bluuebunny/crossref_metadata_2025 huggingface dataset:
Periodic pacing an in vitro epileptic focus
Authors: Jerger K. , Schiff S. J.
Published: December 2017

1. The effects of frequency of orthodromic and antidromic stimulation of CA3 on formation of electrographic seizurelike discharges in CA1 was studied in the high potassium hippocampal slice. 2. Within the range of stimulation of CA3 used, 0.1-10.0 Hz, a narrow range was identified between 1.0 and 1.3 Hz, where the tonic phase of seizure generation in CA1 was suppressed. This suppression was observed for both Schaffer collateral and mossy fiber stimulation.
Coordination in the crayfish swimmeret system: differential excitation causes changes in intersegmental phase
Authors: Braun G. , Mulloney B.
Published: December 2017

1. Gradients of excitation in the swimmeret system were created by applying either pilocarpine or carbachol to selected ganglia in isolated abdominal nerve cords. The state of the system was monitored in each segment with extracellular electrodes on nerves that innervated swimmerets. In preparations that were quiescent before drugs were applied, these cholinergic agonists elicited well-coordinated swimmeret motor patterns from the entire system, including ganglia that were not directly treated with pilocarpine or carbachol. 2. The periods of these patterns depended on the number of ganglia that were directly excited. As this number increased, period decreased. When the same numbers of ganglia were excited by direct application of a drug, the mean period of the swimmeret activity elicited by pilocarpine was greater than that elicited by carbachol. 3. Selective excitation of anterior or posterior ganglia caused significant changes in intersegmental phase at the boundary between excited and nonexcited regions of the nerve cord. When only anterior ganglia were excited directly, the phases of their power-stroke activity relative to the most posterior ganglion were advanced. When only posterior ganglia were excited directly, the phases of power-stroke activity in more anterior ganglia were retarded. Neither pilocarpine nor carbachol caused a complete reversal of the normal phase relations of the swimmeret motor patterns. 4. These results are consistent with an asymmetric-coupling model of the intersegmental coordinating circuit of the swimmeret system but contradict an alternative excitability-gradient model.
Whole cell and single channel properties of a new GABA receptor transiently expressed in the Hippocampus
Authors: Martina M. , Strata F. , Cherubini E.
Published: December 2017

1. The patch-clamp technique was used to characterize, in acutely dissociated CA3 rat hippocampal neurons, the whole cell and single channel properties of a novel response to gamma-aminobutyric acid (GABA) present only during a restricted period of postnatal development. 2. At postnatal days 0-10 (P0-P10), both GABA (100 microM) and isoguvacine (50 microM) evoked at a holding potential of -50 mV, in symmetrical chloride solution, whole cell inward currents. Bicuculline blocked the response to isoguvacine but only reduced the response to GABA (from 512 +/- 137 pA to 60 +/- 13 pA, mean +/- SE). After P12, bicuculline abolished the response to GABA. 3. The bicuculline-insensitive GABA currents were Cl- mediated and antagonized by picrotoxin. The desensitization rate was slower than the conventional bicuculline-sensitive response. The peak to plateau ratio induced by 0.1 or 1 mM of GABA shifted from 4.6 +/- 0.4 and 17.7 +/- 2.6 to 1.5 +/- 0.1 and 3.1 +/- 0.5 in the absence or in the presence of bicuculline, respectively. The recovery from desensitization was significantly faster for the bicuculline-insensitive responses. 4. In excised outside-out patches, GABA (20 microM) activated, in the presence of bicuculline (100 microM), single channel currents having conductances of 14, 22, and 31 pS. These values were similar to those obtained in the same preparation, in the absence of bicuculline. 5. These findings suggest that this new receptor type, which mediates bicuculline-insensitive responses with slow kinetics, may potentiate the depolarizing action of GABA during a critical period of postnatal development and therefore play a crucial role in synaptogenesis.
Zinc downmodulates thf GABAc receptor current in cone horizontal cells acutely isolated from the catfish retina
Authors: Dong C. J. , Werblin F. S.
Published: December 2017

1. We studied the effect of zinc on the gamma-aminobutyric acid-C (GABAC) receptor in acutely isolated catfish cone horizontal cells using the whole cell patch-clamp technique. 2. GABA activates the GABAC receptor with a half-activation concentration (EC50) of 2.99 microM. The Hill coefficient is 1.32. Desensitization of the receptor is evident when GABA concentration is > 3 microM. 3. Zinc downmodulates the GABAc receptor current, elicited by 30 microM GABA, with a half-inhibition concentration (IC50) of 8.20 microM. 4. The inhibition of zinc is both competitive and noncompetitive. In the presence of 10 microM zinc, the maximum GABA response was reduced to approximately 60 percent of control and the EC50 increased to 17.32 microM, whereas the Hill coefficient (1.39) was not significantly altered. 5. The steady-state block by zinc is virtually voltage independent. 6. These results suggest that the GABAC receptor of horizontal cells can be modulated by endogenous zinc found in photoreceptors.
Electrophysiological responses of single olfactory bulb neurons to amino acids in the channel catfish, Ictalurus punctatus
Authors: Kang J. , Caprio J.
Published: December 2017

1. Responses of 89 single olfactory bulb neurons from 43 channel catfish, Ictalurus punctatus, to amino acid odorants were recorded in vivo simultaneously with the electro-olfactogram (EOG). Recording time for individual neurons ranged from 16 to 344 min. The averaged spontaneous frequency ranged from x003C; 1 to 16 action potentials/s with a mean frequency of 5.2 +/- 3.6 (SD) action potentials/s. 2. Histological examinations of carbocyanine dye 1,1'diocadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (DiI)-labeled olfactory bulbs and electrical stimulation of the olfactory tracts in a subset of experiments suggested that the majority of the recorded olfactory bulb neurons in this study were mitral cells. 3. Olfactory bulb neurons responded to amino acids with either an excitation or suppression of the background neural activity. Of the 337 stimulus applications, 28% of the responses were excitatory, and 33% were suppressive. The approximately 1:1 ratio of excitatory to suppressive responses for all stimulus applications suggests that suppressive responses also play important roles in the coding of odorant information in the channel catfish. 4. Responses of single olfactory bulb neurons were highly reproducible over time (up to 5 h). Responses to any amino acid never changed from excitation to suppression, or vice versa over time. 5. Single olfactory bulb neurons responded with excitation or suppression to more than one amino acid previously indicated to bind to independent receptors. 6. Estimated threshold concentrations for activation of an olfactory bulb neuron ranged from 10(-7) to 10(-3) M and were different from neuron to neuron for a particular stimulus and from stimulus to stimulus for a particular neuron. Responses of single olfactory bulb neurons to a given amino acid did not change from excitation to suppression, or vice versa, across different suprathreshold concentrations.
Intrinsic properties of deep dorsal horn neurons in the L6-S1 spinal cord of the intact rat
Authors: Jiang M. C. , Cleland C. L. , Gebhart G. F.
Published: December 2017

1. Stable intracellular recordings were obtained from neurons (n = 62) in the L6-S1 deep dorsal horn of the spinal cord in pentobarbital-sodium-anesthetized, intact rats (n = 26). All neurons responded to natural mechanical stimuli and/or electrical stimulation of peripheral afferents. 2. Intracellular penetrations were maintained for 30 min-2 h. Action potentials occurred spontaneously in most neurons (n = 50) and could be evoked in the remainder (n = 12) by depolarizing current passage. Mean resting membrane potential was -60.9 mV, mean action potential height amplitude was 75.2 mV, mean half-width of the action potentials was 0.33 ms, mean input resistance was 38 M omega, and mean time constant was 9.1 ms. 3. Action potentials were followed by afterpotentials made up of at least three components; a fast afterhyperpolarization (fAHP), a slow afterhyperpolarization (sAHP), and an afterdepolarization (ADP). Most neurons (n = 40) exhibited all three afterpotentials, although some displayed only a fAHP and an ADP (n = 10) or a fAHP and a sAHP (n = 12). The durations and magnitudes of the afterpotentials varied widely among neurons. 4. Steady-state current-voltage relations were investigated in 14 neurons with depolarizing and hyperpolarizing current pulses. Of these 14 neurons, 5 exhibited inward rectification, 3 had outward rectification, and the remaining 6 showed a predominantly linear change of membrane potential to current injection. In addition, several neurons (n = 9) exhibited a postinhibitory rebound that was sometimes (n = 4) accompanied by a "sag" in voltage during the preceding hyperpolarizing current step. 5. Four patterns of spike frequency adaptation occurred during step depolarizing current passage. The firing of most neurons gradually decreased with a simple, approximately exponential time course (n = 21), in some neurons it decreased with both a fast and a slow time course (n = 8), in several it incremented in rate (n = 3), and one neuron showed a complex combination of multiple decrementing and incrementing adaptations. Time constants, magnitude of adaptation, and the slopes of the steady-state current-voltage relation varied widely. 6. Oscillations in membrane potential and firing rate occurred in three neurons. The oscillations arose from endogenous mechanisms in at least one neuron because manipulation of membrane potentials altered the frequency of oscillation; a depolarizing current increased the period of oscillation and eventually produced tonic firing, and a hyperpolarizing current increased the frequency of oscillation and eventually terminated firing. 7. The results demonstrate that neurons in the L6-S1 region of the dorsal horn exhibit a diversity of cellular mechanisms that may significantly modulate normal somatosensory and visceral input.
GABAA and GABAC receptors on hybrid bass retinal bipolar cells
Authors: Qian H. , Dowling J. E.
Published: December 2017

1. gamma-Aminobutyric acid (GABA) responses from solitory hybrid bass retinal bipolar cells were studied with the use of conventional and perforated whole cell patch-clamp recording. 2. GABA elicited a chloride current in bipolar cells that had both transient and sustained components. The transient component was sensitive to bicuculline and resembled GABAA-mediated currents, whereas the more sustained component was resistant to bicuculline and resembled the responses mediated by GABAC receptors. 3. The bicuculline-resistant GABA responses recorded from the bipolar cells could not be modulated by either diazepam or pentobarbital sodium, and they were unaffected by phaclofen and 2-hydroxysaclofen, GABAB receptor antagonists. On the other hand, the bicuculline-resistant GABA responses could be blocked substantially by imidazole-4-acetic acid (I4AA), a competitive antagonist of GABAC receptors. 4. Noise analysis of the GABA-elicited currents suggested a different single channel conductance for GABAA (10.1 pS) and GABAC receptors (3.6 pS). 5. Zinc, a putative modulator of synaptic transmission, strongly inhibited the GABAC responses on bipolar cells, whereas the GABAA responses were not significantly affected by zinc. 6. The proportion of the GABAC to GABAA responses varied widely between bipolar cells. Local application of GABA onto dendrites or axon terminals showed that both types of GABA receptors are present on both regions of the cell. 7. The distinct properties of these two GABA receptor types suggest that they play different roles in retinal function.
Characterization of GABA current in rat septal cholinergic neurons in culture and its modulation by metal cations
Authors: Kumamoto E. , Murata Y.
Published: December 2017

1. With the aim of characterizing the functional and pharmacological properties of gamma-aminobutyric acid-receptor (type A; GABAAR) channels expressed in a given type of brain neurons, we obtained whole cell voltage-clamp recordings from rat septal cholinergic neurons in primary culture. 2. GABA-induced currents (IGABAS) were accompanied by an increase in conductance and reversed the direction at the Cl- equilibrium potential. The permeability sequence of GABA-activated Cl- channel for various anions (ratio to Cl- permeability) was found to be SCN- (1.72) > or = I- (1.60) > or = Br- (1.55) > Cl- (1) > HCO2- (0.42) >> F- (0). 3. GABA applied by local perfusion produced an IGABA that enhanced in amplitude with increasing concentrations (EC50 = 21.4 microM; nH = 1.70) and desensitized at higher concentrations. Bicuculline inhibited IGABA (20 microM) competitively (IC50 = 0.963 microM) with a dissociation constant of approximately 0.5 microM. Picrotoxin depressed IGABA (20 microM) noncompetitively in a dose- and use-dependent manner (IC50: approximately 100 microM for peak IGABA). 4. IGABA was potentiated by diazepam at 1 and 10 microM (by 20% at 1 microM for IGABA evoked at 10 microM) but not at 0.1 and 100 microM. IGABA was facilitated by pentobarbital sodium (5-200 microM) in a dose-dependent fashion with an increase in an apparent affinity for GABA (by 251% at 50 microM). 5. Zn2+ (2-100 microM) inhibited IGABA (limited to approximately 20% decrease) in a noncompetitive manner. IGABA was also depressed by Cu2+ and Cd2+ (by 50 and 15%, respectively, at 100 microM); its recovery process from their depressions was slow and fast, respectively. The Cu2+ but not Cd2+ action persisted in the presence of Zn2+. La3+ (50-500 microM) potentiated IGABA by enhancing an apparent affinity for GABA (by 158% by 100 microM La3+); this action disappeared in the presence of pentobarbital but not Zn2+. La3+ applied alone induced an inward current at negative holding potentials, but this was not due to the activation of GABAAR channels. 6. Septal cholinergic neurons were endowed with GABAAR channels that were similar to those on other types of neurons in the affinities for GABA, bicuculline, picrotoxin, and pentobarbital, and in an anion-permeability sequence, but were greatly different in the actions of metal cations. The septal GABAA response was depressed strikingly by Cu2+ and to a little extent by Zn2+, whose action was shared by Cd2+ but not by Cu2+, while being potentiated by La3+, possibly through the action on a pentobarbital site. It is suggested that a distinction in properties among native GABAAR channels may be largely reflected in the actions of not only Zn2+ but also Cu2+ and La3+.
Ca2+ release from Ca2+ stores, particularly from ryanodine-sensitive Ca2+ stores, is required for the induction of LTD in cultured cerebellar Purkinje cells
Authors: Kohda K. , Inoue T. , Mikoshiba K.
Published: December 2017

1. Primary-cultured cerebellar Purkinje cells (PCs) from mouse embryos were whole cell voltage clamped, and L-glutamate (Glu) was applied iontophoretically to the dendrite. Long-term depression (LTD) of Glu-evoked currents was induced through the conjunction of repeated depolarizations and Glu applications. 2. Thapsigargin, a specific inhibitor of Ca(2+)-ATPase on the endoplasmic reticulum, and ryanodine and ruthenium red, inhibitors of the ryanodine receptor, blocked the induction of LTD. 3. Thapsigargin and ryanodine alone did not affect influx of Ca2+ through voltage-gated Ca2+ channels and inward currents evoked by Glu applications. 4. Our results suggest that Ca2+ release from internal stores, particularly from ryanodine-sensitive stores, is necessary for the induction of LTD in cultured PCs.
Slow and saccadic eye movements evoked by microstimulation in the supplementary eye field of the cebus monkey
Authors: Tian J. R. , Lynch J. C.
Published: December 2017

1. Intracortical microstimulation was used to map the supplementary eye field (SEF) in eight hemispheres of five Cebus apella monkeys. Monkeys were immobilized during experiments with Telazol (tiletamine HCl and zolazepam HCl), a dissociative anesthetic agent that was demonstrated to have no significant effect on microstimulation-induced eye movement parameters compared with similar experiments in alert, behaviorally trained monkeys. The functional subregions were defined with the use of low-threshold current (< or = 50 microA). Electrically elicited eye movements were videotaped and quantified. Both slow and saccadic eye movements were reliably evoked at low threshold by microstimulation in each of eight hemispheres studied. The two types of eye movements were clearly distinguished by their significantly different duration and velocity (P < 0.0001) and their different responses to long stimulus trains. The results strongly support the proposal that the SEF produces not only saccadic eye movements as previously reported but also slow (pursuit) eye movements.
Perception of passive whole-body rotations in the absence of neck and body proprioception
Authors: Blouin J. , Vercher J. L. , Gauthier G. M. , Paillard J. , Bard C. , Lamarre Y.
Published: December 2017

1. This study investigated whether accurate perception of body rotation after passive horizontal whole-body rotations in the dark requires the integration of both vestibular and neck-body proprioceptive signals. 2. In the first experiment, the gain of the vestibuloocular reflex (VOR) of normal subjects ("controls") and of a patient without proprioception of the neck and body muscles was assessed by the use of pulse and sinusoidal stimulation. In the second experiment, the subjects reported verbally the magnitude of the body rotations. Finally, in the third experiment, they shifted gaze to the position fixated before the rotation ("vestibular memory-contingent saccades" paradigm). 3. The VOR gain of the patient was similar to that of controls, although the body rotations of the patient were largely overestimated, regardless of whether the patient reported the perceived magnitude verbally or through a gaze shift toward the position gazed at before the rotation. 4. These results suggest that neck muscle proprioception contributes to the vestibular signal calibration at the perceptual level necessary for determining body orientation accurately after rotations in the dark.
Regional characteristics of the membrane response of an identified crayfish nonspiking interneuron to intracellularly injected current
Authors: Takahashi M. , Takashima A. , Takahata M.
Published: December 2017

1. We investigated the membrane response of the local directionally selective (LDS) interneuron, a nonspiking cell identified in the terminal abdominal ganglion of crayfish, to intracellularly injected current in different regions within the cell by single-electrode, discrete current-clamp experiments. The site of electrode impalement into the cell was visualized in situ together with the cell structure under a dissecting microscope. 2. The LDS interneuron has dendritic branches on both hemiganglia connected by a thick segment crossing the midline. Irrespective of the site of electrode impalement, the interneuron showed outward rectification upon depolarization from the resting potential level. When hyperpolarizing current was injected, a linear relationship was observed between the voltage response of the interneuron and the amount of injected current. Upon large hyperpolarization, however, the interneuron showed inward rectification. 3. The input resistance of the interneuron measured within the linear range of the membrane response was significantly lower in the transverse segment than in lateral dendrites (0.001 < P < 0.01). The time constant of the transient voltage response to step current injection was also significantly shorter in the transverse segment than in the lateral dendrites (0.001 < P < 0.01). 4. Although the regional difference in the input resistance could be accounted for, at least partly, by different geometric conditions of each dendritic branch into which current was injected, the regional difference in the time constant of the membrane response cannot be accounted for by structural differences because the time constant is independent of the membrane area. It is thus suggested that the passive properties of the interneuron membrane that are related to its response time constant show regional variability within the cell.
Recruitment of GABAA inhibition in rat neocortex is limited and not NMDA dependent
Authors: Ling D. S. , Benardo L. S.
Published: December 2017

1. The recruitment of evoked fast inhibitory postsynaptic currents (IPSCs) and excitatory postsynaptic currents (EPSCs) was examined using whole cell voltage-clamp recordings from layer V pyramidal neurons in slices of rat somatosensory cortex. Synaptic currents were evoked with graded electrical stimulation to assess the relative activation of IPSCs and EPSCs. Fast GABAA ergic IPSCs were selectively recorded by holding cells at potentials equal to EPSC reversal (approximately 0 mV). EPSCs were likewise isolated by holding cells at IPSC reversal potential (about -75 mV). 2. As stimulus intensities were increased, the magnitude of the postsynaptic currents also increased. Over the range of stimuli applied (2-10 V), EPSCs did not exhibit an upper limit. However, fast gamma-aminobutyric acid-A (GABAA-mediated IPSCs reached a maximum at intensities approximately 2 times threshold. 3. The limit on fast inhibition was unresponsive to alterations in N-methyl-D-aspartate (NMDA)-mediated excitation. Exposure to nominally magnesium-free solutions or to the NMDA antagonist 3-[(RS)-2-carboxypiperazin-4-yl]-propyl-1-phosphonic acid did not affect the fast IPSC maximum. Shifts in the input-output curves for submaximal activation of IPSCs were seen, which were attributed to polysynaptic excitation. 4.Blockade of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid/kainate (non-NMDA) receptors with 6-cyano-7-nitro-quinoxaline-2,3-dione (CNQX) completely abolished synaptically driven, fast GABAA-mediated inhibition. These findings suggested that neocortical inhibitory cells could be driven exclusively through non-NMDA transmission. 5. By comparison, in hippocampal CA1 pyramidal neurons maximal fast inhibition was sensitive to both NMDA and non-NMDA receptor blockade. 6. The results in neocortex were corroborated by direct intracellular recordings from layer V-VI interneurons. Non-NMDA receptor blockade with CNQX prevented synaptic activation of action potentials in these cells, even during cotreatment with magnesium-free solution. 7. Together, these results suggest that recruitment of GABA(A) ergic IPSCs in neocortex is ultimately driven via glutamatergic afferents arriving at non-NMDA receptors on interneurons. Properties limiting fast inhibition would favor the propagation of enhanced excitatory activity through the neuronal network.
Structural basis of cortical synchronization. II. Effects of cortical lesions
Authors: Munk M. H. , Nowak L. G. , Nelson J. I. , Bullier J.
Published: December 2017

1. To understand the structural basis of the different types of interhemispheric synchronizations described in the preceding paper, we made sections of the corpus callosum and lesions of extrastriate cortex. We measured the effects of such operations on the frequency of encounter, width and strength of T, C, and H peaks in cross-correlation histograms computed from single-unit and multiunit recordings from areas 17-18 of opposite cortical hemispheres in the cat. 2. Sectioning of the corpus callosum led to a complete abolition of T and C couplings and a strong reduction of encounter rate and strength of H coupling. A section limited to the posterior half of the corpus callosum abolished T and C couplings completely. This suggests that T and C couplings are mediated by the direct reciprocal connections between visual cortical areas circulating through the posterior part of the corpus callosum. 3. The encounter rate of H peaks depended on the extent of the callosal cut. Larger lesions gave a more pronounced reduction of the number of H peaks. From this observation we conclude that H peaks are at least partially mediated by polysynaptic pathways involving widely distributed cortical regions. 4. Extensive lesions of extrastriate cortex were made by aspiration of the gray matter or injections of ibotenic acid. These lesions removed the direct inputs from cortical areas sending ipsilateral as well as contralateral inputs to the area 17-18 border region. Encounter rate and coupling strength of C and H peaks were decreased, whereas little effect was observed on T peaks. 5. These results demonstrate that all types of interhemispheric synchronization are mediated by corticocortical connections and that T and C peaks are generated by reciprocal connections between areas 17 and 18 of each hemisphere. Feedback connections play a role in mediating or facilitating the C and H types of interhemispheric synchronization.
Extranuclear dendrites of locus coeruleus neurons: activation by glutamate and modulation of activity by alpha adrenoceptors
Authors: Ivanov A. , Aston-Jones G.
Published: December 2017

1. Locus coeruleus (LC) neurons were recorded extracellularly and intracellularly in rat brain slices. Effects of glutamate applied to the area of distal extranuclear LC dendrites, and of alpha-2 adrenoceptors applied in the bath, were determined on activity of these cells. 2. Glutamate applied to the area of distal dendrites potently activated LC neurons. These responses were not blocked by either 1 microM tetrodotoxin or 2 mM Co(2+)-10 mM Mg2+. This indicates that glutamate acting directly on distal dendrites can potently activate LC neurons. 3. Bath application of the alpha-2 adrenoceptor antagonists yohimbine (1 microM) or idazoxan (1 microM) significantly increased responses of LC neurons evoked by dendritic glutamate application. These antagonist treatments also transiently decreased, and then increased, spontaneous discharge activity in LC neurons. 4. Alterations in spontaneous and glutamate-evoked activities after blockade of alpha-2 adrenoreceptors were not observed in LC neurons of reserpinized rats. This indicates that the altered LC activity and responsiveness to glutamate following alpha-2 antagonist treatment in nonreserpinized slices are mediated via blockade of effects of endogenously released noradrenaline. 5. The alpha-1 antagonist prazosin (1 microM) caused a small but reliable decrease in the spontaneous firing rate of LC neurons. After prazosin pretreatment, alpha-2 antagonists did not evoke the expected delayed increase in LC spontaneous firing and response to glutamate application. These results indicate that activation of alpha-1 adrenoceptors may contribute to the delayed increase in excitability of LC neurons after alpha-2 antagonist administration. The possible roles of alpha-1 and alpha-2 adrenoreceptors in regulation of spontaneous discharge rate and glutamate-evoked responses in LC neurons are discussed.
Vestibular and visual climbing fiber signals evoked in the uvula-nodulus of the rabbit cerebellum by natural stimulation
Authors: Barmack N. H. , Shojaku H.
Published: December 2017

1. The cerebellar uvula-nodulus receives vestibular projections from primary and secondary vestibular afferents as well as vestibularly related climbing fibers. It also receives visually related information from climbing fiber pathways. In this experiment we investigated how this information is mapped onto the uvula-nodulus. We studied the specificity, dynamics, and topographic distribution of climbing fiber responses (CFRs), simple spike responses, and mossy fiber terminal responses evoked by vestibular and optokinetic stimulation in rabbits anesthetized with alpha-chloralose. 2. Vestibularly evoked CFRs were found in the ventral uvula and nodulus. These responses were evoked during static roll tilt of the rabbit about a longitudinal axis and by sinusoidal oscillation about the longitudinal axis. Purely static responses were attributed to stimulation of the utricular otolith by the linear acceleration of gravity. CFRs that lacked a static component were attributed to activation of the semicircular canals. 3. Using a "null technique" we showed that the canal-sensitive CFRs were caused by stimulation of the anterior or posterior semicircular canals. Of the CFRs classified as canal related, 96% could be attributed to stimulation of the vertical semicircular canals. 4. Increases in CFRs were correlated with decreases in simple spike responses in half the Purkinje cells from which we recorded. These climbing-fiber-induced pauses in simple spikes occurred during spontaneous climbing fiber discharge as well as during climbing fiber discharge evoked by vestibular stimulation. The duration of this pause was inversely proportional to the spontaneous level of simple spikes before the occurrence of a CFR. In the other half of the recorded population of Purkinje cells, vestibularly driven CFRs did not alter the simple spike responses. 5. Vestibularly and visually mediated CFRs were topographically represented on the surface of the uvula-nodulus. CFRs driven by ipsilateral otolithic inputs were distributed over the entire mediolateral surface of the uvula-nodulus. CFRs driven by the ipsilateral posterior semicircular canal were distributed in a sagittal strip approximately 1.5 mm wide, extending laterally from the midline of the nodulus. CFRs driven exclusively by horizontal, posterior-->anterior optokinetic stimulation of the ipsilateral eye were distributed in a sagittal strip approximately 0.5 mm wide located 0.5-1.0 mm from the midline and restricted to the ventral nodulus. CFRs driven by the ipsilateral anterior semicircular canal were found in a sagittal strip approximately 1.0 mm wide extending 1.0-2.0 mm from the midline. 6. The sagittal, topographically arrayed climbing fiber strips effectively map a mediolateral gradient of possible postural responses based on vestibular and optokinetic information.
Magnesium-dependent block of the light-activated and trp-dependent conductance in Drosophila photoreceptors
Authors: Hardie R. C. , Mojet M. H.
Published: December 2017

1. The effect of Mg2+ on the light-sensitive conductance in Drosophila photoreceptors was examined with the use of whole cell voltage-clamp recordings from dissociated ommatidia. In wild type (WT) photoreceptors, at resting potential (-70 mV). Mgo2+ reduces response amplitude by up to approximately 4-fold in the presence of normal (1.5 mM) Cao2+ and by up to 20-fold in the absence of Cao2+. The Mg2+ concentration required for 50% maximum block (K1/2) was approximately 1 mM with 1.5 mM Cao2+ and approximately 280 microM in Ca(2+)-free Ringer. 2. The Mg2+ block was largely relieved in photoreceptors of the transient receptor potential mutant (trp): the maximum block being only approximately twofold with a K1/2 of approximately 4 mM in both Ca(2+)-free and 1.5 mM Cao2+. 3. The Mg2+ block in WT, but not in trp, was strongly voltage dependent, being relieved by both hyperpolarization and depolarization. The Mg2+ block in WT also resulted in slower response kinetics because of the associated decrease in Ca2+ influx. 4. Noise analysis indicates that, with normal Ca(zero)2+, the Mg2+ block in WT is associated with a approximately 10-fold reduction in effective single-channel conductance al resting potential. 5. The results support the hypothesis that the trp gene encodes a subunit of a light-sensitive channel, which is required for sensitivity to block by Mg2+. The concentration and voltage dependence of the Mg2+ block suggest it plays an important physiological role in determining the gain, kinetics, and signal-to-noise of transduction.
Halothane-induced synaptic depression at both in vivo and in vitro reconstructed synapses between identified Lymnaea neurons
Authors: Spencer G. E. , Syed N. I. , Lukowiak K. , Winlow W.
Published: December 2017

1. In the present study we tested the ability of the general anesthetic, halothane, to affect synaptic transmission at in vivo and in vitro reconstructed peptidergic synapses between identified neurons of Lymnaea stagnalis. 2. An identified respiratory interneuron, visceral dorsal 4 (VD4), innervates a number of postsynaptic cells in the central ring ganglia of Lymnaea. Because VD4 has previously been shown to exhibit immunoreactivity for FMRFamide-related peptides, it was hypothesized that these peptides may be utilized by VD4 during synaptic transmission. In the intact, isolated CNS of Lymnaea, we have identified novel connections between VD4 and the pedal A (PeA) cells. We demonstrate that VD4 makes inhibitory connections with the PeA neurons, in particular PeA4, and that these synaptic responses are mimicked by exogenous application of FMRFamide. 3. The synaptic transmission between VD4 and the PeA cells in an intact, isolated CNS preparation was completely blocked in 2%, but not 1% halothanc. Interestingly, the postsynaptic responses (PeA) to exogenous FMRFamide were maintained in the presence of both 1 and 2% halothane. 4. To determine the specificity of the observed responses and to determine the precise synaptic site of anesthetic action, we reconstructed the VD4/PeA synapses in vitro. After isolation from their respective ganglia, both cell types extended processes and established neuritic contact. We demonstrated that not only did the presynaptic neuron reestablish the appropriate inhibitory synapses with the PeA neurons, but that the PeA cells also maintained their responsiveness to exogenous FMRFamide. 5. Superfusion of the in vitro synaptically connected VD4 and PeA cells with 2% halothane completely abolished the synaptic transmission between these cells. However, even higher concentrations of 4% halothane failed to block the responsiveness of the PeA neurons to exogenous FMRFamide. Moreover, both 1 and 2% halothane enhanced the duration of the postsynaptic response to exogenously applied FMRFamide. These data suggest that the halothane-induced depression of synaptic transmission most likely occurred at the presynaptic level. 6. This study provides the first direct evidence that peptidergic transmission in the nervous system may also be susceptible to the actions of general anesthetics. In addition, we utilized a novel approach of in vitro reconstructed synapses for studying the effects of general anesthetics on monosynaptic transmission in the absence of other synaptic influences.
Patterns of synaptic activity in forward and feedback pathways within rat visual cortex
Authors: Domenici L. , Harding G. W. , Burkhalter A.
Published: December 2017

1. The laminar and temporal distribution of synaptic activity supplied by forward and feedback connections between different areas of rat visual cortex was determined with the use of current source density (CSD) analysis in in vitro slices. In forward connections, synaptic potentials were evoked by electrically stimulating area 17 and recording in the extrastriate area LM (lateromedial), that ranks at the second hierarchical level, one step above primary visual cortex. For activating feedback connections, the location of stimulating and recording electrodes was reversed. 2. The synaptic interactions in reciprocal intracortical circuits are excitatory, and they are mediated through glutamate receptors that are blocked by kynurenic acid. 3. Forward connections from area 17 to area LM provide input to all layers including a strong input to layer 4. In contrast, feedback input to layer 4 is weak and is mainly directed to superficial and deep layers. This laminar distribution closely resembles that seen anatomically. 4. Both forward and feedback connections evoke distinct temporal patterns of synaptic activation in different layers. Although onset and peak latencies are slightly shorter in the forward than in the feedback pathway, the difference is not statistically significant. 5. The spatiotemporal distribution of synaptic activation by forward connections resembles the pattern evoked by geniculocortical inputs. Feedback connections show greater similarities to long-range connections within area 17, although they are not identical. Our results support the notion derived from anatomic and in vivo physiological studies that forward and feedback pathways belong to functionally distinct cortical circuits.
Glycine at the NMDA receptor in cat visual cortex: saturation and changes with age
Authors: Czepita D. , Daw N. W. , Reid S. N.
Published: December 2017

1. Saturation of the glycine site at the N-methyl-D-aspartate (NMDA) receptor in cat visual cortex was tested by iontophoresing D-serine, and the contribution of this site to the visual response was tested by iontophoresing 7-chlorokynurenic acid (7-Cl-KYNA). Animals were tested at ages 3 wk, 6 wk, 5 mo, and adult. 2. In at least 40% of cells (24/57), D-serine increased the response significantly, showing that the glycine site was not saturated. However, the increase was rarely > 100%. 3. The amount by which D-serine increased the response did not vary significantly with age. 4. In five cases there was positive evidence for saturation of the glycine site. D-Serine did not increase the response significantly; however, when D-serine was applied on top of 7-Cl-KYNA, it did increase the response compared with that seen with 7-Cl-KYNA alone. These cases were all in 3-wk-old animals. In other cases (28/57), D-serine did not increase the response significantly, but we could not be absolutely certain that the D-serine had reached the site of action. 5. The effect of 7-Cl-KYNA was largest in 3-wk animals, in agreement with previous findings that the effect of D-2-amino-5-phosphonovalerate (APV) is largest at this age. 6. These results may provide a small part of the explanation for the finding that the NMDA receptor-mediated component of the visual response decreases between 3 and 6 wk of age, while the number of NMDA receptors is increasing. However, the magnitude of the results make it likely that other factors are more important.
Saccades to somatosensory targets. I. behavioral characteristics
Authors: Groh J. M. , Sparks D. L.
Published: December 2017

1. We compared the properties of saccades to somatosensory and visual targets. This comparison provides insight into the translation of sensory signals coding target location in different sensory coordinate frameworks into motor commands of a common format. Vibrotactile stimuli were delivered to the hands, which were fixed in position and concealed beneath a barrier. Saccades of different directions and amplitudes were elicited by the same somatosensory target from different initial eye positions. Both monkeys and humans served as subjects. 2. Somatosensory saccades were less accurate than visual saccades in both humans and monkeys. When the barrier concealing the hands was removed, somatosensory saccade accuracy improved. While the hands were concealed, the visual frame of reference provided by room illumination did not greatly affect saccade accuracy: accuracy was not degraded in complete darkness for two of three monkeys. 3. The endpoints of saccades to a single somatosensory target varied with initial eye position for the monkeys, but not for the human subjects. 4. We also found evidence of an effect of limb position on somatosensory saccades: when human subjects performed the task with crossed hands, the incidence of curved saccades increased. Saccades often began in the direction of the unstimulated hand and curved markedly toward the stimulated hand. When one subject was required to delay the saccade by 600-1,000 ms after target onset (the delayed saccade task), the saccades were straight. Somatosensory saccades were also straight when the hands were not crossed. 5. The reaction times of somatosensory saccades were longer than the reaction times of visual saccades, and they decreased as a function of saccade amplitude. The delayed saccade task reduced the differences between somatosensory and visual saccade reaction times. The reaction times of saccades to very dim visual targets increased into the range found for saccades to somatosensory targets. When the saccade target was the combination of the somatosensory and visual stimuli at the same location, the reaction time was slightly lower than for visual targets alone. 6. The peak velocities of somatosensory saccades were lower than those of visual saccades of the same amplitude. The velocities of saccades to combined somatosensory and visual targets were indistinguishable from those of saccades to visual targets alone. The differences between somatosensory and visual saccade velocity were maintained in the delayed trial type. These differences suggest that the main sequence or velocity-amplitude relationship characteristic of saccades depends on the modality of the target. 7. The implications of these modality-dependent differences in accuracy, reaction time, and saccade velocity are discussed with regard to models of the saccade generator and the coordinate transformation necessary for somatosensory saccades.
Sympathectomy induces adrenergic excitability of cutaneous C-fiber nociceptors
Authors: Bossut D. F. , Shea V. K. , Perl E. R.
Published: December 2017

1. The effects of ipsilateral removal of the superior cervical ganglion on the subsequent responsiveness of C-fiber polymodal nociceptors (CPMs) of the ear to close-arterial injections of norepinephrine (NE) were evaluated in adult, anesthetized rabbits. 2. In normal unanesthetized rabbits, the two ears were usually at the same temperature. Immediately after the ganglionectomy, the ipsilateral ear was warmer; however, at the time of electrophysiological recordings (4-23 days) the majority of animals had the ipsilateral ear cooler by > or = 1 degree C, suggestive of denervation supersensitivity. 3. NE (50 ng) did not activate any CPMs (n = 28) from intact animals. 4. Seven of 22 CPMs recorded from sympathectomized ears were activated by NE (50 ng). The responses varied considerably but typically consisted of 2-4 impulses in the 60 s after the NE injection. In some instances, repetitive activity continued for many minutes. Such prolonged discharge differs from the adrenergic responses seen after partial nerve damage. 5. The induction of adrenergic excitability in CPMs by sympathectomy is suggested to be a counterpart to postsympathectomy neuralgia in human beings and a possible part of the mechanism leading to sympathetically related pain states.
Impulse initiation in the mammalian muscle spindle during combined fusimotor stimulation and succinyl choline infusion
Authors: Carr R. W. , Morgan D. L. , Proske U.
Published: December 2017

1. This is a report of observations on the responses of the primary and secondary endings of soleus muscle spindles of the anesthetized cat to the combined effects of the depolarizing neuromuscular blocker succinyl choline (SCh), given intravenously, and fusimotor stimulation. The findings were interpreted in terms of a dual pacemaker model for activity generated in the bag1 intrafusal fiber interacting with activity coming from bag2 and chain fibers. 2. In preliminary experiments it was found, using whole ventral root stimulation at fusimotor strength, that spindle responses to fusimotor stimulation were not blocked by SCh, whereas extrafusal junctions blocked rapidly. In the presence of SCh, fusimotor responses of spindle secondary endings were, on average, slightly larger than their control values before SCh was given, whereas fusimotor responses of primary endings were slightly smaller. 3. A study of the responses of spindle primary endings to stimulation of single dynamic (gamma D) and static (gamma S) axons in the presence of SCh revealed a fundamental difference in behavior. None of the responses to stimulation of gamma D axons (9 gamma D axons with 8 primary endings) showed significant summation with the responses to SCh. By contrast, the 20 gamma S axons studied showed varying degrees of summation with the responses to SCh. The responses of secondary endings to gamma S stimulation in the presence of SCh resembled those of primary endings and gamma S stimulation. 4. To explain these differences it is proposed that the primary ending has two separate sites of impulse initiation, one close to terminals on the bag1 intrafusal fiber (innervated by gamma D axons) and a second close to terminals on the bag2 and chain fibers (innervated by gamma S axons). It is proposed that the maintained increase in spindle firing observed during SCh infusion is the result of a bag2 contracture. The response to gamma S stimulation, contracting bag2 and chain fibers, adds to the SCh response. The degree of summation varies depending on whether the gamma S activates bag2 fibers, chain fibers, or both. The bag1 contracture, together with the effects of gamma D stimulation, acts through a separate pacemaker and therefore does not sum with the steady increase in spindle firing in the presence of SCh. There may be pacemaker switching between the bag1 generator and the bag2 and chain generator. 5. If the model is representative of most spindles containing the three kinds of intrafusal fibers, and the contractions of bag2 and chain fibers generate activity through a common impulse generator, then this bears on the question of the functional independence of the bag2 and chain fiber systems.
Diffusion, not uptake, limits glycine concentration in the synaptic cleft
Authors: Titmus M. J. , Korn H. , Faber D. S.
Published: December 2017

1. The question of whether active uptake limits the duration of action of the inhibitory transmitter glycine has been addressed in vivo at inhibitory synapses on the goldfish Mauthner (M) cell. The kinetics of inhibitory postsynaptic potentials and inhibitory postsynaptic currents (IPSCs) evoked antidromically and by eighth-nerve stimulation were recorded in control and in conditions expected to block glycine uptake or slow its diffusion. Theoretical considerations, based on simulated quantal currents, predicted that if diffusion was slow, rapid uptake of glycine would be required and its block would prolong the synaptic responses. 2. Temperature coefficient values for IPSC decay time constants (tau S) are in the range of 2.0 for temperatures between 15 and 23 degrees C, suggesting that diffusion is not the rate-limiting step. 3. Li+, Ch+, or N-methyl-D-glucamine were substituted for 80% of the Na+ in the extracellular fluid to analyze the effects of blocking the Na(+)-dependent glycine uptake. These procedures enhanced the maximum inhibitory shunt produced by glycine iontophoresis, leading to the suggestion that uptake may buffer the concentration of the transmitter in the cleft. In contrast, the Na+ substitutes had no effect on the tau of the recurrent collateral IPSC, which involves synchronous activation of a pool of interneurons and has a monoexponential decay (tau approximately 10-11 ms). 4. The decay phase of the disynaptic IPSCs produced by stimulating the contralateral eighth nerve has fast and slow components, with a prolonged tail lasting up to 100 ms, particularly in the case of repetitive nerve stimulation. The tail is inhibitory, as revealed by its shunt of the antidromic action potential, and it is at least partially Cl- dependent. However, it can be accelerated by superfusion with the glutamate receptor antagonists 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) and DL-2-amino-5-phosphonopentanoic acid (APV). In the presence of these blockers, the IPSC decay remains biexponential (tau fast = 5.2 and 5.9 ms, tau slow = 94 and 130 ms for single and burst stimuli, respectively). Blocking uptake in this condition did not modify tau fast or tau slow. 5. We conclude that an active uptake mechanism does not shape glycinergic IPSCs, including the longer-lasting components that might include a contribution due to persistence of the transmitter. Rather, diffusion alone is sufficient to remove glycine at a rate faster than channel unbinding. 6. To test whether glycine might diffuse to adjacent excitatory synapses and enhance activation of N-methyl-D-aspartate receptors, CNQX and APV were applied locally, by pressure, to the M cell soma, but they had no effect on the prolonged decay of eighth-nerve-evoked responses. Thus the effects of the antagonists when added to the superfusate are exerted at the network level.