bluuebunny/crossref_metadata_2025 huggingface dataset:
Interactions Between Posture and Locomotion: Motor Patterns in Humans Walking With Bent Posture Versus Erect Posture
Authors: Grasso R. , Zago M. , Lacquaniti F.
Published: December 2017

Human erect locomotion is unique among living primates. Evolution selected specific biomechanical features that make human locomotion mechanically efficient. These features are matched by the motor patterns generated in the CNS. What happens when humans walk with bent postures? Are normal motor patterns of erect locomotion maintained or completely reorganized? Five healthy volunteers walked straight and forward at different speeds in three different postures (regular, knee-flexed, and knee- and trunk-flexed) while their motion, ground reaction forces, and electromyographic (EMG) activity were recorded. The three postures imply large differences in the position of the center of body mass relative to the body segments. The elevation angles of the trunk, pelvis, and lower limb segments relative to the vertical in the sagittal plane, the ground reaction forces and the rectified EMGs were analyzed over the gait cycle. The waveforms of the elevation angles along the gait cycle remained essentially unchanged irrespective of the adopted postures. The first two harmonics of these kinematic waveforms explain >95% of their variance. The phase shift but not the amplitude ratio between the first harmonic of the elevation angle waveforms of adjacent pairs was affected systematically by changes in posture. Thigh, shank, and foot angles covaried close to a plane in all conditions, but the plane orientation was systematically different in bent versus erect locomotion. This was explained by the changes in the temporal coupling among the three segments. For walking speeds >1 m s−1, the plane orientation of bent locomotion indicates a much lower mechanical efficiency relative to erect locomotion. Ground reaction forces differed prominently in bent versus erect posture displaying characteristics intermediate between those typical of walking and those of running. Mean EMG activity was greater in bent postures for all recorded muscles independent of the functional role. The waveforms of the muscle activities and muscle synergies also were affected by the adopted posture. We conclude that maintaining bent postures does not interfere either with the generation of segmental kinematic waveforms or with the planar constraint of intersegmental covariation. These characteristics are maintained at the expense of adjustments in kinetic parameters, muscle synergies and the temporal coupling among the oscillating body segments. We argue that an integrated control of gait and posture is made possible because these two motor functions share some common principles of spatial organization.
Adenosine Receptor Expression and Modulation of Ca2+Channels in Rat Striatal Cholinergic Interneurons
Authors: Song Wen-Jie , Tkatch Tatiana , Surmeier D. James
Published: December 2017

Adenosine is a potent regulator of acetylcholine release in the striatum, yet the mechanisms mediating this regulation are largely undefined. To begin to fill this gap, adenosine receptor expression and coupling to voltage-dependent Ca2+channels were studied in cholinergic interneurons by combined whole cell voltage-clamp recording and single-cell reverse transcription–polymerase chain reaction. Cholinergic interneurons were identified by the presence of choline acetyltransferase mRNA. Nearly all of these interneurons (90%, n = 28) expressed detectable levels of A1adenosine receptor mRNA. A2aand A2breceptor mRNAs were less frequently detected. A3receptor mRNA was undetectable. Adenosine rapidly and reversibly reduced N-type Ca2+currents in cholinergic interneurons. The A1receptor antagonist 8-cyclopentyl-1,3-dimethylxanthine completely blocked the effect of adenosine. The IC50of the A1receptor selective agonist 2-chloro-N6-cyclopentyladenosine was 45 nM, whereas it was near 30 μM for the A2areceptor agonist CGS-21680. Dialysis with GDPβS or brief exposure to the G protein (Gi/o) alkylating agent N-ethylmaleimide also blocked the adenosine modulation. The reduction in N-type currents was partially reversed by depolarizing prepulses. A membrane-delimited pathway mediated the modulation, because it was not seen in cell-attached patches when agonist was applied to the bath. Activation of protein kinase C attenuated the adenosine modulation. Taken together, our results argue that activation of A1adenosine receptors in cholinergic interneurons reduces N-type Ca2+currents via a membrane-delimited, Gi/oclass G-protein pathway that is regulated by protein kinase C. These observations establish a cellular mechanism by which adenosine may serve to reduce acetylcholine release.
Effect of Ethanol Upon Respiratory-Related Hypoglossal Nerve Output of Neonatal Rat Brain Stem Slices
Authors: Gibson Ian C. , Berger Albert J.
Published: December 2017

The actions of ethanol (EtOH) on the respiratory output of the neonatal rat brain stem slice preparation in vitro are described. Ethanol inhibited respiratory-related hypoglossal nerve activity in a dose-dependent manner. The effect of EtOH was evident within 5 min and was reversible on EtOH washout. The actions of EtOH were qualitatively similar to those of two other alcohols, methanol and octanol. We investigated the dose-response relationship for each alcohol and determined that the order of potency was methanol < EtOH ≪ octanol, with EC50 values of 291 mM, 39.7 mM, and 49.2 μM respectively. Application of either strychnine (5 μM) or bicuculline (5 μM) alone, partially but not significantly, reversed the inhibition of respiratory-related hypoglossal nerve activity produced by 50 mM EtOH. Preincubation of rhythmic slices with a combination of both strychnine and bicuculline (both 5 μM) partially, but significantly, blocked the inhibitory actions of EtOH, suggesting that other mechanisms also play a role in the action of EtOH. Preincubation of the slices with 25 μM APV reduced the relative degree of inhibition caused by EtOH suggesting that N-methyl-d-aspartate (NMDA)-receptor-mediated events can be affected by EtOH. Furthermore inhibition of protein kinase C by incubation with 100 nM staurosporine also reduced the efficacy of EtOH. These results suggest that the actions of EtOH may be mediated via glycine, GABAA, and NMDA receptors and that activation of protein kinase C is involved in the EtOH-induced inhibition of respiratory-related hypoglossal nerve activity.
Differential Expression of High- and Two Types of Low-Voltage–Activated Calcium Currents in Rod and Cone Bipolar Cells of the Rat Retina
Authors: Pan Zhuo-Hua
Published: December 2017

Whole cell voltage-clamp recordings were performed to investigate voltage-activated Ca2+ currents in acutely isolated retinal bipolar cells of rats. Two groups of morphologically different bipolar cells were observed. Bipolar cells of the first group, which represent the majority of isolated bipolar cells, were immunoreactive to protein kinase C (PKC) and, therefore likely to be rod bipolar cells. Bipolar cells of the second group, which represent only a small population of isolated bipolar cells, did not show PKC immunoreactivity and were likely to be cone bipolar cells. The validity of morphological identification of bipolar cells was further confirmed by the presence of GABAC responses in these cells. Bipolar cells of both groups displayed low-voltage–activated (LVA) Ca2+ currents with similar voltage dependence of activation and steady-state inactivation. However, the activation, inactivation, and deactivation kinetics of the LVA Ca2+ currents between rod and cone bipolar cells differed. Particularly, the LVA Ca2+ currents of rod bipolar cells displayed both transient and sustained components. In contrast, the LVA Ca2+ currents of cone bipolar cells were mainly transient. In addition, the LVA Ca2+ channels of rod bipolar cells were more permeable to Ba2+ than to Ca2+, whereas those of cone bipolar cells were equally or less permeable to Ba2+ than to Ca2+. The LVA Ca2+ currents of both rod and cone bipolar cells were antagonized by high concentrations of nimodipine with IC50of 17 and 23 μM, respectively, but largely resistant to Cd2+ and Ni2+. Bipolar cells of both groups also displayed high-voltage–activated (HVA) Ca2+ currents. The HVA Ca2+ currents were, at least in part, to be L-type that were potentiated by BayK-8644 (1 μM) and largely antagonized by low concentrations of nimodipine (5 μM). The L-type Ca2+channels were almost exclusively located at the axon terminals of rod bipolar cells but expressed at least in the cell soma of cone bipolar cells. Results of this study indicate that rod and cone bipolar cells of the mammalian retina differentially express at least two types of LVA Ca2+ channels. Rod and cone bipolar cells also show different spatial distribution of L-type Ca2+channels.
Time Course of Odorant-Induced Activation in the Human Primary Olfactory Cortex
Authors: Sobel Noam , Prabhakaran Vivek , Zhao Zuo , Desmond John E. , Glover Gary H. , Sullivan Edith V. , Gabrieli John D. E.
Published: December 2017

Paradoxically, attempts to visualize odorant-induced functional magnetic resonance imaging (fMRI) activation in the human have yielded activations in secondary olfactory regions but not in the primary olfactory cortex-piriform cortex. We show that odorant-induced activation in primary olfactory cortex was not previously made evident with fMRI because of the unique time course of activity in this region: in primary olfactory cortex, odorants induced a strong early transient increase in signal amplitude that then habituated within 30–40 s of odorant presence. This time course of activation seen here in the primary olfactory cortex of the human is almost identical to that recorded electrophysiologically in the piriform cortex of the rat. Mapping activation with analyses that are sensitive to both this transient increase in signal amplitude, and temporal-variance, enabled us to use fMRI to consistently visualize odorant-induced activation in the human primary olfactory cortex. The combination of continued accurate odorant detection at the behavioral level despite primary olfactory cortex habituation at the physiological level suggests that the functional neuroanatomy of the olfactory response may change throughout prolonged olfactory stimulation.
Burst Firing Induces a Rebound of Synaptic Strength at Unitary Neocortical Synapses
Authors: Galarreta Mario , Hestrin Shaul
Published: December 2017

High-frequency activity produces transient depression at many synapses but also, as recently demonstrated, may accelerate the recovery from use-dependent depression. We have examined the possible consequences of this synaptic mechanism in neocortical excitatory synapses by recording simultaneously from presynaptic pyramidal neurons and their postsynaptic targets. Brief bursts of high-frequency spikes produced a strong depression of the amplitude of unitary excitatory postsynaptic currents (uEPSCs). However, when burst firing was combined with low-frequency ongoing activity, we found that the strong synaptic depression was followed by a transient rebound of synaptic strength. This rebound overshot the low-frequency baseline values and lasted 1–2 s. These results suggest that in the presence of ongoing activity, neocortical synapses may functionally facilitate following burst firing.
Disparity Sensitivity of Frontal Eye Field Neurons
Authors: Ferraina Stefano , Paré Martin , Wurtz Robert H.
Published: December 2017

Information about depth is necessary to generate saccades to visual stimuli located in three-dimensional space. To determine whether monkey frontal eye field (FEF) neurons play a role in the visuo-motor processes underlying this behavior, we studied their visual responses to stimuli at different disparities. Disparity sensitivity was tested from 3° of crossed disparity (near) to 3° degrees of uncrossed disparity (far). The responses of about two thirds of FEF visual and visuo-movement neurons were sensitive to disparity and showed a broad tuning in depth for near or far disparities. Early phasic and late tonic visual responses often displayed different disparity sensitivity. These findings provide evidence of depth-related signals in FEF and suggest a role for FEF in the control of disconjugate as well as conjugate eye movements.
Human Cerebellum Plays an Important Role in Memory-Timed Finger Movement: An fMRI Study
Authors: Kawashima Ryuta , Okuda Jiro , Umetsu Atsushi , Sugiura Motoaki , Inoue Kentaro , Suzuki Kyoko , Tabuchi Michio , Tsukiura Takashi , Narayan Singh L. , Nagasaka Tatsuo , Yanagawa Isao , Fujii Toshikatsu , Takahashi Shoki , Fukuda Hiroshi , Yamadori Atsushi
Published: December 2017

The purpose of this study was to determine, by using functional magnetic resonance imaging, the areas of the brain activated during a memory-timed finger movement task and compare these with those activated during a visually cued movement task. Because it is likely that subjects engage in subvocalization associated with chronometric counting to achieve accurate timing during memory-timed movements, the authors sought to determine the areas of the brain activated during a silent articulation task in which the subjects were instructed to reproduce the same timing as for the memory-timed movement task without any lip movements or vocalization. The memory-timed finger movement task induced activation of the anterior lobe of the cerebellum (lobules IV and V) bilaterally, the contralateral primary motor area, the supplementary motor area (SMA), the premotor area (PMA), the prefrontal cortex, and the posterior parietal cortex bilaterally, compared with the resting condition. The same areas in the SMA and left prefrontal cortex were activated during the silent articulation task compared with the resting condition. The anterior lobe of the cerebellum on both sides was also activated during the silent articulation task compared with the resting condition, but these activations did not reach statistical significance ( P < 0.05 corrected). In addition, the anterior cerebellum on both sides showed significant activation during the memory-timed movement task when compared with the visually cued finger movement task. The visually cued finger movement task specifically activated the ipsilateral PMA and the intraparietal cortex bilaterally. The results indicate that the anterior lobe of the cerebellum of both sides, the SMA, and the left prefrontal cortex were probably involved in the generation of accurate timing, functioning as a clock within the CNS, and that the dorsal visual pathway may be involved in the generation of visually cued movements.
NMDA-Receptor-Dependent Synaptic Activation of Voltage-Dependent Calcium Channels in Basolateral Amygdala
Authors: Calton Jeffrey L. , Kang Maeng-Hee , Wilson Wilkie A. , Moore Scott D.
Published: December 2017

Afferent stimulation of pyramidal cells in the basolateral amygdala produced mixed excitatory postsynaptic potentials (EPSPs) mediated by N-methyl-d-aspartate (NMDA) and non-NMDA glutamate receptors during whole cell current-clamp recordings. In the presence of GABAA receptor blockade, the mixed EPSPs recruited a large “all-or-none” depolarizing event. This recruited event was voltage dependent and had a distinct activation threshold. An analogous phenomenon elicited by exogenous glutamate in the presence of tetrodotoxin (TTX) was blocked by Cd2+, suggesting that the event was a Ca2+ spike. Selective glutamatergic blockade revealed that these Ca2+ spikes were recruited readily by single afferent stimulus pulses that elicited NMDA EPSPs. In contrast, non-NMDA EPSPs induced by single stimuli failed to elicit the Ca2+ spike even at maximal stimulus intensities although these non-NMDA EPSPs depolarized the soma more effectively than mixed EPSPs. Elongation of non-NMDA EPSPs by cyclothiazide or brief trains of stimulation were also unable to elicit the Ca2+ spike. Blockade of K+ channels with intracellular Cs+enabled single non-NMDA EPSPs to activate the Ca2+ spike. The finding that voltage-dependent calcium channels are activated preferentially by NMDA-receptor-mediated EPSPs provides a mechanism for NMDA-receptor-dependent plasticity independent of Ca2+influx through the NMDA receptor.
Contextual Influence on Orientation Discrimination of Humans and Responses of Neurons in V1 of Alert Monkeys
Authors: Li Wu , Thier Peter , Wehrhahn Christian
Published: December 2017

We studied the effects of various patterns as contextual stimuli on human orientation discrimination, and on responses of neurons in V1 of alert monkeys. When a target line is presented along with various contextual stimuli (masks), human orientation discrimination is impaired. For most V1 neurons, responses elicited by a line in the receptive field (RF) center are suppressed by these contextual patterns. Orientation discrimination thresholds of human observers are elevated slightly when the target line is surrounded by orthogonal lines. For randomly oriented lines, thresholds are elevated further and even more so for lines parallel to the target. Correspondingly, responses of most V1 neurons to a line are suppressed. Although contextual lines inhibit the amplitude of orientation tuning functions of most V1 neurons, they do not systematically alter the tuning width. Elevation of human orientation discrimination thresholds decreases with increasing curvature of masking lines, so does the inhibition of V1 neuronal responses. A mask made of straight lines yields the strongest interference with human orientation discrimination and produces the strongest suppression of neuronal responses. Elevation of human orientation discrimination thresholds is highest when a mask covers only the immediate vicinity of the target line. Increasing the masking area results in less interference. On the contrary, suppression of neuronal responses in V1 increases with increasing mask size. Our data imply that contextual interference observed in human orientation discrimination is in part directly related to contextual inhibition of neuronal activity in V1. However, the finding that interference with orientation discrimination is weaker for larger masks suggests a figure-ground segregation process that is not located in V1.
Three-Dimensional Kinematics of Ocular Drift in Humans With Cerebellar Atrophy
Authors: Straumann D. , Zee D. S. , Solomon D.
Published: December 2017

One of the signs of the cerebellar ocular motor syndrome is the inability to maintain horizontal and vertical fixation. Typically, in the presence of cerebellar atrophy, the eyes show horizontal gaze-evoked and vertical downbeat nystagmus. We investigated whether or not the cerebellar ocular motor syndrome also includes a torsional drift and, specifically, if it is independent from the drift in the horizontal-vertical plane. The existence of such a torsional drift would suggest that the cerebellum is critically involved in maintaining the eyes in Listing's plane. Eighteen patients with cerebellar atrophy (diagnosis confirmed by magnetic resonance imaging) were tested and compared with a group of normal subjects. Three-dimensional eye movements (horizontal, vertical, and torsional) during attempted fixations of targets at different horizontal and vertical eccentricities were recorded by dual search coils in a three-field magnetic frame. The overall ocular drift was composed of an upward drift that increased during lateral gaze, a horizontal centripetal drift that appeared during lateral gaze, and a torsional drift that depended on horizontal eye position. The vertical drift consisted of two subcomponents: a vertical gaze-evoked drift and a constant vertical velocity bias. The increase of upward drift velocity with eccentric horizontal gaze was caused by an increase of the vertical velocity bias; this component did not comply with Listing's law. The horizontal-eye-position–dependent torsional drift was intorsional in abduction and extorsional in adduction, which led to an additional violation of Listing's law. The existence of torsional drift that is eye-position–dependent suggests that the cerebellum is critically involved in the implementation of Listing's law, perhaps by mapping a tonic torsional signal that depends on the direction of the line of sight. The magnitude of this signal might reflect the difference in torsional eye position between the torsional resting position determined by the mechanics of the eye plant and the torsional position required by Listing's law.
Circuit Dynamics and Coding Strategies in Rodent Somatosensory Cortex
Authors: Pinto David J. , Brumberg Joshua C. , Simons Daniel J.
Published: December 2017

Previous experimental studies of both cortical barrel and thalamic barreloid neuron responses in rodent somatosensory cortex have indicated an active role for barrel circuitry in processing thalamic signals. Previous modeling studies of the same system have suggested that a major function of the barrel circuit is to render the response magnitude of barrel neurons particularly sensitive to the temporal distribution of thalamic input. Specifically, thalamic inputs that are initially synchronous strongly engage recurrent excitatory connections in the barrel and generate a response that briefly withstands the strong damping effects of inhibitory circuitry. To test this experimentally, we recorded responses from 40 cortical barrel neurons and 63 thalamic barreloid neurons evoked by whisker deflections varying in velocity and amplitude. This stimulus evoked thalamic response profiles that varied in terms of both their magnitude and timing. The magnitude of the thalamic population response, measured as the average number of evoked spikes per stimulus, increased with both deflection velocity and amplitude. On the other hand, the degree of initial synchrony, measured from population peristimulus time histograms, was highly correlated with the velocity of whisker deflection, deflection amplitude having little or no effect on thalamic synchrony. Consistent with the predictions of the model, the cortical population response was determined largely by whisker velocity and was highly correlated with the degree of initial synchrony among thalamic neurons ( R 2 = 0.91), as compared with the average number of evoked thalamic spikes ( R 2 = 0.38). Individually, the response of nearly all cortical cells displayed a positive correlation with deflection velocity; this homogeneity is consistent with the dependence of the cortical response on local circuit interactions as proposed by the model. By contrast, the response of individual thalamic neurons varied widely. These findings validate the predictions of the modeling studies and, more importantly, demonstrate that the mechanism by which the cortex processes an afferent signal is inextricably linked with, and in fact determines, the saliency of neural codes embedded in the thalamic response.
Exon 5 and Spermine Regulate Deactivation of NMDA Receptor Subtypes
Authors: Rumbaugh Gavin , Prybylowski Kate , Wang Jian Feng , Vicini Stefano
Published: December 2017

Deactivation of N-methyl-d-aspartate (NMDA) channels after brief agonist exposure determines the duration of their synaptic activation during excitatory neurotransmission. We performed patch-clamp recordings of l-glutamate responses from human embryonic kidney tumoral cells (HEK293) expressing NR1 subunit variants lacking exon 5 together with the NR2B subunit. These responses had deactivation components that lasted several seconds. The presence of exon 5 or spermine greatly accelerated deactivation ofl-glutamate responses through alterations in desensitization. These effects were also observed at positive holding potentials and in the presence of physiological Mg2+. Thus NR1 splicing and polyamines may have profound effects on the kinetics of NMDA receptor–mediated synaptic transmission.
Selective Inhibition by Adenosine of mGluR IPSPs in Dopamine Neurons After Cocaine Treatment
Authors: Fiorillo Christopher D. , Williams John T.
Published: December 2017

With repeated exposure to psychostimulants such as cocaine and amphetamine, long-lasting changes occur in the mesolimbic dopamine system that are thought to underlie continued drug-seeking and relapse. One consequence of repeated cocaine treatment is an increase in extracellular adenosine in the ventral tegmental area (VTA), which results in tonic inhibition of synaptic input to dopamine neurons. The synapse specificity of this increased adenosine tone was examined on glutamate- and GABA-mediated responses using the selective A1 receptor antagonist 1,3-dipropyl-8-cyclopentylxanthine (DPCPX). The slow, metabotropic glutamate receptor (mGluR)-mediated inhibitory postsynaptic potential (IPSP) was enhanced by DPCPX only in slices from psychostimulant-treated animals. Under resting conditions, DPCPX was without effect on fast excitatory postsynaptic currents (EPSCs) in slices from saline- or cocaine-treated animals. However, in the presence of amphetamine, DPCPX did augment fast EPSCs in slices from cocaine-treated rats. Although DPCPX increased GABAB IPSPs, the magnitude of the increase was not altered by cocaine pretreatment, even in the presence of amphetamine. This suggests that the elevated adenosine tone induced by cocaine treatment acts preferentially on glutamate terminals. Furthermore, the inhibition of the mGluR IPSP by endogenous adenosine may result in more effective burst firing mediated by glutamate afferents in cocaine-treated rats, a phenomenon known to enhance dopamine release.
Responses of Neurons in the Inferior Colliculus to Dynamic Interaural Phase Cues: Evidence for a Mechanism of Binaural Adaptation
Authors: McAlpine David , Jiang Dan , Shackleton Trevor M. , Palmer Alan R.
Published: December 2017

Responses to sound stimuli that humans perceive as moving were obtained for 89 neurons in the inferior colliculus (IC) of urethan-anesthetized guinea pigs. Triangular and sinusoidal interaural phase modulation (IPM), which produced dynamically varying interaural phase disparities (IPDs), was used to present stimuli with different depths, directions, centers, and rates of apparent motion. Many neurons appeared sensitive to dynamic IPDs, with responses at any given IPD depending strongly on the IPDs the stimulus had just passed through. However, it was the temporal pattern of the response, rather than the motion cues in the IPM, that determined sensitivity to features such as motion depth, direction, and center locus. IPM restricted only to the center of the IPD responsive area, evoked lower discharge rates than when the stimulus either moved through the IPD responsive area from outside, or up and down its flanks. When the stimulus was moved through the response area first in one direction and then back in the other, and the same IPDs evoked different responses, the response to the motion away from the center of the IPD responsive area was always lower than the response to the motion toward the center. When the IPD was closer at which the direction of motion reversed was to the center, the response to the following motion was lower. In no case did we find any evidence for neurons that under all conditions preferred one direction of motion to the other. We conclude that responses of IC neurons to IPM stimuli depend not on the history of stimulation, per se, but on the history of their response to stimulation, irrespective of the specific motion cues that evoke those responses. These data are consistent with the involvement of an adaptation mechanism that resides at or above the level of binaural integration. We conclude that our data provide no evidence for specialized motion detection involving dynamic IPD cues in the auditory midbrain of the mammal.
NMDA and AMPA Receptors in the Dorsal Nucleus of the Lateral Lemniscus Shape Binaural Responses in Rat Inferior Colliculus
Authors: Kelly Jack B. , Kidd Sean A.
Published: December 2017

Binaural responses of single neurons in the rat's central nucleus of the inferior colliculus (ICC) were recorded before and after local injection of excitatory amino acid receptor antagonists (either 1,2,3,4-tetrahydro-6-nitro-2,3-dioxo-benzo[f]quinoxaline-7-sulfonamide disodium [NBQX], (±)-3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid [CPP], 6-cyano-7-nitroquinoxaline-2,3-dione [CNQX], or (±)-2amino-5-phosphonovaleric acid [APV]) into the dorsal nucleus of the lateral lemniscus (DNLL). Responses were evoked by clicks delivered separately to the two ears at interaural time delays between −1.0 and +30 ms (positive values referring to ipsilateral leading contralateral click pairs). The neurons in our sample were excited by contralateral stimulation and inhibited by ipsilateral stimulation, and the probability of action potentials was reduced as the ipsilateral stimulus was advanced. Binaural inhibition resulted in response suppression that lasted up to 30 ms. Injection of excitatory amino acid antagonists into the DNLL contralateral to the recording site reduced the strength of binaural inhibition in the ICC. The α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonist NBQX preferentially affected responses at small interaural time intervals (0–1.0 ms), whereas the N-methyl-d-aspartate (NMDA) antagonist CPP preferentially affected responses at longer intervals (1–30 ms). Both CNQX and APV produced a release from binaural inhibition, but neither drug was selective for specific intervals. The data support the idea that binaural inhibition in the rat ICC is influenced by both AMPA and NMDA receptor–mediated excitatory events in the contralateral DNLL. The results suggest that the AMPA receptors contribute selectively to the initial component of binaural inhibition and the NMDA receptors to a longer lasting component.
Facilitatory I Wave Interaction in Proximal Arm and Lower Limb Muscle Representations of the Human Motor Cortex
Authors: Chen Robert , Garg Rami
Published: December 2017

Transcranial magnetic stimulation (TMS) of the human motor cortex elicits direct and indirect (I) waves in the corticospinal tract. Facilitatory I wave interaction has been demonstrated with a suprathreshold first stimulus (S1) followed by a subthreshold to threshold second stimulus (S2). Intracortical inhibition (ICI) and intracortical facilitation (ICF) can be studied by another paired TMS paradigm with a subthreshold conditioning stimulus (CS) followed by a suprathreshold test stimulus. Facilitatory I wave interaction in motor representations other than the hand area and its relationship to ICI and ICF has not been studied. We studied I wave interaction, ICI and ICF in an intrinsic hand muscle (abductor pollicis brevis, APB), in a proximal arm muscle (biceps brachii, BB) and in a lower limb muscle (tibialis anterior, TA) in 11 normal subjects. I wave facilitation was studied by paired TMS at 24 interstimulus intervals (ISIs) from 0.5 to 5.1 ms. For APB and TA, facilitation occurred in three distinct peaks at ISIs of 0.9–1.7, 2.5–3.5, and 4.1–5.1 ms. For BB, facilitation was significant for the first two peaks. The latencies of the peaks were similar among different muscles, but the magnitude of facilitation was much greater for APB and TA compared with BB. For all three muscles, changing the S2 to transcranial electrical stimulation (TES) resulted in much less facilitation of the first peak. For APB, there was significant I wave facilitation with S2 at 72% motor threshold (MT). The same stimulus used as the CS did not elicit ICF at ISI of 15 ms, suggesting that the threshold for eliciting I wave facilitation is lower than that for ICF. For BB and TA, there was no I wave facilitation with S2 at 90% of APB MT, and the same stimulus used as CS led to ICI. Thus in BB and TA the threshold for eliciting ICI is lower than that for I wave facilitation. We conclude that the circuits that mediate I wave interactions are present in the proximal arm and lower limb representations of the motor cortex. I wave facilitation occurs predominately in the cortex and may be primarily related to the monosynaptic corticomotoneuronal (CM) system. The reduced I wave facilitation for BB compared with APB and TA may be related to less extensive CM projection and involvement of other polysynaptic descending pathways. I wave facilitation, ICI, and ICF appears to be mediated by different neuronal circuits.
Sodium Pump Activity, Not Glial Spatial Buffering, Clears Potassium After Epileptiform Activity Induced in the Dentate Gyrus
Authors: Xiong Zhi-Qi , Stringer Janet L.
Published: December 2017

A number of mechanisms have been proposed to play a role in the regulation of activity-dependent variations in extracellular potassium concentration ([K+]o). We tested possible regulatory mechanisms for [K+]oduring spontaneous recurrent epileptiform activity induced in the dentate gyrus of hippocampal slices from adult rats by perfusion with 8 mM potassium and 0-added calcium medium in an interface chamber. Local application of tetrodotoxin blocked local [K+]ochanges, suggesting that potassium is released and taken up locally. Perfusion with barium or cesium, blockers of the inward rectifying potassium channel, did not alter the baseline [K+]o, the ceiling level of [K+]oreached during the burst, or the rate of [K+]orecovery after termination of the bursts. Decreasing gap junctional conductance did not change the baseline [K+]oor the half-time of recovery of the [K+]oafter the bursts but did cause a decrease in the ceiling level of [K+]o. Perfusion with furosemide, which will block cation/chloride cotransporters, or perfusion with low chloride did not change the baseline [K+]oor the half-time of recovery of the [K+]oafter the bursts but did increase the ceiling level of [K+]o. Bath or local application of ouabain, a Na+/K+-ATPase inhibitor, increased the baseline [K+]o, slowed the rate of [K+]orecovery, and induced spreading depression. These findings suggest that potassium redistribution by glia only plays a minor role in the regulation of [K+]oin this model. The major regulator of [K+]oin this model appears to be uptake via a Na+/K+-ATPase, most likely neuronal.
Primate Translational Vestibuloocular Reflexes. I. High-Frequency Dynamics and Three-Dimensional Properties During Lateral Motion
Authors: Angelaki Dora E. , McHenry M. Quinn , Hess Bernhard J. M.
Published: December 2017

The dynamics and three-dimensional (3-D) properties of the primate translational vestibuloocular reflex (trVOR) for high-frequency (4–12 Hz, ±0.3–0.4 g) lateral motion were investigated during near-target viewing at center and eccentric targets. Horizontal response gains increased with frequency and depended on target eccentricity. The larger the horizontal and vertical target eccentricity, the steeper the dependence of horizontal response gain on frequency. In addition to horizontal eye movements, robust torsional response components also were present at all frequencies. During center-target fixation, torsional response phase was opposite (anticompensatory) to that expected for an “apparent” tilt response. Instead torsional response components depended systematically on vertical-target eccentricity, increasing in amplitude when looking down and reversing phase when looking up. As a result the trVOR eye velocity vector systematically tilted away from a purely horizontal direction, through an angle that increased with vertical eccentricity with a slope of ∼0.7. This systematic dependence of torsional eye velocity tilt on vertical eye position suggests that the trVOR might follow the 3-D kinematic requirements that have been shown to govern visually guided eye movements and near-target fixation.
Fast Reaction to Different Sensory Modalities Activates Common Fields in the Motor Areas, but the Anterior Cingulate Cortex is Involved in the Speed of Reaction
Authors: Naito Eiichi , Kinomura Shigeo , Geyer Stefan , Kawashima Ryuta , Roland Per E. , Zilles Karl
Published: December 2017

We examined which motor areas would participate in the coding of a simple opposition of the thumb triggered by auditory, somatosensory and visual signals. We tested which motor areas might be active in response to all three modalities, which motor structures would be activated specifically in response to each modality, and which neural populations would be involved in the speed of the reaction. The subjects were required to press a button with their right thumb as soon as they detected a change in the sensory signal. The regional cerebral blood flow (rCBF) was measured quantitatively with 15O-butanol and positron emission tomography (PET) in nine normal male subjects. Cytoarchitectural areas were delimited in 10 post mortem brains by objective and quantitative methods. The images of the post mortem brains subsequently were transformed into standard anatomic format. One PET scanning for each of the sensory modalities was done. The control condition was rest with the subjects having their eyes closed. The rCBF images were anatomically standardized, and clusters of significant changes in rCBF were identified. These were localized to motor areas delimited on a preliminary basis, such as supplementary motor area (SMA), dorsal premotor zone (PMD), rostral cingulate motor area (CMAr), and within areas delimited by using microstructural i.e., cytoarchitectonic criteria, such as areas 4a, 4p, 3a, 3b, and 1. Fields of activation observed as a main effect for all three modalities were located bilaterally in the SMA, CMAr, contralateral PMD, primary motor (M1), and primary somatosensory cortex (SI). The activation in M1 engaged areas 4a and 4p and expanded into area 6. The activation in SI engaged areas 3b, 1, and extended into somatosensory association areas and the supramarginal gyrus posteriorly. We identified significant activations that were specific for each modality in the respective sensory association cortices, though no modality specific regions were found in the motor areas. Fields in the anterior cingulate cortex, rostral to the CMAr, consistently showed significant negative correlation with mean reaction time (RT) in all three tasks. These results show that simple reaction time tasks activate many subdivisions of the motor cortices. The information from different sensory modalities converge onto the common structures: the contralateral areas 4a, 4p, 3b, 1, the PMD, and bilaterally on the SMA and the CMAr. The anterior cingulate cortex might be a key structure which determine the speed of reaction in simple RT tasks.
Ca2+- and Metabolism-Related Changes of Mitochondrial Potential in Voltage-Clamped CA1 Pyramidal Neurons In Situ
Authors: Schuchmann S. , Lückermann M. , Kulik A. , Heinemann U. , Ballanyi K.
Published: December 2017

In hippocampal slices from rats, dialysis with rhodamine-123 (Rh-123) and/or fura-2 via the patch electrode allowed monitoring of mitochondrial potential (ΔΨ) changes and intracellular Ca2+([Ca2+]i) of CA1 pyramidal neurons. Plasmalemmal depolarization to 0 mV caused a mean [Ca2+]irise of 300 nM and increased Rh-123 fluorescence signal (RFS) by ≤50% of control. The evoked RFS, indicating depolarization of ΔΨ, and the [Ca2+]itransient were abolished by Ca2+-free superfusate or exposure of Ni2+/Cd2+. Simultaneous measurements of RFS and [Ca2+]ishowed that the kinetics of both the Ca2+rise and recovery were considerably faster than those of the ΔΨ depolarization. The plasmalemmal Ca2+/H+pump blocker eosin-B potentiated the peak of the depolarization-induced RFS and delayed recovery of both the RFS and [Ca2+]itransient. Thus the ΔΨ depolarization due to plasmalemmal depolarization is related to mitochondrial Ca2+sequestration secondary to Ca2+influx through voltage-gated Ca2+channels. CN−elevated [Ca2+]iby <50 nM but increased RFS by 221% as a result of extensive depolarization of ΔΨ. Oligomycin decreased RFS by 52% without affecting [Ca2+]i. In the presence of oligomycin, CN−and p-trifluoromethoxy-phenylhydrazone (FCCP) elevated [Ca2+]iby <50 nM and increased RFS by 285 and 290%, respectively. Accordingly, the metabolism-related ΔΨ changes are independent of [Ca2+]i. Imaging techniques revealed that evoked [Ca2+]irises are distributed uniformly over the soma and primary dendrites, whereas corresponding changes in RFS occur more localized in subregions within the soma. The results show that microfluorometric measurement of the relation between mitochondrial function and intracellular Ca2+is feasible in whole cell recorded mammalian neurons in situ.
Dopamine-Mediated Stabilization of Delay-Period Activity in a Network Model of Prefrontal Cortex
Authors: Durstewitz Daniel , Seamans Jeremy K. , Sejnowski Terrence J.
Published: December 2017

The prefrontal cortex (PFC) is critically involved in working memory, which underlies memory-guided, goal-directed behavior. During working-memory tasks, PFC neurons exhibit sustained elevated activity, which may reflect the active holding of goal-related information or the preparation of forthcoming actions. Dopamine via the D1 receptor strongly modulates both this sustained (delay-period) activity and behavioral performance in working-memory tasks. However, the function of dopamine during delay-period activity and the underlying neural mechanisms are only poorly understood. Recently we proposed that dopamine might stabilize active neural representations in PFC circuits during tasks involving working memory and render them robust against interfering stimuli and noise. To further test this idea and to examine the dopamine-modulated ionic currents that could give rise to increased stability of neural representations, we developed a network model of the PFC consisting of multicompartment neurons equipped with Hodgkin-Huxley-like channel kinetics that could reproduce in vitro whole cell and in vivo recordings from PFC neurons. Dopaminergic effects on intrinsic ionic and synaptic conductances were implemented in the model based on in vitro data. Simulated dopamine strongly enhanced high, delay-type activity but not low, spontaneous activity in the model network. Furthermore the strength of an afferent stimulation needed to disrupt delay-type activity increased with the magnitude of the dopamine-induced shifts in network parameters, making the currently active representation much more stable. Stability could be increased by dopamine-induced enhancements of the persistent Na+and N-methyl-d-aspartate (NMDA) conductances. Stability also was enhanced by a reductionin AMPA conductances. The increase in GABAA conductances that occurs after stimulation of dopaminergic D1 receptors was necessary in this context to prevent uncontrolled, spontaneous switches into high-activity states (i.e., spontaneous activation of task-irrelevant representations). In conclusion, the dopamine-induced changes in the biophysical properties of intrinsic ionic and synaptic conductances conjointly acted to highly increase stability of activated representations in PFC networks and at the same time retain control over network behavior and thus preserve its ability to adequately respond to task-related stimuli. Predictions of the model can be tested in vivo by locally applying specific D1 receptor, NMDA, or GABAA antagonists while recording from PFC neurons in delayed reaction-type tasks with interfering stimuli.
Distribution of Slow AHP Channels on Hippocampal CA1 Pyramidal Neurons
Authors: Bekkers John M.
Published: December 2017

This work was designed to localize the Ca2+-activated K+ channels underlying the slow afterhyperpolarization (sAHP) in hippocampal CA1 pyramidal cells. Cell-attached patches on the proximal 100 μm of the apical dendrite contained K+ channels, but not sAHP channels, activated by backpropagating action potentials. Amputation of the apical dendrite ∼30 μm from the soma, while simultaneously recording the sAHP whole cell current at the soma, depressed the sAHP amplitude by only ∼30% compared with control. Somatic cell-attached and nucleated patches did not contain sAHP current. Amputation of the axon ≥20 μm from the soma had little effect on the amplitude of the sAHP recorded in cortical pyramidal cells. By this process of elimination, it is suggested that sAHP channels may be concentrated in the basal dendrites of CA1 pyramids.
Adenosine Receptor Antagonists Induce Persistent Bursting in the Rat Hippocampal CA3 Region Via an NMDA Receptor-Dependent Mechanism
Authors: Thümmler Susanne , Dunwiddie Thomas V.
Published: December 2017

Adenosine receptor antagonists initiate repetitive bursting activity in the CA3 region of hippocampal slices. Although some studies have suggested that this effect is irreversible, this has been difficult to establish because many adenosine antagonists wash out of brain slices extremely slowly. Furthermore the cellular mechanism that underlies persistent bursting is unknown. To resolve these issues, we studied the effects of nonselective (8-p-sulfophenyltheophylline, 8SPT, 50–100 μM), Al-selective (8-cyclopentyl-1,3-dipropylxanthine, 100 nM; xanthine carboxylic acid congener, 200 nM), and A2A-selective (chlorostyryl-caffeine; 200 nM) adenosine antagonists in the CA3 region of rat hippocampal slices using extracellular recording. Superfusion with all of the adenosine antagonists except chlorostyryl-caffeine induced bursting, and the burst frequency after 30 min drug superfusion did not differ for the different antagonists. Most slices showed a period of rapid initial bursting, followed either by stable bursting at a lower frequency or a pattern of oscillating burst frequency. In either case, the bursting continued after drug washout. Virtually identical patterns of long-term bursting activity were observed when 8SPT was washed out or applied continuously. Control experiments using exogenous adenosine to characterize the persistence of 8SPT in tissue demonstrated >95% washout at 60 min, a time when nearly all slices still showed regular bursting activity. When the N-methyl-d-aspartate (NMDA) antagonistsdl−2-amino-5-phosphonovaleric acid (AP5; 50 μM) or dizocilpine (10 μM) were applied before and during 8SPT superfusion, bursting occurred in the presence of the NMDA antagonists but did not persist once the 8SPT was washed out. AP5 had no effect on persistent bursting when applied after the initiation of spiking. The selective calcium/calmodulin-dependent protein kinase inhibitor 1-[ N,O- bis-(5-isoquinolinesulfonyl)- N-methyl-l-tyrosyl]-4-phenylpiperazine (KN-62; 3 μM), which has been shown to block NMDA receptor-dependent synaptic plasticity in the CA1 region, also significantly decreased the long-term effect of 8SPT. Thus adenosine antagonists initiate persistent spiking in the CA3 region; this activity does not depend on continued occupation of adenosine receptors by antagonists, and can be blocked by treatments that prevent NMDA receptor-dependent plasticity.