Journal of Neurophysiology

Mott, D. D.; Xie, C. W.; Wilson, W. A.; Swartzwelder, H. S.; Lewis, D. V.

doi: N/Apmid: 8096539

Abstract 1. Activity-dependent depression (fading) of polysynaptic inhibition and the effects of this disinhibition on signal transmission were studied in the dentate gyrus of the rat hippocampal slice with the use of intracellular and extracellular recordings. 2. Polysynaptic inhibitory postsynaptic potentials/currents (IPSP/Cs) were evoked in dentate granule cells by stimulation of mossy fibers in stratum lucidum of area CA3b/c. These mossy fiber-evoked IPSP/Cs consisted of an early GABAA receptor-mediated component (IPSP/CA) and a late GABAB receptor-mediated component (IPSP/CB). 3. When paired stimuli were delivered 200 ms apart under voltage clamp, the amplitude of the IPSCA and IPSCB evoked by the second stimulus was reduced by 37.0 +/- 4.0 and 61.6 +/- 7.8% (mean +/- SE), respectively. Paired-pulse depression of both IPSCA and IPSCB was greatest at interstimulus intervals of 100-400 ms with a maximal effect when stimuli were delivered 200 ms apart. 4. (+/-) Baclofen, a GABAB receptor agonist, suppressed both components of the mossy fiber-evoked IPSP in a concentration-dependent fashion. At a concentration that only partially suppressed the initial IPSP, baclofen occluded paired-pulse depression of IPSPA. In addition, paired-pulse depression of IPSPA was blocked in a concentration-dependent fashion by 2-hydroxy-saclofen (10-400 microM), a GABAB receptor antagonist. 5. The contribution of the IPSPB conductance increase to paired-pulse depression of IPSPA was evaluated. Paired-pulse depression of IPSPA was significantly greater than was the depression of the response to a current pulse delivered 200 ms after the mossy fiber stimulus. In addition, injection of granule cells with GTP gamma S, a nonhydrolyzable guanosine triphosphate (GTP) analogue, occluded both IPSPB as well as the effects of baclofen on the granule cell membrane by activating G proteins but did not reduce paired-pulse depression of IPSPA or suppression of IPSPA by baclofen. Finally, examination of the first and second IPSCA evoked by paired stimuli 200 ms apart revealed no significant differences in response kinetics. Taken together, these results indicate that postsynaptic GABAB receptors on the granule cells are not responsible for paired-pulse depression of IPSPA. 6. Monosynaptic IPSPs were evoked by direct stimulation of inhibitory neurons in the inner molecular layer of the dentate gyrus during pharmacological blockade of excitatory transmission with D(-)-2-amino-5-phosphonovaleric acid (D-APV), an N-methyl-D-aspartate (NMDA) receptor antagonist and 6,7-dinitroquinoxaline-2,3-dione (DNQX), a non-NMDA glutamate receptor antagonist.(ABSTRACT TRUNCATED AT 400 WORDS) Copyright © 1993 the American Physiological Society

Jackson, M. B.

doi: N/Apmid: 8385189

Abstract 1. Patch-clamp techniques were used to study the morphology and electrotonic properties of the terminal arborizations of the posterior pituitary. 2. Neurobiotin-labeling experiments revealed axons and swellings connected to the structure that was patch clamped. The large swellings were en passant and situated along axons in a topological arrangement identical to that of the small varicosities. Axons had many varicosities and few branches, reflecting a predominant architectural motif of beads on a string rather than berries on a bush. 3. Cable theory was used to analyze passive current transients produced by voltage steps under whole-cell clamp. Most charging transients were not consistent with an equivalent cylinder representation as posited by the Rall model for a motoneuron. A few charging transients were consistent with the Rall model and provided estimates for basic membrane and cable properties. 4. Some of the charging transients that violated predictions of the Rall model were consistent with an alternative model, in which the patch-clamped swelling was assumed to be coupled to another swelling by a segment of axon. This model was called the Dumbbell model, and it, together with the neurobiotin-labeling experiments, indicated that a significant number of large swellings were less than one length constant away from another large swelling. 5. Large swellings can have diameters approximately 30 times larger than the diameters of the connecting axons. These swellings lie along the axon such that action potentials must propagate through them to spread excitation through the entire terminal arborization. These large swellings could be sites where action-potential propagation is more likely to fail. 6. The information presented here about neurohypophysial nerve terminals should be useful in further investigations of how terminal arborization geometry and membrane properties influence neurosecretion and synaptic transmission. Copyright © 1993 the American Physiological Society

Meech, R. W.; Mackie, G. O.

doi: N/Apmid: 7681867

Abstract 1. In the motor system of the jellyfish, Aglantha digitale, there are eight giant axons connected by chemical synapses to a muscle epithelium. The simplicity of this structure makes it possible to assess the contribution of different ion conductances in the axon membrane to the two forms of swimming that provide the behavioral output of the system. In situ recordings from large clusters of ion channels provide a means of studying these membrane conductances in isolation so that the features that permit them to perform their behavioral function may be identified. 2. In Aglantha motor axons, low-amplitude, low-threshold spikes are associated with slow swimming, whereas escape swimming depends on a higher-threshold, overshooting action potential. The action potential was abolished by a sodium-free (choline-containing) bathing medium but was resistant to tetrodotoxin (0.09 mM; 3 x 10(-5) g/ml). It was prolonged by tetraethylammonium (TEA) ions (50 mM) but little affected by changes in holding potential in the range of -51 to -82 mV. The low-threshold spikes were unaffected by sodium-free saline containing TEA (30 mM). They were inactivated by holding the membrane potential at -51 mV. Average axon resting potentials were -63 +/- 6 (SD) mV (n = 17). 3. Shortened axons studied with the two-electrode voltage-clamp technique had a transient inward current with a low threshold for activation (about -60 mV). The inward current was fully inactivated at -51 mV; it was present in sodium-free saline and abolished by Mg2+ (120 mM) just like the low-threshold spike. 4. Calcium-dependent low-threshold spikes and sodium action potentials coexist in the same axons but may be elicited separately because an outward current limits the peak of the low-threshold spike to a level below the threshold of the action potential (about -20 mV). 5. Analysis of ensemble currents showed that axon-attached membrane patches contained clusters of different voltage-dependent potassium channels. Three channel classes were distinguished by prepulse inactivation experiments. All three channels were found to inactivate, but they had different voltage-dependencies and different inactivation kinetics (fast, intermediate, or slow). Recovery from inactivation was slow in each case (time constant 2–10 s). 6. All axon-attached membrane patches were found to contain one or two of the three classes of potassium channel. Channels with intermediate kinetics were found less frequently and may have been present at lower density.(ABSTRACT TRUNCATED AT 400 WORDS) Copyright © 1993 the American Physiological Society

Liu, Y. B.; Disterhoft, J. F.; Slater, N. T.

doi: N/Apmid: 8385186

Abstract 1. The long-term enhancement of synaptic excitability in CA1 hippocampal pyramidal neurons produced by activation of metabotropic glutamate receptors (mGluRs) was studied in rabbit hippocampal slices in vitro. 2. Bath application of the mGluR agonist (1S,3R)-1-aminocyclopentane-1,3- dicarboxylic acid (1S,3R-ACPD) (5-20 microM) for 20 min produced a reversible depolarization of membrane potentiatil, blockade of spike accommodation, and increase in input resistance of CA1 neurons. However, a long-lasting increase in synaptic excitability was observed: single stimuli applied to the Schaffer collateral commisural fiber pathway evoked epileptiform discharges in the presence of 1S,3R-ACPD and after the washout of 1S,3R-ACPD, persistent paroxysmal depolarization shifts (PDSs) were evoked by afferent stimulation. A long-lasting enhancement of synaptic excitability was also observed in the presence of the NMDA receptor antagonist D-(-)-2-amino-5-phosphonopentanoic acid (D-AP5), which blocked the stimulation-evoked PDS and associated afterdischarges. 3. When biphasic, monosynaptically evoked inhibitory post-synaptic potentials (IPSPs) were recorded in the presence of the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and N-methyl-D-aspartate receptor antagonists 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) (10–15 microM) and D-AP5 (20 microM), the bath application of 1S,3R-ACPD produced a significant reduction (approximately 50%) of both components of the IPSP, which persisted after the washout of the drug.(ABSTRACT TRUNCATED AT 250 WORDS) Copyright © 1993 the American Physiological Society

Bushnell, M. C.; Duncan, G. H.; Tremblay, N.

doi: N/Apmid: 8463817

Abstract 1. The role of the thalamic ventroposterior medial (VPM) nucleus in the discriminative aspects of nociception and thermoreception was evaluated in alert, trained rhesus monkeys. Single-unit responses were recorded from VPM while the monkeys performed a battery of tasks involving noxious heat, innocuous cool, and air-puff stimuli presented to the face. The discriminative ability of the monkey was compared directly with the responses of single neurons, to determine whether the neuronal response could subserve the monkey's discriminative behavior. 2. Most thermally sensitive neurons exhibited multimodal properties. Only 18% responded exclusively to heat (HT-Heat neurons), whereas 27% responded to innocuous mechanical, as well as noxious mechanical and heat stimuli (WDR-Heat). Twenty-three percent responded to innocuous mechanical stimuli and innocuous skin cooling (Mechano-Cool), and 32% responded to mechanical, innocuous cool, and noxious heat stimuli (WDR-Heat-Cool). 3. Almost all mechanical receptive fields were confined to one division of the trigeminal nerve. This was true for all of the above categories of VPM neurons, even those showing highly convergent properties (WDR-Heat-Cool). 4. Heat-activated neurons produced graded responses to noxious skin heating in the 46 to 49 degrees C range. Stimulus-response functions of neurons that responded to both heat and cool did not differ from those of neurons that responded exclusively to skin heating. 5. When the monkeys were detecting small changes in the intensity of a noxious heat stimulus (e.g., from 47 to 47.1–47.8 degrees C), heat-activated neurons responded to the smallest temperature changes that could be detected by the monkeys. Further, there was a high correlation between the monkey's success in detecting the stimulus changes and the magnitude of the neuronal responses to those changes. 6. Although the responsiveness of VPM cool-activated neurons was not compared with the monkeys' threshold for detecting cooling changes, larger stimulus changes (2 degrees C) that the monkey reliably detected produced significant neuronal responses. Further studies are needed to determine whether VPM neurons respond to the smallest detectable changes in skin cooling. 7. Several thermally sensitive VPM neurons were tested under two attentional conditions: 1) while the monkey was required to attend to a visual stimulus, and 2) while it was required to attend to the thermal stimulus to obtain reward. None showed a significant difference in heat- or cool-evoked activity in the two attentional states.(ABSTRACT TRUNCATED AT 400 WORDS) Copyright © 1993 the American Physiological Society

O'Malley, D. M.; Masland, R. H.

doi: N/Apmid: 8385192

Abstract 1. Rabbit retinas were isolated from the eye and incubated in the presence of 3H-choline. Samples of retina taken from a defined midperipheral eccentricity were spread over the domed end of a fiberoptic bundle that formed the floor of a superfusion chamber. The rate of release of labeled acetylcholine by the starburst amacrine cells was studied. 2. When the retina was stimulated by moving gratings, the cells vigorously increased their secretion of acetylcholine. Responses were observed when the bars were as small as 60 microns in width. Systematically varying the spatial and temporal frequency of stimulation revealed that temporal frequency was the dominant variable: the cells responded best to stimuli of 1–4 Hz, whether those stimuli were flashing lights, fine gratings moving slowly, or coarse gratings moving rapidly. 3. With temporal frequency constant, the cells' responses decreased as the spatial frequency of the grating increased. The decreased response to fine gratings is most likely due, at least in part, to lateral interactions that become stronger as the light and dark bars become more closely spaced. These could occur in either the outer or inner retina. 4. The velocity tuning curve for the starburst cells' release of acetylcholine matched fairly well the velocity tuning of ON-OFF directionally selective cells in the rabbit. It did not correspond at all well with the tuning curve for the ON directionally selective cells. If the ON cells receive input from the starburst cells, that input appears to be quite indirect.(ABSTRACT TRUNCATED AT 400 WORDS) Copyright © 1993 the American Physiological Society

Glimcher, P. W.; Sparks, D. L.

doi: N/Apmid: 8463820

Abstract 1. The first experiment of this study determined the effects of low-frequency stimulation of the monkey superior colliculus on spontaneous saccades in the dark. Stimulation trains, subthreshold for eliciting short-latency fixed-vector saccades, were highly effective at biasing the metrics (direction and amplitude) of spontaneous movements. During low-frequency stimulation, the distribution of saccade metrics was biased toward the direction and amplitude of movements induced by suprathreshold stimulation of the same collicular location. 2. Low-frequency stimulation biased the distribution of saccade metrics but did not initiate movements. The distribution of intervals between stimulation onset and the onset of the next saccade did not differ significantly from the distribution of intervals between an arbitrary point in time and the onset of the next saccade under unstimulated conditions. 3. Results of our second experiment indicate that low-frequency stimulation also influenced the metrics of visually guided saccades. The magnitude of the stimulation-induced bias increased as stimulation current or frequency was increased. 4. The time course of these effects was analyzed by terminating stimulation immediately before, during, or after visually guided saccades. Stimulation trains terminated at the onset of a movement were as effective as stimulation trains that continued throughout the movement. No effects were observed if stimulation ended 40–60 ms before the movement began. 5. These results show that low-frequency collicular stimulation can influence the direction and amplitude of spontaneous or visually guided saccades without initiating a movement. These data are compatible with the hypothesis that the collicular activity responsible for specifying the horizontal and vertical amplitude of a saccade differs from the type of collicular activity that initiates a saccade. Copyright © 1993 the American Physiological Society

Vogt, M. B.; Smith, D. V.

doi: N/Apmid: 8385188

Abstract 1. Although taste experience typically arises from a mixture of gustatory stimuli, nearly all previous neurophysiological studies of the mammalian central gustatory system have focused on responses to single chemical stimuli. To begin to systematically examine CNS responses to taste mixtures, we recorded the extracellular activity of single third-order neurons in the hamster PbN to anterior tongue stimulation with binary mixtures of sucrose and QHCl. In experiment 1, neurons were tested with four concentrations of sucrose (0.001, 0.01, and 1.0 M) presented alone and mixed with 0.1 M QHCl. In experiment 2, neurons were tested with four concentrations of QHCl (0.00032, 0.0032, 0.032, and 0.1 M) presented alone and mixed with 1.0 M sucrose. 2. The response to each binary mixture was compared with the response to the more effective component (MEC) presented alone, and those that differed by more than a selected criterion (based on response variability) were identified. Of all mixture responses, 37% (59/158) involved mixture suppression (mixture response < MEC response), only 4% (6/158) were greater than the MEC, and 59% (94/158) were classified as not different than the response to the MEC. Most neurons that displayed mixture suppression did so at several mixture concentrations. 3. Sucrose suppression (mixture response < sucrose response) was prevalent among neurons most responsive to sucrose and for the mixtures that contained the stronger sucrose concentrations. Among neurons that displayed sucrose suppression, the magnitude of suppression was significantly correlated with sucrose response magnitude but not with QHCl response magnitude. These and other factors suggest that a neuron's capacity to display sucrose suppression to sucrose+QHCl mixtures is related to its sucrose sensitivity. 4. QHCl suppression (mixture response < QHCl response) was less prevalent than sucrose suppression, and the neurons that displayed QHCl suppression were almost exclusively a subset of those that displayed sucrose suppression to the same or different mixtures. This finding and the observation that one-third of all mixture responses involved mutual suppression (response to the mixture less than that to either component alone), suggest an association between the factors underlying sucrose suppression and QHCl suppression. 5. The across-neuron patterns (ANPs) of taste responses, which are thought to represent taste quality, were compared for mixtures and components. In general, the ANP for each mixture was similar to (significantly correlated with) the ANP of the more stimulatory component. However, for the mixture that evoked the greatest sucrose suppression, the mixture ANP was more similar to the ANP of the less stimulatory component.(ABSTRACT TRUNCATED AT 400 WORDS) Copyright © 1993 the American Physiological Society

Thio, C. L.; Waxman, S. G.; Sontheimer, H.

doi: N/Apmid: 7681866

Abstract 1. Astrocytes cultured from rat spinal cord express voltage-activated Na+ channels in high densities (up to 8 channels per microns2). Stellate astrocytes express Na+ currents at all times in vitro. In pancake astrocytes, Na+ channel expression shows a distinct temporal pattern, an absence of channel expression at 1–3 days in vitro (DIV), and peak Na+ channel density at 7–8 DIV. 2. Coculture of spinal cord astrocytes with dorsal root ganglion (DRG) neurons substantially reduces the expression of voltage-activated Na+ channels in both spinal cord astrocyte types. In pancake spinal cord astrocytes, both the percentage of cells expressing Na+ channels and the channel density in Na+ channel-expressing cells are markedly reduced. In stellate spinal cord astrocytes, the percentage of Na+ channel-expressing cells is unchanged, but the Na+ channel density per cell is markedly reduced in coculture. 3. Culturing spinal cord astrocytes in neuron-conditioned media reduces Na+ channel expression in both spinal cord astrocyte types to levels intermediate between coculture and control, suggesting that, at least in part, neuronal effects on Na+ channel expression are mediated by a soluble factor secreted into the media by neurons. 4. As with the expression of voltage-activated Na+ channels, the expression of voltage-activated K+ channels is reduced in both spinal cord astrocyte types cocultured with DRG neurons. The effect is not mimicked by culturing cells in neuron-conditioned media, suggesting that effects on K+ channel expression are mediated by a less stable and more readily degradable factor. 5. Coculture with DRG neurons or culture in neuron-conditioned media do not alter the biophysical properties of voltage-activated Na+ currents in pancake spinal cord astrocytes. Thus steady-state activation, steady-state inactivation, and the time constants of activation and inactivation are virtually unchanged under the various culture conditions. Copyright © 1993 the American Physiological Society

Tremblay, N.; Bushnell, M. C.; Duncan, G. H.

doi: N/Apmid: 8385193

Abstract 1. Single-unit activity was recorded in the ventral posterior medial (VPM) thalamic nucleus of awake monkeys while they performed detection and discrimination tasks involving tactile air-puff stimuli presented to the face. Neuronal responsiveness was compared directly with the monkey's discriminative performance. In addition, neuronal activity was compared when the monkey's attention was directed to the air-puff stimulus and when it was directed to a concurrent visual stimulus. 2. Neurons responding to the air-puff stimuli were classified as slowly adapting (SA), rapidly adapting (RA), inhibitory (IN), or multimodal (MM), according to their responses to manual and thermal stimulation, as well as their adaption rates to the air puff. Of 47 neurons responsive to air-puff stimulation and studied extensively in the behavioral task, 14 were classified as RA, 15 as SA, 6 as IN, and 12 as MM. The 12 MM neurons were so classified because, in addition to air puff, they responded to noxious heat, innocuous cooling, or noxious pinch. 3. Neurons from each class had restricted contralateral receptive fields localized within one division of the trigeminal nerve. There was no systematic difference in receptive-field size among groups. 4. A prominent difference in tactile responsiveness of MM neurons was response latency. Although the mean latency for RA, SA, and IN neurons was not significantly different (6.1, 9.1, and 12.2 ms, respectively), the mean latency for MM neurons was significantly longer than that for each of the other neuronal categories (28.8 ms; Ps < 0.001). These data suggest that the excitatory tactile afferent input to MM neurons is different from that to low-threshold neurons. 5. For RA, SA, and MM neurons the frequency of the neuronal discharge evoked by the air-puff stimulation was proportional to the intensity of the air puff. Thus responses of each neuronal class coded air-puff stimulus intensity. 6. The monkeys' ability to detect air-puff stimuli of various intensities was compared with the frequency of neuronal responses to those stimuli. Both the percent success in detecting differences in air-puff intensity and the detection latency were highly correlated with neuronal response frequency. The responses of all three excitatory neuronal categories corresponded well with the monkey's performance. Thus any or all of RA, SA, and MM neurons could play a role in the discrimination of air-puff intensities.(ABSTRACT TRUNCATED AT 400 WORDS) Copyright © 1993 the American Physiological Society