bluuebunny/crossref_metadata_2025 huggingface dataset:
Activation of metabotropic glutamate receptors induces long-term depression of GABAergic inhibition in hippocampus
Authors: Liu Y. B. , Disterhoft J. F. , Slater N. T.
Published: December 2017

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)
The spinal GABA system modulates burst frequency and intersegmental coordination in the lamprey: differential effects of GABAA and GABAB receptors
Authors: Tegner J. , Matsushima T. , el Manira A. , Grillner S.
Published: December 2017

1. The effect of spinal GABAergic neurons on the segmental neuronal network generating locomotion has been analyzed in the lamprey spinal cord in vitro. It is shown that gamma-aminobutyric acid (GABA)A- and GABAB-mediated effects influence the burst frequency and the intersegmental coordination and that the GABA system is active during normal locomotor activity. 2. Fictive locomotor activity was induced by superfusing the spinal cord with a Ringer solution containing N-methyl-D-aspartate (NMDA, 150 microM). The efferent locomotor activity was recorded by suction electrodes from the ventral roots or intracellularly from interneurons or motoneurons. If a GABA uptake blocker was added to the perfusate, the burst rate decreased. This effect was counteracted by GABAB receptor blockade by phaclofen or 2-(OH)-saclofen. If instead a GABAB receptor agonist (baclofen) was added during fictive locomotion, a depression of the burst rate occurred. It was concluded that a GABAB receptor activation due to an endogenous release of GABA caused a depression of the burst activity with a maintained well-coordinated locomotor activity. 3. If a GABAA receptor antagonist (bicuculline) is applied during fictive locomotion elicited by NMDA, a certain increase of the burst rate occurred. Conversely, if a selective GABAA agonist (muscimol) was administered, the burst rate decreased. Similarly, if the GABAA receptor activity was potentiated by activation of a benzodiazepine site by diazepam, the burst rate was reduced. If, however the GABAergic effect was first enhanced by an uptake blocker (nipecotic acid), an administration of a GABAA antagonist (bicuculline) increased the burst rate, but in addition, the burst pattern became less regular with recurrent shorter periods without clear reciprocal burst activity. The GABAA receptor activity appears important for the rate control and for permitting a regular burst pattern. 4. The intersegmental coordination in the lamprey is characterized by a rostrocaudal constant phase lag of approximately 1% of the cycle duration between the activation of consecutive segments during forward swimming. This rostrocaudal phase lag can be reversed during backward swimming, which can be induced also experimentally in the isolated spinal cord by providing a higher excitability to the caudal segments. In a split-bath configuration, a GABA uptake blocker or a GABAB agonist was administered to the rostral part of the spinal cord, which caused a reversal of the phase lag as during backward swimming. If GABAA receptors were blocked under similar conditions, the intersegmental coordination became irregular. It is concluded that an increased GABA activity in a spinal cord region can modify the intersegmental coordination.(ABSTRACT TRUNCATED AT 400 WORDS)
Effect of eye position within the orbit on electrically elicited saccadic eye movements: a comparison of the macaque monkey's frontal and supplementary eye fields
Authors: Russo G. S. , Bruce C. J.
Published: December 2017

1. We quantitatively compared the effects of eye position within the orbit on saccadic eye movements electrically elicited from two oculomotor areas of the macaque monkey's frontal lobe cortex: the frontal eye field (FEF) and the supplementary eye field (SEF). 2. The effect of eye position on electrically elicited saccades was studied by delivering 70-ms trains of intracortical microstimulation while the monkeys fixated a spot of light. Tests of different fixation points located across a rectangular array were randomly intermixed. Complete experiments were carried out on 38 sites in three FEFs of two monkeys and 59 sites from three SEFs of the same two monkeys. Stimulation currents for the array experiments were usually 10–20 microA above the site threshold; the average current used was 36 microA for FEF and 49 microA for SEF. 3. The magnitude of effect of the initial eye position on the elicited saccade's dimensions was quantified at each site by computing the linear regression of saccadic eye movement displacement on the eye position within the orbit when stimulation was applied. This computation was done separately for the horizontal and vertical axes. We call the resulting pair of regression coefficients “orbital perturbation indexes.” Indexes of 0.0 represent elicited saccades that do not change their trajectory with different initial eye positions (constant-vector saccades), whereas indexes of -1.0 represent elicited saccades that end at the same orbital position regardless of initial eye position (goal-directed saccades). 4. The effect of eye position varied across sites. In both FEF and SEF, the orbital perturbation indexes were distributed between approximately 0.0 and -0.5, with the horizontal and vertical indexes highly correlated across sites. 5. The average orbital perturbation indexes were small for both eye fields and were not significantly different. The mean horizontal indexes were -0.13 and -0.16 for SEF and FEF, respectively. The mean vertical indexes were -0.16 and -0.13. Neither SEF versus FEF difference was statistically significant. 6. In both SEF and FEF, sites yielding larger-amplitude saccades generally had larger orbital effects than sites yielding smaller saccades. This relationship accounted for the majority of the variability of the orbital perturbation indexes across sites in both SEF and FEF. 7. These results indicate that SEF and FEF are not distinguished from each other by the orbital dependence of their electrically elicited saccades. Thus they do not confirm the previously hypothesized dichotomy that FEF codes constant-vector saccades and SEF codes goal-directed saccades.(ABSTRACT TRUNCATED AT 400 WORDS)
Ionic currents in giant motor axons of the jellyfish, Aglantha digitale
Authors: Meech R. W. , Mackie G. O.
Published: December 2017

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)
A molecularly defined cardiorespiratory interneuron expressing SDPFLRFamide/GDPFLRFamide in the snail Lymnaea: monosynaptic connections and pharmacology
Authors: Skingsley D. R. , Bright K. , Santama N. , van Minnen J. , Brierley M. J. , Burke J. F. , Benjamin P. R.
Published: December 2017

1. Neuron-specific expression of alternately spliced exons of the gene encoding the Phe-Met-Arg-Phe-NH2 (FMRFamide) family of neuropeptides and the role of encoded peptides in synaptic transmission were examined in an identified cardiorespiratory interneuron, the visceral white interneuron (VWI), in the snail Lymnaea. 2. In situ hybridization using exon-specific probes showed VWI cytoplasmic expression of the exon encoding the Lymnaea heptapeptides Gly-Asp-Pro-Phe-Leu-Arg-Phe-NH2 (GDPFLRF amide) Ser-Asp-Pro-Phe-Leu-Arg-Phe-NH2 (SDPFLRF amide) but not the exon encoding the tetrapeptides FMRFamide and Phe-Leu-Arg-Phe-NH2 (FLRFamide). 3. The absence of the tetrapeptides (FMRFamide and FLRFamide) in the VWI was indirectly confirmed by the lack of immunoreactivity to a specific antibody raised against the sequence Leu-Tyr. This sequence is present in the Lymnaea tetrapeptide precursor, but not the heptapeptide precursor. 4. The VWI has monosynaptic connections with many identifiable neurons in the CNS. These were excitatory on three clusters of identified neurons [B group (Bgp), E group (Egp), and F group (Fgp)], inhibitory on another cluster [A group (Agp)] or biphasic (excitation followed by inhibition) on a single giant neuron [right pedal dorsal 1 (RPeD1)]. 5. The role of GDPFLRFamide/SDPFLRFamide as putative neurotransmitters was examined by comparing neuronally evoked postsynaptic responses with the effects of focal peptide application. 6. The heptapeptides closely mimicked the inhibitory responses (threshold pressure pipette concentration 10(-9) M) on the Agp cells and RPeD1, including an increase in membrane conductance. FMRFamide was 1 order of magnitude less potent. GDPFLRFamide/SDPFLRFamide, applied either alone or in “cocktails” (combinations of GDPFLRFamide, SDPFLRFamide, FMRFamide, and FLRFamide), did not reproduce the excitatory effect of the VWI on the Bgp, Egp, and Fgp cells. These peptides, applied either together or separately, inhibited the cells. 7. FMRFamide or FLRFamide, but not GDPFLRFamide or SDPFLRFamide, could reproduce the initial depolarizing component of the biphasic response on RPeD1. This only occurred at concentrations of > or = 10(-4) M (10(-3) M was necessary to get spikes on RPeD1) and may not be physiologically significant. 8. We conclude that at least one so far unidentified co-transmitter must be present in the VWI to account for its full range of synaptic responses.
Monkey superior colliculus represents rapid eye movements in a two-dimensional motor map
Authors: Hepp K. , Van Opstal A. J. , Straumann D. , Hess B. J. , Henn V.
Published: December 2017

1. Although the eye has three rotational degrees of freedom, eye positions, during fixations, saccades, and smooth pursuit, with the head stationary and upright, are constrained to a plane by ListingR's law. We investigated whether Listing's law for rapid eye movements is implemented at the level of the deeper layers of the superior colliculus (SC). 2. In three alert rhesus monkeys we tested whether the saccadic motor map of the SC is two dimensional, representing oculocentric target vectors (the vector or V-model), or three dimensional, representing the coordinates of the rotation of the eye from initial to final position (the quaternion or Q-model). 3. Monkeys made spontaneous saccadic eye movements both in the light and in the dark. They were also rotated about various axes to evoke quick phases of vestibular nystagmus, which have three degrees of freedom. Eye positions were measured in three dimensions with the magnetic search coil technique. 4. While the monkey made spontaneous eye movements, we electrically stimulated the deeper layers of the SC and elicited saccades from a wide range of initial positions. According to the Q-model, the torsional component of eye position after stimulation should be uniquely related to saccade onset position. However, stimulation at 110 sites induced no eye torsion, in line with the prediction of the V-model. 5. Activity of saccade-related burst neurons in the deeper layers of the SC was analyzed during rapid eye movements in three dimensions. No systematic eye-position dependence of the movement fields, as predicted by the Q-model, could be detected for these cells. Instead, the data fitted closely the predictions made by the V-model. 6. In two monkeys, both SC were reversibly inactivated by symmetrical bilateral injections of muscimol. The frequency of spontaneous saccades in the light decreased dramatically. Although the remaining spontaneous saccades were slow, Listing's law was still obeyed, both during fixations and saccadic gaze shifts. In the dark, vestibularly elicited fast phases of nystagmus could still be generated in three dimensions. Although the fastest quick phases of horizontal and vertical nystagmus were slower by about a factor of 1.5, those of torsional quick phases were unaffected. 7. On the basis of the electrical stimulation data and the properties revealed by the movement field analysis, we conclude that the collicular motor map is two dimensional. The reversible inactivation results suggest that the SC is not the site where three-dimensional fast phases of vestibular nystagmus are generated.(ABSTRACT TRUNCATED AT 400 WORDS)
Properties of a presynaptic metabotropic glutamate receptor in rat neostriatal slices
Authors: Lovinger D. M. , Tyler E. , Fidler S. , Merritt A.
Published: December 2017

1. The effect of the metabotropic glutamate receptor agonist trans-1-aminocyclopentane-1,3-dicarboxylic acid (t-ACPD) on glutamatergic transmission at corticostriate synapses was examined using slices of neostriatum. Field potential recordings were performed in slices from adult animals, and the effects of t-ACPD on the synaptically driven population spike were examined. Tight-seal whole-cell recordings were made in slices from 2 to 4-wk-old rats, and effects of t-ACPD on the amplitude of excitatory postsynaptic potentials (EPSPs) and postsynaptic neuronal membrane properties were examined. In addition, the effects of putative metabotropic receptor agonists and antagonists and 4-aminopyridine were examined. The ability of these compounds to mimic t-ACPD or block its actions were determined. 2. Application of t-ACPD (5-100 microM) depressed the maximal amplitude of the synaptically driven population spike during field potential recording. This compound likewise depressed the amplitude of EPSPs observed with whole-cell recording. The 1S,3R isomer of t-ACPD was effective in depressing transmission, whereas the 1R,3S isomer was without effect at 50 microM. The cis isomer of ACPD (c-ACPD) also depressed transmission at concentrations from 25 to 100 microM. 3. Depression of population spike or EPSP amplitude by t-ACPD was not altered in the presence of the putative metabotropic receptor antagonist L-aminophosphonopropionic acid (AP3, 1 mM). In addition, the depressant action of t-ACPD on the population spike was not mimicked by aminophosphonobutyric acid, which has been shown to produce synaptic depression at other excitatory synapses.(ABSTRACT TRUNCATED AT 250 WORDS)
Epileptogenesis in chronically injured cortex: in vitro studies
Authors: Prince D. A. , Tseng G. F.
Published: December 2017

1. Field potentials and intracellular activities were examined in neocortical slices obtained through areas of chronic cortical injury produced by cortical undercutting and transcortical lesions made in vivo 7-122 days before the terminal in vitro slice experiment. 2. Abnormal field potentials characterized by long- and variable-latency multiphasic events could be evoked by layer VI-white matter or subpial stimulation in 9 of 15 animals that had adequate partial cortical isolations. These "epileptiform" field potentials were recorded in layers II-V and propagated across the cortex. They appeared at threshold in an all-or-none fashion and, in most slices, could be blocked by increasing stimulus intensity. In one slice, spontaneous epileptiform events occurred that were similar to those evoked by extracellular stimulation. 3. Intracellular activities during the epileptiform field potentials consisted of polyphasic synaptic events that were predominantly depolarizing and that could last < or = 400-500 ms, synchronous with the field potential activities. A variety of observations suggested that the neuronal activities underlying epileptiform field potentials were relatively asynchronous and much less intense than those previously found in chemically induced epileptogenesis within the neocortex. 4. Inhibitory postsynaptic potentials (IPSPs) were not prominent in neurons when threshold stimuli evoked epileptiform events; however, suprathreshold stimuli could elicit biphasic IPSPs and block the long-latency polysynaptic activity and abnormal field potential in most slices. Depolarizing components of the polysynaptic activity had the appearance of excitatory postsynaptic potentials in terms of their responses to alterations in membrane potential. 5. Comparison of spike parameters in layer V neurons of epileptogenic slices with those in control layer V neurons showed no significant differences in spike height, threshold, duration, or rise time. Resting membrane potentials were also not significantly different. 6. There was a highly significant difference in input resistance (RN) between layer V neurons in control and injured slices; the mean value for neurons in lesioned cortex was 68.1 M omega, whereas that in control cells was 30.5 M omega. There was also a significant prolongation of the slow membrane time constant in neurons of injured cortex (19.4 ms) as opposed to that in control cells (12.2 ms), suggesting that a change in specific resistivity or capacitance contributed to the higher RNS. 7. The relationship between adapted spike frequency and applied current (f-I slope) was steeper in layer V neurons from injured cortical slices (44.3 Hz/nA) than in normal layer V cells (28.2 Hz/nA).(ABSTRACT TRUNCATED AT 400 WORDS)
Visual-response properties of units in the turtle cerebellar granular layer in vitro
Authors: Fan T. X. , Rosenberg A. F. , Ariel M.
Published: December 2017

1. Single units were recorded extracellularly in the turtle's cerebellar cortex from an isolated brain preparation during visual stimulation. Only a small fraction of the isolated units responded to visual stimuli. For these visually responsive units, the most effective visual stimulus was a moving check pattern that covered the entire surface of the retinal eyecup. The visually responsive units had little or no spontaneous spike activity, nor were they driven by flashes of diffuse light or stationary patterns. 2. All the visually responsive units were direction sensitive and were driven exclusively by the contralateral eye. This direction tuning was well fit by a limacon model (mean correlation coefficient, 0.89). The distribution of the entire sample indicates a slight preponderance of upward preferred directions. 3. The direction tuning of these cerebellar units was independent of stimulus contrast or the pattern's configuration (such as checkerboards or random check or dot patterns). In the preferred direction, a unit's spike frequency increased monotonically as a function of stimulus velocity until approximately 10 degrees/s, but remained direction sensitive (relative to the opposite direction) at speeds as fast as 100 degrees/s. 4. In some experiments the ventrocaudal brain stem was transected in the frontal plane just caudal to the cerebellar peduncles. Although this lesion presumably removes climbing fiber input from the inferior olivary nuclei, the visual-response properties in the cerebellar cortex were unaffected. 5. The response properties of these units indicate that they encode retinal slip information in the cerebellum.(ABSTRACT TRUNCATED AT 250 WORDS)
Properties and modulation of a calcium-activated potassium channel in rat olfactory bulb neurons
Authors: Egan T. M. , Dagan D. , Levitan I. B.
Published: December 2017

1. Single calcium-activated potassium channels (KCa channels) were recorded from membrane patches of rat olfactory bulb neurons in culture. Only one kind of KCa channel was seen, and it was present in approximately 50% of detached patches. 2. This channel, like maxi-KCa channels of other tissues, had a single-channel conductance of 270 pS, a reversal potential (Erev) of 0 mV in symmetrical K+, and was highly selective for K+ over Na+ and Cl-. 3. The KCa channel was blocked by d-tubocurarine (d-TC) on the cytoplasmic side, and charybdotoxin (CTX) on the extracellular side. This pharmacology is identical to that of one type of KCa channel from rat brain, observed previously in artificial bilayers and called the type 1 KCa channel. 4. The probability that the channel was in the open state (Po) increased with membrane depolarization. The position of the Po versus transmembrane voltage (Vm) curve was shifted by changes in [Ca2+]i so that the channel was open more often in higher [Ca2+]i. The gating kinetics resembled those of the type 1 KCa channel observed in bilayers. 5. Po was increased after superfusion of the cytoplasmic membrane surface with the active catalytic subunit of cyclic AMP-dependent protein kinase (PK-A), together with MgATP. Phosphorylation altered the distribution of channel closed times but had little effect on open times. The results suggest that phosphorylation is an important molecular mechanism in modulating the activity of this KCa channel from mammalian brain.
Static and dynamic responses of periodontal ligament mechanoreceptors and intradental mechanoreceptors
Authors: Dong W. K. , Shiwaku T. , Kawakami Y. , Chudler E. H.
Published: December 2017

1. The response properties of 39 periodontal ligament mechanoreceptors (PDLMs) and 12 intradental mechanoreceptors (IMs) related to the intact mandibular canine tooth were isolated by extracellular recording methods from the ipsilateral trigeminal semilunar ganglion. 2. The stimulus threshold and response magnitude of individual PDLMs depended on the direction of steady force applied to the intact canine tooth. Canine PDLMs as a population, however, did not have a preferred stimulus direction. IMs were activated only by a rapid mechanical transient applied to the intact tooth in any direction. The stimulus threshold and response magnitude of each IM were approximately equipotent in all stimulus directions. 3. Application of quantifiable ramp-and-hold stimulation showed that PDLMs can encode the intensity of steady forces as well as the rate of force ramps. Increasing the ramp rates decreased the total ramp discharge but increased the peak discharge frequency. IMs encoded only the rate of force ramps that were applied by percussion. Higher ramp rates increased both the total discharges and peak discharge frequency of IMs. 4. The dynamic response properties of PDLMs and IMs were clearly differentiated by sinusoidal vibratory stimulation. The maximum frequencies for entrainment of IM discharge at the stimulus cycle length (251 +/- 103 Hz, mean +/- SD) and at any periodicity including multiples of the stimulus cycle length (295 +/- 100 Hz) were significantly higher than the maximum frequencies for PDLM discharge entrainment at the stimulus cycle length (103 +/- 53 Hz) and at any periodicity (133 +/- 62 Hz). 5. The functional similarities of PDLMs and IMs, respectively, to slowly adapting type II mechanoreceptors and Pacinian corpuscle receptors in the skin are discussed. Our present findings, which complement earlier anatomic and behavioral evidence, strongly suggest that IMs subserve nonnociceptive and nonpain functions. Both PDLMs and IMs may provide a continuum of dynamic afferent inputs necessary for tactile sensibility of teeth.
Actions of 5-hydroxytryptamine on neurons of the rat cingulate cortex
Authors: Tanaka E. , North R. A.
Published: December 2017

1. Intracellular recordings were made from layer V pyramidal neurons in slices of rat cingulate cortex. Electrodes contained potassium methylsulphate and biocytin for subsequent histology. 2. Synaptic potentials were separated pharmacologically with DL-2-amino-5-phosphonovaleric acid (APV), 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), bicuculline, and 2-hydroxysaclofen into components mediated, respectively, by N-methyl-D-aspartate (NMDA) type excitatory amino acid, non-NMDA type excitatory amino acid, gamma-aminobutyric acid (GABAA), and GABAB receptors. Components mediated at excitatory amino acid, GABAA and GABAB receptors reversed polarity at -11, -76, and -108 mV, respectively. 3. When synaptic potentials were evoked by stimulation to the subcortical white matter, 5-hydroxytryptamine (5-HT; 1-100 microM) reversibly reduced the amplitude of NMDA, non-NMDA, GABAA, and GABAB components. Selective agonists and antagonists were used to show that this resulted from activation of 5-HT1B receptors. 4. When synaptic potentials were evoked by stimulation within layer V, 5-HT reduced the amplitude only of the NMDA and non-NMDA components but did not affect the GABAA and GABAB components. 5-HT did not change the amplitude of depolarizations evoked by direct application of glutamate. 5. It is concluded that 5-HT presynaptically inhibits the release of excitatory amino acids at synapses onto prefrontal pyramidal neurons and at synapses onto local feed-forward inhibitory interneurons. 6. 5-HT also hyperpolarized, depolarized, or did not change the membrane potential. The hyperpolarization involved 5-HT1A receptors and resulted from potassium conductance increase. The depolarization involved 5-HT2 receptors and resulted from potassium conductance decrease.
The relationship of monkey frontal eye field activity to saccade dynamics
Authors: Segraves M. A. , Park K.
Published: December 2017

1. In this study, we compared the temporal waveforms of the activity of monkey frontal eye field movement neurons with the dynamics of saccadic eye movements. 2. Movement neurons in the frontal eye field were selected according to previously published criteria. They had little or no response to visual stimuli in a fixation task, and equivalent activity before visually guided and memory-guided saccades. We studied corticotectal neurons and corticopontine neurons identified by antidromic excitation, as well as neurons whose projections were not identified. 3. These neurons had a peak activation at a mean of 13 ms before the saccade began. However, rather than falling off rapidly as the saccade ended, most neurons continued to fire after the saccade, returning to baseline at a mean of 93 ms after the end of the saccade. 4. We measured the decrement in activity for these neurons during the saccade. Although a few neurons showed decrements of > 60% of their peak activity level, the average activity dropped only 16.9%, with some neurons actually showing a rise in activity during the saccade. If we ignored the latency between peak in activity and saccade start and measured the fall in activity for a period equal to one saccade duration after the peak, the average drop in activity was still only 34.9%. Thus the activity of these neurons did not appear to be closely related to dynamic motor error, which falls from its maximum value to zero over the time course of a saccade. 5. These results suggest that a focus of movement activity within the topographic map in the frontal eye field specifies the amplitude and direction for an impending saccade, whereas the peak of movement activity signals the time to initiate a saccade. 6. Unlike the superior colliculus, the activity of frontal eye field movement neurons does not appear to be related to dynamic events that occur during the saccade, such as motor error.
Local anesthetics block transient outward potassium currents in rat neocortical neurons
Authors: Andreasen M. , Hablitz J. J.
Published: December 2017

1. Whole-cell patch clamp techniques were used to record transient outward potassium currents in embryonic rat neocortical neurons maintained in culture. The effect of lidocaine and its quaternary derivative QX222 on this transient outward current (TOC) was examined. 2. Extracellular application of lidocaine produced a progressive decrease in peak TOC amplitude with no change in the overall current waveform. Peak amplitude was reduced to 74 +/- 6% (mean +/- SE) of control by 0.5 mM and to 48 +/- 2% by 2 mM lidocaine. The effect of lidocaine was fully reversible. Intracellular application of QX222 also resulted in a concentration-dependent reduction of the TOC with 0.5 mM reducing the peak amplitude to 73 +/- 8% of control and 1 mM reducing it to 41 +/- 4%. 3. Lidocaine reduced TOCs when applied intracellularly but the rate of block was considerably slower than with extracellular application. QX222 had no effect on the TOC when applied extracellularly. 4. Lidocaine (1 mM) induced a 4-5 mV hyperpolarizing shift in the voltage-dependence of activation and steady-state inactivation with no change in the slope factor. This small hyperpolarizing shift could not account for the > 30% reduction in peak amplitude produced by 1 mM lidocaine. Hyperpolarizing shifts were not seen with 0.5 mM intracellular QX222. The lack of effect on the slope of the activation and steady-state inactivation curves indicates that local anesthetic (LA) actions were not voltage-dependent. 5. Lidocaine or QX222 did not produce a significant change in the TOC decay time-constant. The lack of any significant change in the voltage-dependence of steady-state inactivation or time course of recovery from inactivation indicates that LAs were not altering inactivation mechanisms. 6. Application of lidocaine or QX222 during a 60-s period, when the TOC channels were kept in the resting state, reduced the peak amplitude of the first evoked TOC. The reduction was not as large as when TOCs were evoked at regular 0.1-Hz intervals during drug application. This indicates that the amount of tonic block induced by the LA is dependent on channel activation. Increasing the activation frequency to 1 Hz after a steady-state had been obtained with lidocaine or QX222 did not result in additional reductions in the TOC. 7. It is proposed that lidocaine and QX222 tonically block TOCs by binding to a site within the channel protein complex, rendering the channel non-conductive.(ABSTRACT TRUNCATED AT 400 WORDS)
Encoding of head acceleration in vestibular neurons. I. Spatiotemporal response properties to linear acceleration
Authors: Bush G. A. , Perachio A. A. , Angelaki D. E.
Published: December 2017

1. Extracellular recordings were made in and around the medial vestibular nuclei in decerebrated rats. Neurons were functionally identified according to their semicircular canal input on the basis of their responses to angular head rotations around the yaw, pitch, and roll head axes. Those cells responding to angular acceleration were classified as either horizontal semicircular canal-related (HC) or vertical semicircular canal-related (VC) neurons. The HC neurons were further characterized as either type I or type II, depending on the direction of rotation producing excitation. Cells that lacked a response to angular head acceleration, but exhibited sensitivity to a change in head position, were classified as purely otolith organ-related (OTO) neurons. All vestibular neurons were then tested for their response to sinusoidal linear translation in the horizontal head plane. 2. Convergence of macular and canal inputs onto central vestibular nuclei neurons occurred in 73% of the type I HC, 79% of the type II HC, and 86% of the VC neurons. Out of the 223 neurons identified as receiving macular input, 94 neurons were further studied, and their spatiotemporal response properties to sinusoidal stimulation with pure linear acceleration were quantified. Data were obtained from 33 type I HC, 22 type II HC, 22 VC, and 17 OTO neurons. 3. For each neuron the angle of the translational stimulus vector was varied by 15, 30, or 45 degrees increments in the horizontal head plane. In all tested neurons, a direction of maximum sensitivity was identified. An interesting difference among neurons was their response to translation along the direction perpendicular to that that produced the maximum response ("null" direction). For the majority of neurons tested, it was possible to evoke a nonzero response during stimulation along the null direction always had response phases that varied as a function of stimulus direction. 4. These spatiotemporal response properties were quantified in two independent ways. First, the data were evaluated on the basis of the traditional one-dimensional principle governed by the "cosine gain rule" and constant response phase at different stimulus orientations. Second, the response gain and phase values that were empirically determined for each orientation of the applied linear stimulus vector were fitted on the basis of a newly developed formalism that treats neuronal responses as exhibiting two-dimensional spatial sensitivity. Thus two response vectors were determined for each neuron on the basis of its response gain and phase at different stimulus directions in the horizontal head plane.(ABSTRACT TRUNCATED AT 400 WORDS)
Multiple potassium conductances and their role in action potential repolarization and repetitive firing behavior of neonatal rat hypoglossal motoneurons
Authors: Viana F. , Bayliss D. A. , Berger A. J.
Published: December 2017

1. The role of multiple potassium conductances in action potential repolarization and repetitive firing behavior of hypoglossal motoneurons was investigated using intracellular recording techniques in a brain stem slice preparation of the neonatal rat (0-15 days old). 2. The action potential was followed by two distinct afterhyperpolarizations (AHPs). The early one was of short duration and is termed the fAHP; the later AHP was of longer duration and is termed the mAHP. The amplitudes of both AHPs were enhanced by membrane potential depolarization (further from EK). In addition, their amplitudes were reduced by high extracellular K+ concentration, suggesting that activation of potassium conductances underlies both phases of the AHP. 3. Prolongation of the action potential and blockade of the fAHP were observed after application of 1) tetraethylammonium (TEA) (1-10 mM) and 2) 4-aminopyridine (4-AP) (0.1-0.5 mM). Calcium channel blockers had little or no effect on the fAHP or action potential duration. 4. The size of the mAHP was diminished by 1) manganese, 2) lowering external Ca2+, 3) apamin, and 4) intracellular injection of ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA) suggesting that influx of calcium activates the potassium conductance that underlies the mAHP. 5. The mAHP was unaffected by nifedipine (20 microM), but was strongly reduced by focal application of omega-conotoxin GVIA, suggesting that N-type calcium channels represent the major calcium influx pathway for activation of the calcium-dependent K+ conductance underlying the mAHP. 6. Repetitive firing properties were investigated by injecting long-duration depolarizing current pulses. Steady-state firing rose linearly with injected current amplitude. The slope of the firing frequency-current (f-I) relationship averaged approximately 30 Hz/nA in control conditions. Blockade of the conductance underlying the mAHP caused a marked increase in the minimal repetitive firing frequency and in the slope of the f-I plot, indicating a prominent role for the conductance underlying the mAHP in controlling repetitive firing behavior. 7. We conclude that action potential repolarization and AHPs are due to activation of pharmacologically distinct potassium conductances. Whereas repolarization of the action potential and the fAHP involves primarily a voltage-dependent, calcium-independent potassium conductance that is TEA- and 4-AP-sensitive, the mAHP requires the influx of extracellular calcium and is apamin sensitive. Activation of the calcium-activated potassium conductance greatly influences the normal repetitive firing of neonatal hypoglossal motoneurons.
Facilitation in ON-OFF directionally selective ganglion cells of the rabbit retina
Authors: Grzywacz N. M. , Amthor F. R.
Published: December 2017

1. We have investigated the facilitation of extracellularly recorded responses of ON-OFF directionally selective (DS) ganglion cells of the rabbit retina to two-slit preferred-direction apparent motion produced by both prolonged light steps, which simulate movement of an edge past two apertures, and light flashes, which simulate movement of a spot or slit. 2. Within the excitatory receptive-field center of DS ganglion cells, apparent motion with prolonged light steps elicits preferred-direction facilitation whose rise time (220 +/- 150 ms, average rise to 90% of maximum for 6 cells) is typically longer than the rise time of the excitatory response elicited by each slit. The decay time to baseline of facilitation during prolonged light steps is generally longer than 500 ms and hence greatly exceeds the typical duration of the excitatory response elicited by the slits. 3. Prolonged light steps are generally effective for facilitating any given excitatory receptive-field locus from a roughly ovoid area that typically extends on the order of 100-200 microns in the preferred direction, which is less than one-half the size of the excitatory receptive-field center. Within 100 microns, facilitation can occur for motion diagonal to the preferred-null axis as long as the projection of the motion on the preferred-null axis points in the preferred direction. 4. The time course of preferred-direction facilitation between two slits does not appear to have a strong systematical dependence on the interslit distance over the range in which facilitation is effective. 5. Short light flashes are ineffective for eliciting facilitation and, at sufficiently long interslit delays, elicit inhibition all around the test slit. This inhibition may be due to the antagonistic surround mechanism within the receptive-field center, which is effectively elicited by short-duration stimuli. 6. The effect of preferred-direction facilitation is addition-like, rather than multiplication-like. That is, the facilitatory effect of the first slit appears as the addition of a fixed value to the response-versus-contrast curve of the second slit, rather than a multiplication of the curve by a constant factor. The functional relationship between strength of facilitation and contrast of the first slit is sigmoidal, however, and thus nonlinear. 7. Experiments with long light steps show that the interaction between excitation and preferred-direction facilitation is largely segregated between the ON and OFF pathways.(ABSTRACT TRUNCATED AT 400 WORDS)
Activity of medullary reticulospinal neurons during fictive locomotion
Authors: Perreault M. C. , Drew T. , Rossignol S.
Published: December 2017

1. The pattern of discharge of medullary reticulospinal neurons, identified by antidromic stimulation applied at the L1-L2 segment of the spinal cord, was studied during fictive locomotion, occurring spontaneously, or evoked by stimulation of the mesencephalic locomotor region in high-decerebrate, paralyzed cats. Unitary recordings were made in the medial reticular formation (P5.0-14.0 mm; L0.5-2.0 mm), and the fictive locomotor pattern was monitored by recording the electroneurogram (ENG) of representative flexor and extensor muscle nerves from each of the four limbs. 2. In total, 117 reticulospinal neurons were recorded in 15 cats. Among these, 73.5% (86/117) modified their discharge at the onset of locomotion. These cells were divided into three subpopulations: 34/86 of the cells always maintained a fixed temporal relationship with the activity of one of the recorded nerves (ENG-related = 39.6%); the pattern of discharge of 42/86 cells was related to the locomotor rhythm [(LR-related-48%)] but was not temporally correlated with any of the recorded nerves; and the remaining 10 cells increased their firing frequency at the onset of locomotion but remained tonic (TONIC-11.6%). 3. Of the ENG-related neurons, 64.8% were temporally correlated to extensor nerve activity, whereas the remaining 35.2% were correlated to flexor nerves. These neurons were either related to forelimb (55.9%) or hindlimb (44.1%) nerves lying either ipsilateral (38.2%) or contralateral (61.8%) to the recording site. A few neurons (n = 3; 8.8%) were related to nerve activity of more than one limb. 4. The pattern of discharge of the LR-related neurons, although not correlated to the activity of any one recorded nerve, could be preferentially related to the locomotor rhythm in either the forelimbs (12/23) or hindlimbs (11/23). 5. ENG- and LR-related reticulospinal neurons were intermingled in the medial reticular formation. In both cases, cells related to the forelimbs were located more dorsally than those related to the hindlimbs. It is suggested that both the ENG- and LR-related neurons represent a single functional population of reticulospinal neurons that is part of an intrinsically organized reticulospinal system that functions to coordinate the activity of the skeletal musculature. 6. The present results show that the majority of reticular neurons projecting as far as the lumbar spinal cord are phasically modulated during locomotion, even in the absence of phasic peripheral afferent inputs. Moreover, the complexity of the discharge patterns in paralyzed animals was found to be similar to that observed in the intact cat.(ABSTRACT TRUNCATED AT 400 WORDS)
The excitatory and inhibitory amino acid receptors on horizontal cells isolated from the white perch retina
Authors: Zhou Z. J. , Fain G. L. , Dowling J. E.
Published: December 2017

1. The distribution and the properties of receptors to the inhibitory amino acid glycine (GLY) and the excitatory amino acid glutamate (GLU) and its analogues kainate (KA), quisqualate (QUIS), alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), and N-methyl-D-aspartate (NMDA), were studied with whole-cell and outside-out patch-clamp techniques on all four types of horizontal cells isolated from the retina of white perch. 2. Glycine at concentrations above 30 microM evoked whole-cell current responses from two types of horizontal cells (H2 and H4). The other two types of horizontal cells (H1 and H3) were unresponsive to GLY (30 microM-3 mM). 3. Responses elicited by GLY from H2 and H4 cells were similar, consisting of inward currents that desensitized with a half-decay time of 0.5-2 s at glycine concentrations between 100 and 500 microM. GLY-activated currents were inhibited by the glycine receptor antagonist strychnine (STRYCH). Current responses evoked by GLY reversed at the Cl- equilibrium potential. 4. Dose-response analysis of peak currents induced by GLY revealed a Hill coefficient of 2.0 +/- 0.1 (mean +/- SD, n = 3) and an median effective concentration (EC50) of 85 +/- 2 microM (n = 3). 5. Single glycine receptor channels recorded from outside-out patches had a main-state conductance of 47 +/- 4 pS (n = 3). 6. Every type of horizontal cell from the white perch responded to GLU, KA, QUIS, and AMPA but none responded to exogenously applied NMDA (200 microM) or NMDA (200 microM) + GLY (1 microM) in a Mg+2-free bathing solution. 7. The ratio of the amplitude of responses to GLU, KA, QUIS, and AMPA remained nearly constant among all the horizontal cells tested, suggesting there might be only a single population of non-NMDA receptors on these cells. 8. QUIS and KA both elicited responses from the horizontal cells. When applied together with KA, QUIS competitively antagonized the responses of horizontal cells to KA. 9. The results demonstrated the existence of an inhomogeneous distribution of strychnine-sensitive glycine receptors and a homogeneous distribution of non-NMDA type glutamate receptors among the four types of white perch horizontal cells.