bluuebunny/crossref_metadata_2025 huggingface dataset:
Saccade-Related Activity in the Parietal Reach Region
Authors: Snyder Lawrence H. , Batista Aaron P. , Andersen Richard A.
Published: December 2017

In previous experiments, we showed that cells in the parietal reach region (PRR) in monkey posterior parietal cortex code intended reaching movements in an eye-centered frame of reference. These cells are more active when an arm compared with an eye movement is being planned. Despite this clear preference for arm movements, we now report that PRR neurons also fire around the time of a saccade. Of 206 cells tested, 29% had perisaccadic activity in a delayed-saccade task. Two findings indicate that saccade-related activity does not reflect saccade planning or execution. First, activity is often peri- or postsaccadic but seldom presaccadic. Second, cells with saccade-related activity were no more likely to show strong saccadic delay period activity than cells without saccade-related activity. These findings indicate that PRR cells do not take part in saccade planning. Instead, the saccade-related activity in PRR may reflect cross-coupling between reach and saccade pathways that may be used to facilitate eye-hand coordination. Alternatively, saccade-related activity may reflect eye position information that could be used to maintain an eye-centered representation of intended reach targets across eye movements.
Development of Glutamatergic Synaptic Activity in Cultured Spinal Neurons
Authors: Robert Antoine , Howe James R. , Waxman Stephen G.
Published: December 2017

The development of glutamatergic synapses involves a sequence of events that are still not well understood. We have studied the time course of the development of glutamatergic synapses in cultured spinal neurons by characterizing spontaneous synaptic currents recorded from cells maintained in vitro for different times. At short times in culture (2 days in vitro; DIV2), spontaneous synaptic activity consisted almost solely of N-methyl-d-aspartate (NMDA) receptor (NMDAR) openings. In contrast, older neurons (DIV5 to DIV8) displayed clear α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor (AMPAR)–mediated synaptic currents, while the NMDAR-mediated activity remained small. Between 8 and 14 days in vitro there was a large increase in the density of synaptically activated NMDARs, although there was no significant increase in the density of the NMDAR-mediated current activated by exogenous glutamate. The results indicate that there is a switch in NMDAR targeting from somatic to synaptic regions during the course of the second in vitro week. Finally, our results support the conclusion that the spontaneous synaptic activity displayed in culture depends on ongoing NMDAR-mediated activity, even when the expression of synaptic NMDARs is low.
Inactivation Properties of Human Recombinant Class E Calcium Channels
Authors: Jouvenceau Anne , Giovannini Federica , Bath Cath P. , Trotman Emily , Sher Emanuele
Published: December 2017

The electrophysiological and pharmacological properties of α1E-containing Ca2+channels were investigated by using the patch-clamp technique in the whole cell configuration, in HEK 293 cells stably expressing the human α1Etogether with α2band β1baccessory subunits. These channels had current-voltage ( I-V) characteristics resembling those of high-voltage–activated (HVA) Ca2+channels (threshold at −30 mV and peak amplitude at +10 mV in 5 mM Ca2+). The currents activated and deactivated with a fast rate, in a time- and voltage-dependent manner. No difference was found in their relative permeability to Ca2+and Ba2+. Inorganic Ca2+channel blockers (Cd2+, Ni2+) blocked completely and potently the α1E,/α2bδ/β1bmediated currents (IC50= 4 and 24.6 μM, respectively). α1E-mediated currents inactivated rapidly and mainly in a non–Ca2+-dependent manner, as evidenced by the fact that 1) decreasing extracellular Ca2+from 10 to 2 mM and 2) changing the intracellular concentration of the Ca2+chelator 1.2-bis(2-aminophenoxy) ethane- N,N,N′,N′-tetraacetic acid (BAPTA), did not affect the inactivation characteristics; 3) there was no clear-cut bell-shaped relationship between test potential and inactivation, as would be expected from a Ca2+-dependent event. Although Ba2+substitution did not affect the inactivation of α1Echannels, Na+substitution revealed a small but significant reduction in the extent and rate of inactivation, suggesting that besides the presence of dominant voltage-dependent inactivation, α1Echannels are also affected by a divalent cation-dependent inactivation process. We have analyzed the Ca2+currents produced by a range of imposed action potential–like voltage protocols (APVPs). The amplitude and area of the current were dependent on the duration of the waveform employed and were relatively similar to those described for HVA calcium channels. However, the peak latency resembled that obtained for low-voltage–activated (LVA) calcium channels. Short bursts of APVPs applied at 100 Hz produced a depression of the Ca2+current amplitude, suggesting an accumulation of inactivation likely to be calcium dependent. The human α1Egene seems to participate to a Ca2+channel type with biophysical and pharmacological properties partly resembling those of LVA and those of HVA channels, with inactivation characteristics more complex than previously believed.
Neuropeptide Y5 Receptors Reduce Synaptic Excitation in Proximal Subiculum, But Not Epileptiform Activity in Rat Hippocampal Slices
Authors: Ho Melisa W. Y. , Beck-Sickinger Annette G. , Colmers William F.
Published: December 2017

Neuropeptide Y (NPY) potently inhibits excitatory synaptic transmission in the hippocampus, acting predominantly via a presynaptic Y2 receptor. Recent reports that the Y5 receptor may mediate the anticonvulsant actions of NPY in vivo prompted us to test the hypothesis that Y5receptors inhibit synaptic excitation in the hippocampal slice and, furthermore, that they are effective in an in vitro model of anticonvulsant action. Two putative Y5 receptor–preferring agonists inhibited excitatory postsynaptic currents (EPSCs) evoked by stimulation of stratum radiatum in pyramidal cells. We recorded initially from area CA1 pyramidal cells, but subsequently switched to cells from the subiculum, where a much greater frequency of response was observed to Y5 agonist application. Bothd-Trp32NPY (1 μM) and [ahx8–20]Pro34NPY (3 μM), a centrally truncated, Y1/Y5 agonist we synthesized, inhibited stimulus-evoked EPSCs in subicular pyramidal cells by 44.0 ± 5.7% and 51.3 ± 3.5% (mean ± SE), in 37 and 58% of cells, respectively. By contrast, the less selective centrally truncated agonist, [ahx8–20] NPY (1 μM), was more potent (66.4 ± 4.1% inhibition) and more widely effective, suppressing the EPSC in 86% of subicular neurons. The site of action of all NPY agonists tested was most probably presynaptic, because agonist application caused no changes in postsynaptic membrane properties. The selective Y1 antagonist, BIBP3226 (1 μM), did not reduce the effect of either more selective agonist, indicating that they activated presynaptic Y5 receptors. Y5 receptor–mediated synaptic inhibition was more frequently observed in slices from younger animals, whereas the nonselective agonist appeared equally effective at all ages tested. Because of the similarity with the previously reported actions of Y2 receptors, we tested the ability of Y5receptor agonists to suppress stimulus train-induced bursting (STIB), an in vitro model of ictaform activity, in both area CA3 and the subiculum. Neither [ahx8–20]Pro34NPY nord-Trp32NPY were significantly effective in suppressing or shortening STIB-induced afterdischarge, with <20% of slices responding to these agonists in recordings from CA3 and none in subiculum. By contrast, 1 μM each of [ahx8–20]NPY, the Y2 agonist, [ahx5–24]NPY, and particularly NPY itself suppressed the afterdischarge in area CA3 and the subiculum, as reported earlier. We conclude that Y5receptors appear to regulate excitability to some degree in the subiculum of young rats, but their contribution is relatively small compared with those of Y2 receptors, declines with age, and is insufficient to block or significantly attenuate STIB-induced afterdischarges.
Responses of Reticulospinal Neurons in Intact Lamprey to Vestibular and Visual Inputs
Authors: Deliagina T. G. , Fagerstedt P.
Published: December 2017

A lamprey maintains the dorsal-side-up orientation due to the activity of postural control system driven by vestibular input. Visual input can affect the body orientation: illumination of one eye evokes ipsilateral roll tilt. An important element of the postural network is the reticulospinal (RS) neurons transmitting commands from the brain stem to the spinal cord. Here we describe responses to vestibular and visual stimuli in RS neurons of the intact lamprey. We recorded activity from the axons of larger RS neurons with six extracellular electrodes chronically implanted on the surface of the spinal cord. From these multielectrode recordings of mass activity, discharges in individual axons were extracted by means of a spike-sorting program, and the axon position in the spinal cord and its conduction velocity were determined. Vestibular stimulation was performed by rotating the animal around its longitudinal axis in steps of 45° through 360°. Nonpatterned visual stimulation was performed by unilateral eye illumination. All RS neurons were classified into two groups depending on their pattern of response to vestibular and visual stimuli; the groups also differed in the axon position in the spinal cord and its conduction velocity. Each group consisted of two symmetrical, left and right, subgroups. In group 1neurons, rotation of the animal evoked both dynamic and static responses; these responses were much larger when rotation was directed toward the contralateral labyrinth, and the dynamic responses to stepwise rotation occurred at any initial orientation of the animal, but they were more pronounced within the angular zone of 0–135°. The zone of static responses approximately coincided with the zone of pronounced dynamic responses. The group 1 neurons received excitatory input from the ipsilateral eye and inhibitory input from the contralateral eye. When vestibular stimulation was combined with illumination of the ipsilateral eye, both dynamic and static vestibular responses were augmented. Contralateral eye illumination caused a decrease of both types of responses. Group 2neurons responded dynamically to rotation in both directions throughout 360°. They received excitatory inputs from both eyes. Axons of the group 2 neurons had higher conduction velocity and were located more medially in the spinal cord as compared with the group 1 neurons. We suggest that the reticulospinal neurons of group 1 constitute an essential part of the postural network in the lamprey. They transmit orientation-dependent command signals to the spinal cord causing postural corrections. The role of these neurons is discussed in relation to the model of the roll control system formulated in our previous studies.
Activity-Dependent Activation of Presynaptic Metabotropic Glutamate Receptors in Locus Coeruleus
Authors: Dubé G. R. , Marshall K. C.
Published: December 2017

Synaptic activation of metabotropic glutamate receptors (mGluRs) in the locus coeruleus (LC) was investigated in adult rat brain slice preparations. Evoked excitatory postsynaptic potentials (EPSPs) resulting from stimulation of LC afferents were measured with current clamp from intracellularly recorded LC neurons. In this preparation, mGluR agonists (±)-1-aminocyclopentane- trans-1,3-dicarboxylic acid ( t-ACPD) and L(+)-2-amino-4-phosphonobutyric acid (L-AP4) activate distinct presynaptic mGluRs, resulting in an inhibition of EPSPs. When two stimuli were applied to afferents at intervals >200 ms, the amplitude of the second [test (T)] EPSP was identical in amplitude to the first [control(C)]. However, when a stimulation volley was delivered before T, the amplitude of the latter EPSP was consistently smaller than C. The activity-dependent depression (ADD) was dependent on the frequency and duration of the train and the interval between the train and T. ADD was potentiated in the presence of an excitatory amino acid (EAA) uptake inhibitorL- trans-pyrrolidine-2,4-dicarboxylic acid ( t-PDC, 100 μM), changing the T/C ratio from 0.84 ± 0.05 (mean ± SE) in control to 0.69 ± 0.04 in t-PDC ( n = 9). In the presence of t-PDC, the depolarizing response of LC neurons to focally applied glutamate was also increased. Together, these results suggest that accumulation of EAA after synaptic stimulation may be responsible for ADD. To test if ADD is a result of the activation of presynaptic mGluRs, the effect of selective mGluR antagonists on ADD was assessed. In the presence of t-PDC, bath applied (S)-amino-2-methyl-4-phosphonobutanoic acid (MAP4, 500 μM), a mGluR group III antagonist, significantly reversed the decrease in T/C ratio after a train stimulation [from 0.66 ± 0.04 to 0.81 ± 0.02 (mean ± SE), n = 5]. The T/C ratio in the presence of MAP4 was not different from that measured in the absence of a stimulation volley. Conversely, ethyl glutamic acid (EGLU, 500 μM), a mGluR group II antagonist, failed to alter the T/C ratio. Together, these results suggest that, in LC, group III presynaptic mGluR activation provides a feedback mechanism by which excitatory synaptic transmission can be negatively modulated during high-frequency synaptic activity. Furthermore, this study provides functional differentiation between presynaptic groups II and III mGluR in LC and suggests that the group II mGluR may be involved in functions distinct from those of group III mGluRs.
Predictive Modulation of Muscle Coordination Pattern Magnitude Scales Fingertip Force Magnitude Over the Voluntary Range
Authors: Valero-Cuevas Francisco J.
Published: December 2017

Human fingers have sufficiently more muscles than joints such that every fingertip force of submaximal magnitude can be produced by an infinite number of muscle coordination patterns. Nevertheless, the nervous system seems to effortlessly select muscle coordination patterns when sequentially producing fingertip forces of low, moderate, and maximal magnitude. The hypothesis of this study is that the selection of coordination patterns to produce submaximal forces is simplified by the appropriate modulation of the magnitude of a muscle coordination pattern capable of producing the largest expected fingertip force. In each of three directions, eight subjects were asked to sequentially produce fingertip forces of low, moderate, and maximal magnitude with their dominant forefinger. Muscle activity was described by fine-wire electromyograms (EMGs) simultaneously collected from all muscles of the forefinger. A muscle coordination pattern was defined as the vector list of the EMG activity of each muscle. For all force directions, statistically significant muscle coordination patterns similar to those previously reported for 100% of maximal fingertip forces were found for 50% of maximal voluntary force. Furthermore the coordination pattern and fingertip force vector magnitudes were highly correlated ( r > 0.88). Average coordination pattern vectors at 50 and 100% of maximal force were highly correlated with each other, as well as with individual coordination pattern vectors in the ramp transitions preceding them. In contrast to this consistency of EMG coordination patterns, predictions using a musculoskeletal computer model of the forefinger show that force magnitudes ≤50% of maximal fingertip force can be produced by coordination patterns drastically different from those needed for maximal force. Thus when modulating fingertip force magnitude across the voluntary range, the number of contributing muscles and the relative activity among them was not changed. Rather, the production of low and moderate forces seems to be simplified by appropriately scaling the magnitude of a coordination pattern capable of producing the highest force expected.
Functional Expression of Three P2X2 Receptor Splice Variants From Guinea Pig Cochlea
Authors: Chen Chu , Parker Margarett S. , Barnes Anthony P. , Deininger Prescott , Bobbin Richard P.
Published: December 2017

ATP has been suggested to act as a neurotransmitter or a neuromodulator in the cochlea. The responses to ATP in different cell types of the cochlea vary in terms of the rate of desensitization and magnitude, suggesting that there may be different subtypes of P2X receptors distributed in the cochlea. Recently three ionotropic P2X2 receptor splice variants, P2X2–1, P2X2–2, and P2X2–3, were isolated and sequenced from a guinea pig cochlear cDNA library. To test the hypothesis that these different splice variants could be expressed as functional homomeric receptors, the three P2X2 receptor variants were individually and transiently expressed in human embryonic kidney cells (HEK293). The biophysical and pharmacological properties of these receptors were characterized using the whole cell patch-clamp technique. Extracellular application of ATP induced an inward current in HEK293 cells containing each of the three splice variants in a dose-dependent manner indicating the expression of homomeric receptors. Current-voltage ( I-V) relationships for the ATP-gated current show that the three subtypes of the P2X2 receptor had a similar reversal potential and an inward rectification index ( I 50 mV/ I −50 mV). However, the ATP-induced currents in cells expressing P2X2–1 and P2X2–2 variants were large and desensitized rapidly whereas the current in those cells expressing the P2X2–3 variant was much smaller and desensitized slower. The order of potency to ATP agonists was 2-MeSATP > ATP > α,β -MeATP for all three expressed splice variants. The ATP receptor antagonists suramin and PPADS reduced the effects of ATP on all three variants. Results demonstrate that three P2X2splice variants from guinea pig cochlea, P2X2–1, P2X2–2, and P2X2–3, can individually form nonselective cation receptor channels when these subunits are expressed in HEK293 cells. The distinct properties of these P2X2receptor splice variants may contribute to the differences in the response to ATP observed in native cochlear cells.
Local Infusion of Scopolamine Into Intraparietal Cortex Slows Covert Orienting in Rhesus Monkeys
Authors: Davidson M. C. , Marrocco R. T.
Published: December 2017

There is accumulating evidence to suggest that cholinergic neurotransmission may play an important role in visuospatial attention, but the brain sites at which acetylcholine modulates attention are not well understood. The present work tested the hypothesis that the cholinergic influences within the intraparietal cortex are necessary for normal attentional shifting (covert orienting) in nonhuman primates. Two rhesus monkeys were trained to perform a visual, cued target detection task for liquid reinforcement. The animals pressed a lever to produce a visual display in which a central fixation point was flanked by two circles. Shortly after fixation was established, one of the circles brightened (cue), and a target appeared subsequently within one of the circles. Detection was signaled by a manual response and the reaction time to the appearance of the target was recorded. Four types of trials were presented. For valid cue trials, the cue and target were at the same spatial location; for invalid cues, cue and target were in opposite hemifields; for double cues, both cues were brightened but the target appeared in either the left or right circle; in no-cue trials, the cue was omitted. We localized the intraparietal region by recording attention-related, cellular activity with intracerebral microelectrodes. Among visually responsive cells in this area, valid cues presented to the receptive fields of visual neurons enhanced the responses to target stimuli in about half the cells and inhibited those responses in the remainder. In addition, some cells showed longer response latencies to invalid cues than to valid cues. We then infused scopolamine into attention-related activity sites and assessed its effect on performance. Scopolamine produced a dose-dependent increase in reaction times and decrease in performance accuracy that lasted more than 1 h. Neither vehicle injections in the same locations nor scopolamine outside the physiologically defined area produced any significant change in behavior. Under our conditions of measurement, we conclude that activity mediated by muscarinic cholinergic receptors within the intraparietal cortex is necessary for normal covert orienting.
Rapid Activation of GABAergic Interneurons and Possible Calcium Independent GABA Release in the Mormyrid Electrosensory Lobe
Authors: Han Victor Z. , Grant Kirsty , Bell Curtis C.
Published: December 2017

The primary afferent fibers from the electroreceptors of mormyrid electric fish terminate centrally in the granular layer of the electrosensory lobe (ELL). This study examines the excitatory and inhibitory processes that take place in this layer using an in vitro slice preparation and field potentials evoked by stimulation of primary afferent fibers in the deep fiber layer of ELL. The postsynaptic response to stimulation of the afferent fibers was still present after blocking chemical transmission in three different ways: by adding glutamate receptor antagonists to the medium, by substituting a nominally calcium-free medium for normal medium, and by blocking calcium channels with cadmium. Blockade of chemical transmission was demonstrated by disappearance of control responses to parallel fiber stimulation. The continued presence of a postsynaptic response in the absence of chemical excitation is consistent with previous anatomic and physiological evidence for electrical synapses between afferent fibers and granular cells in ELL. Granular cell activation by primary afferent fibers was followed by a powerful, short-latency inhibition mediated by GABA and GABAAreceptors, as indicated by a large increase in the postsynaptic response to afferent fiber stimulation following application of the GABAAreceptor antagonist, bicuculline. Bicuculline caused a marked increase of the postsynaptic response even after chemical synaptic excitation had been blocked by glutamate receptor antagonists, by a calcium-free medium, or by cadmium. Thus activation of the inhibitory interneurons responsible for GABA release did not require chemical excitation. Nonchemical excitation of the inhibitory interneurons could be mediated either by electrical synapses between afferent fibers and inhibitory interneurons, or by nonsynaptic activation of the large GABAergic terminals that are known to be present on granular cells. The marked increase of the postsynaptic response caused by bicuculline in a calcium-free medium or in the presence of cadmium suggests that the release of GABA by inhibitory terminals was not entirely dependent on calcium influx. This effect of bicuculline on the postsynaptic response in a calcium-free medium or in the presence of cadmium was markedly reduced by prior addition of the GABA transporter antagonist, nipecotic acid. Thus calcium-independent release of GABA may occur in ELL and may be partly dependent on reversal of a GABA transporter. Rapid and powerful inhibition at the first stage in the processing of electrosensory information could serve to enhance the small differences in latency among afferent fibers that appear to encode small differences in stimulus intensity.
Diverse Synaptic Connections Between Peptidergic Radula Mechanoafferent Neurons and Neurons in the Feeding System ofAplysia
Authors: Rosen Steven C. , Miller Mark W. , Evans Colin G. , Cropper Elizabeth C. , Kupfermann Irving
Published: December 2017

The buccal ganglion of Aplysia contains a heterogeneous population of peptidergic, radula mechanoafferent (RM) neurons. To investigate their function, two of the larger RM cells (B21, B22) were identified by morphological and electrophysiological criteria. Both are low-threshold, rapidly adapting, mechanoafferent neurons that responded to touch of the radula, the structure that grasps food during ingestive and egestive feeding movements. Sensory responses of the cells consisted of spike bursts at frequencies of 8–35 Hz. Each cell was found to make chemical, electrical, or combined synapses with other sensory neurons, motor neurons and interneurons involved in radula closure and/or protraction-retraction movements of the odontophore. Motor neurons receiving input included the following: B8a/b, B15, and B16, which innervate muscles contributing to radula closing; and B82, a newly identified neuron that innervates the anterodorsal region of the I1/I3 muscles of the buccal mass. B21 and B22 can affect buccal motor programs by way of their connections to interneurons such as B19 and B64. Fast, chemical, excitatory postsynaptic potentials (EPSPs) produced by RM neurons, such as B21, exhibited strong, frequency-dependent facilitation, a form of homosynaptic plasticity. Firing B21 also produced a slow EPSP in B15 that increased the excitability of the cell. Thus a sensory neuron mediating a behavioral response may have modulatory effects. The data suggest multiple functions for RM neurons including 1) triggering of phase transitions in rhythmic motor programs, 2) adjusting the force of radula closure, 3) switching from biting to swallowing or swallowing to rejection, and 4) enhancing food-induced arousal.
Primate Translational Vestibuloocular Reflexes. III. Effects of Bilateral Labyrinthine Electrical Stimulation
Authors: Angelaki Dora E. , McHenry M. Quinn , Dickman J. David , Perachio Adrian A.
Published: December 2017

The effects of functional, reversible ablation and potential recruitment of the most irregular otolith afferents on the dynamics and sensitivity of the translational vestibuloocular reflexes (trVORs) were investigated in rhesus monkeys trained to fixate near and far targets. Translational motion stimuli consisted of either steady-state lateral and fore-aft sinusoidal oscillations or short-lasting transient lateral head displacements. Short-duration (usually <2 s) anodal (inhibitory) and cathodal (excitatory) currents (50–100 μA) were delivered bilaterally during motion. In the presence of anodal labyrinthine stimulation, trVOR sensitivity and its dependence on viewing distance were significantly decreased. In addition, anodal currents significantly increased phase lags. During transient motion, anodal stimulation resulted in significantly lower initial eye acceleration and more sluggish responses. Cathodal currents tended to have opposite effects. The main characteristics of these results were simulated by a simple model where both regularly and irregularly discharging afferents contribute to the trVORs. Anodal labyrinthine currents also were found to decrease eye velocity during long-duration, constant velocity rotations, although results were generally more variable compared with those during translational motion.
Rostrocaudal Distinction of the Dorsal Premotor Area Based on Oculomotor Involvement
Authors: Fujii Naotaka , Mushiake Hajime , Tanji Jun
Published: December 2017

To investigate functional differences between the rostral and caudal parts of the dorsal premotor cortex (PMd), we first examined the effects of intracortical microstimulation (ICMS) while monkeys were performing oculomotor and limb motor tasks or while they were at rest. We found that saccades were evoked from the rostral part (PMdr) whereas ICMS in the caudal part (PMdc) predominantly produced forelimb or body movements. Subsequently, we examined neuronal activity in relation to the performance of visually cued and memorized saccades while monkeys reached an arm toward a visual target. We found that roughly equal numbers of PMdr neurons were active during performance of the oculomotor and limb motor tasks. In contrast, the majority of PMdc neurons were related preferentially to arm movements and not to saccades. In the subsequent analysis, we found that the oculomotor effects evoked in the PMdr differ from the effects evoked in either the frontal eye field (FEF) or supplementary eye field (SEF). These findings suggest that the PMdr is involved in oculomotor as well as limb motor behavior. However, the oculomotor involvement of the PMdr seems to have a functional aspect different from that operating in the FEF and SEF.
Histamine H2 Receptor Activated Chloride Conductance in Myenteric Neurons From Guinea Pig Small Intestine
Authors: Starodub Alexander M. , Wood Jackie D.
Published: December 2017

Whole cell perforated patch-clamp methods were used to investigate ionic mechanisms underlying histamine-evoked excitatory responses in small intestinal AH-type myenteric neurons. When physiological concentrations of Na+, Ca2+, and Cl− were in the bathing medium, application of histamine significantly increased total conductance as determined by stepping to 50 mV from a holding potential of −30 mV. The current reversed at a membrane potential of −30 ± 5 (SE) mV and current-voltage relations exhibited outward rectification. The reversal potential for the histamine-activated current was unchanged by removal of Na+ and Ca2+ from the bathing medium. Reduction of Cl−from 155 mM to 55 mM suppressed the current when the neurons were in solutions with depleted Na+ and Ca2+. Current-voltage curves in solutions with reduced Cl− were linear and the reversal potential was changed from −30 ± 5 mV to 7 ± 4 mV. Niflumic acid, but not anthracene-9-carboxylic acid (9-AC) nor 4,4′-diisothiocyanatostilbene-2,2′-disulfonic acid (DIDS), suppressed the histamine-activated current. A membrane permeable analogue of cAMP evoked currents similar to those activated by histamine. A selective histamine H2 receptor agonist (dimaprit) mimicked the action of histamine and a selective histamine H2 receptor antagonist (cimetidine) blocked the conductance increase evoked by histamine. A selective adenosine A1receptor agonist (CCPA) reduced the histamine-activated current and a selective adenosine A1 receptor antagonist (CPT) reversed the inhibitory action. The results suggest that histamine acts at histamine H2 receptors to increase Cl−conductance in AH-type enteric neurons. Cyclic AMP appears to be a second messenger in the signal transduction process. Results with a selective adenosine A1 receptor agonist and antagonist add to existing evidence for co-coupling of inhibitory adenosine A1 receptors and histamine H2 receptors to adenylate cyclase in AH-type enteric neurons.
Modifications of Reward Expectation-Related Neuronal Activity During Learning in Primate Orbitofrontal Cortex
Authors: Tremblay Léon , Schultz Wolfram
Published: December 2017

This study investigated how neuronal activity in orbitofrontal cortex related to the expectation of reward changed while monkeys repeatedly learned to associate new instruction pictures with known behavioral reactions and reinforcers. In a delayed go-nogo task with several trial types, an initial picture instructed the animal to execute or withhold a reaching movement and to expect a liquid reward or a conditioned auditory reinforcer. When novel instruction pictures were presented, animals learned according to a trial-and-error strategy. After experience with a large number of novel pictures, learning occurred in a few trials, and correct performance usually exceeded 70% in the first 60–90 trials. About 150 task-related neurons in orbitofrontal cortex were studied in both familiar and learning conditions and showed two major forms of changes during learning. Quantitative changes of responses to the initial instruction were seen as appearance of new responses, increase of existing responses, or decrease or complete disappearance of responses. The changes usually outlasted initial learning trials and persisted during subsequent consolidation. They often modified the trial selectivities of activations. Increases might reflect the increased attention during learning and induce neuronal changes underlying the behavioral adaptations. Decreases might be related to the unreliable reward-predicting value of frequently changing learning instructions. The second form of changes reflected the adaptation of reward expectations during learning. In initial learning trials, animals reacted as if they expected liquid reward in every trial type, although only two of the three trial types were rewarded with liquid. In close correspondence, neuronal activations related to the expectation of reward occurred initially in every trial type. The behavioral indices for reward expectation and their neuronal correlates adapted in parallel during the course of learning and became restricted to rewarded trials. In conclusion, these data support the notion that neurons in orbitofrontal cortex code reward information in a flexible and adaptive manner during behavioral changes after novel stimuli.
A Model for Pleiotropic Muscarinic Potentiation of Fast Synaptic Transmission
Authors: Schobesberger Hermann , Wheeler Diek W. , Horn John P.
Published: December 2017

The predominant form of muscarinic excitation in the forebrain and in sympathetic ganglia arises from m1 receptors coupled to the Gq/11signal transduction pathway. Functional components of this system have been most completely mapped in frog sympathetic B neurons. Presynaptic stimulation of the B neuron produces a dual-component muscarinic excitatory postsynaptic potential (EPSP) mediated by suppression of voltage-dependent M-type K+channels and activation of a voltage-insensitive cation current. Evidence from mammalian systems suggests that the cation current is mediated by cyclic GMP-gated channels. This paper describes the use of a computational model to analyze the consequences of pleiotropic muscarinic signaling for synaptic integration. The results show that the resting potential of B neurons is a logarithmic function of the leak conductance over a broad range of experimentally observable conditions. Small increases (<4 nS) in the muscarinically regulated cation conductance produce potent excitatory effects. Damage introduced by intracellular recording can mask the excitatory effect of the muscarinic leak current. Synaptic activation of the leak conductance combines synergistically with suppression of the M-conductance (40 → 20 nS) to strengthen fast nicotinic transmission. Overall, this effect can more than double synaptic strength, as measured by the ability of a fast nicotinic EPSP to trigger an action potential. Pleiotropic muscarinic excitation can also double the temporal window of summation between subthreshold nicotinic EPSPs and thereby promote firing. Activation of a chloride leak or suppression of a K+leak can substitute for the cation conductance in producing excitatory muscarinic actions. The results are discussed in terms of their implications for synaptic integration in sympathetic ganglia and other circuits.
Olfactory Inputs Activate the Medial Entorhinal Cortex Via the Hippocampus
Authors: Biella Gerardo , de Curtis Marco
Published: December 2017

The lateral and medial regions of the entorhinal cortex differ substantially in terms of connectivity and pattern of activation. With regard to olfactory input, a detailed and extensive physiological map of the olfactory projection to the entorhinal cortex is missing, even if anatomic studies suggest that the olfactory afferents are confined to the lateral and rostral entorhinal region. We studied the contribution of the medial and lateral entorhinal areas to olfactory processing by analyzing the responses induced by lateral olfactory tract stimulation in different entorhinal subfields of the in vitro isolated guinea pig brain. The pattern of synaptic activation of the medial and lateral entorhinal regions was reconstructed either by performing simultaneous multisite recordings or by applying current source density analysis on field potential laminar profiles obtained with 16-channel silicon probes. Current source density analysis demonstrated the existence of a direct monosynaptic olfactory input into the superficial 300 μm of the most rostral part of the lateral entorhinal cortex exclusively, whereas disynaptic sinks mediated by associative fibers arising from the piriform cortex were observed at 100–350 μm depth in the entire lateral aspect of the cortex. No local field responses were recorded in the medial entorhinal region unless a large population spike was generated in the hippocampus (dentate gyrus and CA1 region) by a stimulus 3–5× the intensity necessary to obtain a maximal monosynaptic response in the piriform cortex. In these conditions, a late sink was recorded at a depth of 600-1000 μm in the medial entorhinal area (layers III–V) 10.6 ± 0.9 (SD) msec after a population spike was simultaneously recorded in CA1. Diffuse activation of the medial entorhinal region was also obtained by repetitive low-intensity stimulation of the lateral olfactory tract at 2–8 Hz. Higher or lower stimulation frequencies did not induce hippocampal-medial entorhinal cortex activation. These results suggest that the medial and the lateral entorhinal regions have substantially different roles in processing olfactory sensory inputs.
Stretch and H Reflexes in Triceps Surae Are Similar During Tonic and Rhythmic Contractions in High Decerebrate Cats
Authors: Misiaszek J. E. , de Serres S. J. , Stein R. B. , Jiang W. , Pearson K. G.
Published: December 2017

During locomotion in decerebrate and spinal cats the group Ia afferents from hind leg muscles are depolarized rhythmically. An earlier study concluded that this locomotor-related primary afferent depolarization (PAD) does not contribute to modulation of monosynaptic reflex pathways during locomotion. This finding indicated that the neural network generating the locomotor rhythm, the central pattern generator (CPG), does not presynaptically inhibit monosynaptic reflexes. In this investigation we tested this prediction in decerebrate cats by measuring the magnitude of reflexes evoked in ankle extensor muscles during periods of tonic contractions and during sequences of rhythmic contractions. The latter occurred when the animal was induced to walk on a treadmill. At the similar levels of activity in the soleus muscle there was no significant difference in the magnitude of the soleus H reflex in these two behavioral situations. Similar results were obtained for reflexes evoked by brief stretches of the soleus muscle. We also examined the reflexes evoked by ramp-and-hold stretches during periods of rhythmic and tonic activity of the isolated medial gastrocnemius (MG) muscle. At similar levels of background activity, the reflexes evoked in the MG muscle were the same during rhythmic and tonic contractions. Our failure to observe a reduction in the magnitude of H reflexes and stretch reflexes during rhythmic contractions, compared with reflexes evoked at the same level of background activity during tonic contractions, is consistent with the notion that the CPG for stepping does not presynaptically inhibit monosynaptic reflexes during the extension phase of locomotor activity. Our results indicate that presynaptic inhibition of the monosynaptic reflex associated with normal locomotion in cats or humans arises from sources other than the extensor burst generating system of the central pattern generator.
Population Reconstruction of the Locomotor Cycle From Interneuron Activity in the Mammalian Spinal Cord
Authors: Tresch Matthew C. , Kiehn Ole
Published: December 2017

Lesion studies have shown that neuronal networks in the ventromedial regions of the neonatal rat spinal cord are critical for the production of locomotion. We examined whether the locomotor cycle could be accurately predicted based on the activity recorded in a population of spinal interneurons located in these regions during pharmacologically induced locomotion. We used a Bayesian probabilistic reconstruction procedure to predict the most likely phase of locomotion given the observed activity in the neuronal population. The population reconstruction was able to predict the correct locomotor phase with high accuracy using a relatively small number of neurons. This result demonstrates that although the spike activity of individual spinal interneurons in the ventromedial region is weak and varies from cycle to cycle, the locomotor phase can be accurately predicted when information from the population is combined. This result is consistent with the proposed involvement of interneurons within these regions of the spinal cord in the production of locomotion.
9–16 Hz Oscillation Precedes Secondary Generalization of Seizures in the Rat Tetanus Toxin Model of Epilepsy
Authors: Finnerty G. T. , Jefferys J.G.R.
Published: December 2017

Unilateral intrahippocampal injection of tetanus toxin results in a chronic syndrome of intermittent epileptic seizures. During some of these seizures, rats develop a stereotypic, pathological motor behavior that indicates secondary generalization of epileptic activity. We report that secondary generalization was preceded by a 9–16 Hz oscillation of field potentials which was synchronized between the right and left dorsal hippocampi. The oscillation was associated with increased synchrony of population spike firing in right and left CA1 subregions which form the major output of the hippocampi. Cutting the ventral commissure abolished synchrony across the hippocampi and reduced the probability that the 9–16 Hz activity would be followed by secondary generalization. We concluded that a bilaterally synchronous 9–16 Hz hippocampal oscillation played a role in the secondary generalization of focal seizures in this chronic model of limbic epilepsy.
Foveal Attention Modulates Responses to Peripheral Stimuli
Authors: Vanni Simo , Uutela Kimmo
Published: December 2017

When attending to a visual object, peripheral stimuli must be monitored for appropriate redirection of attention and gaze. Earlier work has revealed precentral and posterior parietal activation when attention has been directed to peripheral vision. We wanted to find out whether similar cortical areas are active when stimuli are presented in nonattended regions of the visual field. The timing and distribution of neuromagnetic responses to a peripheral luminance stimulus were studied in human subjects with and without attention to fixation. Cortical current distribution was analyzed with a minimum L1-norm estimate. Attention enhanced responses 100–160 ms after the stimulus onset in the right precentral cortex, close to the known location of the right frontal eye field. In subjects whose right precentral region was not distinctly active before 160 ms, focused attention commonly enhanced right inferior parietal responses between 180 and 240 ms, whereas in the subjects with clear earlier precentral response no parietal enhancement was detected. In control studies both attended and nonattended stimuli in the peripheral visual field evoked the right precentral response, whereas during auditory attention the visual stimuli failed to evoke such response. These results show that during focused visual attention the right precentral cortex is sensitive to stimuli in all parts of the visual field. A rapid response suggests bypassing of elaborate analysis of stimulus features, possibly to encode target location for a saccade or redirection of attention. In addition, load for frontal and parietal nodi of the attentional network seem to vary between individuals.
Texture Segregation in the Human Visual Cortex: A Functional MRI Study
Authors: Kastner Sabine , De Weerd Peter , Ungerleider Leslie G.
Published: December 2017

The segregation of visual scenes based on contour information is a fundamental process of early vision. Contours can be defined by simple cues, such as luminance, as well as by more complex cues, such as texture. Single-cell recording studies in monkeys suggest that the neural processing of complex contours starts as early as primary visual cortex. Additionally, lesion studies in monkeys indicate an important contribution of higher order areas to these processes. Using functional MRI, we have investigated the level at which neural correlates of texture segregation can be found in the human visual cortex. Activity evoked by line textures, with and without texture-defined boundaries, was compared in five healthy subjects. Areas V1, V2/VP, V4, TEO, and V3A were activated by both kinds of line textures as compared with blank presentations. Textures with boundaries forming a checkerboard pattern, relative to uniform textures, evoked significantly more activity in areas V4, TEO, less reliably in V3A, but not in V1 or V2/VP. These results provide evidence that higher order areas with large receptive fields play an important role in the segregation of visual scenes based on texture-defined boundaries.
Sweet Taste Transduction in Hamster: Role of Protein Kinases
Authors: Varkevisser Brian , Kinnamon Sue C.
Published: December 2017

Two different second-messenger pathways have been implicated in sweet taste transduction: sugars produce cyclic AMP (cAMP), whereas synthetic sweeteners stimulate production of inositol 1,4,5-tris-phosphate (IP3) and diacylglycerol (DAG). Both sugars and sweeteners depolarize taste cells by blocking the same resting K+conductance, but the intermediate steps in the transduction pathways have not been examined. In this study, the loose-patch recording technique was used to examine the role of protein kinases and other downstream regulatory proteins in the two sweet transduction pathways. Bursts of action currents were elicited from ∼35% of fungiform taste buds in response to sucrose (200 mM) or NC-00274–01 (NC-01, 200 μM), a synthetic sweetener. To determine whether protein kinase C (PKC) plays a role in sweet transduction, taste buds were stimulated with the PKC activator PDBu (10 μM). In all sweet-responsive taste buds tested ( n = 11), PDBu elicited burst of action currents. In contrast, PDBu elicited responses in only 4 of 19 sweet-unresponsive taste buds. Inhibition of PKC by bisindolylmaleimide I (0.15 μM) resulted in inhibition of the NC-01 response by ∼75%, whereas the response to sucrose either increased or remained unchanged. These data suggest that activation of PKC is required for the transduction of synthetic sweeteners. To determine whether protein kinase A (PKA) is required for the transduction of sugars, sweet responses were examined in the presence of the membrane-permeant PKA inhibitor H-89 (10 and 19 μM). Surprisingly, H-89 did not decrease responses to either sucrose or NC-01. Instead, responses to both compounds were increased in the presence of the inhibitor. These data suggest that PKA is not required for the transduction of sugars, but may play a modulatory role in both pathways, such as adaptation of the response. We also examined whether Ca2+-calmodulin dependent cAMP phosphodiesterase (CaM-PDE) plays a role in sweet taste transduction, by examining responses to sucrose and synthetic sweeteners in the presence of the CaM-PDE inhibitor W-7 (100 μM). Inhibition resulted in an increase in the response to sucrose, whereas the response to NC-01 remained unchanged. These data suggest that the pathways for sugars and sweeteners are negatively coupled; the Ca2+ that is released from intracellular stores during stimulation with synthetic sweeteners may inhibit the response to sucrose by activation of CaM-PDE.