bluuebunny/crossref_metadata_2025 huggingface dataset:
Blink-Perturbed Saccades in Monkey. II. Superior Colliculus Activity
Authors: Goossens H.H.L.M. , Van Opstal A. J.
Published: December 2017

Trigeminal reflex blinks evoked near the onset of a saccade cause profound spatial-temporal perturbations of the saccade that are typically compensated in mid-flight. This paper investigates the influence of reflex blinks on the discharge properties of saccade-related burst neurons (SRBNs) in intermediate and deep layers of the monkey superior colliculus (SC). Twenty-nine SRBNs, recorded in three monkeys, were tested in the blink-perturbation paradigm. We report that the air puff stimuli, used to elicit blinks, resulted in a short-latency (∼10 ms) transient suppression of saccade-related SRBN activity. Shortly after this suppression (within 10–30 ms), all neurons resumed their activity, and their burst discharge then continued until the perturbed saccade ended near the extinguished target. This was found regardless whether the compensatory movement was into the cell's movement field or not. In the limited number of trials where no compensation occurred, the neurons typically stopped firing well before the end of the eye movement. Several aspects of the saccade-related activity could be further quantified for 25 SRBNs. It appeared that 1) the increase in duration of the high-frequency burst was well correlated with the (two- to threefold) increase in duration of the perturbed movement. 2) The number of spikes in the burst for control and perturbed saccades was quite similar. On average, the number of spikes increased only 14%, whereas the mean firing rate in the burst decreased by 52%. 3) An identical number of spikes were obtained between control and perturbed responses when burst and postsaccadic activity were both included in the spike count. 4) The decrease of the mean firing rate in the burst was well correlated with the decrease in the velocity of perturbed saccades. 5) Monotonic relations between instantaneous firing rate and dynamic motor error were obtained for control responses but not for perturbed responses. And 6) the high-frequency burst of SRBNs with short-lead and long-lead presaccadic activity (also referred to as burst and buildup neurons, respectively) showed very similar features. Our findings show that blinking interacts with the saccade premotor system already at the level of the SC. The data also indicate that a neural mechanism, rather than passive elastic restoring forces within the oculomotor plant, underlies the compensation for blink-related perturbations. We propose that these interactions occur downstream from the motor SC and that the latter may encode the desired displacement vector of the eyes by sending an approximately fixed number of spikes to the brainstem saccadic burst generator.
Inaudible High-Frequency Sounds Affect Brain Activity: Hypersonic Effect
Authors: Oohashi Tsutomu , Nishina Emi , Honda Manabu , Yonekura Yoshiharu , Fuwamoto Yoshitaka , Kawai Norie , Maekawa Tadao , Nakamura Satoshi , Fukuyama Hidenao , Shibasaki Hiroshi
Published: December 2017

Although it is generally accepted that humans cannot perceive sounds in the frequency range above 20 kHz, the question of whether the existence of such “inaudible” high-frequency components may affect the acoustic perception of audible sounds remains unanswered. In this study, we used noninvasive physiological measurements of brain responses to provide evidence that sounds containing high-frequency components (HFCs) above the audible range significantly affect the brain activity of listeners. We used the gamelan music of Bali, which is extremely rich in HFCs with a nonstationary structure, as a natural sound source, dividing it into two components: an audible low-frequency component (LFC) below 22 kHz and an HFC above 22 kHz. Brain electrical activity and regional cerebral blood flow (rCBF) were measured as markers of neuronal activity while subjects were exposed to sounds with various combinations of LFCs and HFCs. None of the subjects recognized the HFC as sound when it was presented alone. Nevertheless, the power spectra of the alpha frequency range of the spontaneous electroencephalogram (alpha-EEG) recorded from the occipital region increased with statistical significance when the subjects were exposed to sound containing both an HFC and an LFC, compared with an otherwise identical sound from which the HFC was removed (i.e., LFC alone). In contrast, compared with the baseline, no enhancement of alpha-EEG was evident when either an HFC or an LFC was presented separately. Positron emission tomography measurements revealed that, when an HFC and an LFC were presented together, the rCBF in the brain stem and the left thalamus increased significantly compared with a sound lacking the HFC above 22 kHz but that was otherwise identical. Simultaneous EEG measurements showed that the power of occipital alpha-EEGs correlated significantly with the rCBF in the left thalamus. Psychological evaluation indicated that the subjects felt the sound containing an HFC to be more pleasant than the same sound lacking an HFC. These results suggest the existence of a previously unrecognized response to complex sound containing particular types of high frequencies above the audible range. We term this phenomenon the “hypersonic effect.”
Electrical Stimulation of the Frontal Eye Field in a Monkey Produces Combined Eye and Head Movements
Authors: Tu Tyson A. , Keating E. Gregory
Published: December 2017

The frontal eye field (FEF), an area in the primate frontal lobe, has long been considered important for the production of eye movements. Past studies have evoked saccade-like movements from the FEF using electrical stimulation in animals that were not allowed to move their heads. Using electrical stimulation in two monkeys that were free to move their heads, we have found that the FEF produces gaze shifts that are composed of both eye and head movements. Repeated stimulation at a site evoked gaze shifts of roughly constant amplitude. However, that gaze shift could be accomplished with varied amounts of head and eye movements, depending on their (head and eye) respective starting positions. This evidence suggests that the FEF controls visually orienting movements using both eye and head rotations rather than just shifting the eyes as previously thought.
Competitive Inhibition of NMDA Receptor–Mediated Currents by Extracellular Calcium Chelators
Authors: Chen Nansheng , Murphy Timothy H. , Raymond Lynn A.
Published: December 2017

Calcium chelators have been widely used in electrophysiological recordings of N-methyl-d-aspartate (NMDA) receptor–mediated currents, as well as in studies of excitotoxicity. Intracellularly applied calcium chelators are known to inhibit, at least in part, such calcium-dependent processes as calmodulin-dependent inactivation, calcineurin-dependent desensitization, and rundown of NMDA receptors. On the other hand, the functional consequences and potential nonspecific effects of extracellularly applied chelators have not been extensively investigated. In whole-cell patch-clamp recordings from human embryonic kidney (HEK) 293 cells transiently transfected with recombinant NMDA receptors, we found that addition of calcium chelators such as EGTA shifted the glutamate dose-response curve to the right, from an EC50 for NR1A/NR2A of 8 μM in 1.8 mM Ca2+ to ∼24 μM in a solution containing nominal 0 Ca2+/5 mM EGTA and further to ∼80 μM in 20 mM EGTA. A similar shift in glutamate dose-response was observed for NR1A/NR2B currents. This dose-response shift was not due to a decrease in extracellular Ca2+ concentration because there was no change in the glutamate EC50 at Ca2+concentrations ranging from 10 mM to nominal 0/200 μM EGTA. Moreover, addition of 5 mM EGTA fully chelated with 6.8 mM Ca2+ did not produce any shift in the glutamate dose-response curve. We propose that calcium chelators, containing four free carboxyl moieties, competitively inhibit glutamate binding to NMDA receptors.
Response Properties and Organization of Nociceptive Neurons in Area 1 of Monkey Primary Somatosensory Cortex
Authors: Kenshalo Dan R. , Iwata Koichi , Sholas Maurice , Thomas David A.
Published: December 2017

The organization and response properties of nociceptive neurons in area 1 of the primary somatosensory cortex (SI) of anesthetized monkeys were examined. The receptive fields of nociceptive neurons were classified as either wide-dynamic-range (WDR) neurons that were preferentially responsive to noxious mechanical stimulation, or nociceptive specific (NS) that were responsive to only noxious stimuli. The cortical locations and the responses of the two classes of neurons were compared. An examination of the neuronal stimulus-response functions obtained during noxious thermal stimulation of the glabrous skin of the foot or the hand indicated that WDR neurons exhibited significantly greater sensitivity to noxious thermal stimuli than did NS neurons. The receptive fields of WDR neurons were significantly larger than the receptive fields of NS neurons. Nociceptive SI neurons were somatotopically organized. Nociceptive neurons with receptive fields on the foot were located more medial in area 1 of SI than those with receptive fields on the hand. In the foot representation, the recording sites of nociceptive neurons were near the boundary between areas 3b and 1, whereas in the hand area, there was a tendency for them to be located more caudal in area 1. The majority of nociceptive neurons were located in the middle layers (III and IV) of area 1. The fact that nociceptive neurons were not evenly distributed across the layers of area 1 suggested that columns of nociceptive neurons probably do not exist in the somatosensory cortex. In electrode tracks where nociceptive neurons were found, approximately half of all subsequently isolated neurons were also classified as nociceptive. Low-threshold mechanoreceptive (LTM) neurons were intermingled with nociceptive neurons. Both WDR and NS neurons were found in close proximity to one another. In instances where the receptive field shifted, subsequently isolated cells were also classified as nociceptive. These data suggest that nociceptive neurons in area 1 of SI are organized in vertically orientated aggregations or clusters in layers III and IV.
Synaptic Actions of Neuropeptide FF in the Rat Parabrachial Nucleus: Interactions With Opioid Receptors
Authors: Chen Xihua , Zidichouski Jeffrey A. , Harris Kim H. , Jhamandas Jack H.
Published: December 2017

The pontine parabrachial nucleus (PBN) receives both opioid and Neuropeptide FF (NPFF) projections from the lower brain stem and/or the spinal cord. Because of this anatomical convergence and previous evidence that NPFF displays both pro- and anti-opioid activities, this study examined the synaptic effects of NPFF in the PBN and the mechanisms underlying these effects using an in vitro brain slice preparation and the nystatin-perforated patch-clamp recording technique. Under voltage-clamp conditions, NPFF reversibly reduced the evoked excitatory postsynaptic currents (EPSCs) in a dose-dependent fashion. This effect was not accompanied by apparent changes in the holding current, the current-voltage relationship or α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid–induced inward currents in the PBN cells. When a paired-pulse protocol was used, NPFF increased the ratio of these synaptic currents. Analysis of miniature EPSCs showed that NPFF caused a rightward shift in the frequency-distribution curve, whereas the amplitude-distribution curve remained unchanged. Collectively, these experiments indicate that NPFF reduces the evoked EPSCs through a presynaptic mechanism of action. The synaptic effects induced by NPFF (5 μM) could not be blocked by the specific μ-opioid receptor antagonist,d-Phe-Cys-Tyr-d-Trp-Arg-Thr-Pen-Thr-NH2(1 μM), but application of δ-opioid receptor antagonist Tyr-Tic-Phe-Phe (5 μM) almost completely prevented effects of NPFF. Moreover, the δ-opioid receptor agonist, Deltorphin (1 μM), mimicked the effects as NPFF and also occluded NPFF's actions on synaptic currents. These results indicate that NPFF modulates excitatory synaptic transmission in the PBN through an interaction with presynaptic δ-opioid receptors. These observations provide a cellular basis for NPFF enhancement of the antinociceptive effects consequent to central activation of δ-opioid receptors.
Cocaine and Kindling Alter the Sensitivity of Group II and III Metabotropic Glutamate Receptors in the Central Amygdala
Authors: Neugebauer Volker , Zinebi Fatiha , Russell Rex , Gallagher Joel P. , Shinnick-Gallagher Patricia
Published: December 2017

G-protein-coupled metabotropic glutamate receptors (mGluRs) are being implicated in various forms of neuroplasticity and CNS disorders. This study examined whether the sensitivities of mGluR agonists are modulated in a distinct fashion in different models of synaptic plasticity, specifically, kindling and chronic cocaine treatment. The influence of kindling and chronic cocaine exposure in vivo was examined in vitro on the modulation of synaptic transmission by group II and III metabotropic glutamate receptors using whole cell voltage-clamp recordings of central amygdala (CeA) neurons. Synaptic transmission was evoked by electrical stimulation of the basolateral amygdala (BLA) and ventral amygdaloid pathway (VAP) afferents in brain slices from control rats and from rats treated with cocaine or exposed to three to five stage-five kindled seizures. This study shows that after chemical stimulation with chronic cocaine exposure or after electrical stimulation with kindling the receptor sensitivities for mGluR agonists are altered in opposite ways. In slices from control rats, group II agonists, (2S,1′S,2′S)-2-(carboxycyclopropyl)glycine (LCCG1) and (+)-2-aminobicyclo[3.1.0]hexane-2,6-dicarboxylic acid (LY354740), depressed neurotransmission more potently at the BLA-CeA than at the VAP-CeA synapse while group III agonist, L(+)-2-amino-4-phosphonobutyrate (LAP4), depressed neurotransmission more potently at the VAP-CeA synapse than at the BLA-CeA. These agonist actions were not seen (were absent) in amygdala neurons from chronic cocaine-treated animals. In contrast, after kindling, concentration response relationships for LCCG1 and LAP4 were shifted to the left, suggesting that sensitivity to these agonists is increased. Except at high concentrations, LCCG1, LY354740, and LAP4 neither induced membrane currents nor changed current-voltage relationships. Loss of mGluR inhibition with chronic cocaine treatment may contribute to counter-adaptive changes including anxiety and depression in cocaine withdrawal. Drugs that restore the inhibitory effects of group II and III mGluRs may be novel tools in the treatment of cocaine dependence. The enhanced sensitivity to group II and III mGluR agonists in kindling is similar to that recorded at the lateral to BLA synapse in the amygdala where they reduce epileptiform bursting. These findings suggest that drugs modifying mGluRs may prove useful in the treatment of cocaine withdrawal or epilepsy.
Hyperpolarization-Activated, Mixed-Cation Current (I h) in Octopus Cells of the Mammalian Cochlear Nucleus
Authors: Bal Ramazan , Oertel Donata
Published: December 2017

Octopus cells in the posteroventral cochlear nucleus of mammals detect the coincidence of synchronous firing in populations of auditory nerve fibers and convey the timing of that coincidence with great temporal precision. Earlier recordings in current clamp have shown that two conductances contribute to the low input resistance and therefore to the ability of octopus cells to encode timing precisely, a low-threshold K+ conductance and a hyperpolarization-activated mixed-cation conductance, g h. The present experiments describe the properties of g h in octopus cells as they are revealed under voltage clamp with whole-cell, patch recordings. The hyperpolarization-activated current, I h, was blocked by extracellular Cs+ (5 mM) and 4-( N-ethyl- N-phenylamino)-1,2-dimethyl-6-(methylamino) pyridinium chloride (50–100 nM) but not by extracellular Ba2+ (2 mM). The reversal potential for I h in octopus cells under normal physiological conditions was −38 mV. Increasing the extracellular potassium concentration from 3 to 12 mM shifted the reversal potential to −26 mV; lowering extracellular sodium concentration from 138 to 10 mM shifted the reversal potential to −77 mV. These pharmacological and ion substitution experiments show that I h in octopus cells is a mixed-cation current that resembles I h in other neurons and in heart muscle cells. Under control conditions when cells were perfused intracellularly with ATP and GTP, I h had an activation threshold between about −35 to −40 mV and became fully activated at −110 mV. The maximum conductance associated with hyperpolarizing voltage steps to −112 mV ranged from 87 to 212 nS [150 ± 30 (SD) nS, n = 36]. The voltage dependence of g h obtained from peak tail currents is fit by a Boltzmann function with a half-activation potential of −65 ± 3 mV and a slope factor of 7.7 ± 0.7. This relationship reveals that g h was activated 41% at the mean resting potential of octopus cells, −62 mV, and that at rest I h contributes a steady inward current of between 0.9 and 2.1 nA. The voltage dependence of g h was unaffected by the extracellular application of dibutyryl cAMP but was shifted in hyperpolarizing direction, independent of the presence or absence of dibutyryl cAMP, by the removal of intracellular ATP and GTP.
Time Course and Magnitude of Movement-Related Gating of Tactile Detection in Humans. II. Effects of Stimulus Intensity
Authors: Williams Stephan R. , Chapman C. Elaine
Published: December 2017

This study examined the effect of systematically varying stimulus intensity on the time course and magnitude of movement-related gating of tactile detection and scaling in 17 human subjects trained to perform a rapid abduction of the right index finger (D2) in response to a visual cue. Electrical stimulation was delivered to D2 at five different intensities. At the lowest intensity, approximately 90% of stimuli were detected at rest (1 × P90); four multiples of this intensity were also tested (1.25, 1.5, 1.75, and 2.0 × P90). At all intensities of stimulation, detection of stimuli applied to the moving digit was diminished significantly and in a time-dependent manner, with peak decreases occurring within ±12 ms of the onset of electromyographic activity in the first dorsal interosseous (25–45 ms before movement onset). Reductions in the proportion of stimuli detected were greatest at the lowest stimulus intensity and progressively smaller at higher intensities. No shift in the timing of the decreases in performance was seen with increasing intensity. Once the weakest intensity at which most stimuli were perceived during movement had been established (2 × P90), magnitude estimation experiments were performed using two stimulus intensities, 2 × P90 (5 subjects) and 3 × P90 (3 subjects). Significant movement-related decreases in estimated stimulus magnitude were observed at both intensities, the time course of which was similar to the time course of reductions in detection performance. As stimulus intensity increased, the magnitude of the movement-related decrease in scaling diminished. A model of detection performance that accurately described the effect of stimulus intensity and timing on movement-related reductions in detection was created. This model was then combined with a previous model that described the effects of stimulus localization and timing to predict detection performance at a given stimulation site, intensity, and time during movement. Movement-related gating of tactile perception represents the end result of movement-related effects on the transmission and subsequent processing of the stimulus. The combined model clearly defines many of the requirements that proposed physiological mechanisms of movement-related gating will have to fulfill.
pH Sensitivity of Non-Synaptic Field Bursts in the Dentate Gyrus
Authors: Schweitzer Jeffrey S. , Wang Haiwei , Xiong Zhi-Qi , Stringer Janet L.
Published: December 2017

Under conditions of low [Ca2+]o and high [K+]o, the rat dentate granule cell layer in vitro develops recurrent spontaneous prolonged field bursts that resemble an in vivo phenomenon called maximal dentate activation. To understand how pH changes in vivo might affect this phenomenon, the slices were exposed to different extracellular pH environments in vitro. The field bursts were highly sensitive to extracellular pH over the range 7.0–7.6 and were suppressed at low pH and enhanced at high pH. Granule cell resting membrane potential, action potentials, and postsynaptic potentials were not significantly altered by pH changes within the range that suppressed the bursts. The pH sensitivity of the bursts was not altered by pharmacologic blockade of N-methyl-d-aspartate (NMDA), non-NMDA, and GABAA receptors at concentrations of these agents sufficient to eliminate both spontaneous and evoked synaptic potentials. Gap junction patency is known to be sensitive to pH, and agents that block gap junctions, including octanol, oleamide, and carbenoxolone, blocked the prolonged field bursts in a manner similar to low pH. Perfusion with gap junction blockers or acidic pH suppressed field bursts but did not block spontaneous firing of single and multiple units, including burst firing. These data suggest that the pH sensitivity of seizures and epileptiform phenomena in vivo may be mediated in large part through mechanisms other than suppression of NMDA-mediated or other excitatory synaptic transmission. Alterations in electrotonic coupling via gap junctions, affecting field synchronization, may be one such process.
Auditory Thalamus Neurons During Sleep: Changes in Frequency Selectivity, Threshold, and Receptive Field Size
Authors: Edeline Jean-Marc , Manunta Yves , Hennevin Elizabeth
Published: December 2017

The present study describes how the frequency receptive fields (RF) of auditory thalamus neurons are modified when the state of vigilance of an unanesthetized animal naturally fluctuates among wakefulness (W), slow-wave sleep (SWS), and paradoxical sleep (PS). Systematic quantification of several RF parameters—including strength of the evoked responses, response latency, acoustic threshold, shape of rate-level function, frequency selectivity, and RF size—was performed while undrugged, restrained guinea pigs presented spontaneous alternances of W, SWS, and PS. Data are from 102 cells recorded during W and SWS and from 53 cells recorded during W, SWS, and PS. During SWS, thalamic cells behaved as an homogeneous population: as compared with W, most of them (97/102 cells) exhibited decreased evoked spike rates. The frequency selectivity was enhanced and the RF size was reduced. In contrast during PS, two populations of cells were identified: one (32/53 cells) showed the same pattern of changes as during SWS, whereas the other (21/53 cells) expressed values of evoked spike rates and RF properties that did not significantly differ from those in W. These two populations were equally distributed in the different anatomical divisions of the auditory thalamus. Last, during both SWS and PS, the responses latency was longer and the acoustic threshold was higher than in W but the proportion of monotonic versus nonmonotonic rate-level functions was unchanged. During both SWS and PS, no relationship was found between the changes in burst percentage and the changes of the RF properties. These results point out the dual aspect of sensory processing during sleep. On the one hand, they show that the auditory messages sent by thalamic cells to cortical neurons are reduced both in terms of firing rate at a given frequency and in terms of frequency range. On the other hand, the fact that the frequency selectivity and the rate-level function are preserved suggests that the messages sent to cortical cells are not deprived of informative content, and that the analysis of complex acoustic sounds should remain possible. This can explain why, although attenuated, reactivity to biologically relevant stimuli is possible during sleep.
Characteristics of the Pupillary Light Reflex in the Macaque Monkey: Discharge Patterns of Pretectal Neurons
Authors: Pong Milton , Fuchs Albert F.
Published: December 2017

Anatomical and physiological data have implicated the pretectal olivary nucleus (PON) as the midbrain relay for the pupillary light reflex in a variety of species. To determine the nature of the discharge of pretectal light reflex relay neurons, we recorded their activity in monkeys that were fixating a stationary spot while a full-field random-dot stimulus was flashed on for 1 s. Based on their discharge patterns, neurons in or near the PON came in two varieties. The most prevalent neuron discharged a burst of spikes 56 ms (on average) after the light came on followed by a sustained rate for the duration of the stimulus (burst-sustained neurons). When the light went off, nearly all neurons (33/34) ceased firing, and then all the neurons with a resting response in the dark ( n = 15) resumed firing. Both the firing rate within the burst and the sustained discharge rate increased with log light intensity and the latency of the burst decreased. The burst and cessation of firing were better aligned with the stimulus occurrence than with the onset of pupillary constriction or dilation. Taken together, these data suggest that burst-sustained neurons respond to the visual stimulus eliciting the pupillary change rather than dictating the metrics of the subsequent pupillary response. Electrical stimulation at the site of four of five burst-sustained neurons elicited pupillary constriction at low stimulus strengths after a latency of ∼100 ms. When the electrode was moved 250 μm away from the burst-sustained neuron, the elicited response disappeared. Reconstructions of the locations of burst-sustained luminance neurons place them in the PON or its immediate vicinity. We suggest that PON burst-sustained neurons constitute the pretectal relay for the pupillary light reflex. A minority of our recorded pretectal neurons discharged a burst of spikes at both light onset and light offset. For most of these transient neurons, neither the burst rate nor the interburst rate was significantly related to light intensity. We conclude that these neurons are not involved in the light reflex but subserve some other pretectal function.
Prior Information in Motor and Premotor Cortex: Activity During the Delay Period and Effect on Pre-Movement Activity
Authors: Crammond Donald J. , Kalaska John F.
Published: December 2017

In instructed-delay (ID) tasks, instructional cues provide prior information about the nature of a movement to execute after a delay. Neuronal responses in dorsal premotor cortex (PMd) during the instructed-delay period (IDP) between the CUE and subsequent GO signals are presumed to reflect early planning stages initiated by the prior information. In contrast, in multiple-choice reaction-time (RT) tasks, all motor planning and execution processes must occur after the GO signal. These assumptions predict that neuronal planning correlates recorded during the IDP of ID trials should share common features with early post-GO activity in RT trials, and that those response components need not be recapitulated after the GO signal of ID trials. These two predictions were tested by comparing activity recorded in RT and ID tasks from 503 neurons in PMd and caudal (MIc) and rostral (MIr) primary motor cortex. The incidence and strength of directionally tuned IDP activity declined progressively from PMd to MIc. The directional tuning of activity during the IDP of ID trials was more similar to that in the reaction-time epoch (RTE) of RT trials than after movement onset, especially in PMd. A modulation of post-GO activity was often observed between RT and ID trials and was confined mainly to the RTE. This effect was also most prominent in PMd. The most common change was a reduction in intensity of short-latency phasic responses to the GO signal between RT and ID trials, especially in PMd cells with a short-latency phasic response to CUE signals. However, the largest group of cells in each area showed no large change in peak RTE activity between RT and ID trials, whether they were active in the IDP or not. Since early phasic CUE-related responses are least likely to be recapitulated after the GO signal in ID trials, they may be a neuronal correlate of an early planning stage such as response selection. Tonic IDP responses, which are not as strongly associated with a post-GO reduction in activity, may be related to other aspects of motor planning and preparation. Finally, a major component of the movement-related activity in both MI and PMd is not susceptible to modification by prior information and is indivisibly coupled temporally to movement execution.
Similarity in the Response of Smooth Pursuit and Manual Tracking to a Change in the Direction of Target Motion
Authors: Engel Kevin C. , Anderson John H. , Soechting John F.
Published: December 2017

Subjects were asked to track, with their eyes or their hand, the movement of a target that maintained a constant speed and made a single, abrupt change in direction. The tracking speed and direction of motion after the step change in target direction were compared for the eyes and the hand. After removal of the saccades from the eye movement records, it was found that in both cases, there was a slow rotation from the initial direction to the new direction. For the eyes and the hand, it was found that this change in direction of movement occurred at a similar rate that was proportional to the magnitude of the abrupt change in target direction. This was further described by comparing the direction of pursuit tracking with the response of a second-order system to a step input. In addition, it was found that the speed of manual and pursuit tracking was modulated in a similar manner, with a reduction in tracking speed occurring before the change in tracking direction. This reduction in speed following the change in the direction of target motion was very similar for the hand and the eye, despite the large difference in the inertias of the two systems. Taken together, these data suggest that the neural mechanisms for smooth pursuit and manual tracking have common functional elements and that musculoskeletal dynamics do not appear to be a rate-limiting factor.
Position of Spinothalamic Tract Axons in Upper Cervical Spinal Cord of Monkeys
Authors: Zhang Xijing , Honda Christopher N. , Giesler Glenn J.
Published: December 2017

Percutaneous upper cervical cordotomy continues to be performed on patients suffering from several types of severe chronic pain. It is believed that the operation is effective because it cuts the spinothalamic tract (STT), a primary pathway carrying nociceptive information from the spinal cord to the brain in humans. In recent years, there has been controversy regarding the location of STT axons within the spinal cord. The aim of this study was to determine the locations of STT axons within the spinal cord white matter of C2 segment in monkeys using methods of antidromic activation. Twenty lumbar STT cells were isolated. Eleven were classified as wide dynamic range neurons, six as high-threshold cells, and three as low-threshold cells. Eleven STT neurons were recorded in the deep dorsal horn and nine in superficial dorsal horn. The axons of the examined neurons were located at antidromic low-threshold points (<30 μA) within the contralateral lateral funiculus of C2. All low-threshold points were located ventral to the denticulate ligament, within the lateral half of the ventral lateral funiculus (VLF). None were found in the dorsal half of the lateral funiculus. The present findings support our previous suggestion that STT axons migrate ventrally as they ascend the length of the spinal cord. Also, the present findings indicate that surgical cordotomies that interrupt the VLF in C2 likely disrupt the entire lumbar STT.
An Associational Model of Birdsong Sensorimotor Learning I. Efference Copy and the Learning of Song Syllables
Authors: Troyer Todd W. , Doupe Allison J.
Published: December 2017

Birdsong learning provides an ideal model system for studying temporally complex motor behavior. Guided by the well-characterized functional anatomy of the song system, we have constructed a computational model of the sensorimotor phase of song learning. Our model uses simple Hebbian and reinforcement learning rules and demonstrates the plausibility of a detailed set of hypotheses concerning sensory-motor interactions during song learning. The model focuses on the motor nuclei HVc and robust nucleus of the archistriatum (RA) of zebra finches and incorporates the long-standing hypothesis that a series of song nuclei, the Anterior Forebrain Pathway (AFP), plays an important role in comparing the bird's own vocalizations with a previously memorized song, or “template.” This “AFP comparison hypothesis” is challenged by the significant delay that would be experienced by presumptive auditory feedback signals processed in the AFP. We propose that the AFP does not directly evaluate auditory feedback, but instead, receives an internally generated prediction of the feedback signal corresponding to each vocal gesture, or song “syllable.” This prediction, or “efference copy,” is learned in HVc by associating premotor activity in RA-projecting HVc neurons with the resulting auditory feedback registered within AFP-projecting HVc neurons. We also demonstrate how negative feedback “adaptation” can be used to separate sensory and motor signals within HVc. The model predicts that motor signals recorded in the AFP during singing carry sensory information and that the primary role for auditory feedback during song learning is to maintain an accurate efference copy. The simplicity of the model suggests that associational efference copy learning may be a common strategy for overcoming feedback delay during sensorimotor learning.
Transient Removal of Extracellular Mg2+ Elicits Persistent Suppression of LTP at Hippocampal CA1 Synapses Via PKC Activation
Authors: Hsu Kuei-Sen , Ho Wen-Chia , Huang Chiung-Chun , Tsai Jing-Jane
Published: December 2017

Previous work has shown that seizure-like activity can disrupt the induction of long-term potentiation (LTP). However, how seizure-like event disrupts the LTP induction remains unknown. To understand the cellular and molecular mechanisms underlying this process better, a set of studies was implemented in area CA1 of rat hippocampal slices using extracellular recording methods. We showed here that prior transient seizure-like activity generated by perfused slices with Mg2+-free artificial cerebrospinal fluid (ACSF) exhibited a persistent suppression of LTP induction. This effect lasted between 2 and 3 h after normal ACSF replacement and was specifically inhibited by N-methyl-d-aspartate (NMDA) receptor antagonistd-2-amino-5-phosphovaleric acid (d-APV) and L-type voltage-operated Ca2+ channel (VOCC) blocker nimodipine, but not by non-NMDA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX). In addition, this suppressive effect was specifically blocked by the selective protein kinase C (PKC) inhibitor NPC-15437. However, neither Ca2+/calmodulin-dependent protein kinase II inhibitor KN-62 nor cAMP-dependent protein kinase inhibitor Rp-adenosine 3′,5′-cyclic monophosphothioate (Rp-cAMPS) affected this suppressive effect. This persistent suppression of LTP was not secondary to the long-lasting changes in NMDA receptor activation, because the isolated NMDA receptor–mediated responses did not show a long-term enhancement in response to a 30-min Mg2+-free ACSF application. Additionally, in prior Mg2+-free ACSF–treated slices, the entire frequency-response curve of LTP and long-term depression (LTD) is shifted systematically to favor LTD. These results suggest that the increase of Ca2+ influx through NMDA channels and L-type VOCCs in turn triggering a PKC-dependent signaling cascade is a possible cellular basis underlying this seizure-like activity-induced inhibition of LTP.
17-β-Estradiol Modulation of Area Postrema Potassium Currents
Authors: Li Zhicheng , Hay Meredith
Published: December 2017

The purpose of this study was to determine the effects of 17-β-estradiol on area postrema neuronal activity in vivo and on area postrema potassium currents (IK) in vitro. In anesthetized rats, intravenous injection of 17-β-estradiol (10 ng/kg bw) -inhibited area postrema neuronal activity in 8/8 neurons tested. The averaged firing rate decreased from 2.9 ± 1.1 to 1.1 ± 0.3 Hz. The inhibitory effects of 17-β-estradiol on area postrema neuronal activity were rapid in onset (within 1 min) and long-lasting (>8 min). To study the cellular mechanisms involved in this response, the effects of 17-β-estradiol were examined in dissociated area postrema neurons. In these cells, 17-β-estradiol (0.5 nM) increased the averaged peak IK 27 ± 8%. The time course for the potentiation was observed within ∼0.5–1 min after the application of 17-β-estradiol. Full recovery from the potentiation usually occurred within ∼3–4 min after the washout of 17-β-estradiol. The biologically inactive 17-α-estradiol had no effect on area postrema IK and the 17-β-estradiol antagonist, ICI 182,780 blocked the effects of 17-β-estradiol on area postrema IK. Finally, big conductance calcium-activated potassium current (MaxiK+) was identified in area postrema neurons ( n = 12/12). Blockade of MaxiK+ with 100 nM iberiotoxin blocked the effects of 17-β-estradiol on IK. These results suggested 17-β-estradiol might modulate area postrema neuronal activity by increasing MaxiK+ current.
Dendrosomatic Voltage and Charge Transfer in Rat Neocortical Pyramidal Cells In Vitro
Authors: Ulrich Daniel , Stricker Christian
Published: December 2017

Most excitatory synapses on neocortical pyramidal cells are located on dendrites, which are endowed with a variety of active conductances. The main origin for action potentials is thought to be at the initial segment of the axon, although local regenerative activity can be initiated in the dendrites. The transfer characteristics of synaptic voltage and charge along the dendrite to the soma remains largely unknown, although this is an essential determinant of neural input-output transformations. Here we perform dual whole-cell recordings from layer V pyramidal cells in slices from somatosensory cortex of juvenile rats. Steady-state and sinusoidal current injections are applied to characterize the voltage transfer characteristics of the apical dendrite under resting conditions. Furthermore, dendrosomatic charge and voltage transfer are determined by mimicking synapses via dynamic current-clamping. We find that around rest, the dendrite behaves like a linear cable. The cutoff frequency for somatopetal current transfer is around 4 Hz, i.e., synaptic inputs are heavily low-pass filtered. In agreement with linearity, transfer resistances are reciprocal in opposite directions, and the centroids of the synaptic time course are on the order of the membrane time constant. Transfer of excitatory postsynaptic potential (EPSP) charge, but not peak amplitude, is positively correlated with membrane potential. We conclude that the integrative properties of dendrites in infragranular neocortical pyramidal cells appear to be linear near resting membrane potential. However, at polarized potentials charge transferred is voltage-dependent with a loss of charge at hyperpolarized and a gain of charge at depolarized potentials.
Synaptic Background Activity Enhances the Responsiveness of Neocortical Pyramidal Neurons
Authors: Hô Nicolas , Destexhe Alain
Published: December 2017

Neocortical pyramidal neurons in vivo are subject to an intense synaptic background activity but little is known of how this activity affects cellular responsiveness and what function it may serve. These issues were examined in morphologically reconstructed neocortical pyramidal neurons in which synaptic background activity was simulated based on recent measurements in cat parietal cortex. We show that background activity can be decomposed into two components: a tonically active conductance and voltage fluctuations. Previous studies have mostly focused on the conductance effect, revealing that background activity is responsible for a decrease in responsiveness, which imposes severe conditions of coincidence of inputs necessary to discharge the cell. It is shown here, in contrast, that responsiveness is enhanced if voltage fluctuations are taken into account; in this case the model can produce responses to inputs that would normally be subthreshold. This effect is analyzed by dissecting and comparing the different components of background activity, as well as by evaluating the contribution of parameters such as the dendritic morphology, the distribution of leak currents, the value of axial resistivity, the densities of voltage-dependent currents, and the release parameters underlying background activity. Interestingly, the model's optimal responsiveness was obtained when voltage fluctuations were of the same order as those measured intracellularly in vivo. Possible consequences were also investigated at the population level, where the presence of background activity allowed networks of pyramidal neurons to instantaneously detect inputs that are small compared with the classical detection threshold. These results suggest, at the single-cell level, that the presence of voltage fluctuations has a determining influence on cellular responsiveness and that these should be taken into account in models of background activity. At the network level, we predict that background activity provides the necessary drive for detecting events that would normally be undetectable. Experiments are suggested to explore this possible functional role for background activity.
Intracellular Correlates of Fast (>200 Hz) Electrical Oscillations in Rat Somatosensory Cortex
Authors: Jones Michael S. , MacDonald Kurt D. , Choi ByungJu , Dudek F. Edward , Barth Daniel S.
Published: December 2017

Oscillatory activity in excess of several hundred hertz has been observed in somatosensory evoked potentials (SEP) recorded in both humans and animals and is attracting increasing interest regarding its role in brain function. Currently, however, little is known about the cellular events underlying these oscillations. The present study employed simultaneous in-vivo intracellular and epipial field-potential recording to investigate the cellular correlates of fast oscillations in rat somatosensory cortex evoked by vibrissa stimulation. Two distinct types of fast oscillations were observed, here termed “fast oscillations” (FO) (200–400 Hz) and “very fast oscillations” (VFO) (400–600 Hz). FO coincided with the earliest slow-wave components of the SEP whereas VFO typically were later and of smaller amplitude. Regular spiking (RS) cells exhibited vibrissa-evoked responses associated with one or both types of fast oscillations and consisted of combinations of spike and/or subthreshold events that, when superimposed across trials, clustered at latencies separated by successive cycles of FO or VFO activity, or a combination of both. Fast spiking (FS) cells responded to vibrissae stimulation with bursts of action potentials that closely approximated the periodicity of the surface VFO. No cells were encountered that produced action potential bursts related to FO activity in an analogous fashion. We propose that fast oscillations define preferred latencies for action potential generation in cortical RS cells, with VFO generated by inhibitory interneurons and FO reflecting both sequential and recurrent activity of stations in the cortical lamina.
Conditional Spike Backpropagation Generates Burst Discharge in a Sensory Neuron
Authors: Lemon N. , Turner R. W.
Published: December 2017

Backpropagating dendritic Na+spikes generate a depolarizing afterpotential (DAP) at the soma of pyramidal cells in the electrosensory lateral line lobe (ELL) of weakly electric fish. Repetitive spike discharge is associated with a progressive depolarizing shift in somatic spike afterpotentials that eventually triggers a high-frequency spike doublet and subsequent burst afterhyperpolarization (bAHP). The rhythmic generation of a spike doublet and bAHP groups spike discharge into an oscillatory burst pattern. This study examined the soma-dendritic mechanisms controlling the depolarizing shift in somatic spike afterpotentials, and the mechanism by which spike doublets terminate spike discharge. Intracellular recordings were obtained from ELL pyramidal somata and apical dendrites in an in vitro slice preparation. The pattern of spike discharge was equivalent in somatic and dendritic regions, reflecting the backpropagation of spikes from soma to dendrites. There was a clear frequency-dependent threshold in the transition from tonic to burst discharge, with bursts initiated when interspike intervals fell between ∼3–7 ms. Removal of all backpropagating spikes by dendritic TTX ejection revealed that the isolated somatic AHPs were entirely stable at the interspike intervals that generated burst discharge. As such, the depolarizing membrane potential shift during repetitive discharge could be attributed to a potentiation of DAP amplitude. Potentiation of the DAP was due to a frequency-dependent broadening and temporal summation of backpropagating dendritic Na+ spikes. Spike doublets were generated with an interspike interval close to, but not within, the somatic spike refractory period. In contrast, the interspike interval of spike doublets always fell within the longer dendritic refractory period, preventing backpropagation of the second spike of the doublet. The dendritic depolarization was thus abruptly removed from one spike to the next, allowing the burst to terminate when the bAHP hyperpolarized the membrane. The transition from tonic to burst discharge was dependent on the number and frequency of spikes invoking dendritic spike summation, indicating that burst threshold depends on the immediate history of cell discharge. Spike frequency thus represents an important condition that determines the success of dendritic spike invasion, establishing an intrinsic mechanism by which backpropagating spikes can be used to generate a rhythmic burst output.
Distribution, Density, and Clustering of Functional Glutamate Receptors Before and After Synaptogenesis in Hippocampal Neurons
Authors: Cottrell Jeffrey R. , Dubé Gilles R. , Egles Christophe , Liu Guosong
Published: December 2017

Postsynaptic differentiation during glutamatergic synapse formation is poorly understood. Using a novel biophysical approach, we have investigated the distribution and density of functional glutamate receptors and characterized their clustering during synaptogenesis in cultured hippocampal neurons. We found that functional α-amino-3-hydroxy-5-methyl-4-isoxazolpropionate (AMPA) and N-methyl-d-aspartate (NMDA) receptors are evenly distributed in the dendritic membrane before synaptogenesis with an estimated density of 3 receptors/μm2. Following synaptogenesis, functional AMPA and NMDA receptors are clustered at synapses with a density estimated to be on the order of 104 receptors/μm2, which corresponds to ∼400 receptors/synapse. Meanwhile there is no reduction in the extrasynaptic receptor density, which indicates that the aggregation of the existing pool of receptors is not the primary mechanism of glutamate receptor clustering. Furthermore our data suggest that the ratio of AMPA to NMDA receptor density may be regulated to be close to one in all dendritic locations. We also demonstrate that synaptic AMPA and NMDA receptor clusters form with a similar time course during synaptogenesis and that functional AMPA receptors cluster independently of activity and glutamate receptor activation, including following the deletion of the NMDA receptor NR1 subunit. Thus glutamate receptor activation is not necessary for the insertion, clustering, and activation of functional AMPA receptors during synapse formation, and this process is likely controlled by an activity-independent signal.