bluuebunny/crossref_metadata_2025 huggingface dataset:
Dopamine Increases Excitability of Pyramidal Neurons in Primate Prefrontal Cortex
Authors: Henze Darrell A. , González-Burgos Guillermo R. , Urban Nathaniel N. , Lewis David A. , Barrionuevo German
Published: December 2017

Dopaminergic modulation of neuronal networks in the dorsolateral prefrontal cortex (PFC) is believed to play an important role in information processing during working memory tasks in both humans and nonhuman primates. To understand the basic cellular mechanisms that underlie these actions of dopamine (DA), we have investigated the influence of DA on the cellular properties of layer 3 pyramidal cells in area 46 of the macaque monkey PFC. Intracellular voltage recordings were obtained with sharp and whole cell patch-clamp electrodes in a PFC brain-slice preparation. All of the recorded neurons in layer 3 ( n = 86) exhibited regular spiking firing properties consistent with those of pyramidal neurons. We found that DA had no significant effects on resting membrane potential or input resistance of these cells. However DA, at concentrations as low as 0.5 μM, increased the excitability of PFC cells in response to depolarizing current steps injected at the soma. Enhanced excitability was associated with a hyperpolarizing shift in action potential threshold and a decreased first interspike interval. These effects required activation of D1-like but not D2-like receptors since they were inhibited by the D1 receptor antagonist SCH23390 (3 μM) but not significantly altered by the D2 antagonist sulpiride (2.5 μM). These results show, for the first time, that DA modulates the activity of layer 3 pyramidal neurons in area 46 of monkey dorsolateral PFC in vitro. Furthermore the results suggest that, by means of these effects alone, DA modulation would generally enhance the response of PFC pyramidal neurons to excitatory currents that reach the action potential initiation site.
Properties of Rhythmic Activity Generated by the Isolated Spinal Cord of the Neonatal Mouse
Authors: Whelan Patrick , Bonnot Agnes , O'Donovan Michael J.
Published: December 2017

We examined the ability of the isolated lumbosacral spinal cord of the neonatal mouse (P0–7) to generate rhythmic motor activity under several different conditions. In the absence of electrical or pharmacological stimulation, we recorded several patterns of spontaneous ventral root depolarization and discharge. Spontaneous, alternating discharge between contralateral ventral roots could occur two to three times over a 10-min interval. We also observed other patterns, including left-right synchrony and rhythmic activity restricted to one side of the cord. Trains of stimuli delivered to the lumbar/coccygeal dorsal roots or the sural nerve reliably evoked episodes of rhythmic activity. During these evoked episodes, rhythmic ventral root discharges could occur on one side of the cord or could alternate from side to side. Bath application of a combination of N-methyl-d,l-aspartate (NMA), serotonin, and dopamine produced rhythmic activity that could last for several hours. Under these conditions, the discharge recorded from the left and right L1–L3 ventral roots alternated. In the L4–L5segments, the discharge had two peaks in each cycle, coincident with discharge of the ipsilateral and contralateral L1–L3 roots. The L6 ventral root discharge alternated with that recorded from the ipsilateral L1–L3 roots. We established that the drug-induced rhythm was locomotor-like by recording an alternating pattern of discharge between ipsilateral flexor and extensor hindlimb muscle nerves. In addition, by recording simultaneously from ventral roots and muscle nerves, we established that ankle flexor discharge was in phase with ipsilateral L1/L2 ventral root discharge, while extensor discharge was in phase with ipsilateral L6 ventral root discharge. Rhythmic patterns of ventral root discharge were preserved following mid-sagittal section of the spinal cord, demonstrating that reciprocal inhibitory connections between the left and right sides of the cord are not essential for rhythmogenesis in the neonatal mouse cord. Blocking N-methyl-d-aspartate receptors, in both the intact and the hemisected preparation, revealed that these receptors contribute to but are not essential for rhythmogenesis. In contrast, the rhythm was abolished following blockade of kainate/AMPA receptors with 6-cyano-7-nitroquinoxalene-2,3-dione. These findings demonstrate that the isolated mouse spinal cord can produce a variety of coordinated activities, including locomotor-like activity. The ability to study these behaviors under a variety of different conditions offers promise for future studies of rhythmogenic mechanisms in this preparation.
Tracking the Hemodynamic Responses to Reward and Punishment in the Striatum
Authors: Delgado M. R. , Nystrom L. E. , Fissell C. , Noll D. C. , Fiez J. A.
Published: December 2017

Research suggests that the basal ganglia complex is a major component of the neural circuitry that mediates reward-related processing. However, human studies have not yet characterized the response of the basal ganglia to an isolated reward, as has been done in animals. We developed an event-related functional magnetic resonance imaging paradigm to identify brain areas that are activated after presentation of a reward. Subjects guessed whether the value of a card was higher or lower than the number 5, with monetary rewards as an incentive for correct guesses. They received reward, punishment, or neutral feedback on different trials. Regions in the dorsal and ventral striatum were activated by the paradigm, showing differential responses to reward and punishment. Activation was sustained following a reward feedback, but decreased below baseline following a punishment feedback.
Brief and Short-Term Corticofugal Modulation of Subcortical Auditory Responses in the Big Brown Bat, Eptesicus fuscus
Authors: Zhou Xiaoming , Jen Philip H.-S.
Published: December 2017

Recent studies show that the auditory corticofugal system modulates and improves ongoing signal processing and reorganizes frequency map according to auditory experience in the central nucleus of bat inferior colliculus. However, whether all corticofugally affected collicular neurons are involved in both types of modulation has not been determined. In this study, we demonstrate that one group (51%) of collicular neurons participates only in corticofugal modulation of ongoing signal processing, while a second group (49%) of collicular neurons participates in both modulation of ongoing signal processing and in reorganization of the auditory system.
Dendritic Modulation of Burst-Like Firing in Sensory Neurons
Authors: Bastian Joseph , Nguyenkim Jerry
Published: December 2017

This report describes the variability of spontaneous firing characteristics of sensory neurons, electrosensory lateral line lobe (ELL) pyramidal cells, within the electrosensory lateral line lobe of weakly electric fish in vivo. We show that these cells' spontaneous firing frequency, measures of spike train regularity (interspike interval coefficient of variation), and the tendency of these cells to produce bursts of action potentials are correlated with the size of the cell's apical dendritic arbor. We also show that bursting behavior may be influenced or controlled by descending inputs from higher centers that provide excitatory and inhibitory inputs to the pyramidal cells' apical dendrites. Pyramidal cells were classified as “bursty” or “nonbursty” according to whether or not spike trains deviated significantly from the expected properties of random (Poisson) spike trains of the same average firing frequency, and, in the case of bursty cells, the maximum within-burst interspike interval characteristic of bursts was determined. Each cell's probability of producing bursts above the level expected for a Poisson spike train was determined and related to spontaneous firing frequency and dendritic morphology. Pyramidal cells with large apical dendritic arbors have lower rates of spontaneous activity and higher probabilities of producing bursts above the expected level, while cells with smaller apical dendrites fire at higher frequencies and are less bursty. The effect of blocking non- N-methyl-d-aspartate (non-NMDA) glutamatergic synaptic inputs to the apical dendrites of these cells, and to local inhibitory interneurons, significantly reduced the spontaneous occurrence of spike bursts and intracellular injection of hyperpolarizing current mimicked this effect. The results suggest that bursty firing of ELL pyramidal cells may be under descending control allowing activity in electrosensory feedback pathways to influence the firing properties of sensory neurons early in the processing hierarchy.
Influence of Contrast on the Responses of Marmoset Lateral Geniculate Cells to Drifting Gratings
Authors: Kremers Jan , Silveira Luiz Carlos L. , Kilavik Bjørg E.
Published: December 2017

The responses of lateral geniculate nucleus (LGN) cells in the common marmoset ( Callithrix jacchus) to drifting luminance or cone isolating gratings of different spatial frequencies and contrasts were measured. The response noise, defined as the variability of the responses to single sweeps in the complex plane, was independent of stimulus contrast and spatial frequency but increased with increasing overall responsiveness of the cell. The signal-to-noise ratio of parvocellular (PC) cells was smaller than of magnocellular (MC) cells. At each contrast, the response amplitude as a function of spatial frequency could be described with a difference of Gaussians model. With this model, the sizes and the peak sensitivities of the receptive field centers and surrounds were estimated. It was found that receptive field center and surround sizes of LGN cells decrease slightly with increasing contrast. Further, the peak sensitivity decreases with increasing contrast. The two factors are involved in a decrease in responsivity (the response per unit contrast) with increasing contrast which is compatible to response saturation for low spatial frequency stimuli. PC cells did not saturate as much to luminance stimuli although some saturation was found with cone isolating gratings. We found that the response phase lag of both PC and MC cells decreased with increasing contrast, which cannot be explained on the basis of linear response behavior. Apparently the phase of LGN cell responses to drifting gratings is altered in comparison with the retinal inputs by additional nonlinearities.
Circuitry Underlying Antiopioid Actions of Cholecystokinin Within the Rostral Ventromedial Medulla
Authors: Heinricher M. M. , McGaraughty S. , Tortorici V.
Published: December 2017

It is now well established that the analgesic actions of opioids can be modified by “anti-analgesic” or “antiopioid” peptides, among them cholecystokinin (CCK). Although the focus of much recent work concerned with CCK-opioid interactions has been at the level of the spinal cord, CCK also acts within the brain to modify opioid analgesia. The aim of the present study was to characterize the actions of CCK in a brain region in which the circuitry mediating the analgesic actions of opioids is relatively well understood, the rostral ventromedial medulla (RVM). Single-cell recording was combined with local infusion of CCK in the RVM and systemic administration of morphine in lightly anesthetized rats. The tail-flick reflex was used as a behavioral index of nociceptive responsiveness. Two classes of RVM neurons with distinct responses to opioids have been identified. off cells are activated, indirectly, by morphine and μ-opioid agonists, and there is strong evidence that this activation is crucial to opioid antinociception. on cells, thought to facilitate nociception, are directly inhibited by opioids. Cells of a third class,neutral cells, do not respond to opioids, and whether they have any role in nociceptive modulation is unknown. CCK microinjected into the RVM by itself had no effect on tail flick latency or the firing of any cell class but significantly attenuated opioid activation of off cells and inhibition of the tail flick. Opioid suppression of on-cell firing was not significantly altered by CCK. Thus CCK acting within the RVM attenuates the analgesic effect of systemically administered morphine by preventing activation of the putative pain inhibiting output neurons of the RVM, the offcells. CCK thus differs from another antiopioid peptide, orphanin FQ/nociceptin, which interferes with opioid analgesia by potently suppressing all off-cell firing.
Fast, But Not Slow, Effects of Olivocochlear Activation Are Resistant to Apamin
Authors: Yoshida Naohiro , Liberman M. Charles , Brown M. Christian , Sewell William F.
Published: December 2017

Olivocochlear (OC) efferent suppression of auditory-nerve responses comprises a fast effect lasting tens of milliseconds and a slow effect building and decaying over tens of seconds. Both fast and slow effects are mediated by activation of the same alpha 9 nicotinic receptor. We have hypothesized that fast effects are generated at the OC synapse, but that slow effects reflect activation of calcium-activated potassium (KCa) channels by calcium release from the subsurface cisternae on the basolateral wall of the hair cells. We measured in vivo effects of apamin, a blocker of small-conductance (SK) KCa channels, and charybdotoxin, a blocker of large-conductance KCa channels, perfused through scala tympani, on fast and slow effects evoked by electrical stimulation of the OC bundle in anesthetized guinea pigs. Apamin selectively and reversibly reduced slow-effect amplitude without altering fast effects or baseline amplitude of the auditory-nerve response, but only when perfused at concentrations of 100 μM. In contrast, the effects of charybdotoxin were noted at 30 nM, but were not specific, reducing both afferent and efferent responses. The very high concentrations of apamin needed to block efferent effects contrasts with the high sensitivity of isolated hair cells to apamin's block of acetylcholine's effects. The results suggest that in vivo fast OC effects are dominated by a conductance that is not apamin sensitive.
Effect of Stance Width on Multidirectional Postural Responses
Authors: Henry Sharon M. , Fung Joyce , Horak Fay B.
Published: December 2017

The effect of stance width on postural responses to 12 different directions of surface translations was examined. Postural responses were characterized by recording 11 lower limb and trunk muscles, body kinematics, and forces exerted under each foot of 7 healthy subjects while they were subjected to horizontal surface translations in 12 different, randomly presented directions. A quasi-static approach of force analysis was done, examining force integrals in three different epochs (background, passive, and active periods). The latency and amplitude of muscle responses were quantified for each direction, and muscle tuning curves were used to determine the spatial activation patterns for each muscle. The results demonstrate that the horizontal force constraint exerted at the ground was lessened in the wide, compared with narrow, stance for humans, a similar finding to that reported by Macpherson for cats. Despite more trunk displacement in narrow stance, there were no significant changes in body center of mass (CoM) displacement due to large changes in center of pressure (CoP), especially in response to lateral translations. Electromyographic (EMG) magnitude decreased for all directions in wide stance, particularly for the more proximal muscles, whereas latencies remained the same from narrow to wide stance. Equilibrium control in narrow stance was more of an active postural strategy that included regulating the loading/unloading of the limbs and the direction of horizontal force vectors. In wide stance, equilibrium control relied more on an increase in passive stiffness resulting from changes in limb geometry. The selective latency modulation of the proximal muscles with translation direction suggests that the trunk was being actively controlled in all directions. The similar EMG latencies for both narrow and wide stance, with modulation of only the muscle activation magnitude as stance width changed, suggest that the same postural synergy was only slightly modified for a change in stance width. Nevertheless, the magnitude of the trunk displacement, as well as of CoP displacement, was modified based on the degree of passive stiffness in the musculoskeletal system, which increased with stance width. The change from a more passive to an active horizontal force constraint, to larger EMG magnitudes especially in the trunk muscles and larger trunk and CoP excursions in narrow stance are consistent with a more effortful response for equilibrium control in narrow stance to perturbations in all directions.
BK Channels in Human Glioma Cells
Authors: Ransom Christopher B. , Sontheimer Harald
Published: December 2017

Ion channels in inexcitable cells are involved in proliferation and volume regulation. Glioma cells robustly proliferate and undergo shape and volume changes during invasive migration. We investigated ion channel expression in two human glioma cell lines (D54MG and STTG-1). With low [Ca2+]i, both cell types displayed voltage-dependent currents that activated at positive voltages (more than +50 mV). Current density was sensitive to intracellular cation replacement with the following rank order; K+> Cs+≈ Li+> Na+. Currents were >80% inhibited by iberiotoxin (33 nM), charybdotoxin (50 nM), quinine (1 mM), tetrandrine (30 μM), and tetraethylammonium ion (TEA; 1 mM). Extracellular phloretin (100 μM), an activator of BK(Ca2+) channels, and elevated intracellular Ca2+negatively shifted the I-V curve of whole cell currents. With 0, 0.1, and 1 μM [Ca2+]i, the half-maximal voltages, V0.5, for whole cell current activation were +150, +65, and +12 mV, respectively. Elevating [K+]opotentiated whole cell currents in a fashion proportional to the square-root of [K+]o. Recording from cell-attached patches revealed large conductance channels (150–200 pS) with similar voltage dependence and activation kinetics as whole cell currents. These data indicate that human glioma cells express large-conductance, Ca2+-activated K+(BK) channels. In amphotericin-perforated patches bradykinin (1 μM) activated TEA-sensitive currents that were abolished by preincubation with bis-( o-aminophenoxy)- N,N,N′,N′-tetraacetic acid-AM (BAPTA-AM). The BK channels described here may influence the responses of glioma cells to stimuli that increase [Ca2+]i.
High-Affinity Zinc Potentiation of Inhibitory Postsynaptic Glycinergic Currents in the Zebrafish Hindbrain
Authors: Suwa Hiroshi , Saint-Amant Louis , Triller Antoine , Drapeau Pierre , Legendre Pascal
Published: December 2017

Zinc has been reported to potentiate glycine receptors (GlyR), but the physiological significance of this observation has been put in doubt by the relatively high values of the EC50, 0.5–1 μM, since such concentrations may not be attained in the synaptic cleft of glycinergic synapses. We have re-evaluated this observation in the frame of the hypothesis that contaminant heavy metals present in usual solutions may have lead to underestimate the affinity of the zinc binding site, and therefore to underestimate the potential physiological role of zinc. Using chelators either to complex heavy metals or to apply zinc at controlled concentrations, we have examined the action of zinc on GlyR kinetics in outside-out patches from 50-h-old zebrafish Mauthner cells. Chelating contaminating heavy metals with tricine or N,N,N′,N′-tetrakis-(2-pyridylmethyl)-ethylenediamine (TPEN) decreased the duration of the currents evoked by glycine, confirming that traces of heavy metals alter the GlyR response in control conditions. Using tricine- (10 mM) buffered zinc solution, we then showed that zinc increases the amplitude of outside-out responses evoked by 0.1–0.5 mM glycine with an EC50of 15 nM. In contrast zinc had no effect on the amplitude of currents evoked by a saturating concentration (3–10 mM) of glycine. This suggests that zinc enhances GlyR apparent affinity for glycine. The study of the effects of zinc on the kinetics of the response indicates that this increase of apparent affinity is due to a decrease of the glycine dissociation rate constant. We then analyzed the effects of zinc on postsynaptic GlyRs in whole cell recordings of glycinergic miniature inhibitory postsynaptic currents (mIPSCs). Chelation of contaminant heavy metals decreased the amplitude and the duration of the mIPSCs; inverse effects were observed by adding zinc in buffered solutions containing nanomolar free zinc concentrations. Zinc plus tricine or tricine alone did not change the coefficient of variation (≈0.85) of the mIPSC amplitude distributions. These results suggest that postsynaptic GlyRs are not saturated after the release of one vesicle.
Initiation and Propagation of Calcium-Dependent Action Potentials in a Coupled Network of Olfactory Interneurons
Authors: Wang Jing W. , Denk Winfried , Flores Jorge , Gelperin Alan
Published: December 2017

Coherent oscillatory electrical activity and apical-basal wave propagation have been described previously in the procerebral (PC) lobe, an olfactory center of the terrestrial slug Limax maximus. In this study, we investigate the physiological basis of oscillatory activity and wave propagation in the PC lobe. Calcium green dextran was locally deposited in the PC lobe; this led to cellular uptake and transport of dye by bursting and nonbursting neurons of the PC lobe. The change of intracellular calcium concentration was measured at several different positions in neurites of individual bursting neurons in the PC lobe with a two-photon laser-scanning microscope. Fluorescence measurements were also made from neurons intracellularly injected with calcium green-1. Two different morphological classes of bursting neurons were found, varicose (VB) and smooth (SB). Our results from concurrent optical and intracellular recordings suggest that Ca2+is the major carrier for the inward current during action potentials of bursting neurons. Intracellular recordings from bursting neurons with nystatin perforated-patch electrodes made while simultaneously recording the local field potential (LFP) with extracellular electrodes indicate that the burster spikes are precisely phase-locked to the periodic LFP events. By referencing successive calcium measurements to the common LFP signal, we could therefore accurately determine the relative timing of calcium transients at different points along a neurite. Measuring the relation of temporal to spatial differences allowed us to estimate the velocity of action potential propagation, which was 4.3 ± 0.2 (SE) mm/s in VBs, and 1.3 ± 0.2 mm/s in SB.
Specific Force of the Rat Extraocular Muscles, Levator and Superior Rectus, Measured In Situ
Authors: Frueh Bartley R. , Gregorevic Paul , Williams David A. , Lynch Gordon S.
Published: December 2017

Extraocular muscles are characterized by their faster rates of contraction and their higher resistance to fatigue relative to limb skeletal muscles. Another often reported characteristic of extraocular muscles is that they generate lower specific forces ( sP o, force per muscle cross-sectional area, kN/m2) than limb skeletal muscles. To investigate this perplexing issue, the isometric contractile properties of the levator palpebrae superioris (levator) and superior rectus muscles of the rat were examined in situ with nerve and blood supply intact. The extraocular muscles were attached to a force transducer, and the cranial nerves exposed for direct stimulation. After determination of optimal muscle length ( L o) and stimulation voltage, a full frequency-force relationship was established for each muscle. Maximum isometric tetanic force ( P o) for the levator and superior rectus muscles was 177 ± 13 and 280 ± 10 mN (mean ± SE), respectively. For the calculation of specific force, a number of rat levator and superior rectus muscles were stored in a 20% nitric acid-based solution to isolate individual muscle fibers. Muscle fiber lengths ( L f) were expressed as a percentage of overall muscle length, allowing a mean L f to L o ratio to be used in the estimation of muscle cross-sectional area. Mean L f: L owas determined to be 0.38 for the levator muscle and 0.45 for the superior rectus muscle. The sP o for the rat levator and superior rectus muscles measured in situ was 275 and 280 kN/m2, respectively. These values are within the range of sP o values commonly reported for rat skeletal muscles. Furthermore P o and sP o for the rat levator and superior rectus muscles measured in situ were significantly higher ( P < 0.001) than P oand sP o for these muscles measured in vitro. The results indicate that the force output of intact extraocular muscles differs greatly depending on the mode of testing. Although in vitro evaluation of extraocular muscle contractility will continue to reveal important information about this group of understudied muscles, the lower sP o values of these preparations should be recognized as being significantly less than their true potential. We conclude that extraocular muscles are not intrinsically weaker than skeletal muscles.
Visual Influences on the Development and Recovery of the Vestibuloocular Reflex in the Chicken
Authors: Goode Christopher T. , Maney Donna L. , Rubel Edwin W , Fuchs Albert F.
Published: December 2017

Whenever the head turns, the vestibuloocular reflex (VOR) produces compensatory eye movements to help stabilize the image of the visual world on the retina. Uncompensated slip of the visual world across the retina results in a gradual change in VOR gain to minimize the image motion. VOR gain changes naturally during normal development and during recovery from neuronal damage. We ask here whether visual slip is necessary for the development of the chicken VOR (as in other species) and whether it is required for the recovery of the VOR after hair cell loss and regeneration. In the first experiment, chickens were reared under stroboscopic illumination, which eliminated visual slip. The horizontal and vertical VORs (h- and vVORs) were measured at different ages and compared with those of chickens reared in normal light. Strobe-rearing prevented the normal development of both h- and vVORs. After 8 wk of strobe-rearing, 3 days of exposure to normal light caused the VORs to recover partially but not to normal values. In the second experiment, 1-wk-old chicks were treated with streptomycin, which destroys most vestibular hair cells and reduces hVOR gain to zero. In birds, vestibular hair cells regenerate so that after 8 wk in normal illumination they appear normal and hVOR gain returns to values that are normal for birds of that age. The treated birds in this study recovered in either normal or stroboscopic illumination. Their hVOR and vVOR and vestibulocollic reflexes (VCR) were measured and compared with those of untreated, age-matched controls at 8 wk posthatch, when hair cell regeneration is known to be complete. As in previous studies, the gain of the VOR decreased immediately to zero after streptomycin treatment. After 8 wk of recovery under normal light, the hVOR was normal, but vVOR gain was less than normal. After 8 wk of recovery under stroboscopic illumination, hVOR gain was less than normal at all frequencies. VCR recovery was not affected by the strobe environment. When streptomycin-treated, strobe-recovered birds were then placed in normal light for 2 days, hVOR gain returned to normal. Taken together, the results of these experiments suggest that continuous visual feedback can adjust VOR gain. In the absence of appropriate visual stimuli, however, there is a default VOR gain and phase to which birds recover or revert, regardless of age. Thus an 8-wk-old chicken raised in a strobe environment from hatch would have the same gain as a streptomycin-treated chicken that recovers in a strobe environment.
High-Frequency Stimulation Produces a Transient Blockade of Voltage-Gated Currents in Subthalamic Neurons
Authors: Beurrier Corinne , Bioulac Bernard , Audin Jacques , Hammond Constance
Published: December 2017

The effect of high-frequency stimulation (HFS) of the subthalamic nucleus (STN) was analyzed with patch-clamp techniques (whole cell configuration, current- and voltage-clamp modes) in rat STN slices in vitro. A brief tetanus, consisting of 100-μs bipolar stimuli at a frequency of 100–250 Hz during 1 min, produced a full blockade of ongoing STN activity whether it was in the tonic or bursting mode. This HFS-induced silence lasted around 6 min after the end of stimulation, was frequency dependent, could be repeated without alteration, and was not synaptically induced as it was still observed in the presence of blockers of ionotropic GABA and glutamate receptors or in the presence of cobalt at a concentration (2 mM) that blocks voltage-gated Ca2+ channels and synaptic transmission. During HFS-induced silence, the following alterations were observed: the persistent Na+ current ( I NaP) was totally blocked (by 99%), the Ca2+-mediated responses were strongly reduced including the posthyperpolarization rebound (−62% in amplitude) and the plateau potential (−76% in duration), suggesting that T- and L-type Ca2+ currents are transiently depressed by HFS, whereas the Cs+-sensitive, hyperpolarization-activated cationic current ( I h) was little affected. Thus a high-frequency tetanus produces a blockade of the spontaneous activities of STN neurons as a result of a strong depression of intrinsic voltage-gated currents underlying single-spike and bursting modes of discharge. These effects of HFS, which are completely independent of synaptic transmission, provide a mechanism for interrupting ongoing activities of STN neurons.
Spermine Mediates Inward Rectification in Potassium Channels of Turtle Retinal Müller Cells
Authors: Solessio Eduardo , Rapp Kevin , Perlman Ido , Lasater Eric M.
Published: December 2017

Retinal Müller cells are highly permeable to potassium as a consequence of their intrinsic membrane properties. Therefore these cells are able to play an important role in maintaining potassium homeostasis in the vertebrate retina during light-induced neuronal activity. Polyamines and other factors present in Müller cells have the potential to modulate the rectifying properties of potassium channels and alter the Müller cells capacity to siphon potassium from the extracellular space. In this study, the properties of potassium currents in turtle Müller cells were investigated using whole cell voltage-clamp recordings from isolated cells. Overall, the currents were inwardly rectifying. Depolarization elicited an outward current characterized by a fast transient that slowly recovered to a steady level along a double exponential time course. On hyperpolarization the evoked inward current was characterized by an instantaneous onset (or step) followed by a slowly developing sustained inward current. The kinetics of the time-dependent components (block of the transient outward current and slowly developing inward current) were dependent on holding potential and changes in the intracellular levels of magnesium ions and polyamines. In contrast, the instantaneous inward and the sustained outward currents were ohmic in character and remained relatively unaltered with changes in holding potential and concentration of applied spermine (0.5–2 mM). Our data suggest that cellular regulation in vivo of polyamine levels can differentially alter specific aspects of potassium siphoning by Müller cells in the turtle retina by modulating potassium channel function.
Model for Olfactory Discrimination and Learning inLimaxProcerebrum Incorporating Oscillatory Dynamics and Wave Propagation
Authors: Ermentrout B. , Wang Jing W. , Flores Jorge , Gelperin A.
Published: December 2017

We extend our model of the procerebral (PC) lobe of Limax, which is comprised of a layer of coupled oscillators and a layer of memory neurons, each layer 4 rows by 20 columns, corresponding to the cell body layer (burster cells) and neuropil layer (nonburster cells) of the PC lobe. A gradient of connections in the layer of model burster cells induces periodic wave propagation, as measured in the PC lobe. We study odor representations in the biological PC lobe using the technique of Kimura and coworkers. Lucifer yellow injection into intact Limax after appetitive or aversive odor learning results in a band or patch of labeled cells in the PC lobe with the band long axis normal to the axis of wave propagation. Learning two odors yields two parallel bands of labeled PC cells. We introduce olfactory input to our model PC lobe such that each odor maximally activates a unique row of four cells which produces a short-term memory trace of odor stimulation. A winner-take-all synaptic competition enabled by collapse of the phase gradient during odor presentation produces a single short-term memory band for each odor. The short-term memory is converted to long-term memory if odor stimulation is followed by activation of an input pathway for the unconditioned stimulus (US) which presumably results in release of one or more neuromodulatory amines or peptides in the PC lobe.
Inactivation of Voltage-Activated Na+Currents Contributes to Different Adaptation Properties of Paired Mechanosensory Neurons
Authors: Torkkeli Päivi H. , Sekizawa Shin-Ichi , French Andrew S.
Published: December 2017

Voltage-activated sodium current ( INa) is primarily responsible for the leading edge of the action potential in many neurons. While INagenerally activates rapidly when a neuron is depolarized, its inactivation properties differ significantly between different neurons and even within one neuron, where INaoften has slowly and rapidly inactivating components. INainactivation has been suggested to regulate action potential firing frequency in some cells, but no clear picture of this relationship has emerged. We studied INain both members of the paired mechanosensory neurons of a spider slit-sense organ, where one neuron adapts rapidly (type A) and the other slowly (type B) in response to a step depolarization. In both neuron types INaactivated and inactivated with single time constants of 2–3 ms and 5–10 ms, respectively, varying with the stimulus intensity. However, there was a clear difference in the steady-state inactivation properties of the two neuron types, with the half-maximal inactivation ( V50) being −40.1 mV in type A neurons and −58.1 mV in type B neurons. Therefore INainactivated closer to the resting potential in the more slowly adapting neurons. INaalso recovered from inactivation significantly faster in type B than type A neurons, and the recovery was dependent on conditioning voltage. These results suggest that while the rate of INainactivation is not responsible for the difference in the adaptation behavior of these two neuron types, the rate of recovery from inactivation may play a major role. Inactivation at lower potentials could therefore be crucial for more rapid recovery.
Theta-Frequency Facilitation of AMPA Receptor-Mediated Synaptic Currents in the Principal Cells of the Medial Septum
Authors: Armstrong John N. , MacVicar Brian A.
Published: December 2017

Recent evidence suggests that Ca2+-permeable AMPA receptors display rapid, short-lasting current facilitation. In this study, we investigated the properties of AMPA receptor-mediated synaptic currents in medial septal neurons of the rat in an in vitro slice preparation. Immunocytochemistry with a selective antibody to the GluR2 subunit revealed that both choline acetyltransferase-containing and parvalbumin-containing neurons of the medial septum express no detectable GluR2 subunit immunoreactivity. We used whole cell voltage-clamp recordings to measure synaptically evoked AMPA receptor-mediated currents from medial septal neurons following stimulation of midline afferents. The GYKI 52466 (50 μM)- and 2,3-dioxo-6-nitro-1,2,3,4-tetrahydrobenzo[f]quinoxaline-7-sulfonamide (NBQX) (20 μM)-sensitive AMPA receptor-mediated component of the synaptic response was isolated by blocking GABAA- and N-methyl-d-aspartate receptor-mediated currents with 30 μM bicuculline and 100 μM 2-amino-5-phosphonovaleric acid, respectively. In some cases, patched cells were filled with Lucifer yellow (0.1%) and imaged using 2-photon laser scanning microscopy. AMPA receptor-mediated currents that were observed in large medial septal neurons (20–30 μm) displayed rectification. These currents were sensitive to external application of philanthotoxin-343 (PhTx-343, 50 μM), a potent, high-affinity antagonist of Ca2+-permeable, GluR2-lacking AMPA receptors. Rectifying AMPA receptor-mediated currents also displayed a rapid increase in amplitude when evoked five times at low frequency such as 6 Hz. In contrast to currents observed in large medial septal neurons, AMPA-receptor mediated currents evoked in the remaining small (8–11 μm) neurons were nonrectifying and displayed rapid synaptic depression when stimulated five times at 6 Hz. The currents evoked in these cells were unaffected by external application of PhTx-343 and were therefore GluR2-containing AMPA receptors. The results of the present study demonstrate that the principal projection neurons of the medial septum contain PhTx-343-sensitive, GluR2-lacking AMPA receptors that display rapid current facilitation when stimulated at low frequencies.
Spinal Allografts of Adrenal Medulla Block Nociceptive Facilitation in the Dorsal Horn
Authors: Hentall Ian D. , Noga Brian R. , Sagen Jacqueline
Published: December 2017

Transplantation of chromaffin cells into the lumbar subarachnoid space has been found to produce analgesia, most conspicuously against chronic neuropathic pain. To ascertain the neurophysiological mechanism, we recorded electrical activity from wide-dynamic-range dorsal horn neurons in vivo, measuring the short-lasting homosynaptic facilitatory effect known as windup, which is induced by repetitive C-fiber input. Rats were given adrenal medulla allografts, or, as controls, striated-muscle allografts. The adrenal-transplanted rats showed analgesia 3–4 wk after transplantation, measured as a reduction in flinching reflexes 30–55 min after subcutaneous formalin injection. Recordings were made under halothane anesthesia, 3–7 days following the behavioral testing. The average C-fiber response and subsequent afterdischarge were facilitated severalfold in control rats by 1-Hz cutaneous electrical stimulation. Such facilitation was essentially absent in adrenal-transplanted animals and also in the A-fiber response of both preparations. Extirpation of transplanted tissue several hours prior to recording did not significantly affect this difference. In conclusion, the adrenal transplants block short-term spinal nociceptive facilitation, probably by stimulating some persistent cellular process that may be an important determinant, but not the only one, of their analgesic effect.
Differential Expression of Functionally Identified and Immunohistochemically Identified NK1Receptors on Sympathetic Neurons
Authors: Jobling Phillip , Messenger Jennifer P. , Gibbins Ian L.
Published: December 2017

We have used multiple-labeling immunohistochemistry, intracellular dye-filling, and intracellular microelectrode recordings to characterize the distribution of tachykinin receptors and substance P boutons on subpopulations of neurons within the guinea pig celiac ganglion. Superfusion of substance P (SP, 1 μM for 1 min) depolarized 42% of tonic neurons and inhibited afterhyperpolarizations in 66% of long afterhyperpolarizing (LAH) neurons without significant desensitization. Twenty-one percent of tonic neurons and 24% of LAH neurons responded to the NK3agonist senktide but did not respond to SP, indicating SP did not activate NK3receptors at this concentration. All effects of SP were abolished by the selective NK1receptor antagonist, SR140333, but not by the selective NK3receptor antagonist, SR142801, suggesting that exogenous SP activated a receptor with NK1pharmacology. No dye-filled LAH neuron and only 50% of tonic neurons responding to SP expressed NK1receptor immunoreactivity (NK1-IR). All neurons responding to SP had SP immunoreactive fibers within one cell diameter, indicating good spatial matching between SP release sites and target neurons. These results indicate that SP may act via a receptor with NK1-like pharmacology that has a C terminus not recognized by antibodies to the intracellular domain of the conventional NK1receptor. Inward currents evoked by SP acting on this NK1-like receptor or senktide acting through NK3receptors had identical current-voltage relationships. In LAH neurons, both agonists suppressed IsAHPwithout reducing IAHP. Responses evoked by SP and senktide were resistant to PKC inhibitors, suggesting that the transduction mechanisms for the NK1-like receptor and the NK3receptor may be similar.
Two Types of Neurons in the Rat Cerebellar Nuclei as Distinguished by Membrane Potentials and Intracellular Fillings
Authors: Czubayko Uwe , Sultan Fahad , Thier Peter , Schwarz Cornelius
Published: December 2017

Classically, three classes of neurons in the cerebellar nuclei (CN), defined by different projection targets and content of transmitters, have been distinguished. However, evidence for different types of neurons based on different intrinsic properties is lacking. The present study reports two types of neurons defined mainly by their intrinsic properties, as determined by whole-cell patch recordings. The majority of cells (type I, n = 63) showed cyclic burst firing whereas a small subset (type II, n = 7) did not. Burst firing was used to distinguish the two types of neurons because, as it turned out, pharmacological interference could not be used to convert the non-bursting cells to bursting ones. Some of the membrane potentials exclusively present in type I neurons, such as sodium and calcium plateau potentials, low-threshold calcium spikes, and a slow calcium-dependent afterhyperpolarization, were found to contribute to the generation of burst firing. Other membrane potentials of type I neurons were not obviously related to the generation of bursts. These were 1) the lower amplitude and width of the action potential during spontaneous activity, 2) a sequence of afterhyperpolarization–afterdepolarization–afterhyperpolarization following each spike, and 3) the high spontaneous firing rate. In contrast, type II neurons lacked slow plateau potentials and low threshold spikes. Their action potentials showed higher amplitude and width and were followed by a single deep afterhyperpolarization. Furthermore, they showed a lower firing rate at rest. In both types of neurons, a delayed inward rectification was present. Neurons filled with neurobiotin revealed that the sizes of the somata and dendritic fields of type I neurons comprised the whole range known from Golgi studies, whereas those of the few type II neurons recovered were found to be in the lowest range. In view of their size and scarcity, we propose that type II neurons may correspond to CN interneurons.
Neural Representations of Temporally Asymmetric Stimuli in the Auditory Cortex of Awake Primates
Authors: Lu Thomas , Liang Li , Wang Xiaoqin
Published: December 2017

The representation of rapid acoustic transients by the auditory cortex is a fundamental issue that is still unresolved. Auditory cortical neurons have been shown to be limited in their stimulus-synchronized responses, yet the perceptual performances of humans and animals in discriminating temporal variations in complex sounds are better than what existing neurophysiological data would predict. This study investigated the neural representation of temporally asymmetric stimuli in the primary auditory cortex of awake marmoset monkeys. The stimuli, ramped and damped sinusoids, were systematically manipulated (by means of half-life of the exponential envelope) within a cortical neuron's presumed temporal integration window. The main findings of this study are as follows: 1) temporal asymmetry in ramped and damped sinusoids with a short period (25 ms) was clearly reflected by average discharge rate but not necessarily by temporal discharge patterns of auditory cortical neurons. There was considerable response specificity to these stimuli such that some neurons were strongly responsive to a ramped sinusoid but almost completely unresponsive to its damped counterpart or vice versa. Of 181 neurons studied, 140 (77%) showed significant response asymmetry in at least one of the tested half-life values of the exponential envelope. Forty-six neurons showed significant response asymmetry over all half-lives tested. Sustained firing, commonly observed under awake conditions, contributed to greater response asymmetry than that of onset responses in many neurons. 2) A greater proportion of the neurons (32/46) that exhibited significant overall response asymmetry showed stronger responses to the ramped sinusoids than to the damped sinusoids, possibly contributing to the difference in the perceived loudness between these two classes of sounds. 3) The asymmetry preference of a neuron to ramped or damped sinusoids did not appear to be correlated with its characteristic frequency or minimum response latency, suggesting that this is a general phenomenon that exists across populations of cortical neurons. Moreover, the intensity of the stimuli did not have significant effects on the measure of the asymmetry preference based on discharge rate. 4) A population measure of response preference, based on discharge rate, of cortical neurons to the temporally asymmetric stimuli was qualitatively similar to the performance of human listeners in discriminating ramped versus damped sinusoids at different half-life values. These findings suggest that rapid acoustic transients embedded in complex sounds can be represented by discharge rates of cortical neurons instead of or in the absence of stimulus-synchronized discharges.
GABAA-Dependent Chloride Influx Modulates Reversal Potential of GABAB-Mediated IPSPs in Hippocampal Pyramidal Cells
Authors: Lopantsev Valeri , Schwartzkroin Philip A.
Published: December 2017

Changes in intracellular chloride concentration, mediated by chloride influx through GABAA receptor–gated channels, may modulate GABAB receptor–mediated inhibitory postsynaptic potentials (GABAB IPSPs) via unknown mechanisms. Recording from CA3 pyramidal cells in hippocampal slices, we investigated the impact of chloride influx during GABAA receptor–mediated IPSPs (GABAA IPSPs) on the properties of GABAB IPSPs. At relatively positive membrane potentials (near −55 mV), mossy fiber–evoked GABAB IPSPs were reduced (compared with their magnitude at −60 mV) when preceded by GABAAreceptor–mediated chloride influx. This effect was not associated with a correlated reduction in membrane permeability during the GABAB IPSP. The mossy fiber–evoked GABAB IPSP showed a positive shift in reversal potential (from −99 to −93 mV) when it was preceded by a GABAA IPSP evoked at cell membrane potential of −55 mV as compared with −60 mV. Similarly, when intracellular chloride concentration was raised via chloride diffusion from an intracellular microelectrode, there was a reduction of the pharmacologically isolated monosynaptic GABABIPSP and a concurrent shift of GABAB IPSP reversal potential from −98 to −90 mV. We conclude that in hippocampal pyramidal cells, in which “resting” membrane potential is near action potential threshold, chloride influx via GABAA IPSPs shifts the reversal potential of subsequent GABAB receptor–mediated postsynaptic responses in a positive direction and reduces their magnitude.