bluuebunny/crossref_metadata_2025 huggingface dataset:
Motor Cortical Representation of Speed and Direction During Reaching
Authors: Moran Daniel W. , Schwartz Andrew B.
Published: December 2017

The motor cortical substrate associated with reaching was studied as monkeys moved their hands from a central position to one of eight targets spaced around a circle. Single-cell activity patterns were recorded in the proximal arm area of motor cortex during the task. In addition to the well-studied average directional selectivity (“preferred direction”) of single-cell activity, we also found the time-varying speed of movement to be represented in the cortical activity. A single equation relating motor cortical discharge rate to these two parameters was developed. This equation, which has both independent (speed only) and interactive (speed and direction) components, described a large portion of the time-varying motor cortical activity during the task. Electromyographic activity from a number of upper arm muscles was recorded during this task. Muscle activity was also found to be directionally tuned; however, the distributions of preferred directions were found to be significantly different from cortical activity. In addition, the effect of speed on cortical and muscle activity was also found to be significantly different.
Patterned Activity in Stratum Lacunosum Moleculare Inhibits CA1 Pyramidal Neuron Firing
Authors: Dvorak-Carbone Hannah , Schuman Erin M.
Published: December 2017

CA1 pyramidal cells are the primary output neurons of the hippocampus, carrying information about the result of hippocampal network processing to the subiculum and entorhinal cortex (EC) and thence out to the rest of the brain. The primary excitatory drive to the CA1 pyramidal cells comes via the Schaffer collateral (SC) projection from area CA3. There is also a direct projection from EC to stratum lacunosum-moleculare (SLM) of CA1, an input well positioned to modulate information flow through the hippocampus. High-frequency stimulation in SLM evokes an inhibition sufficiently strong to prevent CA1 pyramidal cells from spiking in response to SC input, a phenomenon we refer to as spike-blocking. We characterized the spike-blocking efficacy of burst stimulation (10 stimuli at 100 Hz) in SLM and found that it is greatest at ∼300–600 ms after the burst, consistent with the time course of the slow GABABsignaling pathway. Spike-blocking efficacy increases in potency with the number of SLM stimuli in a burst, but also decreases with repeated presentations of SLM bursts. Spike-blocking was eliminated in the presence of GABABantagonists. We have identified a candidate population of interneurons in SLM and distal stratum radiatum (SR) that may mediate this spike-blocking effect. We conclude that the output of CA1 pyramidal cells, and hence the hippocampus, is modulated in an input pattern-dependent manner by activation of the direct pathway from EC.
Cesium Induces Spontaneous Epileptiform Activity Without Changing Extracellular Potassium Regulation in Rat Hippocampus
Authors: Xiong Zhi-Qi , Stringer Janet L.
Published: December 2017

Cesium has been widely used to study the roles of the hyperpolarization-activated (Ih) and inwardly rectifying potassium (KIR) channels in many neuronal and nonneuronal cell types. Recently, extracellular application of cesium has been shown to produce epileptiform activity in brain slices, but the mechanisms for this are not known. It has been proposed that cesium blocks the KIR in glia, resulting in an abnormal accumulation of potassium in the extracellular space and inducing epileptiform activity. This hypothesis has been tested in hippocampal slices and cultured hippocampal neurons using potassium-sensitive microelectrodes. In the present study, application of cesium produced spontaneous epileptiform discharges at physiological extracellular potassium concentration ([K+]o) in the CA1 and CA3 regions of hippocampal slices. This epileptiform activity was not mimicked by increasing the [K+]o. The epileptiform discharges induced by cesium were not blocked by the N-methyl-d- aspartate (NMDA) receptor antagonist AP-5, but were blocked by the non-NMDA receptor antagonist CNQX. In the dentate gyrus, cesium induced the appearance of spontaneous nonsynaptic field bursts in 0 added calcium and 3 mM potassium. Moreover, cesium increased the frequency of field bursts already present. In contrast, ZD-7288, a specific Ihblocker, did not cause spontaneous epileptiform activity in CA1 and CA3, nor did it affect the field bursts in the dentate gyrus, suggesting that cesium induced epileptiform activity is not directly related to blockade of the Ih. When potassium-sensitive microelectrodes were used to measure [K+]o, there was no significant increase in [K+]o in CA1 and CA3 after cesium application. In the dentate gyrus, cesium did not change the baseline level of [K+]o or the rate of [K+]o clearance after the field bursts. In cultured hippocampal neurons, which have a large and relatively unrestricted extracellular space, cesium also produced cellular burst activity without significantly changing the resting membrane potential, which might indicate an increase in [K+]o. Our results suggest that cesium causes epileptiform activity by a mechanism unrelated to an alteration in [K+]o regulation.
Specificity and Strength of Retinogeniculate Connections
Authors: Usrey W. Martin , Reppas John B. , Reid R. Clay
Published: December 2017

Retinal ganglion cells and their target neurons in the principal layers of the lateral geniculate nucleus (LGN) of the thalamus have very similar, center-surround receptive fields. Although some geniculate neurons are dominated by a single retinal afferent, others receive both strong and weak inputs from several retinal afferents. In the present study, experiments were performed in the cat that examined the specificity and strength of monosynaptic connections between retinal ganglion cells and their target neurons. The responses of 205 pairs of retinal ganglion cells and geniculate neurons with overlapping receptive-field centers or surrounds were studied. Receptive fields were mapped quantitatively using a white-noise stimulus; connectivity was assessed by cross-correlating the retinal and geniculate spike trains. Of the 205 pairs, 12 were determined to have monosynaptic connections. Both the likelihood that cells were connected and the strength of connections increased with increasing similarity between retinal and geniculate receptive fields. Connections were never found between cells with <50% spatial overlap between their centers. The results suggest that although geniculate neurons often receive input from several retinal afferents, these multiple afferents represent a select subset of the retinal ganglion cells with overlapping receptive-field centers.
Properties of Miniature Glutamatergic EPSCs in Neurons of the Locomotor Regions of the Developing Zebrafish
Authors: Ali Declan W. , Buss Robert R. , Drapeau Pierre
Published: December 2017

As a first step in understanding the development of synaptic activation in the locomotor network of the zebrafish, we examined the properties of spontaneous, glutamatergic miniature excitatory postsynaptic currents (mEPSCs). Whole cell patch-clamp recordings were obtained from visually identified hindbrain reticulospinal neurons and spinal motoneurons of curarized zebrafish 1–5 days postfertilization (larvae hatch after the 2nd day of embryogenesis). In the presence of tetrodotoxin (TTX) and blockers of inhibitory receptors (strychnine and picrotoxin), we detected fast glutamatergic mEPSCs that were blocked by the AMPA/kainate receptor-selective antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX). At positive voltages or in the absence of Mg2+, a second, slower component of the mEPSCs was revealed that the N-methyl-d-aspartate (NMDA) receptor-selective antagonistdl−2-amino-5-phosphonovalerate (AP-5) abolished. In the presence of both CNQX and AP-5, all mEPSCs were eliminated. The NMDA component of reticulospinal mEPSCs had a large single-channel conductance estimated to be 48 pS. Larval AMPA/kainate and NMDA components of the mEPSCs decayed with biexponential time courses that changed little during development. At all stages examined, approximately one-half of synapses had only NMDA responses (lacking AMPA/kainate receptors), whereas the remainder of the synapses were composed of a mixture of AMPA/kainate and NMDA receptors. There was an overall increase in the frequency and amplitude of mEPSCs with an NMDA component in reticulospinal (but not motoneurons) during development. These results indicate that glutamate is a prominent excitatory transmitter in the locomotor regions of the developing zebrafish and that it activates either NMDA receptors alone at functionally silent synapses or together with AMPA/kainate receptors.
Evidence for Paracrine Signaling Between Macrophages and Bovine Adrenal Chromaffin Cell Ca2+Channels
Authors: Currie Kevin P. M. , Zhou Zhong , Fox Aaron P.
Published: December 2017

The adrenal gland contains resident macrophages, some of which lie adjacent to the catecholamine producing chromaffin cells. Because macrophages release a variety of secretory products, it is possible that paracrine signaling between these two cell types exists. Of particular interest is the potential paracrine modulation of voltage-gated calcium channels ( ICa), which are the main calcium influx pathway triggering catecholamine release from chromaffin cells. We report that prostaglandin E2(PGE2), one of the main signals produced by macrophages, inhibited ICain cultured bovine adrenal chromaffin cells. The inhibition is rapid, robust, and voltage dependent; the activation kinetics are slowed and inhibition is largely reversed by a large depolarizing prepulse, suggesting that the inhibition is mediated by a direct G-protein βγ subunit interaction with the calcium channels. About half of the response to PGE2was sensitive to pertussis toxin (PTX) incubation, suggesting both PTX-sensitive and -insensitive G proteins were involved. We show that activation of macrophages by endotoxin rapidly (within minutes) releases a signal that inhibits ICain chromaffin cells. The inhibition is voltage dependent and partially PTX sensitive. PGE2is not responsible for this inhibition as blocking cyclooxygenase with ibuprofen did not prevent the production of the inhibitory signal by the macrophages. Nor did blocking the lipoxygenase pathway with nordihydroguaiaretic acid alter production of the inhibitory signal. Our results suggest that macrophages may modulate ICaand catecholamine secretion by releasing PGE2and other chemical signal(s).
Nucleus-Specific Differences in GABAA-Receptor-Mediated Inhibition Are Enhanced During Thalamic Development
Authors: Huntsman Molly M. , Huguenard John R.
Published: December 2017

Inhibitory postsynaptic currents (IPSCs) mediated by GABAA receptors are much slower in neurons of the thalamic reticular nucleus (RTN) versus those in the ventrobasal complex (VB) of young rats. Here we confirm and extend those findings regarding GABAA response heterogeneity especially in relation to development. Whole cell patch-clamp recordings were used to investigate GABAAspontaneous and electrically evoked IPSCs (sIPSCs/eIPSCs) in RTN and VB cells of different aged rats. Consistent with earlier findings, sIPSC duration at P8–12 was considerably longer in RTN (weighted decay time constant: τD,W = 56.2 ± 4.9 ms; mean ± SE) than in VB (τD,W = 15.8 ± 1.0 ms) neurons. Decay kinetics in RTN neurons did not differ at P21–30 (45.5 ± 4.7 ms) or P42–60 (51.6 ± 10.6 ms). In contrast, VB sIPSCs were significantly faster at both P21–30 (τD,W = 10.8 ± 0.9 ms) and P42–60 (τD,W = 9.2 ± 0.4 ms) compared with P8–12 animals. IPSCs displayed differential outward rectification and temperature dependence, providing further support for nucleus-specific responses. τD,W increased with membrane depolarization but with a net larger effect in VB. By contrast, τD,W was always smaller at higher temperatures but with relatively greater difference observed in RTN. Thus nuclear differences in GABAA IPSCs are not only maintained, but enhanced in the mature rodent under physiological conditions. These findings support our hypothesis that unique GABAA receptors mediate slowly decaying RTN IPSCs that are a critical and enduring feature of the thalamic circuit. This promotes powerful intranuclear inhibition and likely prevents epileptiform thalamocortical hypersynchrony.
Amplification of Odor-Induced Ca2+ Transients by Store-Operated Ca2+ Release and Its Role in Olfactory Signal Transduction
Authors: Zufall Frank , Leinders-Zufall Trese , Greer Charles A.
Published: December 2017

A critical role of Ca2+ in vertebrate olfactory receptor neurons (ORNs) is to couple odor-induced excitation to intracellular feedback pathways that are responsible for the regulation of the sensitivity of the sense of smell, but the role of intracellular Ca2+ stores in this process remains unclear. Using confocal Ca2+ imaging and perforated patch recording, we show that salamander ORNs contain a releasable pool of Ca2+ that can be discharged at rest by the SERCA inhibitor thapsigargin and the ryanodine receptor agonist caffeine. The Ca2+ stores are spatially restricted; emptying produces compartmentalized Ca2+ release and capacitative-like Ca2+ entry in the dendrite and soma but not in the cilia, the site of odor transduction. We deplete the stores to show that odor stimulation causes store-dependent Ca2+ mobilization. This odor-induced Ca2+ release does not seem to be necessary for generation of an immediate electrophysiological response, nor does it contribute significantly to the Ca2+ transients in the olfactory cilia. Rather, it is important for amplifying the magnitude and duration of Ca2+ transients in the dendrite and soma and is thus necessary for the spread of an odor-induced Ca2+ wave from the cilia to the soma. We show that this amplification process depends on Ca2+-induced Ca2+ release. The results indicate that stimulation of ORNs with odorants can produce Ca2+ mobilization from intracellular stores without an immediate effect on the receptor potential. Odor-induced, store-dependent Ca2+ mobilization may be part of a feedback pathway by which information is transferred from the distal dendrite of an ORN to its soma.
Activity of Smooth Pursuit-Related Neurons in the Monkey Periarcuate Cortex During Pursuit and Passive Whole-Body Rotation
Authors: Fukushima Kikuro , Sato Toshikazu , Fukushima Junko , Shinmei Yasuhiro , Kaneko Chris R. S.
Published: December 2017

Smooth pursuit and vestibularly induced eye movements interact to maintain the accuracy of eye movements in space (i.e., gaze). To understand the role played by the frontal eye fields in pursuit-vestibular interactions, we examined activity of 110 neurons in the periarcuate areas of head-stabilized Japanese monkeys during pursuit eye movements and passive whole-body rotation. The majority (92%) responded with the peak of their modulation near peak stimulus velocity during suppression of the vestibuloocular reflex (VOR) when the monkeys tracked a target that moved with the same amplitude and phase and in the same plane as the chair. We classified pursuit-related neurons ( n = 100) as gaze- velocity if their peak modulation occurred for eye (pursuit) and head (VOR suppression) movements in the same direction; the amplitude of modulation during one less than twice that of the other; and modulation was lower during target-stationary-in-space condition (VOR ×1) than during VOR suppression. In addition, we examined responses during VOR enhancement (×2) in which the target moved with equal amplitude as, but opposite direction to, the chair. Gaze-velocity neurons responded maximally for opposite directions during VOR ×2 and suppression. Based on these criteria, the majority of pursuit-related neurons (66%) were classified as gaze-velocity with preferred directions uniformly distributed. Because the majority of the remaining cells (32/34) also responded during VOR suppression, they were classified as eye/head-velocity neurons. Thirteen preferred pursuit and VOR suppression in the same direction; 13 in the opposite direction, and 6 showed biphasic modulation during VOR suppression. Eye- and gaze-velocity sensitivity of the two groups of cells were similar; mean (± SD) was 0.53 ± 0.30 and 0.50 ± 0.44 spikes/s per °/s, respectively. Gaze-velocity (but not eye/head-velocity) neurons showed significant correlation between eye- and gaze-velocity sensitivity, and both groups maintained their responses when the tracking target was extinguished briefly. The majority of pursuit-related neurons (28/43 = about 65%) responded to chair rotation in complete darkness. When the monkeys fixated a stationary target, more than half of cells tested (21/40) discharged in proportion to the velocity of retinal motion of a second laser spot (mean velocity sensitivity = 0.20 ± 0.16 spikes/s per °/s). Preferred directions of individual cells to the second spot were similar to those during pursuit. Visual responses to the second spot movement were maintained even when it was extinguished briefly. These results indicate that both retinal image- and gaze-velocity signals are carried by single periarcuate pursuit-related neurons, suggesting that these signals can provide target-velocity-in-space and gaze-velocity commands during pursuit-vestibular interactions.
Recurrent Excitatory Connectivity in the Dentate Gyrus of Kindled and Kainic Acid–Treated Rats
Authors: Lynch Michael , Sutula Thomas
Published: December 2017

Repeated seizures induce mossy fiber axon sprouting, which reorganizes synaptic connectivity in the dentate gyrus. To examine the possibility that sprouted mossy fiber axons may form recurrent excitatory circuits, connectivity between granule cells in the dentate gyrus was examined in transverse hippocampal slices from normal rats and epileptic rats that experienced seizures induced by kindling and kainic acid. The experiments were designed to functionally assess seizure-induced development of recurrent circuitry by exploiting information available about the time course of seizure-induced synaptic reorganization in the kindling model and detailed anatomic characterization of sprouted fibers in the kainic acid model. When recurrent inhibitory circuits were blocked by the GABAAreceptor antagonist bicuculline, focal application of glutamate microdrops at locations in the granule cell layer remote from the recorded granule cell evoked trains of excitatory postsynaptic potentials (EPSPs) and population burst discharges in epileptic rats, which were never observed in slices from normal rats. The EPSPs and burst discharges were blocked by bath application of 1 μM tetrodotoxin and were therefore dependent on network-driven synaptic events. Excitatory connections were detected between blades of the dentate gyrus in hippocampal slices from rats that experienced kainic acid–induced status epilepticus. Trains of EPSPs and burst discharges were also evoked in granule cells from kindled rats obtained after ≥1 wk of kindled seizures, but were not evoked in slices examined 24 h after a single afterdischarge, before the development of sprouting. Excitatory connectivity between blades of the dentate gyrus was also assessed in slices deafferented by transection of the perforant path, and bathed in artificial cerebrospinal fluid (ACSF) containing bicuculline to block GABAA receptor–dependent recurrent inhibitory circuits and 10 mM [Ca2+]o to suppress polysynaptic activity. Low-intensity electrical stimulation of the infrapyramidal blade under these conditions failed to evoke a response in suprapyramidal granule cells from normal rats ( n = 15), but in slices from epileptic rats evoked an EPSP at a short latency (2.59 ± 0.36 ms) in 5 of 18 suprapyramidal granule cells. The results are consistent with formation of monosynaptic excitatory connections between blades of the dentate gyrus. Recurrent excitatory circuits developed in the dentate gyrus of epileptic rats in a time course that corresponded to the development of mossy fiber sprouting and demonstrated patterns of functional connectivity corresponding to anatomic features of the sprouted mossy fiber pathway.
Na+ and K+ Concentrations, Extra- and Intracellular Voltages, and the Effect of TTX in Hypoxic Rat Hippocampal Slices
Authors: Müller Michael , Somjen George G.
Published: December 2017

Severe hypoxia causes rapid depolarization of CA1 neurons and glial cells that resembles spreading depression (SD). In brain slices in vitro, the SD-like depolarization and the associated irreversible loss of function can be postponed, but not prevented, by blockade of Na+ currents by tetrodotoxin (TTX). To investigate the role of Na+ flux, we made recordings from the CA1 region in hippocampal slices in the presence and absence of TTX. We measured membrane changes in single CA1 pyramidal neurons simultaneously with extracellular DC potential ( V o) and either extracellular [K+] or [Na+]; alternatively, we simultaneously recorded [Na+]o, [K+]o, and V o. Confirming previous reports, early during hypoxia, before SD onset, [K+]o began to rise, whereas [Na+]o still remained normal and V o showed a slight, gradual, negative shift; neurons first hyperpolarized and then began to gradually depolarize. The SD-like abrupt negative Δ V ocorresponded to a near complete depolarization of pyramidal neurons and an 89% decrease in input resistance. [K+]oincreased by 47 mM and [Na+]o dropped by 91 mM. Changes in intracellular Na+ and K+concentrations, estimated on the basis of the measured extracellular ion levels and the relative volume fractions of the neuronal, glial, and extracellular compartment, were much more moderate. Because [Na+]o dropped more than [K+]o increased, simple exchange of Na+ for K+ cannot account for these ionic changes. The apparent imbalance of charge could be made up by Cl− influx into neurons paralleling Na+ flux and release of Mg2+ from cells. The hypoxia-induced changes in interneurons resembled those observed in pyramidal neurons. Astrocytes responded with an initial slow depolarization as [K+]o rose. It was followed by a rapid but incomplete depolarization as soon as SD occurred, which could be accounted for by the reduced ratio, [K+]i/[K+]o. TTX (1 μM) markedly postponed SD, but the SD-related changes in [K+]o and [Na+]owere only reduced by 23 and 12%, respectively. In TTX-treated pyramidal neurons, the delayed SD-like depolarization took off from a more positive level, but the final depolarized intracellular potential and input resistance were not different from control. We conclude that TTX-sensitive channels mediate only a fraction of the Na+influx, and that some of the K+ is released in exchange for Na+. Even though TTX-sensitive Na+ currents are not essential for the self-regenerative membrane changes during hypoxic SD, in control solutions their activation may trigger the transition from gradual to rapid depolarization of neurons, thereby synchronizing the SD-like event.
Responses to Efferent Activation and Excitatory Response-Intensity Relations of Turtle Posterior-Crista Afferents
Authors: Brichta Alan M. , Goldberg Jay M.
Published: December 2017

Multivariate statistical formulas were used to infer the morphological type and longitudinal position of extracellularly recorded afferents. Efferent fibers were stimulated electrically in the nerve branch interconnecting the anterior and posterior VIIIth nerves. Responses of bouton (B) units depended on their inferred position: BP units (near the planum semilunatum) showed small excitatory responses; BT units (near the torus) were inhibited; BM units (in an intermediate position) had a mixed response, including an initial inhibition and a delayed excitation. Calyx-bearing (CD-high) units with an appreciable background discharge showed large per-train excitatory responses followed by smaller post-train responses that could outlast the shock train by 100 s. Excitatory responses were smaller in calyx-bearing (CD-low) units having little or no background activity than in CD-high units. Excitatory response-intensity functions, derived from the discharge during 2-s angular-velocity ramps varying in intensity, were fit by empirical functions that gave estimates of the maximal response ( rMAX), a threshold velocity ( vT), and the velocity producing a half-maximal response ( v1/2). Linear gain is equal to rMAX/ vS, vS= v1/2− vT. vSprovides a measure of the velocity range over which the response is nearly linear. For B units, rMAXdeclines by as much as twofold over the 2-s ramp, whereas for CD units, rMAXincreases by 15% during the same time period. At the end of the ramp, rMAXis on average twice as high in CD as in B units. Thresholds are negligible in most spontaneously active units, including almost all B and CD-high units. Silent CD-low units typically have thresholds of 10–100 deg/s. BT units have very high linear gains and vS< 10 deg/s. Linear gains are considerably lower in BP units and vS> 150 deg/s. CD-high units have intermediate gains and near 100 deg/s vSvalues. CD-low units have low gains and vSvalues ranging from 150 to more than 300 deg/s. The results suggest that BT units are designed to measure the small head movements involved in postural control, whereas BP and CD units are more appropriate for monitoring large volitional head movements. The former units are silenced by efferent activation, whereas the latter units are excited. This suggests that the efferent system switches the turtle posterior crista from a “postural” to a “volitional” mode.
Spontaneous Activity in the Statoacoustic Ganglion of the Chicken Embryo
Authors: Jones Timothy A. , Jones Sherri M.
Published: December 2017

Statoacoustic ganglion cells in the mature bird include neurons that are responsive to sound (auditory) and those that are not (nonauditory). Those that are nonauditory have been shown to innervate an otolith organ, the macula lagena, whereas auditory neurons innervate the basilar papilla. In the present study, single-unit recordings of statoacoustic ganglion cells were made in embryonic (E19, mean = 19.2 days of incubation) and hatchling (P6–P14, mean = 8.6 days posthatch) chickens. Spontaneous activity from the two age groups was compared with developmental changes. Activity was evaluated for 47 auditory, 11 nonauditory, and 6 undefined eighth nerve neurons in embryos and 29 auditory, 26 nonauditory, and 1 undefined neurons in hatchlings. For auditory neurons, spontaneous activity displayed an irregular pattern [discharge interval coefficient of variation (CV) was >0.5, mean CV for embryos was 1.46 ± 0.58 and for hatchlings was 1.02 ± 0.25; means ± SD]. Embryonic discharge rates ranged from 0.05 to 97.6 spikes per second (sp/s) for all neurons (mean 18.6 ± 16.9 sp/s). Hatchling spontaneous rates ranged from 1.2 to 185.2 sp/s (mean 66.5 ± 39.6 sp/s). Discharge rates were significantly higher for hatchlings ( P < 0.001). Many embryonic auditory neurons displayed long silent periods between irregular bursts of neural activity, a feature not seen posthatch. All regular bursting discharge patterns were correlated with heart rate in both embryos and hatchlings. Preferred intervals were visible in the time interval histograms (TIHs) of only one embryonic neuron in contrast to 55% of the neurons in posthatch animals. Generally, the embryonic auditory TIH displayed a modified quasi-Poisson distribution. Nonauditory units generally displayed regular (CV <0.5) or irregular (CV >0.5) activity and Gaussian and modified-Gaussian TIHs. Long silent periods or bursting patterns were not a characteristic of embryonic nonauditory neurons. CV varied systematically as a function of discharge rate in nonauditory but not auditory primary afferents. Minimum spike intervals (dead time) and interval modes for auditory neurons were longer in embryos (dead time: embryos 2.88 ± 6.85 ms; hatchlings 1.50 ± 1.76 ms; modal intervals: embryo 10.09 ± 22.50 ms, hatchling 3.54 ± 3.29 ms). The results show that significant developmental changes occur in spontaneous activity between E19 and posthatch. It is likely that both presynaptic and postsynaptic changes in the neuroepithelium contribute to maturational refinements during this period of development.
Reward-Related Neuronal Activity During Go-Nogo Task Performance in Primate Orbitofrontal Cortex
Authors: Tremblay Léon , Schultz Wolfram
Published: December 2017

The orbitofrontal cortex appears to be involved in the control of voluntary, goal-directed behavior by motivational outcomes. This study investigated how orbitofrontal neurons process information about rewards in a task that depends on intact orbitofrontal functions. In a delayed go-nogo task, animals executed or withheld a reaching movement and obtained liquid or a conditioned sound as reinforcement. An initial instruction picture indicated the behavioral reaction to be performed (movement vs. nonmovement) and the reinforcer to be obtained (liquid vs. sound) after a subsequent trigger stimulus. We found task-related activations in 188 of 505 neurons in rostral orbitofrontal area 13, entire area 11, and lateral area 14. The principal task-related activations consisted of responses to instructions, activations preceding reinforcers, or responses to reinforcers. Most activations reflected the reinforcing event rather than other task components. Instruction responses occurred either in liquid- or sound-reinforced trials but rarely distinguished between movement and nonmovement reactions. These instruction responses reflected the predicted motivational outcome rather than the behavioral reaction necessary for obtaining that outcome. Activations preceding the reinforcer began slowly and terminated immediately after the reinforcer, even when the reinforcer occurred earlier or later than usually. These activations preceded usually the liquid reward but rarely the conditioned auditory reinforcer. The activations also preceded expected drops of liquid delivered outside the task, suggesting a primary appetitive rather than a task-reinforcing relationship that apparently was related to the expectation of reward. Responses after the reinforcer occurred in liquid- but rarely in sound-reinforced trials. Reward-preceding activations and reward responses were unrelated temporally to licking movements. Several neurons showed reward responses outside the task but instruction responses during the task, indicating a response transfer from primary reward to the reward-predicting instruction, possibly reflecting the temporal unpredictability of reward. In conclusion, orbitofrontal neurons report stimuli associated with reinforcers are concerned with the expectation of reward and detect reward delivery at trial end. These activities may contribute to the processing of reward information for the motivational control of goal-directed behavior.
Integration of Foveal Orientation Signals: Distinct Local and Long-Range Spatial Domains
Authors: Brincat Scott L. , Westheimer Gerald
Published: December 2017

Human observers can discriminate the orientation of a stimulus configuration composed of a pair of collinear visual patterns much better than that of a single component pattern alone. Previous investigations of this type of orientation signal integration and of other similar visual integrative functions have shown that, for closely spaced elements, there is integration only for stimuli with the same contrast polarity (i.e., both lighter or both darker than the background) but, at greater separations, integration is independent of contrast polarity. Is this effect specific to differences in contrast polarity, which is known to be an important parameter in the organization of the visual system, or might there be a cluster of other stimulus dimensions that show similar effects, indicating a more widespread distinction between the processes limiting integration at local and long-range spatial scales? Here, we report a similar distance dependence for orientation signal integration across stimulus differences in binocular disparity, direction of motion, and direction of figure-ground assignment. We also demonstrate that the selectivity found at short separations cannot be explained only by “end-cuts,” the small borders created at the junction of abutting contrasting patterns. These findings imply the existence of two distinct spatial domains for the integration of foveal orientation information: a local zone in which integration is highly selective for a number of salient stimulus parameters and a long-range domain in which integration is relatively unselective and only requires that patterns be roughly collinear.
Effects of Lesions of the Oculomotor Cerebellar Vermis on Eye Movements in Primate: Smooth Pursuit
Authors: Takagi Mineo , Zee David S. , Tamargo Rafael J.
Published: December 2017

We studied the effects on smooth pursuit eye movements of ablation of the dorsal cerebellar vermis (lesions centered on lobules VI and VII) in three monkeys in which the cerebellar nuclei were spared. Following the lesion the latencies to pursuit initiation were unchanged. Monkeys showed a small decrease (up to 15%) in gain during triangular-wave tracking. More striking were changes in the dynamic properties of pursuit as determined in the open-loop period (the 1st 100 ms) of smooth tracking. Changes included a decrease in peak eye acceleration (e.g., in one monkey from ∼650°/s2, prelesion to ∼220–380°/s2, postlesion) and a decrease in the velocity at the end of the open-loop period [e.g., in another monkey from a gain (eye velocity/target velocity at 100 ms of tracking) of 0.93, prelesion to 0.53, postlesion]. In individual monkeys, the pattern of deficits in the open-loop period of pursuit was usually comparable to that of saccades, especially when comparing the changes in the acceleration of pursuit to the changes in the velocity of saccades. These findings support the hypothesis that saccades and the open-loop period of pursuit are controlled by the cerebellar vermis in an analogous way. Saccades could be generated by eye velocity commands to bring the eyes to a certain position and pursuit by eye acceleration commands to bring the eyes toward a certain velocity. On the other hand, changes in gain during triangular-wave tracking did not correlate with either the saccade or the open-loop pursuit deficits, implying different contributions of the oculomotor vermis to the open loop and to the sustained portions of pursuit tracking. Finally, in a pursuit adaptation paradigm (×0.5 or ×2, calling for a halving or doubling of eye velocity, respectively) intact animals could adaptively adjust eye acceleration in the open-loop period. The main pattern of change was a decrease in peak acceleration for ×0.5 training and an increase in the duration of peak acceleration for ×2 training. Following the lesion in the oculomotor vermis, this adaptive capability was impaired. In conclusion, as for saccades, the oculomotor vermis plays a critical role both in the immediate on-line and in the short-term adaptive control of pursuit.
Effects of Reversible Inactivation of the Primate Mesencephalic Reticular Formation. II. Hypometric Vertical Saccades
Authors: Waitzman David M. , Silakov Valentine L. , DePalma-Bowles Stacy , Ayers Amanda S.
Published: December 2017

Electrical microstimulation and single-unit recording have suggested that a group of long-lead burst neurons (LLBNs) in the mesencephalic reticular formation (MRF) just lateral to the interstitial nucleus of Cajal (INC) (the peri-INC MRF, piMRF) may play a role in the generation of vertical rapid eye movements. Inactivation of this region with muscimol (a GABAA agonist) rapidly produced vertical saccade hypometria (6 injections). In three of six injections, there was a marked reduction in the velocity of vertical saccades out of proportion to saccade amplitude (i.e., saccades fell below the main sequence). This was associated with a moderate increase in saccade duration. Inadvertent inactivation of the INC could not account for these observations because vertical, postsaccadic drift was not observed. Similarly, pure downward saccade hypometria, the hallmark of rostral interstitial nucleus of the medial longitudinal fasciculus (riMLF) inactivation, was always preceded by loss of upward saccades in our experiments. We also found a downward and ipsiversive displacement of initial eye position and evidence of a contraversive head tilt following piMRF injections. Saccade latency was shorter after two of six injections. Simulation of a local feedback model provided three possible explanations for vertical saccade hypometria: 1) a shift in the input to the model to request smaller saccades, 2) a reduction of LLBN input to the vertical saccade medium lead burst neurons (MLBNs), or 3) an increase in the gain of the feedback pathway. However, when the second hypothesis was coupled to a shortened duration of the saccade trigger (i.e., the discharge of the omnipause neurons), the physiological observations of piMRF inactivation could be replicated. This suggested that muscimol had targeted structures that provided both long-lead burst activity to the MLBNs in the riMLF and were critical for reactivation of the omnipause neurons. Evidence of markedly reduced vertical saccade amplitude, curved saccade trajectories, increased saccade duration, and saccades that fall below the amplitude/velocity main sequence in these monkeys closely parallels the oculomotor findings of patients with progressive supranuclear palsy (PSP).
Epileptogenesis Up-Regulates Metabotropic Glutamate Receptor Activation of Sodium-Calcium Exchange Current in the Amygdala
Authors: Keele N. Bradley , Zinebi Fatiha , Neugebauer Volker , Shinnick-Gallagher P.
Published: December 2017

Postsynaptic metabotropic glutamate (mGlu) receptor-activated inward current mediated by Na+-Ca2+ exchange was compared in basolateral amygdala (BLA) neurons from brain slices of control (naı̈ve and sham-operated) and amygdala-kindled rats. In control neurons, the mGlu agonist, quisqualate (QUIS; 1–100 μM), evoked an inward current not associated with a significant change in membrane slope conductance, measured from current-voltage relationships between −110 and −60 mV, consistent with activation of the Na+-Ca2+ exchanger. Application of the group I selective mGlu receptor agonist ( S)-3,5-dihydroxyphenylglycine [( S)-DHPG; 10–1000 μM] or the endogenous agonist, glutamate (10–1000 μM), elicited the exchange current. QUIS was more potent than either ( S)-DHPG or glutamate (apparent EC50 = 19 μM, 57 μM, and 0.6 mM, respectively) in activating the Na+-Ca2+ exchange current. The selective mGlu5 agonist, ( R,S)-2-chloro-5-hydroxyphenylglycine [( R,S)-CHPG; apparent EC50 = 2.6 mM] also induced the exchange current. The maximum response to ( R,S) -DHPG was about half of that of the other agonists suggesting partial agonist action. Concentration-response relationships of agonist-evoked inward currents were compared in control neurons and in neurons from kindled animals. The maximum value for the concentration-response relationship of the partial agonist ( S)-DHPG- (but not the full agonist- [QUIS or ( R, S)-CHPG]) induced inward current was shifted upward suggesting enhanced efficacy of this agonist in kindled neurons. Altogether, these data are consistent with a kindling-induced up-regulation of a group I mGlu-, possibly mGlu5-, mediated responses coupled to Na+-Ca2+ exchange in BLA neurons.
Activation of Presynaptic Group III Metabotropic Receptors Enhances Glutamate Release in Rat Entorhinal Cortex
Authors: Evans D. Ieuan , Jones Roland S. G. , Woodhall Gavin
Published: December 2017

The role of group III metabotropic glutamate receptors (mGluRs) in modulating excitatory synaptic transmission was investigated in the rat entorhinal cortex (EC) in vitro. AMPA receptor-mediated excitatory postsynaptic currents (EPSCs) were recorded in the whole cell configuration of the patch-clamp technique from visually identified neurons in layers V and II. In layer V, bath application of the specific group III mGluR agonist L(+)-2-amino-4-phosphonobutyric acid (L-AP4, 500 μM) resulted in a marked facilitation of both spontaneous and activity-independent “miniature” (s/mEPSC) event frequency. The facilitatory effect of L-AP4 (100 μM) on sEPSC frequency prevailed in the presence ofdl−2-amino-5-phosphonopentanoic acid (100 μM) but was abolished by the group III antagonist (RS)-cyclopropyl-4-phosphonophenylglycine (20 μM). These data confirmed that group III mGluRs, and not N-methyl-d-aspartate (NMDA) receptors were involved in the response to L-AP4. Bath application of the specific mGluR4a agonist (1S,3R,4S)-1-aminocyclopentane-1,2,4-tricarboxylic acid (20 μM) also had a facilitatory effect on sEPSC frequency, suggesting involvement of mGluR4a. In layer II neurons, L-AP4 caused a reduction in sEPSC frequency but did not affect mEPSCs recorded in the presence of tetrodotoxin. These findings suggest that a group III mGluR with mGluR4a-like pharmacology is involved in modulating synaptic transmission in layer V cells of the EC. The effect on mEPSCs suggests that this receptor is located presynaptically and that its activation results in a direct facilitation of glutamate release. This novel facilitatory effect is specific to layer V and, to our knowledge, is the first report of a direct facilitatory action of group III mGluRs on synaptic transmission. In layer II, L-AP4 had an inhibitory effect on glutamate release similar to that reported in other brain regions.
Ca2+ Channels Involved in the Generation of the Slow Afterhyperpolarization in Cultured Rat Hippocampal Pyramidal Neurons
Authors: Shah M. , Haylett D. G.
Published: December 2017

The advantages of using isolated cells have led us to develop short-term cultures of hippocampal pyramidal cells, which retain many of the properties of cells in acute preparations and in particular the ability to generate afterhyperpolarizations after a train of action potentials. Using perforated-patch recordings, both medium and slow afterhyperpolarization currents (m I AHP and s I AHP, respectively) could be obtained from pyramidal cells that were cultured for 8–15 days. The s I AHP demonstrated the kinetics and pharmacologic characteristics reported for pyramidal cells in slices. In addition to confirming the insensitivity to 100 nM apamin and 1 mM TEA, we have shown that the s I AHP is also insensitive to 100 nM charybdotoxin but is inhibited by 100 μMd-tubocurarine. Concentrations of nifedipine (10 μM) and nimodipine (3 μM) that maximally inhibit L-type calcium channels reduced the s I AHP by 30 and 50%, respectively. However, higher concentrations of nimodipine (10 μM) abolished the s I AHP, which can be partially explained by an effect on action potentials. Both nifedipine and nimodipine at maximal concentrations were found to reduce the HVA calcium current in freshly dissociated neurons to the same extent. The N-type calcium channel inhibitor, ω-conotoxin GVIA (100 nM), irreversibly inhibited the s I AHP by 37%. Together, ω-conotoxin (100 nM) and nifedipine (10 μM) inhibited the s I AHP by 70%. 10 μM ryanodine also reduced the s I AHP by 30%, suggesting a role for calcium-induced calcium release. It is concluded that activation of the s I AHP in cultured hippocampal pyramidal cells is mediated by a rise in intracellular calcium involving multiple pathways and not just entry via L-type calcium channels.
Sound-Induced Synchronization of Neural Activity Between and Within Three Auditory Cortical Areas
Authors: Eggermont Jos J.
Published: December 2017

Neural synchrony within and between auditory cortical fields is evaluated with respect to its potential role in feature binding and in the coding of tone and noise sound pressure level. Simultaneous recordings were made in 24 cats with either two electrodes in primary auditory cortex (AI) and one in anterior auditory field (AAF) or one electrode each in AI, AAF, and secondary auditory cortex. Cross-correlograms (CCHs) for 1-ms binwidth were calculated for tone pips, noise bursts, and silence (i.e., poststimulus) as a function of intensity level. Across stimuli and intensity levels the total percentage of significant stimulus onset CCHs was 62% and that of significant poststimulus CCHs was 58% of 1,868 pairs calculated for each condition. The cross-correlation coefficient to stimulus onsets was higher for single-electrode pairs than for dual-electrode pairs and higher for noise bursts compared with tone pips. The onset correlation for single-electrode pairs was only marginally larger than the poststimulus correlation. For pairs from electrodes across area boundaries, the onset correlations were a factor 3–4 higher than the poststimulus correlations. The within-AI dual-electrode peak correlation was higher than that across areas, especially for spontaneous conditions. Correlation strengths for between area pairs were independent of the difference in characteristic frequency (CF), thereby providing a mechanism of feature binding for broadband sounds. For noise-burst stimulation, the onset correlation for between area pairs was independent of stimulus intensity regardless the difference in CF. In contrast, for tone-pip stimulation a significant dependence on intensity level of the peak correlation strength was found for pairs involving AI and/or AAF with CF difference less than one octave. Across all areas, driven rate, between-area peak correlation strength, or a combination of the two did not predict stimulus intensity. However, between-area peak correlation strength performs better than firing rate to decide if a stimulus is present or absent.
Group I mGluR Activation Turns on a Voltage-Gated Inward Current in Hippocampal Pyramidal Cells
Authors: Chuang Shih-Chieh , Bianchi Riccardo , Wong Robert K. S.
Published: December 2017

A unique property of the group I metabotropic glutamate receptor (mGluR)-induced depolarization in hippocampal cells is that the amplitude of the depolarization is larger when the response is elicited at more depolarized membrane potentials. Our understanding of the conductance mechanism underlying this voltage-dependent response is incomplete. Through the use of current-clamp and single-electrode voltage-clamp recordings in guinea pig hippocampal slices, we examined the group I mGluR-induced depolarization in CA3 pyramidal cells. The group I mGluR agonists ( S)-3-hydroxyphenylglycine and ( S)-3,5-dihydroxyphenylglycine turned on a voltage-gated inward current ( I mGluR(V)), which was pharmacologically distinct from the voltage-gated sodium and calcium currents intrinsic to the cells. I mGluR(V)was a slowly activating, noninactivating current with a threshold at about −75 mV. In addition to the activation of I mGluR(V), group I mGluR stimulation also produced a voltage-independent decrease in the K+conductance. Our results suggest that the depolarization induced by group I mGluR activation is generated by two ionic mechanisms—a heretofore unrecognized voltage-gated inward current ( I mGluR(V)) that is turned on by depolarization and a voltage-insensitive inward current that results from a turn-off of the K+ conductance. The low-threshold and noninactivating properties of I mGluR(V)allow the current to play a significant role in setting the resting potential and firing pattern of CA3 pyramidal cells.