bluuebunny/crossref_metadata_2025 huggingface dataset:
Voltage-Gated and Ca2+-Activated Conductances Mediating and Controlling Graded Electrical Activity in Crayfish Muscle
Authors: Araque Alfonso , Marchand Alain , Buño Washington
Published: December 2017

Araque, Alfonso, Alain Marchand, and Washington Buño. Voltage-gated and Ca2+-activated conductances mediating and controlling graded electrical activity in crayfish muscle. J. Neurophysiol. 79: 2338–2344, 1998. Crayfish opener muscle fibers provide a unique preparation to quantitatively evaluate the relationships between the voltage-gated Ca2+ ( I Ca) and Ca2+-activated K+ ( I K(Ca)) currents underlying the graded action potentials (GAPs) that typify these fibers. I Ca, I K(Ca), and the voltage-gated K+ current ( I K) were studied using two-electrode voltage-clamp applying voltage commands that simulated the GAPs evoked in current-clamp conditions by 60-ms current pulses. This methodology, unlike traditional voltage-clamp step commands, provides a description of the dynamic aspects of the interaction between different conductances participating in the generation of the natural GAP. The initial depolarizing phase of the GAP was due to activation of the I Ca on depolarization above approximately −40 mV. The resulting Ca2+ inflow induced the activation of the fast I K(Ca) (<3 ms), which rapidly repolarized the fiber (<6 ms). Because of its relatively slow activation, the contribution of I K to the GAP repolarization was delayed. During the final steady GAP depolarization I Ca and I K(Ca) were simultaneously activated with similar magnitudes, whereas I K aided in the control of the delayed sustained response. The larger GAPs evoked by higher intensity stimulations were due to the increase in I Ca. The resulting larger Ca2+ inflow increased I K(Ca), which acted as a negative feedback that precisely controlled the fiber's depolarization. Hence I K(Ca) regulated the Ca2+-inflow needed for the contraction and controlled the depolarization that this Ca2+ inflow would otherwise elicit.
Regulation of Action-Potential Firing in Spiny Neurons of the Rat Neostriatum In Vivo
Authors: Wickens J. R. , Wilson C. J.
Published: December 2017

Wickens, J. R. and C. J. Wilson. Regulation of action-potential firing in spiny neurons of the rat neostriatum in vivo. J. Neurophysiol. 79: 2358–2364, 1998. Both silent and spontaneously firing spiny projection neurons have been described in the neostriatum, but the reason for their differences in firing activity are unknown. We compared properties of spontaneously firing and silent spiny neurons in urethan-anesthetized rats. Neurons were identified as spiny projection neurons after labeling by intracellular injection of biocytin. The threshold for action-potential firing was measured under three different conditions: 1) electrical stimulation of the contralateral cerebral cortex, 2) brief directly applied current pulses, and 3) spontaneous action-potentials occurring during spontaneous episodes of depolarization (up state). The average membrane potential and the amplitude of noiselike fluctuations of membrane potential in the up state were determined by fitting a Gaussian curve to the membrane-potential distribution. All neurons in the sample exhibited spontaneous membrane potential shifts between a hyperpolarized down state and a depolarized up state, but not all fired action potentials while in the up state. The difference between the spontaneously firing and the silent spiny neurons was in the average membrane potential in the up state, which was significantly more depolarized in the spontaneously firing than in the silent spiny neurons. There were no significant differences in the threshold, the amplitude of the noiselike fluctuations of membrane potential in the up state, or in the proportion of time that the membrane potential was in the up state. In both spontaneously firing and silent neurons, the threshold for action potentials evoked by current pulses was significantly higher than for those evoked by cortical stimulation. Application of more intense current pulses that reproduced the excitatory postsynaptic potential rate of rise produced firing at correspondingly lower thresholds. Because the membrane potential in the up state is mainly determined by the balance between the synaptic drive and the outward potassium conductances activated in the subthreshold range of membrane potentials, either or both of these factors may determine whether firing occurs in response to spontaneous afferent activity.
Pattern of Cardiorespiratory Afferent Convergence to Solitary Tract Neurons Driven by Pulmonary Vagal C-Fiber Stimulation in the Mouse
Authors: Paton Julian F. R.
Published: December 2017

Paton, Julian F. R. Pattern of cardiorespiratory afferent convergence to solitary tract neurons driven by pulmonary vagal C-fiber stimulation in the mouse. J. Neurophysiol. 79: 2365–2373, 1998. The central integration of signals from pulmonary vagal C-fibers (or type-J receptors) with those arising from cardiac, peripheral chemoreceptor, and baroreceptor afferents to neurons within the nucleus of the solitary tract (NTS) was studied in an arterially perfused working heart–brain stem preparation of adult mouse. Pulmonary vagal C-fibers were excited by right atrial injection of phenylbiguanide (PBG) while cardiac receptors were stimulated by left ventricular injection of veratridine (1–3 μg/kg) or mechanically by distension of the left ventricle (20–50 μl perfusate) using an indwelling cannula. Carotid body chemoreceptors were activated by aortic injection of Na cyanide, whereas baroreceptors were stimulated by increasing arterial perfusion pressure. Stimulation of pulmonary C-fibers and cardiac, chemo-, and baroreceptors all produced a reflex bradycardia (23–133 bpm). Central respiratory activity, as recorded from the phrenic nerve, was depressed by stimulating pulmonary C-fibers and cardiac and baroreceptors but enhanced in amplitude and frequency during chemoreceptor stimulation. Twenty-seven NTS neurons were excited and three were inhibited after pulmonary C-fiber stimulation displaying decrementing discharges with a peak firing frequency of up to 42 Hz (15 ± 2.2 Hz, mean ± SE) that lasted for 8.8 ± 0.9 s. These responses occurred <1 s from the end of the PBG injection that was within the pulmonary circulation time. None of these cells responded to increases in right atrial pressure. All cells excited by PBG were also driven synaptically after electrical stimulation of the ipsilateral cervical vagus nerve at a latency of 32.9 ± 3.2 ms (range 20–62 ms). None of these neurons had ongoing activity related to central respiratory activity. Convergence from cardiorespiratory afferents to 21 neurons driven by pulmonary C-fibers was tested. Twenty-five percent of cells were selectively excited by chemical stimulation of cardiac receptors alone, 19% were driven by peripheral chemoreceptors, and 38% responded to both cardiac and chemoreceptor activation. In contrast, only 13% of the cells activated by PBG injection responded to stimulation of baroreceptors and only 6% to cardiac mechanoreceptor stimulation. None of these neurons were activated by increasing right atrial pressure. The data indicate a high proportion of afferent convergence from pulmonary C-fibers, cardiac receptors, and peripheral chemoreceptors in the NTS. However, these neurons appear not to integrate inputs from cardiovascular mechanoreceptors. The significance of the data is discussed in relation to pathological disease states such as pulmonary congestion and cardiac failure.
Passive Electrical Properties of Ventral Horn Neurons in Rat Spinal Cord Slices
Authors: Thurbon David , Lüscher Hans-R. , Hofstetter Thomas , Redman Stephen J.
Published: December 2017

Thurbon, David, Hans-R. Lüscher, Thomas Hofstetter, and Stephen J. Redman. Passive electrical properties of ventral horn neurons in rat spinal cord slices. J. Neurophysiol. 79: 2485–2502, 1998. Recordings were made from large neurons located in the ventral horn of transverse spinal cord slices from young rats (7–15 days). Whole cell recordings were made simultaneously with two electrodes from the soma of these neurons, visualized using infra-red differential interference contrast optics. Positive identification of motoneurons could not always be achieved. The response of a neuron to a brief pulse of current delivered by one electrode, and recorded by the other electrode, were matched optimally to responses of a compartmental model of the same neuron with an identical current pulse as input. The compartmental model was based on a reconstruction of the neuron, using Biocytin staining. The compartmental model had three free parameters: specific membrane capacitance ( C m), membrane resistivity ( R m), and cytoplasmatic resistivity ( R i), all assumed to be uniform throughout the neuron. The experimental and model responses could be matched unequivocally for four neurons, giving C m = 2.4 ± 0.5 μF/cm2, R m = 5.3 ± 0.9 kΩ/cm2, and R i = 87 ± 22 Ω/cm. No somatic shunt was required. For the remaining six neurons, a less perfect fit (but still within 95% confidence limits) was indicative of nonhomogeneous membrane properties. The electrotonic length of uncut dendrites was 0.85 ± 0.14 λ. The results resolve the issue of a somatic shunt conductance for motoneurons, relegating it to a microelectrode impalement artifact. They are consistent with previous reports on the electrical compactness of motoneurons to steady state currents and voltages. However, the much higher value of C m (than the previously assumed 1 μF/cm2) implies much greater dendritic attenuation of fast synaptic potentials, and a much enhanced integrative response of motoneurons to synaptic potentials.
Specificity in the Interaction of HVA Ca2+Channel Types With Ca2+-Dependent AHPs and Firing Behavior in Neocortical Pyramidal Neurons
Authors: Pineda Juan Carlos , Waters Robert S. , Foehring Robert C.
Published: December 2017

Pineda, Juan Carlos, Roberts S. Waters, and Robert C. Foehring. Specificity in the interaction of HVA Ca2+channel types with Ca2+-dependent AHPs and firing behavior in neocortical pyramidal neurons. J. Neurophysiol. 79: 2522–2534, 1998. Intracellular recordings and organic and inorganic Ca2+channel blockers were used in a neocortical brain slice preparation to test whether high-voltage–activated (HVA) Ca2+channels are differentially coupled to Ca2+-dependent afterhyperpolarizations (AHPs) in sensorimotor neocortical pyramidal neurons. For the most part, spike repolarization was not Ca2+dependent in these cells, although the final phase of repolarization (after the fast AHP) was sensitive to block of N-type current. Between 30 and 60% of the medium afterhyperpolarization (mAHP) and between ∼80 and 90% of the slow AHP (sAHP) were Ca2+dependent. Based on the effects of specific organic Ca2+channel blockers (dihydropyridines, ω-conotoxin GVIA, ω-agatoxin IVA, and ω-conotoxin MVIIC), the sAHP is coupled to N-, P-, and Q-type currents. P-type currents were coupled to the mAHP. L-type current was not involved in the generation of either AHP but (with other HVA currents) contributes to the inward currents that regulate interspike intervals during repetitive firing. These data suggest different functional consequences for modulation of Ca2+current subtypes.
GABA-Receptor–Independent Dorsal Root Afferents Depolarization in the Neonatal Rat Spinal Cord
Authors: Kremer E. , Lev-Tov A.
Published: December 2017

Kremer, E. and A. Lev-Tov. GABA-receptor–independent dorsal root afferents depolarization in the neonatal rat spinal cord. J. Neurophysiol. 79: 2581–2592, 1998. Dorsal root afferent depolarization and antidromic firing were studied in isolated spinal cords of neonatal rats. Spontaneous firing accompanied by occasional bursts could be recorded from most dorsal roots in the majority of the cords. The afferent bursts were enhanced after elevation of the extracellular potassium concentration ([K+]e) by 1–2 mM. More substantial afferent bursts were produced when the cords were isolated with intact brain stems. Rhythmic afferent bursts could be recorded from dorsal roots in some of the cords during motor rhythm induced by bath-applied serotonin and N-methyl-d-aspartate (NMDA). Bilaterally synchronous afferent bursts were produced in pairs of dorsal roots after replacing the NaCl in the perfusate with sodium-2-hydroxyethansulfonate or after application of the γ-aminobutyric acid-A (GABAA) receptor antagonist bicuculline with or without serotonin (5-HT) and NMDA. Antidromic afferent bursts also could be elicited under these conditions by stimulation of adjacent dorsal roots, ventrolateral funiculus axons, or ventral white commissural (VWC) fibers. The antidromic bursts were superimposed on prolonged dorsal root potentials (DRPs) and accompanied by a prolonged increase in intraspinal afferent excitability. Surgical manipulations of the cord revealed that afferent firing in the presence of bicuculline persisted in the hemicords after hemisection and still was observed after removal of their ventral horns. Cutting the VWC throughout its length did not perturb the bilateral synchronicity of the discharge. These findings suggest that the activity of dorsal horn neurons is sufficient to produce the discharge and that the bilateral synchronicity can be maintained by cross connectivity that is relayed from side to side dorsal to the VWC. Antagonists of GABAB, 5-HT2/5-HT1C, or glutamate metabotropic group II and III receptors could not abolish afferent depolarization in the presence of bicuculline. Depolarization comparable in amplitude to DRPs, could be produced in tetrodotoxin-treated cords by elevation of [K+]e to the levels reported to develop in the neonatal rat spinal cord in response to dorsal root stimulation. A mechanism involving potassium transients produced by neuronal activity therefore is suggested to be the major cause of the GABA-independent afferent depolarization reported in our study. Possible implications of potassium transients in the developing and the adult mammalian spinal cord are discussed.
Rescue of α-SNS Sodium Channel Expression in Small Dorsal Root Ganglion Neurons After Axotomy by Nerve Growth Factor In Vivo
Authors: Dib-Hajj S. D. , Black J. A. , Cummins T. R. , Kenney A. M. , Kocsis J. D. , Waxman S. G.
Published: December 2017

Dib-Hajj, S. D., J. A. Black, T. R. Cummins, A. M. Kenney, J. D. Kocsis, and S. G. Waxman. Rescue of α-SNS sodium channel expression in small dorsal root ganglion neurons after axotomy by nerve growth factor in vivo. J. Neurophysiol. 79: 2668–2676, 1998. Small (18–25 μm diam) dorsal root ganglion (DRG) neurons are known to express high levels of tetrodotoxin-resistant (TTX-R) sodium current and the mRNA for the α-SNS sodium channel, which encodes a TTX-R channel when expressed in oocytes. These neurons also preferentially express the high affinity receptor for nerve growth factor (NGF), TrkA. Levels of TTX-R sodium current and of α-SNS mRNA are reduced in these cells after axotomy. To determine whether NGF participates in the regulation of TTX-R current and α-SNS mRNA in small DRG neurons in vivo, we axotomized small lumbar DRG neurons by sciatic nerve transection and administered NGF or Ringer solution to the proximal nerve stump using osmotic pumps. Ten to 12 days after pump implant, whole cell patch-clamp recording demonstrated that TTX-R current density was decreased in Ringer-treated axotomized neurons (154 ± 45 pA/pF; mean ± SE) compared with nonaxotomized control neurons (865 ± 123 pA/pF) and was restored partially toward control levels in NGF-treated axotomized neurons (465 ± 78 pA/pF). The V1/2for steady-state activation and inactivation of TTX-R currents were similar in control, Ringer- and NGF-treated axotomized neurons. Reverse transcription polymerase chain reaction revealed an upregulation of α-SNS mRNA levels in NGF-treated compared with Ringer-treated axotomized DRG. In situ hybridization showed that α-SNS mRNA levels were decreased significantly in small Ringer-treated axotomized DRG neurons in vivo and also in small DRG neurons that were dissociated and maintained in vitro, so as to correspond to the patch-clamp conditions. NGF-treated axotomized neurons had a significant increase in α-SNS mRNA expression, compared with Ringer-treated axotomized cells. These results show that the administration of exogenous NGF in vivo, to the proximal nerve stump of the transected sciatic nerve, results in an upregulation of TTX-R sodium current and of α-SNS mRNA levels in small DRG neurons. Retrogradely transported NGF thus appears to participate in the control of excitability in these cells via actions that include the regulation of sodium channel gene expression in vivo.
Cellular and Network Models for Intrathalamic Augmenting Responses During 10-Hz Stimulation
Authors: Bazhenov Maxim , Timofeev Igor , Steriade Mircea , Sejnowski Terrence J.
Published: December 2017

Bazhenov, Maxim, Igor Timofeev, Mircea Steriade, and Terrence J. Sejnowski. Cellular and network models for intrathalamic augmenting responses during 10-Hz stimulation. J. Neurophysiol. 79: 2730–2748, 1998. Repetitive stimulation of the thalamus at7–14 Hz evokes responses of increasing amplitude in the thalamus and the areas of the neocortex to which the stimulated foci project. Possible mechanisms underlying the thalamic augmenting responses during repetitive stimulation were investigated with computer models of interacting thalamocortical (TC) and thalamic reticular (RE) cells. The ionic currents in these cells were modeled with Hodgkin-Huxley type of kinetics, and the results of the model were compared with in vivo thalamic recordings from decorticated cats. The simplest network model demonstrating an augmenting response was a single pair of coupled RE and TC cells, in which RE-induced inhibitory postsynaptic potentials (IPSPs) in the TC cell led to progressive deinactivation of a low-threshold Ca2+ current. The augmenting responses in two reciprocally interacting chains of RE and TC cells depended also on γ-aminobutyric acid-B (GABAB) IPSPs. Lateral GABAA inhibition between identical RE cells, which weakened bursts in these cells, diminished GABAB IPSPs and delayed the augmenting response in TC cells. The results of these simulations show that the interplay between existing mechanisms in the thalamus explains the basic properties of the intrathalamic augmenting responses.
Shift of Visual Fixation Dependent On Background Illumination
Authors: Barash Shabtai , Melikyan Armenuhi , Sivakov Alexey , Tauber Michael
Published: December 2017

Barash, Shabtai, Armenuhi Melikyan, Alexey Sivakov, and Michael Tauber. Shift of visual fixation dependent on background illumination. J. Neurophysiol. 79: 2766–2781, 1998. Visual fixation, the act of maintaining the eyes directed toward a location of interest, is a highly skilled behavior necessary for high-level vision in primates. In spite of its significance, visual fixation is not well understood; it is not even clear what attributes of the visual input are used to control fixation. Here we show, in four Macaca fascicularis monkeys, that the position the eyes assume during fixation depends on the luminance of the background. Dark background yields fixation positions that are shifted upward with respect to the fixation positions obtained with a dimly illuminated, featureless background. This phenomenon was observed previously in a nutshell by Snodderly; here first we rigorously establish its existence by testing proper controls. We then study the properties of this upshift of the fixation position. We show that, although the size of the upshift varies between monkeys, for all monkeys the upshift is larger than the radius of the fovea. Hence, if the background is dim, the eyes are positioned during fixation so that the target does not fall on the fovea. The size of the upshift remains almost unchanged while the eyes fixate at different orbital positions; thus the upshift is not caused by orbital mechanics. The upshift clearly is present even at the first days of training, but with additional training in fixation with dark background, the upshift increases in size. The upshift rotates with the head. The upshift increases gradually with decreasing levels of background luminosity. Luminosity, not visual contrast, is indeed the primary variable determining the size of the upshift. The contribution of a unit area of the retina to the upshift decreases as inverse square root of distance from the target; therefore, it is the perifoveal region of the retina that mostly contributes to the upshift, while the far periphery has little influence. The upshift can be induced or be canceled in the midst of a fixation by changing the background illumination; hence, the upshift is indeed an attribute of the fixation control system. Finally, the fixation-upshift studied here is different from a previously reported upshift of the endpoints of memory-guided saccades with respect to their target locations. These two types of upshift add up to each other. In discussing the function of the upshift, we note a possible morphological analogue with the retinal rod distribution. The upshift moves the line of gaze to a point intermediate between the fovea and the “dorsal rod peak.” The upshift thus may improve visual acuity in scotopic conditions. The brain structure in which the upshift is generated must be involved in both ocular control and visual sensation. We consider several possibilities, of which we regard as the most likely the cerebellum and superior colliculus.
Spatiotemporal Structure of Cortical Activity: Properties and Behavioral Relevance
Authors: Prut Yifat , Vaadia Eilon , Bergman Hagai , Haalman Iris , Slovin Hamutal , Abeles Moshe
Published: December 2017

Prut, Yifat, Eilon Vaadia, Hagai Bergman, Iris Haalman, Hamutal Slovin, and Moshe Abeles. Spatiotemporal structure of cortical activity: properties and behavioral relevance. J. Neurophysiol. 79: 2857–2874, 1998. The study was designed to reveal occurrences of precise firing sequences (PFSs) in cortical activity and to test their behavioral relevance. Two monkeys were trained to perform a delayed-response paradigm and to open puzzle boxes. Extracellular activity was recorded from neurons in premotor and prefrontal areas with an array of six microelectrodes. An algorithm was developed to detect PFSs, defined as a set of three spikes and two intervals with a precision of ±1 ms repeating significantly more than expected by chance. The expected level of repetition was computed based on the firing rate and the pairwise correlation of the participating units, assuming a Poisson distribution of event counts. Accordingly, the search for PFSs was corrected for rate modulations. PFSs were found in 24/25 recording sessions. Most PFSs (76%) were composed of spikes of more than one unit but usually not more than two units (67%). The PFSs spanned hundreds of milliseconds, and the average interval between two events within the PFSs was 200 ms. No traces of periodic oscillations were found in the PFS intervals. The bins of the matrix that were defined as PFSs were isolated temporally: the spikes that generated PFSs were not associated with high-frequency bursts or rapid coherent rate fluctuations. A given PFS tended to be correlated with the animal's behavior. Furthermore, for 19% of the PFS pairs that shared the same unit composition, each member of the pair was associated with a different type of behavior. The PFSs often appeared in clusters that were associated with particular phases of the behavior. The firing rate of single units did not provide a full explanation for the timing and structure of these clusters. A reduced spike train (RST) was defined for each unit by taking all spikes of that unit that were part of any PFS. In 88% of the cases the degree of modulation of the RST was higher than that of the complete spike train. The results suggest that relevant information is carried by the fine temporal structure of cortical activity. A coding scheme that involves such temporal structures is rich and sufficiently flexible to facilitate a rapid organization of cortical neurons into functional groups. The results can be accounted for by the synfire chain model, which suggests that cortical activity is mediated by synchronous activation of neural groups in a reverberatory mode.
Properties of Horizontal Saccades Accompanied by Blinks
Authors: Rottach Klaus G. , Das Vallabh E. , Wohlgemuth Walter , Zivotofsky Ari Z. , Leigh R. John
Published: December 2017

Rottach, Klaus G., Vallabh E. Das, Walter Wohlgemuth, Ari Z. Zivotofsky, and R. John Leigh. Properties of horizontal saccades accompanied by blinks. J. Neurophysiol. 79: 2895–2902, 1998. Using the magnetic search coil technique to record eye and lid movements, we investigated the effect of voluntary blinks on horizontal saccades in five normal human subjects. The main goal of the study was to determine whether changes in the dynamics of saccades with blinks could be accounted for by a superposition of the eye movements induced by blinks as subjects fixated a stationary target and saccadic movements made without a blink. First, subjects made voluntary blinks as they fixed on stationary targets located straight ahead or 20° to the right or left. They then made saccades between two continuously visible targets 20 or 40° apart, while either attempting not to blink, or voluntarily blinking, with each saccade. During fixation of a target located straight ahead, blinks induced brief downward and nasalward deflections of eye position. When subjects looked at targets located at right or left 20°, similar initial movements were made by four of the subjects, but the amplitude of the adducted eye was reduced by 65% and was followed by a larger temporalward movement. Blinks caused substantial changes in the dynamic properties of saccades. For 20° saccades made with blinks, peak velocity and peak acceleration were decreased by ∼20% in all subjects compared with saccades made without blinks. Blinks caused the duration of 20° saccades to increase, on average, by 36%. On the other hand, blinks had only small effects on the gain of saccades. Blinks had little influence on the relative velocities of centrifugal versus centripetal saccades, and abducting versus adducting saccades. Three of five subjects showed a significantly increased incidence of dynamic overshoot in saccades accompanied by blinks, especially for 20° movements. Taken with other evidence, this finding suggests that saccadic omnipause neurons are inhibited by blinks, which have longer duration than the saccades that company them. In conclusion, the changes in dynamic properties of saccades brought about by blinks cannot be accounted for simply by a summation of gaze perturbations produced by blinks during fixation and saccadic eye movements made without blinks. Our findings, especially the appearance of dynamic overshoots, suggest that blinks affect the central programming of saccades. These effects of blinks need to be taken into account during studies of the dynamic properties of saccades.
Effect of Bicuculline on Thalamic Activity: A Direct Blockade of I AHP in Reticularis Neurons
Authors: Debarbieux Franck , Brunton Jennifer , Charpak Serge
Published: December 2017

Debarbieux, Franck, Jennifer Brunton, and Serge Charpak. Effect of bicuculline on thalamic activity: a direct blockade of I AHP in reticularis neurons. J. Neurophysiol. 79: 2911–2918, 1998. The thalamic reticular nucleus (RTN) is the major source of inhibitory contacts in the thalamus and thus plays an important role in regulating the excitability of the thalamocortical network. Inhibition occurs through GABAergic synapses on relay cells as well as through GABAergic synapses between reticularis neurons themselves. Here we report that the role and mechanisms of this inhibition, which frequently have been studied using N-methyl derivatives of the γ-aminobutyric acid-A (GABAA) receptor antagonist bicuculline, should be revisited. Using the whole cell patch-clamp technique in thalamic slices from young rats, we observed an enhancement by bicuculline methiodide, methobromide, and methochloride (collectively referred to as bicuculline-M; 5–60 μM) of the low-threshold calcium spike burst in RTN neurons that persisted in the presence of tetrodotoxin (1 μM) and was not reproduced in picrotoxin (100–300 μM). The effect did not involve activation of any GABA receptor subtype. Voltage-clamp recordings showed that bicuculline-M blocked the current underlying the low-threshold spike burst afterhyperpolarization (AHP), an effect that was mimicked by apamin (100 nM). Recordings from nucleated patches extracted from reticularis neurons demonstrated that this effect was not mediated by modulation of the release of an unidentified neurotransmitter but that bicuculline-M directly blocks small conductance (SK) channels. The AHP-blocking effect also was observed in other brain regions, demonstrating that although bicuculline-M is a potent GABAA receptor antagonist, it is of limited value in assessing GABAergic network interactions, which should be studied using picrotoxin or bicuculline-free base. However, bicuculline-M may provide a useful tool for developing nonpeptide antagonists of SK channels.
Calcium-Sensitive Calcium Influx in Photoreceptor Inner Segments
Authors: Baldridge William H. , Kurennyi Dmitri E. , Barnes Steven
Published: December 2017

Baldridge, William H., Dmitri E. Kurennyi, and Steven Barnes. Calcium-sensitive calcium influx in photoreceptor inner segments. J. Neurophysiol. 79: 3012–3018, 1998. The effect of external calcium concentration ([Ca2+]o) on membrane potential–dependent calcium signals in isolated tiger salamander rod and cone photoreceptor inner segments was investigated with patch-clamp and calcium imaging techniques. Mild depolarizations led to increases in intracellular Ca2+levels ([Ca2+]i) that were smaller when [Ca2+]owas elevated to 10 mM than when it was 3 mM, even though maximum Ca2+conductance increased 30% with the increase in [Ca2+]o. When external calcium was lowered to 1 mM [Ca2+]o, maximum Ca2+conductance was reduced, as expected, but the mild depolarization-induced increase in [Ca2+]iwas larger than in 3 mM [Ca2+]o. In contrast, when photoreceptors were strongly depolarized, the increase in [Ca2+]iwas less when [Ca2+]owas reduced. An explanation for these observations comes from an assessment of Ca2+channel gating in voltage-clamped photoreceptors under changing conditions of [Ca2+]o. Although Ca2+conductance increased with increasing [Ca2+]o, surface charge effects dictated large shifts in the voltage dependence of Ca2+channel gating. Relative to the control condition (3 mM [Ca2+]o), 10 mM [Ca2+]oshifted Ca2+channel activation 8 mV positive, reducing channel open probability over a broad range of potentials. Reducing [Ca2+]oto 1 mM reduced Ca2+conductance but shifted Ca2+channel activation negative by 6 mV. Thus the intracellular calcium signals reflect a balance between competing changes in gating and permeation of Ca2+channels mediated by [Ca2+]o. In mildly depolarized cells, the [Ca2+]o-induced changes in Ca2+channel activation proved stronger than the [Ca2+]o-induced changes in conductance. In response to the larger depolarizations caused by 80 mM [K+]o, the opposite is true, with conductance changes dominating the effects on channel activation.
Ictal Epileptiform Activity in the CA3 Region of Hippocampal Slices Produced by Pilocarpine
Authors: Rutecki Paul A. , Yang Yili
Published: December 2017

Rutecki, Paul A. and Yili Yang. Ictal epileptiform activity in the CA3 region of hippocampal slices produced by pilocarpine. J. Neurophysiol. 79: 3019–3029, 1998. Pilocarpine, a muscarinic agonist, produces status epilepticus that is associated with the later development of chronic recurrent seizures. When applied to rat hippocampal slices, pilocarpine (10 μM) produced brief (<200 ms) epileptiform discharges that resembled interictal activity that occurs between seizures, as well as more prolonged synchronous neuronal activation that lasted seconds (3–20 s), and was comparable to ictal or seizures-like discharges. We assessed the factors that favored ictal patterns of activity and determined the biophysical properties of the ictal discharge. The probability of observing ictal discharges was increased when extracellular potassium ([K+]o) was increased from 5 to 7.5 mM. Raising [K+]o to 10 mM resulted in loss of ictal patterns and, in 20 of 34 slices, desynchronization of epileptiform activity. Making the artificial cerebrospinal fluid (ACSF) hyposmotic favored ictal discharges at 5 mM [K+]o, but shifted 7.5 mM [K+]o ACSF patterns to interictal discharges or desynchronized activity. Conversely, increasing osmolality suppressed ictal patterns. The pilocarpine-induced ictal discharges were blocked by atropine (1 μM, n = 5), a muscarinic antagonist, and pirenzepine (1 μM, n = 6), a selective M1 receptor antagonist. Kainate/α-amino-3-hydroxy-5-methyl-4-isoxazoleproprionic acid receptor blockade stopped all epileptiform activity ( n = 8). The N-methyl-d-aspartate antagonist d,l-2-amino-5-phosphonovaleric acid (100 μM, n = 34) did not change the pattern of epileptiform activity but significantly increased the rate of interictal discharges and prolonged the duration of ictal discharges. The ictal discharge was characterized intracellularly by a depolarization that was associated with action potential generation and persisted as a membrane oscillation of 4–10 Hz. The ictal oscillations reversed in polarity at −22.7 ± 2.2 mV ( n = 11) with current-clamp recordings and −20.9 ± 3.1 mV ( n = 7) with voltage-clamp recordings. The reversal potential of the ictal discharge in the presence of the γ-aminobutyric acid-A blocker bicuculline (10 μM, n = 6) was −2.2 ± 2.6 mV and was significantly different from that measured without bicuculline. Bicuculline added to 7.5 mM [K+]o and 10 μM pilocarpine did not cause epileptiform activity to change pattern but significantly increased the rate of interictal discharges and prolonged the ictal discharge duration. Both synaptic and nonsynaptic mechanisms are important for the generation of ictal patterns of epileptiform activity. Although the synchronous epileptiform activity produced by pilocarpine required fast glutamate-mediated synaptic transmission, the transition from an interictal to ictal pattern of activity depended on [K+]o and could be influenced by extracellular space.
Single Olivocochlear Neurons in the Guinea Pig. II. Response Plasticity Due to Noise Conditioning
Authors: Brown M. C. , Kujawa S. G. , Liberman M. C.
Published: December 2017

Brown, M. C, S. G. Kujawa, and M. C. Liberman. Single olivocochlear neurons in the guinea pig. II. Response plasticity due to noise conditioning. J. Neurophysiol. 79: 3088–3097, 1998. Previous studies have shown that daily, moderate-level sound exposure, or conditioning, can reduce injury from a subsequent high-level noise exposure. We tested the hypothesis that this conditioning produces an increased activity in the olivocochlear efferent reflex, a reflex known to provide protection to the cochlea. Guinea pigs were conditioned by a 10-day intermittent exposure to 2–4 kHz noise at 85 dB sound pressure level. This conditioning is known to reduce damage from a subsequent high-level exposure to the same noise band. Responses to monaural and binaural sound were recorded from single medial olivocochlear (MOC) efferent neurons, and data from conditioned animals were compared with those obtained from unexposed controls. MOC neurons were classified by their response to noise bursts in the ipsilateral or contralateral ears as ipsi units, contra units, or either-ear units. There were no significant differences in the distributions of these unit types between control and conditioned animals. There were also no differences in other responses to monaural stimuli, including the distribution of characteristic frequencies (CFs), the sharpness of tuning, or thresholds at the CF. For binaural sound at high levels, particularly relevant to sound-evoked activation of the MOC reflex during acoustic overstimulation, the firing rates of MOC neurons with CFs just above the conditioning band showed slight (but statistically significant) elevations relative to control animals. Frequency regions just above the conditioning band also demonstrated maximum conditioning-related protection; thus protection could be due, in part, to long-term changes in MOC discharge rates. For binaural sound at low levels, MOC firing rates in conditioned animals also were increased significantly relative to controls. Again, increases were largest for neurons with CFs just above the conditioning band. For equivalent monaural sound, rates were not significantly increased; thus, conditioning appears to increase binaural facilitation by opposite-ear sound. These data indicate that MOC neurons show long-term plasticity in acoustic responsiveness that is dependent on their acoustic history.
Anatomy and Physiology of Principal Cells of the Medial Nucleus of the Trapezoid Body (MNTB) of the Cat
Authors: Smith Philip H. , Joris Philip X. , Yin Tom C. T.
Published: December 2017

Smith, Philip H., Philip X. Joris, and Tom C. T. Yin. Anatomy and physiology of principal cells of the medial nucleus of the trapezoid body (MNTB) of the cat. J. Neurophysiol. 79: 3127–3142, 1998. We have recorded from principal cells of the medial nucleus of the trapezoid body (MNTB) in the cat's superior olivary complex using either glass micropipettes filled with Neurobiotin or horseradish peroxidase for intracellular recording and subsequent labeling or extracellular metal microelectrodes relying on prepotentials and electrode location. Labeled principal cells had cell bodies that usually gave rise to one or two primary dendrites, which branched profusely in the vicinity of the cell. At the electron microscopic (EM) level, there was a dense synaptic terminal distribution on the cell body and proximal dendrites. Up to half the measured cell surface could be covered with excitatory terminals, whereas inhibitory terminals consistently covered about one-fifth. The distal dendrites were very sparsely innervated. The thick myelinated axon originated from the cell body and innervated nuclei exclusively in the ipsilateral auditory brain stem. These include the lateral superior olive (LSO), ventral nucleus of the lateral lemniscus, medial superior olive, dorsomedial and ventromedial periolivary nuclei, and the MNTB itself. At the EM level the myelinated collaterals gave rise to terminals that contained nonround vesicles and, in the LSO, were seen terminating on cell bodies and primary dendrites. Responses of MNTB cells were similar to their primary excitatory input, the globular bushy cell (GBC), in a number of ways. The spontaneous spike rate of MNTB cells with low characteristic frequencies (CFs) was low, whereas it tended to be higher for higher CF units. In response to short tones, a low frequency MNTB cell showed enhanced phase-locking abilities, relative to auditory nerve fibers. For cells with CFs >1 kHz, the short tone response often resembled the primary-like with notch response seen in many globular bushy cells, with a well-timed onset component. Exceptions to and variations of this standard response were also noted. When compared with GBCs with comparable CFs, the latency of the MNTB cell response was delayed slightly, as would be expected given the synapse interposed between the two cell types. Our data thus confirm that, in the cat, the MNTB receives and converts synaptic inputs from globular bushy cells into a reasonably accurate reproduction of the bushy cell spike response. This MNTB cell output then becomes an important inhibitory input to a number of ipsilateral auditory brain stem nuclei.
Inhibitory Glutamate Receptor Channels in Cultured Lobster Stomatogastric Neurons
Authors: Cleland Thomas A. , Selverston Allen I.
Published: December 2017

Cleland, Thomas A. and Allen I. Selverston. Inhibitory glutamate receptor channels in cultured lobster stomatogastric neurons. J. Neurophysiol. 79: 3189–3196, 1998. Inhibitory glutamate receptor channels (IGluRs) are ligand-gated ionotropic receptors related to ionotropic γ-aminobutyric acid (GABA) and glycine receptors and expressed in neural and muscular tissues. In the crustacean stomatogastric ganglion (STG), IGluRs mediate recurrent synaptic inhibition central to the rhythmogenic capabilities of its embedded neural circuits. IGluRs expressed in cultured spiny lobster STG neurons exhibited an EC50of 1.2 mM and a Hill coefficient of 1.4. They were neither cross-activated nor cross-desensitized by GABA, although a distinct GABA-gated chloride current was observed. Glycine did not evoke any current from STG neurons. The IGluR was weakly blocked by the chloride channel blocker furosemide and the excitatory glutamate receptor antagonist6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), but was not inhibited by bicuculline methiodide, strychnine, kynurenic acid,γ-d-glutamylglycine, or aspartate. Outside-out patch-clamp recordings were analyzed using the mean-variance histogram technique. Under excised-patch conditions, the receptor exhibited only a single open state with an estimated unitary conductance of 80 ± 8.6 (SD) pS. The distinct GABA receptor also displayed a single open state with a conductance of 72 ± 10 pS.
Predictive Reward Signal of Dopamine Neurons
Authors: Schultz Wolfram
Published: December 2017

Schultz, Wolfram. Predictive reward signal of dopamine neurons. J. Neurophysiol. 80: 1–27, 1998. The effects of lesions, receptor blocking, electrical self-stimulation, and drugs of abuse suggest that midbrain dopamine systems are involved in processing reward information and learning approach behavior. Most dopamine neurons show phasic activations after primary liquid and food rewards and conditioned, reward-predicting visual and auditory stimuli. They show biphasic, activation-depression responses after stimuli that resemble reward-predicting stimuli or are novel or particularly salient. However, only few phasic activations follow aversive stimuli. Thus dopamine neurons label environmental stimuli with appetitive value, predict and detect rewards and signal alerting and motivating events. By failing to discriminate between different rewards, dopamine neurons appear to emit an alerting message about the surprising presence or absence of rewards. All responses to rewards and reward-predicting stimuli depend on event predictability. Dopamine neurons are activated by rewarding events that are better than predicted, remain uninfluenced by events that are as good as predicted, and are depressed by events that are worse than predicted. By signaling rewards according to a prediction error, dopamine responses have the formal characteristics of a teaching signal postulated by reinforcement learning theories. Dopamine responses transfer during learning from primary rewards to reward-predicting stimuli. This may contribute to neuronal mechanisms underlying the retrograde action of rewards, one of the main puzzles in reinforcement learning. The impulse response releases a short pulse of dopamine onto many dendrites, thus broadcasting a rather global reinforcement signal to postsynaptic neurons. This signal may improve approach behavior by providing advance reward information before the behavior occurs, and may contribute to learning by modifying synaptic transmission. The dopamine reward signal is supplemented by activity in neurons in striatum, frontal cortex, and amygdala, which process specific reward information but do not emit a global reward prediction error signal. A cooperation between the different reward signals may assure the use of specific rewards for selectively reinforcing behaviors. Among the other projection systems, noradrenaline neurons predominantly serve attentional mechanisms and nucleus basalis neurons code rewards heterogeneously. Cerebellar climbing fibers signal errors in motor performance or errors in the prediction of aversive events to cerebellar Purkinje cells. Most deficits following dopamine-depleting lesions are not easily explained by a defective reward signal but may reflect the absence of a general enabling function of tonic levels of extracellular dopamine. Thus dopamine systems may have two functions, the phasic transmission of reward information and the tonic enabling of postsynaptic neurons.
Substance P Enhances NMDA Channel Function in Hippocampal Dentate Gyrus Granule Cells
Authors: Lieberman David N. , Mody Istvan
Published: December 2017

Lieberman, David N. and Istvan Mody. Substance P enhances NMDA channel function in hippocampal dentate gyrus granule cells. J. Neurophysiol. 80: 113–119, 1998. Substance P (SP)–containing afferents and the NK-1 tachykinin receptor to which SP binds are present in the dentate gyrus of the rat; however, direct actions of SP on principal cells have not been demonstrated in this brain region. We have examined the effect of SP on N-methyl-d-aspartate (NMDA) channels from acutely isolated dentate gyrus granule cells of adult rat hippocampus to assess the ability of SP to regulate glutamatergic input. SP produces a robust enhancement of single NMDA channel function that is mimicked by the NK-1–selective agonist Sar9, Met(O2)11-SP. The SP-induced prolongation of NMDA channel openings is prevented by the selective NK-1 receptor antagonist (+)-(2 S,3 S)-3-(2-methoxybenzylamino)-2-phenylpiperidine (CP-99,994). Calcium influx or activation of protein kinase C were not required for the SP-induced increase in NMDA channel open durations. The dramatic enhancement of excitatory amino acid–mediated excitability by SP places this neuropeptide in a key position to gate activation of hippocampal network activity.
Physiological Signs of the Activation of Bag2 and Chain Intrafusal Muscle Fibers of Gastrocnemius Muscle Spindles in the Cat
Authors: Taylor A. , Ellaway P. H. , Durbaba R.
Published: December 2017

Taylor, A., P. H. Ellaway, and R. Durbaba. Physiological signs of the activation of bag2 and chain intrafusal muscle fibers of gastrocnemius muscle spindles in the cat. J. Neurophysiol. 80: 130–142, 1998. A method is described for identifying the effect of single gamma static (γs) axons on bag2 or chain intrafusal fibers using random (Poisson-distributed) stimuli. The cross-correlogram of the stimuli with the firing of spindle primary afferents took one of three forms. A large, simple, brief response was taken to indicate pure chain fiber activation and a small, prolonged response to indicate pure bag2 activation. A compound response with brief and prolonged components was taken to be a sign of mixed innervation. The correlogram components could be well fitted with lognormal curves. They could also be transformed into curves of gain as a function of frequency, which were convenient for estimating the strength of the effects. In 68 effects of γs axons on Ia afferents, 16 were pure chain, 17 pure bag2, and 35 mixed. This distribution was significantly different ( P < 0.05) from that expected from chance nonspecific innervation of chain and bag2 fibers. Making use of the estimates of the strength of chain and bag2 effects derived from the gain curves, the classification was modified by treating mixed responses that had one effect more than five times stronger than the other as belonging to the dominant type. The distribution was then as follows: chain 16, bag2 28, and mixed 24. This differed very significantly from the prediction of chance distribution ( P < 0.001). This evidence for some degree of specific innervation of chain and bag2 fibers is discussed in relation to previous work and with regard to the ways in which the two fiber types might be used in natural movements.