Trophic and Contact Conditions Modulate Synapse Formation Between Identified NeuronsMagoski, Neil S.; Bulloch, Andrew G. M.
doi: N/Apmid: 9636127
Abstract Magoski, Neil S. and Andrew G. M. Bulloch. Trophic and contact conditions modulate synapse formation between identified neurons. J. Neurophysiol. 79: 3279–3283, 1998. We tested the ability of an identified interneuron from the mollusk, Lymnaea stagnalis , to reestablish appropriate synapses in vitro. In the CNS, the giant dopaminergic neuron, designated as right pedal dorsal one (RPeD1), makes an excitatory, chemical synapse with a pair of essentially identical postsynaptic cells known as visceral dorsal two and three (VD2/3). When the somata of the pre- and postsynaptic neurons were juxtaposed and cultured in vitro in defined medium, i.e., a soma-soma synapse, only an inappropriate electrical synapse was observed. The postsynaptic cell still responded to applied dopamine, the presynaptic transmitter, indicating that the lack of chemical synapse formation was not due to lack of dopamine receptors. When the somata were cultured apart in conditioned medium (medium previously incubated with Lymnaea CNS, thereby deriving trophic factors), the cells exhibited overlapping neurite outgrowth that resulted in an appropriate excitatory, chemical synapse from RPeD1 to VD2/3. On the other hand, when the cell pair was cultured in a soma-soma configuration, but in conditioned medium, a mixed chemical-electrical synapse was observed. Because conditioned medium could partially overcome the limitations of the soma-soma configuration and initiate chemical synapse formation, this data suggests that conditioned medium contains a factor(s) that supports synaptogenesis. Footnotes Address for reprint requests: A.G.M. Bulloch, Dept. of Physiology and Biophysics, University of Calgary, 3330 Hospital Drive N.W., Calgary, Alberta T2N 4N1, Canada. Present address of N. S. Magoski: Yale University, Dept. of Pharmacology, School of Medicine, New Haven, CT 06520.
Anatomy and Physiology of Principal Cells of the Medial Nucleus of the Trapezoid Body (MNTB) of the CatSmith, Philip H.; Joris, Philip X.; Yin, Tom C. T.
doi: N/Apmid: 9636113
Abstract 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. Footnotes Address for reprint requests: Philip Smith, Dept. of Anatomy, University of Wisconsin Medical School, Madison, WI 53706.
Properties of Horizontal Saccades Accompanied by BlinksRottach, Klaus G.; Das, Vallabh E.; Wohlgemuth, Walter; Zivotofsky, Ari Z.; Leigh, R. John
doi: N/Apmid: 9636095
Abstract 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. Footnotes Address for reprint requests: R. J. Leigh, Dept. of Neurology, University Hospitals, 11100 Euclid Ave., Cleveland, OH 44106-5000.
Inhibitory Glutamate Receptor Channels in Cultured Lobster Stomatogastric NeuronsCleland, Thomas A.; Selverston, Allen I.
doi: N/Apmid: 9636118
Abstract 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 EC 50 of 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. Footnotes Present address and address for reprint requests: T. A. Cleland, Dept. of Neuroscience, Tufts University Medical School, 136 Harrison Ave., Boston, MA 02111. Copyright © 1998 the American Physiological Society
Effect of Bicuculline on Thalamic Activity: A Direct Blockade of I AHP in Reticularis NeuronsDebarbieux, Franck; Brunton, Jennifer; Charpak, Serge
doi: N/Apmid: 9636097
Abstract 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 (GABA A ) 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 GABA A 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. Footnotes Address for reprint requests: S. Charpak, Laboratoire de Physiologie, ESPCI, 10 rue Vauquelin, 75005 Paris, France.
Brain Stem Omnipause Neurons and the Control of CombinedEye-Head Gaze Saccades in the Alert CatParé, Martin; Guitton, Daniel
doi: N/Apmid: 9636108
Abstract Paré, Martin and Daniel Guitton. Brain stem omnipause neurons and the control of combined eye-head gaze saccades in the alert cat. J. Neurophysiol. 79: 3060–3076, 1998. When the head is unrestrained, rapid displacements of the visual axis—gaze shifts (eye-re-space)—are made by coordinated movements of the eyes (eye-re-head) and head (head-re-space). To address the problem of the neural control of gaze shifts, we studied and contrasted the discharges of omnipause neurons (OPNs) during a variety of combined eye-head gaze shifts and head-fixed eye saccades executed by alert cats. OPNs discharged tonically during intersaccadic intervals and at a reduced level during slow perisaccadic gaze movements sometimes accompanying saccades. Their activity ceased for the duration of the saccadic gaze shifts the animal executed, either by head-fixed eye saccades alone or by combined eye-head movements. This was true for all types of gaze shifts studied: active movements to visual targets; passive movements induced by whole-body rotation or by head rotation about stationary body; and electrically evoked movements by stimulation of the caudal part of the superior colliculus (SC), a central structure for gaze control. For combined eye-head gaze shifts, the OPN pause was therefore not correlated to the eye-in-head trajectory. For instance, in active gaze movements, the end of the pause was better correlated with the gaze end than with either the eye saccade end or the time of eye counterrotation. The hypothesis that cat OPNs participate in controlling gaze shifts is supported by these results, and also by the observation that the movements of both the eyes and the head were transiently interrupted by stimulation of OPNs during gaze shifts. However, we found that the OPN pause could be dissociated from the gaze-motor-error signal producing the gaze shift. First, OPNs resumed discharging when perturbation of head motion briefly interrupted a gaze shift before its intended amplitude was attained. Second, stimulation of caudal SC sites in head-free cat elicited large head-free gaze shifts consistent with the creation of a large gaze-motor-error signal. However, stimulation of the same sites in head-fixed cat produced small “goal-directed” eye saccades, and OPNs paused only for the duration of the latter; neither a pause nor an eye movement occurred when the same stimulation was applied with the eyes at the goal location. We conclude that OPNs can be controlled by neither a simple eye control system nor an absolute gaze control system. Our data cannot be accounted for by existing models describing the control of combined eye-head gaze shifts and therefore put new constraints on future models, which will have to incorporate all the various signals that act synergistically to control gaze shifts. Footnotes Present address and address for reprint requests: M. Paré, Laboratory of Sensorimotor Research, National Eye Institute, National Institutes of Health, Bethesda, MD 20892. Copyright © 1998 the American Physiological Society
Cooperative Mechanisms Between Leg Joints of Carausius morosusII. Motor Neuron Activity and Influence of ConditionalBursting InterneuronBrunn, Dennis E.; Heuer, Antje
doi: N/Apmid: 9636101
Abstract Brunn, Dennis E. and Antje Heuer. Cooperative mechanisms between leg joints of Carausius morosus. II. Motor neuron activity and influence of conditional bursting interneuron. J. Neurophysiol. 79: 2977–2985, 1998. The activity of the motor neuron pools of the protractor coxae muscle and of the thoracic part of the depressor trochanteris muscle during forward walking in the stick insect was investigated, and a spiking local interneuron, able to produce “endogenous bursting” and innervating both motor neuron pools, was identified. Extracellular recordings of the motor neurons innervating the protractor and the thoracic depressor of front, middle, and rear legs, respectively, were made with oil-hook electrodes from the peripheral nerves nl2c and nl4a while the animals were walking on a styrofoam treadwheel. The corresponding leg movements were registered and phase histograms were created with the software Spike2. Intracellular recordings were made in the neuropile of the metathoracic ganglion with glass electrodes filled with the dye Lucifer yellow. In all three legs measured (front, middle, and rear), both motor neuron pools increased their activity during the swing movement. The increase in the activity of the protractor motor neurons started at the end of the stance ∼100 ms before reaching the posterior extreme position (PEP), and the activity of the large-sized depressor motor neurons increased as soon as the tarsus was lifted at the PEP. A local spiking interneuron was identified that excited both motor neuron pools. In 4 of 23 recordings the interneuron started to burst in synchrony with protractor and thoracic depressor motor neurons. During bursting a depolarizing stimulus reinforced and a hyperpolarizing stimulus inhibited the activity of both motor neuron pools. Thus we conclude that the thoracic part of the depressor trochanteris muscle might be a component of the neuromuscular system that shapes the swing movement. The two proximal joints, subcoxal and coxa-trochanter, connected mechanically via the thoracic part of the depressor trochanteris muscle, are also connected neurally by segmental and intersegmental spiking interneurons (this paper) and by nonspiking local interneurons (see companion paper). Footnotes Address reprint requests to D. E. Brunn.
Pointing Errors Reflect Biases in the Perception of the InitialHand PositionVindras, Philippe; Desmurget, Michel; Prablanc, Claude; Viviani, Paolo
doi: N/Apmid: 9636129
Abstract Vindras, Philippe, Michel Desmurget, Claude Prablanc, and Paolo Viviani. Pointing errors reflect biases in the perception of the initial hand position. J. Neurophysiol. 79: 3290–3294, 1998. By comparing the visuomotor performance of 10 adult, normal subjects in three tasks, we investigated whether errors in pointing movements reflect biased estimations of the hand starting position. In a manual pointing task with no visual feedback, subjects aimed at 48 targets spaced regularly around two starting positions. Nine subjects exhibited a similar pattern of systematic errors across targets, i.e., a parallel shift of the end points that accounted, on average, for 49% of the total variability. The direction of the shift depended on the starting location. Systematic errors decreased dramatically in the second condition where subjects were allowed to see their hand before movement onset. The third task was to use a joystick held by the left hand to estimate the location of their (unseen) right hand. The systematic perceptual errors in this condition were found to be highly correlated with the motor errors in the first condition. The results support the following conclusions. 1 ) Kinesthetic estimation of hand position may be consistently biased. Some of the mechanisms responsible for these biases are always active, irrespective of whether position is estimated overtly (e.g., with a matching paradigm), or covertly as part of the motor planning for aimed movements. 2 ) Pointing errors reflect to a significant extent the erroneous estimation of initial hand position. This suggests that aimed hand movements are planned vectorially, i.e., in terms of distance and direction, rather than in terms of absolute position in space. Footnotes Address for reprint requests: P. Vindras, Université de Genève, Faculté de Psychologie et des Sciences de l'Education, Route de Drize 9, 1227 Carouge, Switzerland.
Ionic Basis for Serotonin-Induced Bistable Membrane Properties in Guinea Pig Trigeminal MotoneuronsHsiao, Chie-Fang; Negro, Christopher A. Del; Trueblood, Peggy R.; Chandler, Scott H.
doi: N/Apmid: 9636091
Abstract Hsiao, Chie-Fang, Christopher A. Del Negro, Peggy R. Trueblood, and Scott H. Chandler. Ionic basis for serotonin-induced bistable membrane properties in guinea pig trigeminal motoneurons. J. Neurophysiol. 79: 2847–2856, 1998. Intracellular recordings and pharmacological manipulations were employed to investigate the ionic basis for serotonin-induced bistable membrane behaviors in guinea pig trigeminal motoneurons (TMNs). In voltage clamp, 10 μM serotonin (5-HT) induced a region of negative slope resistance (NSR) in the steady-state current-voltage ( I-V ) relationship at potentials less negative than −58 mV, creating the necessary conditions for membrane bistability. The contributions of sustained Na + and Ca 2+ currents to the generation of the NSR were investigated using specific ion channel antagonists and agonists. The NSR was eliminated by the L-type Ca 2+ channel antagonist nifedipine (5–10 μM), indicating the contribution of L channels. In nifedipine, inward rectification was present in the I-V relationship in a similar voltage range (greater than −58 mV). This region was subsequently linearized by tetrodotoxin (TTX), indicating the presence of a persistent Na + current. When the 5-HT–induced NSR was eliminated by perfusion in low Ca 2+ solution (0.4 mM), it was restored by the Na + channel agonist veratridine (10 μM). Commensurate with bistability, in current clamp during bath application of 5-HT, plateau potentials were elicited by transient depolarizing or hyperpolarizing stimuli. Plateau potentials evoked by depolarization were observed under control and TTX conditions, but were blocked by nifedipine, suggesting the participation of an L-type Ca 2+ current. Plateau potentials initiated after release from hyperpolarization (anode break) were blocked by 300 μM Ni 2+ , suggesting the responses relied on deinactivation of a T-type Ca 2+ current. Conditional bursting was also observed in 5-HT. Nifedipine or low Ca 2+ solutions blocked bursting, and the L-channel agonist Bay K 8644 (10 μM) extended the duration of individual bursts, demonstrating the role of L-type Ca 2+ currents. Interestingly, when bursting was blocked by nifedipine or low Ca 2+ , it could be restored by veratridine application via enhancement of the persistent Na + current. We conclude that bistable membrane behaviors in TMNs are mediated by L-type Ca 2+ and persistent Na + currents. 5-HT is associated with enhancement of TMN activity during oral-motor activity; the induction of bistable membrane properties by 5-HT represents a cellular mechanism for this enhancement. Footnotes Address for reprint requests: S. H. Chandler, Dept. of Physiological Science, 2851 Slichter Hall, Los Angeles, CA 90095-1568.