites
Authors: Lowe Graeme
Published: December 2017

The mammalian olfactory bulb is a geometrically organized signal-processing array that utilizes lateral inhibitory circuits to transform spatially patterned inputs. A major part of the lateral circuitry consists of extensively radiating secondary dendrites of mitral cells. These dendrites are bidirectional cables: they convey granule cell inhibitory input to the mitral soma, and they conduct backpropagating action potentials that trigger glutamate release at dendrodendritic synapses. This study examined how mitral cell firing is affected by inhibitory inputs at different distances along the secondary dendrite and what happens to backpropagating action potentials when they encounter inhibition. These are key questions for understanding the range and spatial dependence of lateral signaling between mitral cells. Backpropagating action potentials were monitored in vitro by simultaneous somatic and dendritic whole cell recording from individual mitral cells in rat olfactory bulb slices, and inhibition was applied focally to dendrites by laser flash photolysis of caged GABA (2.5-μm spot). Photolysis was calibrated to activate conductances similar in magnitude to GABAA-mediated inhibition from granule cell spines. Under somatic voltage-clamp with CsCl dialysis, uncaging GABA onto the soma, axon initial segment, primary and secondary dendrites evoked bicuculline-sensitive currents (up to −1.4 nA at −60 mV; reversal at ∼0 mV). The currents exhibited a patchy distribution along the axon and dendrites. In current-clamp recordings, repetitive firing driven by somatic current injection was blocked by uncaging GABA on the secondary dendrite ∼140 μm from the soma, and the blocking distance decreased with increasing current. In the secondary dendrites, backpropagated action potentials were measured 93–152 μm from the soma, where they were attenuated by a factor of 0.75 ± 0.07 (mean ± SD) and slightly broadened (1.19 ± 0.10), independent of activity (35–107 Hz). Uncaging GABA on the distal dendrite had little effect on somatic spikes but attenuated backpropagating action potentials by a factor of 0.68 ± 0.15 (0.45–0.60 μJ flash with 1-mM caged GABA); attenuation was localized to a zone of width 16.3 ± 4.2 μm around the point of GABA release. These results reveal the contrasting actions of inhibition at different locations along the dendrite: proximal inhibition blocks firing by shunting somatic current, whereas distal inhibition can impose spatial patterns of dendrodendritic transmission by locally attenuating backpropagating action potentials. The secondary dendrites are designed with a high safety factor for backpropagation, to facilitate reliable transmission of the outgoing spike-coded data stream, in parallel with the integration of inhibitory inputs.
Effects of Excitatory Modulation on Intrinsic Properties of Turtle Motoneurons
Authors: Hornby T. George , McDonagh Jennifer C. , Reinking Robert M. , Stuart Douglas G.
Published: December 2017

The purpose of this study was to quantify the effects of excitatory modulation on the intrinsic properties of motoneurons (MNs) in slices of spinal cord taken from the adult turtle. Responses were noted following application of an excitatory modulator: serotonin (5-HT), muscarine, trans-1-amino-1,3-cyclopentane dicarboxylic acid (tACPD), or all three combined. A sample of 44 MNs was divided into 2 groups, on the basis of whether MNs did (28/44) or did not (16/44) demonstrate a nifedipine-sensitive acceleration of discharge during a 2-s, intracellularly injected stimulus pulse. Such acceleration indicates the development of a plateau potential (PP). Excitatory modulation lowered the MNs' resting potential, increased input resistance, decreased rheobase, reduced several afterhyperpolarization values, and shifted the conventional, one-phase stimulus current–spike frequency ( I-f) relation to the left. For both MN groups, the relative efficacy of excitatory modulation on both non-PP and PP MNs was generally in the following order: combined application > 5-HT ≈ muscarine > tACPD. In many instances, the effects of modulation differed significantly for non-PP versus PP MNs, the most pronounced being in their I-f relation. To describe this difference, it was necessary to measure a two-phase relation. In PP MNs, excitatory modulation considerably increased the slope of the first (initial) phase and flattened the second (later) phase of this relation. The latter result bore similarities to that obtained in a previous study, which addressed MN firing behavior during fictive locomotion of the high-decerebrate cat.
Roles of ATP in Depletion and Replenishment of the Releasable Pool of Synaptic Vesicles
Authors: Heidelberger Ruth , Sterling Peter , Matthews Gary
Published: December 2017

Synaptic terminals of retinal bipolar neurons contain a pool of readily releasable synaptic vesicles that undergo rapid calcium-dependent release. ATP hydrolysis is required for the functional refilling of this vesicle pool. However, it was unclear which steps required ATP hydrolysis: delivery of vesicles to their anatomical release sites or preparation of synaptic vesicles and/or the secretory apparatus for fusion. To address this, we dialyzed single synaptic terminals with ATP or the poorly hydrolyzable analogue ATP-γS and examined the size of the releasable pool, refilling of the releasable pool, and the number of vesicles at anatomical active zones. After minutes of dialysis with ATP-γS, vesicles already in the releasable pool could still be discharged. This pool was not functionally refilled despite the fact that its anatomical correlate, the number of synaptic vesicles tethered to active zone synaptic ribbons, was completely normal. We conclude 1) because the existing releasable pool is stable during prolonged inhibition of ATP hydrolysis, whereas entry into the functional pool is blocked, a vesicle on entering the pool will tend to remain there until it fuses; 2) because the anatomical pool is unaffected by inhibition of ATP hydrolysis, failure to refill the functional pool is not caused by failure of vesicle movement; 3) local vesicle movements important for pool refilling and fusion are independent of conventional ATP-dependent motor proteins; and 4) ATP hydrolysis is required for the biochemical transition of vesicles and/or release sites to fusion-competent status.
Functional Inhibition in Direction-Selective Retinal Ganglion Cells: Spatiotemporal Extent and Intralaminar Interactions
Authors: Stasheff Steven F. , Masland Richard H.
Published: December 2017

We recorded from on-off direction-selective ganglion cells (DS cells) in the rabbit retina to investigate in detail the inhibition that contributes to direction selectivity in these cells. Using paired stimuli moving sequentially across the cells' receptive fields in the preferred direction, we directly confirmed the prediction of Wyatt and Daw (1975) that a wave of inhibition accompanies any moving excitatory stimulus on its null side, at a fixed spatial offset. Varying the interstimulus distance, stimulus size, luminance, and speed yielded a spatiotemporal map of the strength of inhibition within this region. This “null” inhibition was maximal at an intermediate distance behind a moving stimulus: ½ to 1½ times the width of the receptive field. The strength of inhibition depended more on the distance behind the stimulus than on stimulus speed, and the inhibition often lasted 1–2 s. These spatial and temporal parameters appear to account for the known spatial frequency and velocity tuning of on-off DS cells to drifting contrast gratings. Stimuli that elicit distinct onand off responses to leading and trailing edges revealed that an excitatory response of either polarity could inhibit a subsequent response of either polarity. For example, an offresponse inhibited either an on or off response of a subsequent stimulus. This inhibition apparently is conferred by a neural element or network spanning the on andoff sublayers of the inner plexiform layer, such as a multistratified amacrine cell. Trials using a stationary flashing spot as a probe demonstrated that the total amount of inhibition conferred on the DS cell was equivalent for stimuli moving in either the null or preferred direction. Apparently the cell does not act as a classic “integrate and fire” neuron, summing all inputs at the soma. Rather, computation of stimulus direction likely involves interactions between excitatory and inhibitory inputs in local regions of the dendrites.
Modulatory Effect of Cortical Activation on the Lemniscal Auditory Thalamus of the Guinea Pig
Authors: He Jufang , Yu Yan-Qin , Xiong Ying , Hashikawa Tsutomu , Chan Ying-Shing
Published: December 2017

In the present study, we investigated the point-to-point modulatory effects from the auditory cortex to the thalamus in the guinea pig. Corticofugal modulation on thalamic neurons was studied by electrical activation of the auditory cortex. The modulation effect was sampled along the frontal or sagittal planes of the auditory thalamus, focusing on the ventral division (MGv) of the medial geniculate body (MGB). Electrical activation was targeted at the anterior and dorsocaudal auditory fields, to which the MGv projects and from which it assumptively receives reciprocal projections. Of the 101 MGv neurons examined by activation of the auditory cortex through passing pulse trains of 100–200 μA current into one after another of the three implanted electrodes (101 neurons × 3 stimulation sites = 303 cases), 208 cases showed a facilitatory effect, 85 showed no effect, and only 10 cases (7 neurons) showed an inhibitory effect. Among the cases of facilitation, 63 cases showed a facilitatory effect >100%, and 145 cases showed a facilitatory effect from 20–100%. The corticofugal modulatory effect on the MGv of the guinea pig showed a widespread, strong facilitatory effect and very little inhibitory effect. The MGv neurons showed the greatest facilitations to stimulation by the cortical sites, with the closest correspondence in BF. Six of seven neurons showed an elevation of the rate-frequency functions when the auditory cortex was activated. The comparative results of the corticofugal modulatory effects on the MGv of the guinea pig and the cat, together with anatomical findings, hint that the strong facilitatory effect is generated through the strong corticothalamic direct connection and that the weak inhibitory effect might be mainly generated via the interneurons of the MGv. The temporal firing pattern of neuronal response to auditory stimulus was also modulated by cortical stimulation. The mean first-spike latency increased significantly from 15.7 ± 5.3 ms with only noise-burst stimulus to 18.3 ± 4.9 ms ( n = 5, P < 0.01, paired t-test), while the auditory cortex was activated with a train of 10 pulses. Taking these results together with those of previous experiments conducted on the cat, we speculate that the relatively weaker inhibitory effect compared with that in the cat could be due to the smaller number of interneurons in the guinea pig MGB. The corticofugal modulation of the firing pattern of the thalamic neurons might enable single neurons to encode more auditory information using not only the firing rate but also the firing pattern.
Serotonergic Control of Cerebellar Mossy Fiber Activity by Modulation of Signal Transfer by Rat Pontine Nuclei Neurons
Authors: Möck Martin , Schwarz Cornelius , Thier Peter
Published: December 2017

Serotonergic modulation of precerebellar nuclei may be crucial for the function of the entire cerebellar system. To study the effects of serotonin (5-HT) on neurons located within the pontine nuclei (PN), the main source of cerebellar mossy fibers, we performed standard intracellular recordings from PN neurons in a slice preparation of the rat pontine brain stem. Application of 5 μM 5-HT significantly altered several intrinsic membrane properties of PN neurons. First, it depolarized the somatic membrane potential by 6.5 ± 3.5 mV and increased the apparent input resistance from 49.5 ± 14.6 to 62.7 ± 21.1 MΩ. Second, 5-HT altered the I-V relationship of PN neurons: it decreased the inward rectification in hyperpolarizing direction, but increased it when depolarizing currents were applied. Third, it decreased the rheobase from 0.32 ± 0.14 to 0.24 ± 0.14 nA without affecting the firing threshold. Finally, the amplitude of medium-duration afterhyperpolarizations was reduced from −14.9 ± 2.0 to −12.3 ± 2.4 mV. Together, these 5-HT effects on the intrinsic membrane properties result in an increase in excitability and instantaneous firing rate. In addition, application of 5 μM 5-HT also modulated postsynaptic potentials (PSPs) evoked by electric stimulations within the cerebral peduncle. The amplitude, maximal slope, and integral of these PSPs were reduced to 46.2 ± 23.4%, 45.7 ± 23.7%, and 61.4 ± 28.4% of the control value, respectively. In contrast, we found no change in the decay and voltage dependence of PSPs. To test modulatory effects on short-term synaptic facilitation, we applied pairs of electrical stimuli at intervals between 10 and 1,000 ms. 5-HT selectively enhanced the paired-pulse facilitation for interstimulus-intervals >20 ms. The alteration of paired-pulse facilitation points to a presynaptic site of action for 5-HT effects on synaptic transmission. Pharmacological experiments suggested that pre- and postsynaptic effects of 5-HT were mediated by two different kinds of 5-HT receptors: changes in intrinsic membrane properties were blocked by the 5-HT2 receptor antagonist cinanserin while the reduction of PSPs was prevented by the 5-HT1 receptor antagonist cyanopindolol. In conclusion, 5-HT increases the excitability of PN neurons but decreases the synaptic transmission on them. The selective enhancement of synaptic facilitation may, however, allow high-frequency inputs to effectively drive PN neurons, thus the PN may act as a high-pass filter during periods of 5-HT release.
CO2 and pH Independently Modulate L-Type Ca2+ Current in Rabbit Carotid Body Glomus Cells
Authors: Summers Beth A. , Overholt Jeffrey L. , Prabhakar Nanduri R.
Published: December 2017

The carotid bodies respond to changes in arterial O2, CO2, and pH, and Ca2+ influx via voltage-gated Ca2+ channels is an important step in the chemoreception process. The objectives of the present study were as follows: 1) to determine whether hypercapnia modulates Ca2+ current in glomus cells, and if so, to determine if this modulation is secondary to changes in pH; 2) to examine the mechanism of CO2modulation of the Ca2+ current; and 3) to determine whether the effects of hypercapnia and hypoxia on Ca2+ channel activity in glomus cells are synergistic. The effects of CO2 on Ca2+ current were monitored in glomus cells isolated from rabbit carotid bodies using both perforated and conventional patch-clamp techniques. Raising CO2in the extracellular solution from 5 to 10% (hypercapnia) reversibly augmented the whole-cell Ca2+ current. This augmentation was rapid and increased the whole-cell Ca2+ current similarly in both the perforated and the conventional patch configurations by 16 ± 2% ( n = 5) and 15 ± 1% ( n = 32), respectively. The following observations suggest that the effects of CO2 are not secondary to changes in pH: 1) isohydric hypercapnia (pH maintained at 7.4) augmented the Ca2+ current by 24 ± 2% ( n = 6); 2) decreasing the pH of the extra- or intracellular solutions decreased the Ca2+current by 43 ± 4% ( n = 8) and 13 ± 1% ( n = 5), respectively; and 3) hypercapnia did not shift the half-maximal activation voltage ( V 1/2), whereas intracellular and extracellular acidosis alone caused shifts in V 1/2. Furthermore, 100 nM of a membrane-permeable protein kinase A inhibitor prevented the augmentation by CO2, and 500 μM 8-Br-cAMP mimicked the effect of CO2 by augmenting the Ca2+ current by 10 ± 2% ( n= 6). Also, cyclic AMP levels in carotid bodies increased from 1.98 ± 0.6 to 9.0 ± 2 pmol/μg protein in response to hypercapnia. In contrast, decreasing pH in the nominal absence of CO2 did not affect cAMP levels in rabbit carotid bodies. Further, nisoldipine, but not ω-conotoxin MVIIC, prevented augmentation of the Ca2+ current by CO2. In addition, when combined, hypercapnia and hypoxia augmented the Ca2+ current by 26 ± 4% ( n = 7), which is greater than either stimulus alone, suggesting the effects are additive. Taken together, these results indicate that L-type Ca2+ current is augmented by hypercapnia. The effect of CO2 is not secondary to changes in pH and seems to be mediated by a protein kinase A-dependent mechanism. Furthermore, hypercapnia and hypoxia act additively in stimulating Ca2+ current in glomus cells.
Evoked Responses of the Dentate Gyrus During Seizures in Developing Gerbils With Inherited Epilepsy
Authors: Buckmaster Paul S. , Wong Emilia H.
Published: December 2017

When they are 1–2 mo old, domesticated Mongolian gerbils begin having initially mild seizures which become more severe with age. To evaluate the development of this increasing seizure severity, we obtained field potential responses of the dentate gyrus to paired-pulse stimulation of the perforant path during seizures. In 18 gerbils that were 1.5–8.0 mo old, 73 seizures were analyzed. We measured population spike amplitude, the slope of the field excitatory postsynaptic potential (fEPSP), and the population spike amplitude ratio (2nd/1st) to evaluate excitatory and inhibitory synaptic processes. In gerbils <2 mo old, exposure to a novel environment was followed by an increase in population spike amplitude and then by seizure onset, but population spike amplitude ratio and fEPSP slope remained at baseline levels, and multiple population spikes were never evoked. As previously reported for chronically epileptic gerbils, these findings provide little evidence of a disinhibitory seizure-initiating mechanism in the dentate gyrus when young gerbils begin having seizures. In young gerbils evoked responses changed little during the behaviorally mild seizures. In contrast, most seizures in older gerbils included generalized convulsions, postictal depression, and evoked responses that changed dramatically. In older gerbils, shortly after seizure onset the dentate gyrus became hyperexcitable. Population spike amplitude and fEPSP slope peaked, and multiple population spikes were evoked, suggesting that mechanisms for seizure amplification and spread are more developed in older gerbils. Next, dentate gyrus excitability decreased precipitously, and population spike amplitude and fEPSP slope diminished. This period of hypoexcitability began before the end of the seizure, suggesting it may contribute to seizure termination. After the convulsive phase of the seizure, older gerbils remained motionless during a period of postictal depression, and population spike amplitude remained suppressed until the abrupt switch to normal exploratory activity. These findings suggest that the mechanisms of postictal depression may suppress granule cell excitability. The population spike amplitude ratio peaked after the convulsive phase and then gradually returned to the baseline level an average of 12 min after seizure onset, suggesting that granule cell inhibition recovers within minutes after a spontaneous seizure. Although it is unclear whether the seizure-related changes in evoked responses are a cause or an effect of increased seizure severity in older gerbils, their analysis provides clues about developmental changes in the mechanisms of seizure spread and termination.
Forward Models in Visuomotor Control
Authors: Mehta Biren , Schaal Stefan
Published: December 2017

In recent years, an increasing number of research projects investigated whether the central nervous system employs internal models in motor control. While inverse models in the control loop can be identified more readily in both motor behavior and the firing of single neurons, providing direct evidence for the existence of forward models is more complicated. In this paper, we will discuss such an identification of forward models in the context of the visuomotor control of an unstable dynamic system, the balancing of a pole on a finger. Pole balancing imposes stringent constraints on the biological controller, as it needs to cope with the large delays of visual information processing while keeping the pole at an unstable equilibrium. We hypothesize various model-based and non-model-based control schemes of how visuomotor control can be accomplished in this task, including Smith Predictors, predictors with Kalman filters, tapped-delay line control, and delay-uncompensated control. Behavioral experiments with human participants allow exclusion of most of the hypothesized control schemes. In the end, our data support the existence of a forward model in the sensory preprocessing loop of control. As an important part of our research, we will provide a discussion of when and how forward models can be identified and also the possible pitfalls in the search for forward models in control.
Adaptation to a Visuomotor Shift Depends on the Starting Posture
Authors: Baraduc Pierre , Wolpert Daniel M.
Published: December 2017

Previous studies have shown that human subjects can adapt to a new visuomotor relationship that depends on the trajectory of the arm. However, these studies have not distinguished between hand- and joint-based learning models. We have examined whether different endpoint kinematics are necessary to obtain a differential visuomotor shift. The joint trajectory was varied by changing the initial posture, while maintaining a similar finger trajectory. After learning, maximum after-effects were found when movement began with the posture used during exposure to the visuomotor shift and decreased with the difference between initial and trained posture. This was shown to be independent of the final posture attained. Our results show that adaptation to a visual remapping cannot be due to the recoding of a desired final posture and depends on the arm trajectory in joint space.
Reflections of Efferent Activity in Rotational Responses of Chinchilla Vestibular Afferents
Authors: Plotnik Meir , Marlinski Vladimir , Goldberg Jay M.
Published: December 2017

To study presumed efferent-mediated responses, we determined if afferents responded to head rotations that stimulated semicircular canals other than the organ being innervated. To minimize stimulation of an afferent's own canal, its plane was placed nearly orthogonal to the rotation plane. Otolith units were tested in a horizontal head position with the ear placed near the rotation axis to minimize linear forces. Under these circumstances, angular-velocity trapezoids (2-s ramps, 2-s plateau) evoked excitatory responses for both rotation directions. These type III responses were considerably larger in decerebrate than in anesthetized preparations. In addition to their being exclusively excitatory, the responses resembled those obtained with electrical stimulation of efferent pathways in including per-stimulus and more prolonged post-stimulus components and in being larger in irregularly discharging than in regularly discharging units. Responses, which were not seen for rotations <80°/s, grew as velocity increased between 80 and 500°/s but were seldom larger than 20 spikes/s. Complete section of the VIIIth nerve abolished type III responses, leaving conventional afferent responses intact. To study the separate contributions of canals on the two sides, responses were compared when the labyrinths were intact and when the ipsilateral or contralateral horizontal canal was mechanically inactivated. Both sides contributed to the efferent-mediated responses. That afferents could be influenced from the contralateral labyrinth was confirmed with the use of unilateral galvanic currents. Following inactivation, excitatory responses were produced by rotations exciting or inhibiting the intact horizontal canal with the responses resulting from excitatory rotations being much larger. Such a response asymmetry is consistent with a semicircular-canal origin for the type III responses. A similar asymmetry was seen in the post-stimulus responses to contralateral cathodal (excitatory) and anodal (inhibitory) galvanic currents. We conclude that the efferent system receives a sufficiently powerful vestibular input from both the ipsilateral and contralateral labyrinths to affect afferent discharge.
Frequency Response Properties of Lateral Line Superficial Neuromasts in a Vocal Fish, With Evidence for Acoustic Sensitivity
Authors: Weeg Matthew S. , Bass Andrew H.
Published: December 2017

The mechanosensory lateral line of fish is a hair cell based sensory system that detects water motion using canal and superficial neuromasts. The trunk lateral line of the plainfin midshipman fish, Porichthys notatus, only has superficial neuromasts. The posterior lateral line nerve (PLLn) therefore innervates trunk superficial neuromasts exclusively and provides the opportunity to investigate the physiological responses of these receptors without the confounding influence of canal organs. We recorded single-unit activity from PLLn primary afferents in response to a vibrating sphere stimulus calibrated to produce an equal velocity across frequencies. Threshold tuning, isovelocity, and input/output curves were constructed using spike rate and vector strength, a measure of phase locking of spike times to the stimulus waveform. All units responded maximally to frequencies of 20–50 Hz. Units were classified as low-pass, band-pass, broadly tuned, or complex based on the shapes of tuning and isovelocity curves between 20 and 100 Hz. A 100 Hz stimulus caused an increase in spike rate in almost 50%, and significant synchronization in >80%, of all units. Midshipman vocalizations contain significant energy at and below 100 Hz, so these results demonstrate that the midshipman peripheral lateral line system can encode these acoustic signals. These results provide the first direct demonstration that units innervating superficial neuromasts in a teleost fish have heterogeneous frequency response properties, including an upper range of sensitivity that overlaps spectral peaks of behaviorally relevant acoustic stimuli.
Contrast-Dependent Changes in Spatial Frequency Tuning of Macaque V1 Neurons: Effects of a Changing Receptive Field Size
Authors: Sceniak Michael P. , Hawken Michael J. , Shapley Robert
Published: December 2017

Previous studies on single neurons in primary visual cortex have reported that selectivity for orientation and spatial frequency tuning do not change with stimulus contrast. The prevailing hypothesis is that contrast scales the response magnitude but does not differentially affect particular stimuli. Models where responses are normalized over contrast to maintain constant tuning for parameters such as orientation and spatial frequency have been proposed to explain these results. However, our results indicate that a fundamental property of receptive field organization, spatial summation, is not contrast invariant. We examined the spatial frequency tuning of cells that show contrast-dependent changes in spatial summation and have found that spatial frequency selectivity also depends on stimulus contrast. These results indicate that contrast changes in the spatial frequency tuning curves result from spatial reorganization of the receptive field.
Somatosensory Processing in the Human Inferior Prefrontal Cortex
Authors: Hagen Matthew C. , Zald David H. , Thornton Tricia A. , Pardo José V.
Published: December 2017

Three inferior prefrontal regions in the monkey receive afferents from somatosensory cortices: the orbitofrontal cortex (OFC), the ventral area of the principal sulcus, and the anterior frontal operculum. To determine whether these areas show responses to tactile stimuli in humans, we examined data from an ongoing series of PET studies of somatosensory processing. Unlike previous work showing ventral frontal activity to hedonic (pleasant/unpleasant) sensory stimulation, the tactile stimuli used in these studies had a neutral hedonic valence. Our data provide evidence for at least two discrete ventral frontal brain regions responsive to somatosensory stimulation: 1) the posterior inferior frontal gyrus (IFG) and adjacent anterior frontal operculum, and 2) the OFC. The former region (posterior IFG/anterior frontal operculum) may have a more specific role in attending to tactile stimuli.
Direct Comparison of Neural Systems Mediating Conscious and Unconscious Skill Learning
Authors: Willingham Daniel B. , Salidis Joanna , Gabrieli John D.E.
Published: December 2017

Procedural learning, such as perceptual-motor sequence learning, has been suggested to be an obligatory consequence of practiced performance and to reflect adaptive plasticity in the neural systems mediating performance. Prior neuroimaging studies, however, have found that sequence learning accompanied with awareness (declarative learning) of the sequence activates entirely different brain regions than learning without awareness of the sequence (procedural learning). Functional neuroimaging was used to assess whether declarative sequence learning prevents procedural learning in the brain. Awareness of the sequence was controlled by changing the color of the stimuli to match or differ from the color used for random sequences. This allowed direct comparison of brain activation associated with procedural and declarative memory for an identical sequence. Activation occurred in a common neural network whether initial learning had occurred with or without awareness of the sequence, and whether subjects were aware or not aware of the sequence during performance. There was widespread additional activation associated with awareness of the sequence. This supports the view that some types of unconscious procedural learning occurs in the brain whether or not it is accompanied by conscious declarative knowledge.
Prehension Movements in the Macaque Monkey: Effects of Object Size and Location
Authors: Roy Alice C. , Paulignan Yves , Meunier Martine , Boussaoud Driss
Published: December 2017

Prehension movements were examined in freely behaving monkeys and compared with the well-known characteristics of human movements. The degree of independence of the components of movements (i.e., reaching and grasping) was investigated in animals trained to reach for and grasp three-dimensional objects. To this aim, the kinematics of prehension movements was recorded using an Optotrak system in two tasks. In one task, monkeys grasped a small or a large object (size task), in the other, they grasped an object of constant size placed at three different spatial locations (location task). We found that object size and its location affected both reaching and grasping. In particular, in the size task, we found that the maximum grip aperture strongly depended on the selection of the grip and not only on the size of an object. Our results also revealed that, in monkeys as well as in humans, the reaching parameters are highly sensitive to task-related constraints such as accuracy demands. The results of the location task showed a difference between rightward and leftward movements, a pattern of grip aperture that varied across animals, and a large degree of coordination between the two components. These findings argue against a strict postulate of independence between the visuo-motor channels, favoring instead the idea of variable degrees of coordination between the reach and grasp components depending on the task demands. Finally, this work emphasizes the relevance of studying monkey's prehension movements as a useful step to the understanding of visuo-motor control in humans.
BOLD fMRI Identifies Limbic, Paralimbic, and Cerebellar Activation During Air Hunger
Authors: Evans Karleyton C. , Banzett Robert B. , Adams Lewis , McKay Leanne , Frackowiak Richard S. J. , Corfield Douglas R.
Published: December 2017

Air hunger (uncomfortable urge to breathe) is a component of dyspnea (shortness of breath). Three human H215O positron emission tomography (PET) studies have identified activation of phylogenetically ancient structures in limbic and paralimbic regions during dyspnea. Other studies have shown activation of these structures during other sensations that alert the organism to urgent homeostatic imbalance: pain, thirst, and hunger for food. We employed blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI) to examine activation during air hunger. fMRI conferred several advantages over PET: enhanced signal-to-noise, greater spatial resolution, and lack of ionizing radiation, enabling a greater number of trials in each subject. Six healthy men and women were mechanically ventilated at 12–14 breaths/min. The primary experiment was conducted at mean end-tidal Pco2of 41 Torr. Moderate to severe air hunger was evoked during 42-s epochs of lower tidal volume (mean = 0.75 L). Subjects described the sensation as “like breath-hold,” “urge to breathe,” and “starved for air.” In the baseline condition, air hunger was consistently relieved by epochs of higher tidal volume (mean = 1.47 L). A control experiment in the same subjects under a background of mild hypocapnia (mean end-tidal PCO2= 33 Torr) employed similar tidal volumes but did not evoke air hunger, controlling for stimulus variables not related to dyspnea. During each experiment, we maintained constant end-tidal Pco2and PO2to avoid systematic changes in global cerebral blood flow. Whole-brain images were acquired every 5 s (T2*, 56 slices, voxel resolution 3 × 3 × 3 mm). Activations associated with air hunger were determined using voxel-based interaction analysis of covariance that compared data between primary and control experiments (SPM99). We detected activations not seen in the earlier PET study using a similar air hunger stimulus ( Banzett et al. 2000 ). Limbic and paralimbic loci activated in the present study were within anterior insula (seen in all 3 published studies of dyspnea), anterior cingulate, operculum, cerebellum, amygdala, thalamus, and basal ganglia. Elements of frontoparietal attentional networks were also identified. The consistency of anterior insular activation across subjects in this study and across published studies suggests that the insula is essential to dyspnea perception, although present data suggest that the insula acts in concert with a larger neural network.
Optical Imaging of Intrinsic Signals in Ferret Auditory Cortex: Responses to Narrowband Sound Stimuli
Authors: Versnel Huib , Mossop Jennifer E. , Mrsic-Flogel Thomas D. , Ahmed Bashir , Moore David R.
Published: December 2017

This paper describes optical imaging of the auditory cortex in the anesthetized ferret, particularly addressing optimization of narrowband stimuli. The types of sound stimuli used were tone-pip trains and sinusoidal frequency and amplitude modulated (SFM and SAM) tones. By employing short illumination wavelengths (546 nm), we have successfully characterized the tonotopic arrangement, in agreement with the well-established electrophysiological tonotopic maps of the ferret auditory primary field (AI). The magnitude of the optical signal increased with sound level, was maximal for a modulation frequency (MF) of 2–4 Hz, and was larger for tone-pip trains and SFM sounds than for SAM sounds. Accordingly, an optimal narrowband stimulus was defined. Thus optical imaging can be used successfully to obtain frequency maps in auditory cortex by an appropriate choice of stimulus parameters. In addition, background noise consisting of 0.1-Hz oscillations could be reduced by introduction of blood pressure enhancing drugs. The optical maps were largely independent of 1) the type of narrowband stimulus, 2) the sound level, and 3) the MF. This stability of the optical maps was not predicted from the electrophysiological literature.
Interaction Between Peripheral Afferent Activity and Presynaptic Inhibition of Ia Afferents in the Cat
Authors: Enríquez-Denton M. , Morita H. , Christensen L.O.D. , Petersen N. , Sinkjaer T. , Nielsen J. B.
Published: December 2017

It has been demonstrated in man that the H-reflex is more depressed by presynaptic inhibition than the stretch reflex. Here we investigated this finding further in the alpha-chloralose-anesthetized cat. Soleus monosynaptic reflexes were evoked by electrical stimulation of the tibial nerve or by stretch of the triceps surae muscle. Conditioning stimulation of the posterior biceps and semitendinosus nerve (PBSt) produced a significantly stronger depression of the electrically than the mechanically evoked reflexes. The depression of the reflexes has been shown to be caused by presynaptic inhibition of triceps surae Ia afferents. We investigated the hypothesis that repetitive activation of peripheral afferents may reduce their sensitivity to presynaptic inhibition. In triceps surae motoneurones, we measured the effect of presynaptic inhibition on excitatory postsynaptic potentials (EPSPs) produced by repetitive activation of the peripheral afferents or by fast and slow muscle stretch. EPSPs evoked by single electrical stimulation of the tibial nerve or by fast muscle stretch were significantly depressed by PBSt stimulation. However, the last EPSP in a series of EPSPs evoked by a train of electrical stimuli (5–6 shocks, 150–200 Hz) was significantly less depressed by the conditioning stimulation than the first EPSP. In addition, the last part of the long-lasting EPSPs evoked by a slow muscle stretch was also less depressed than the first part. A single EPSP evoked by stimulation of the medial gastrocnemius nerve was less depressed when preceded by a train of stimuli applied to the same nerve than when the same train of stimuli was applied to a synergistic nerve. The decreased sensitivity of the test EPSP to presynaptic inhibition was maximal when it was evoked within 20 ms after the train of EPSPs. It was not observed at intervals longer than 30 ms. These findings suggest that afferent activity may decrease the efficiency of presynaptic inhibition. We propose that the described interaction between afferent nerve activity and presynaptic inhibition may partly explain why electrically and mechanically evoked reflexes are differently sensitive to presynaptic inhibition.
Comparison of Morphine and Kainic Acid Microinjections Into Identical PAG Sites on the Activity of RVM Neurons
Authors: Tortorici V. , Morgan M. M.
Published: December 2017

The rostral ventromedial medulla (RVM) modulates nociception through changes in the activity of two classes of neuron, on- andoff-cells. The activity of these neurons is regulated, in part, by input from the periaqueductal gray (PAG). The objective of this study was to determine whether PAG-mediated antinociception is associated with excitation of both on- andoff-cells in the RVM. Microinjection of morphine into the ventrolateral PAG produced antinociception at 50% of the injection sites. This antinociception was associated with continuous activation of RVM off-cells and inhibition of both the spontaneous and reflex-related activity of RVM on-cells. Microinjection of kainic acid into the same injection sites produced antinociception 92% (37/40) of the time. Although kainic acid directly excites PAG output neurons, the changes in on- and off-cell activity associated with microinjection of kainic acid into the ventrolateral PAG were the same as when morphine was injected. That is,on-cells were inhibited and off-cells were activated. These data indicate that the excitatory connection between the PAG and RVM is directed at RVM off-cells specifically. In addition, these data suggest that direct activation of PAG output neurons, as occurs with kainic acid, is much more likely to produce antinociception than disinhibition of output neurons as occurs following morphine administration.
In Multiple-Step Gaze Shifts: Omnipause (OPNs) and Collicular Fixation Neurons Encode Gaze Position Error; OPNs Gate Saccades
Authors: Bergeron André , Guitton Daniel
Published: December 2017

The superior colliculus (SC), via its projections to the pons, is a critical structure for driving rapid orienting movements of the visual axis, called gaze saccades, composed of coordinated eye-head movements. The SC contains a motor map that encodes small saccade vectors rostrally and large ones caudally. A zone in the rostral pole may have a different function. It contains superior colliculus fixation neurons (SCFNs) with probable projections to omnipause neurons (OPNs) of the pons. SCFNs and OPNs discharge tonically during visual fixation and pause during single-step gaze saccades. The OPN tonic discharge inhibits saccades and its cessation (pause) permits saccade generation. We have proposed that SCFNs control the OPN discharge. We compared the discharges of SCFNs and OPNs recorded while cats oriented horizontally, to the left and right, in the dark to a remembered target. Cats used multiple-step gaze shifts composed of a series of small gaze saccades, of variable amplitude and number, separated by periods of variable duration (plateaus) in which gaze was immobile or moving at low velocity (<25°/s). Just after contralaterally (ipsilaterally) presented targets, the firing frequency of SCFNs decreased to almost zero (remained constant at background). As multiple-step gaze shifts progressed in either direction in the dark, these activity levels prevailed until the distance between gaze and target [gaze position error (GPE)] reached ∼16°. At this point, firing frequency gradually increased, without saccade-related pauses, until a maximum was reached when gaze arrived on target location (GPE = 0°). SCFN firing frequency encoded GPE; activity was not correlated to characteristics or occurrence of gaze saccades. By comparison, after target presentation to left or right, OPN activity remained steady at pretarget background until first gaze saccade onset, during which activity paused. During the first plateau, activity resumed at a level lower than background and continued at this level during subsequent plateaus until GPE ∼8° was reached. As GPE decreased further, tonic activity during plateaus gradually increased until a maximum (greater than background) was reached when gaze was on goal (GPE = 0°). OPNs, like SCFNs, encoded GPE, but they paused during every gaze saccade, thereby revealing, unlike for SCFNs, strong coupling to motor events. The firing frequency increase in SCFNs as GPE decreased, irrespective of trajectory characteristics, implies these cells get feedback on GPE, which they may communicate to OPNs. We hypothesize that at the end of a gaze-step sequence, impulses from SCFNs onto OPNs may suppress further movements away from the target.
Effects of Antidromic Discharges in Crayfish Primary Afferents
Authors: Cattaert Daniel , Bévengut Michelle
Published: December 2017

Contrary to orthodromic spikes that are generated in sensory organs and conveyed to CNS, antidromic spikes are generated in the axon terminals of the sensory neurons within the CNS and are conveyed to the peripheral sensory organ. Antidromic discharges are observed in primary afferent neurons of both vertebrates and invertebrates and seem to be related to the rhythmic activity of central neural networks. In this study, we analyzed the effect of antidromic discharges on the sensory activity of a leg proprioceptor in in vitro preparations of the crayfish CNS. Intracellular microelectrodes were used both to record the orthodromic spikes and to elicit antidromic spikes by injecting squares pulses of depolarizing current at various frequencies. Experiments were performed on the three types of identified sensory afferents (tonic, phasotonic, and phasic). The main results showed a reduction of the firing frequency of the orthodromic activity in 82% of the tested afferents. In tonic afferents, during their occurrences and according to their frequency, antidromic spikes or bursts reduced or suppressed the orthodromic activity. Following their terminations, they also induced a silent period and a gradual recovery of the orthodromic activity, both of which increased as the duration and the frequency of the antidromic bursts increased. In phasotonic and phasic afferents, antidromic bursts reduced or suppressed the phasic responses as their frequency and durations increased. In phasotonic afferents, if elicited prior to the movements, long-duration bursts with increasing frequency reduced more rapidly the tonic background activity than the phasic one whereas short-duration bursts at high frequency produced strong decreases of both. The effect of antidromic bursts accumulated when they are repetitively elicited. Antidromic bursts induced a much larger decrease of the sensory activity than adaptation alone. The occurrences of antidromic spikes or bursts may have a functional role in modulating the incoming sensory messages during locomotion. The mechanisms by which antidromic spikes modulate the firing sensitivity of the primary afferents may well lie in modifications of the properties of either mecanotransduction and/or spike initiation.
Parietal Representation of Object-Based Saccades
Authors: Sabes Philip N. , Breznen Boris , Andersen Richard A.
Published: December 2017

When monkeys make saccadic eye movements to simple visual targets, neurons in the lateral intraparietal area (LIP) display a retinotopic, or eye-centered, coding of the target location. However natural saccadic eye movements are often directed at objects or parts of objects in the visual scene. In this paper we investigate whether LIP represents saccadic eye movements differently when the target is specified as part of a visually displayed object. Monkeys were trained to perform an object-based saccade task that required them to make saccades to previously cued parts of an abstract object after the object reappeared in a new orientation. We recorded single neurons in area LIP of two macaque monkeys and analyzed their activity in the object-based saccade task, as well as two control tasks: a standard memory saccade task and a fixation task with passive object viewing. The majority of LIP neurons that were tuned in the memory saccade task were also tuned in the object-based saccade task. Using a hierarchical generalized linear model analysis, we compared the effects of three different spatial variables on the firing rate: the retinotopic location of the target, the object-fixed location of the target, and the orientation of the object in space. There was no evidence of an explicit object-fixed representation in the activity in LIP during either of the object-based tasks. In other words, no cells had receptive fields that rotated with the object. While some cells showed a modulation of activity due to the location of the target on the object, these variations were small compared to the retinotopic effects. For most cells, firing rates were best accounted for by either the retinotopic direction of the movement, the orientation of the object, or both spatial variables. The preferred direction of these retinotopic and object orientation effects were found to be invariant across tasks. On average, the object orientation effects were consistent with the retinotopic coding of potential target locations on the object. This interpretation is supported by the fact that the magnitude of these two effects were roughly equal in the early portions of the trial, but around the time of the motor response, the retinotopic effects dominated. We conclude that LIP uses the same retinotopic coding of saccade target whether the target is specified as an absolute point in space or as a location on a moving object.