bluuebunny/crossref_metadata_2025 huggingface dataset:
Role of vagal afferents and spinal pathways modulating inhibition of bradykinin-induced plasma extravasation by intrathecal nicotine
Authors: Miao F. J. , Janig W. , Dallman M. F. , Benowitz N. L. , Heller P. H. , Basbaum A. I. , Levine J. D.
Published: December 2017

1. Nicotine, a major active component of tobacco smoke, has been shown to modulate the inflammatory response via both peripheral and central nervous system pathways. Recently we found that spinal intrathecal administration of nicotine dose-dependently inhibits bradykinin-induced plasma extravasation (BK-induced PE) in the knee joint of the rat and that the dose-response curve for the inhibition of BK-induced PE by intrathecal nicotine is shifted to the left, by six orders of magnitude, after surgical interventions in the abdominal cavity, which might have interrupted visceral afferents to the neuraxis. Therefore we focused, in this study, on the contribution of the vagal afferents to depression of BK-induced PE by intrathecal nicotine. Furthermore, the effect of acute spinalization at the level C6-C8 was investigated. The hypothesis was that impulse activity in vagal afferents has a pronounced inhibitory effect on the modulation of BK-induced PE by intrathecal nicotine and that spinal pathways are important in mediating this effect. 2. Chronic subdiaphragmatic vagotomy and elimination of vagal afferents, by neonatal capsaicin treatment or by application of kainic acid to the nodose ganglia, enhanced the potency of intrathecal nicotine depression of BK-induced PE, by six to seven orders of magnitude when compared with the control. 3. Acute subdiaphragmatic vagotomy enhanced the potency of intrathecal nicotine-induced depression of BK-induced PE (without changing its maximum effect), by about three to four orders of magnitude when compared with the sham-operated (control) animals (with intact vagus nerves).(ABSTRACT TRUNCATED AT 250 WORDS)
Local intracortical connections in the cat's visual cortex: postnatal development and plasticity
Authors: Ghose G. M. , Freeman R. D. , Ohzawa I.
Published: December 2017

1. We have studied the nature, development, and plasticity of local intracortical interactions by examining the visual responses from pairs of cells in the visual cortex of anesthetized and paralyzed adult cats and kittens at postnatal age 4 wk. Simultaneous discharge from nearby cells was analyzed by the cross-correlation method to infer three types of neuronal interactions: monosynaptic excitation, monosynaptic inhibition, and polysynaptic excitation. 2. Among cell pairs that exhibit correlated discharge, the nature of these interactions is similar in kittens and adults. For example, the mean monosynaptic delay is the same for cell pairs in the adult cat and the kitten: 0.8 ms. The primary difference in the distribution of neural interactions is the increased prevalence of inhibitory interactions among adult cat cell pairs compared with kitten cell pairs. However, in both age groups and in nearly all laminae, polysynaptic interactions are the most commonly observed type of interaction. 3. Neural interactions revealed by cross-correlation analysis also were studied with respect to the receptive field properties of the cells. The hierarchical theory proposed by Hubel and Wiesel suggests that monosynaptic excitation should be seen from simple to complex cells. It further suggests that complex cells do not provide monosynaptic excitation either to simple or to other complex cells. However, we find no cases of monosynaptic excitation from simple to complex cells in the adult cat. Moreover, we find explicitly antihierarchical connections, i.e., excitatory connections from complex to simple cells, in both kittens and adults. The excitatory influence of complex cells on simple cell receptive field properties is not incorporated into current models of receptive field structure formation. Our results suggest that complex cells might have an important modulatory role in simple cell discharge. 4. Plasticity of intracortical synaptic connections was studied by examining the dynamics of monosynaptic peaks with cross-correlograms. We examined Hebb's seminal hypothesis regarding synaptic plasticity that the excitatory connections between two neurons should strengthen with simultaneous activity. To test directly whether Hebbian plasticity can be rapidly induced by stimulus-evoked activity, the strength of monosynaptic excitation between pairs of neurons was monitored during periods of visual stimulation lasting < or = 2 h. Synaptic strength was computed by summing the cross-correlogram bins containing the monosynaptic peak. Transient increases in monosynaptic peak area are found among cell pairs linked by monosynaptic excitation after 8-15 min of visual stimulation. The duration and amplitude of these changes are similar in adult cats and kittens.(ABSTRACT TRUNCATED AT 400 WORDS)
Agonist and antagonist effects of nicotine on chick neuronal nicotinic receptors are defined by alpha and beta subunits
Authors: Hussy N. , Ballivet M. , Bertrand D.
Published: December 2017

1. Functional neuronal nicotinic receptors were reconstituted in Xenopus oocytes by the nuclear injection of different combinations of chick and rat cDNAs encoding alpha and beta subunits. The pharmacology of these nicotinic receptors was investigated using two-electrode voltage clamp. 2. The sensitivity of the chick alpha 3/beta 2, alpha 3/beta 4, and alpha 4/beta 2 receptors to acetylcholine (ACh) and neuronal bungarotoxin differed markedly, indicating that both subunits contribute to the pharmacological properties of the receptors. 3. Nicotine acted as an agonist on the chick alpha 3/beta 4 and alpha 4/beta 2 receptors and rat alpha 3/beta 2 receptor. In contrast, nicotine (at concentrations > 3 microM) was only a weak partial agonist of the chick alpha 3/beta 2 receptor. Moreover, nicotine coapplied with 3 microM ACh on the chick alpha 3/beta 2 receptor acted as a potent competitive antagonist, with an IC50 of 0.43 microM. No antagonist effect of nicotine could be revealed on the other nicotinic receptors. 4. The effect of nicotine was tested on hybrid receptors obtained by coinjection of chick and rat cDNAs encoding the alpha 3 and beta 2 subunits (yielding the rat alpha 3/chick beta 2 and chick alpha 3/rat beta 2 receptors). Nicotine (10 microM) strongly inhibited both hybrid receptors. 5. Chimeric subunits were constructed by exchanging a segment located in the extracellular N-termini of chick alpha 3 and alpha 4 subunits and chick alpha 3 and rat alpha 3 subunits. These subunits were coexpressed in oocytes with chick or rat beta 2 subunits. The effect of nicotine on these receptors pointed to the importance of a 15 amino acid stretch located 3' of the first transmembrane segment in the determination of the agonist and antagonist action of nicotine. 6. Within this 15 amino acid segment, a single residue differs in chick and rat alpha 3 subunits, at position 198, within the ligand binding site of alpha subunits. Gln198 of the rat alpha 3 subunit was replaced by Thr as found in the chick alpha 3 subunit, using site-directed mutagenesis. The mutant subunit was coexpressed with the rat beta 2 subunit, yielding receptors which were inhibited by nicotine. 7. It is concluded that both alpha and beta subunits not only alter considerably the sensitivity of the nicotinic receptor to agonists and antagonists, but also can turn an agonist into a potent antagonist of one receptor subtype.(ABSTRACT TRUNCATED AT 400 WORDS)
Modulatory role for the serotonergic cerebral giant cells in the feeding system of the snail, Lymnaea. II. Photoinactivation
Authors: Yeoman M. S. , Kemenes G. , Benjamin P. R. , Elliott C. J.
Published: December 2017

1. Photoinactivation of dye-filled neurons was used to examine the modulatory role of the paired cerebral giant cells (CGCs) in the Lymnaea feeding system. 2. Both CGCs were filled with fluorescent dyes. Lucifer yellow was used for "soma" kills and injected via intracellular microelectrodes. CGC axons were retrogradely filled with 5 (6)-carboxyfluorescein (5-CF), through the cut ends of the ventro- and lateral buccal nerves, for "axonal" kills. 3. Irradiation of the CGC soma with a blue laser light (0.5 MW/m2) led to a loss of their recorded membrane potentials and the synaptic responses with their postsynaptic cells (feeding motor neurons). CGC coupling and axonal fluorescence were lost after axonal irradiation. 4. The tonic firing rate of CGC axon spikes in peripheral nerve roots following bilateral soma kills was reduced to approximately 15% of preirradiation levels (n = 2; from 52.5 +/- 3.75 spikes/min to 8.2 +/- 0.95 spikes/min; mean +/- SE) but spike activity was not completely eliminated. 5. The fictive feeding rhythm was evoked by depolarizing a modulatory neuron, the slow oscillator (SO), before and after laser irradiation. Thirty minutes after both the CGCs were irradiated (n = 8), the frequency of the SO-driven feeding rhythm was reduced. Mean fictive feeding rates were reduced from 8.3 to 4.5 cycles/min for soma kills (n = 3) and from 16.2 to 9.6 cycles/min for axonal kills (n = 5; P < 0.05). 6. The results suggest that the CGCs play a modulatory role in controlling the frequency of oscillation of the feeding central pattern generator (CPG) in Lymnaea. The SO could still drive a full fictive feeding rhythm after irradiation but at a reduced rate. At least in the soma kills, the residual spike activity retained in the distal branches of the CGCs appeared sufficient to allow the SO to drive this slow rhythm.
Testing models of the oculomotor velocity-to-position transformation
Authors: Tweed D. , Misslisch H. , Fetter M.
Published: December 2017

1. Do neural computations in premotor circuits mirror the physical properties of the systems they control? In 1987, Tweed and Vilis showed that oculomotor theories where a neural integrator converts eye angular velocity commands into position commands cannot be correct, because angular position is not the integral of angular velocity. Recently Schnabolk and Raphan proposed that an angular velocity integrator is nevertheless used to generate tonic commands in the oculomotor system. Here we test the Schnabolk-Raphan (S-R) model against Tweed and Vilis's quaternion (Q) model of the velocity to position transformation. 2. The S-R model predicts large (up to 7 degrees) transient (approximately 700 ms) deviations ("blips") in torsional eye position during attempted horizontal and vertical saccades. The Q model predicts no blips. Search coil recordings of saccades by 7 normal human subjects showed no large blips. 3. For approximately 200 saccades by each subject, we plotted the area under the torsional blip versus the product of saccade eccentricity and magnitude. According to the S-R model, this graph should form a straight line with slope 1.00. According to the Q model, the slope should be zero. Measured slopes averaged 0.016 (range -0.073 to 0.061) for saccade targets at 20 degrees eccentricity and 0.040 (range 0.004-0.076) for targets at 40 degrees. 4. No parameter change can significantly improve the S-R model, but lowering one parameter eradicates the tiny inaccuracy in the Q model. We show that the fundamental reason for the S-R model's failure is its use of a commutative controller to steer a noncommutative plant.
The cerebellar nodulus and ventral uvula control the torsional vestibulo-ocular reflex
Authors: Angelaki D. E. , Hess B. J.
Published: December 2017

1. The vestibulo-ocular reflex (VOR) was investigated in rhesus monkeys before and after surgical ablation of the cerebellar nodulus and ventral uvula. The lesion resulted in an alteration of the torsional VOR: compensatory eye movements were poor in the low frequency range and the time constant was reduced to values comparable to those of primary semicircular canal afferents. In addition, animals permanently lost their ability to generate torsional optokinetic nystagmus (OKN). 2. The effects of the lesion on the torsional VOR differed from those observed in the horizontal and vertical vestibulo-ocular systems. While the vertical VOR and OKN were unaltered, the horizontal VOR and OKN were characterized by increased time constants and smaller phase leads during low frequency head oscillations. 3. These results suggest that the cerebellar nodulus and/or ventral uvula exert a distinct and specific dynamic control on the torsional vestibulo-ocular and optokinetic reflexes. Such specific effects on the torsional system could reflect a functional segregation of the vestibulo-cerebellum in terms of the controls of torsional versus horizontal and vertical slow phase eye movements.
Recruitment of a projection neuron determines gastric mill motor pattern selection in the stomatogastric nervous system of the crab, Cancer borealis
Authors: Norris B. J. , Coleman M. J. , Nusbaum M. P.
Published: December 2017

1. In the isolated stomatogastric nervous system of the crab Cancer borealis (Fig. 1), the muscarinic agonist oxotremorine elicits several distinct gastric mill motor patterns from neurons in the stomatogastric ganglion (STG; Fig. 2). Selection of a particular gastric mill rhythm is determined by activation of distinct projection neurons that influence gastric mill neurons within the STG. In this paper we identify one such neuron, called commissural projection neuron 2 (CPN2), whose rhythmic activity is integral in producing one form of the gastric mill rhythm. 2. There is a CPN2 soma and neuropilar arborization in each commissural ganglion (CoG). The CPN2 axon projects through the superior esophageal nerve (son) and the stomatogastric nerve (stn) to influence neurons in the STG (Figs. 3 and 4A). 3. CPN2 activity influences most of the gastric mill neurons in the STG. Specifically, CPN2 excites gastric mill neurons GM and LG (gastric mill and lateral gastric, respectively) and inhibits the dorsal gastric (DG), anterior median (AM), medial gastric (MG), and inferior cardiac (IC) neurons (Figs. 5 and 6). CPN2 also indirectly inhibits gastric mill neurons Int1 and VD (interneuron 1 and ventricular dilator neuron, respectively) through its activation of LG. The CPN2 excitatory effects are mediated at least partly via discrete excitatory postsynaptic potentials (EPSPs; Fig. 4B), whereas its inhibitory effects are produced via smooth hyperpolarizations. 4. Within the CoG, CPN2 receives excitatory synaptic input from the anterior gastric receptor neuron (AGR), a gastric mill proprioceptive sensory neuron (Fig. 7) and inhibitory synaptic input from the gastric mill interneuron, Int1 (Fig. 8). 5. During one form of the gastric mill rhythm, CPN2 fires rhythmically in time with the gastric mill motor pattern, whereas it is silent or fires weakly during other gastric mill rhythms (Fig. 9). 6. When CPN2 rhythmic activity is suppressed during a CPN2-influenced gastric mill rhythm, the gastric mill rhythm continues, but the pattern is altered (Fig. 10). Moreover, transiently stimulating CPN2 during any ongoing gastric mill motor pattern can reset the timing of that rhythm (Fig. 11). 7. Tonic activity in CPN2 is insufficient to elicit a gastric mill rhythm (Fig. 12). Phasic activity in CPN2 can elicit a gastric mill rhythm only in preparations in which gastric mill neurons are already in an excited state (Figs. 12 and 13). 8. CPN2 recruitment plays a pivotal role in determining the final form of the gastric mill rhythm.(ABSTRACT TRUNCATED AT 400 WORDS)
Blockade of NMDA-activated channels by magnesium in the immature rat hippocampus
Authors: Strecker G. J. , Jackson M. B. , Dudek F. E.
Published: December 2017

1. N-methyl-D-aspartate (NMDA)-receptor single-channel currents were examined in outside-out patches from thin slices of rat hippocampus to examine possible age dependence in the Mg(2+)-block of NMDA-mediated responses. The kinetics of Mg2+ block, among other channel properties, were compared between CA1 pyramidal cells from neonatal and 2-wk-old animals and dentate gyrus granule cells from neonatal and 4-wk-old animals. 2. Two distinct conductance states were seen consistently in nominally Mg(2+)-free solutions. The main conductance state was 50 and 56 pS in pyramidal cells and granule cells, respectively. The difference in NMDA-receptor channel conductance between the two cell types was statistically significant at all ages examined. Both cell types exhibited a less frequent 35- to 40-pS conductance state. 3. Channel closing rates showed no intrinsic voltage dependence in Mg(2+)-free solutions in any group. Open times became strongly voltage dependent when Mg2+ was added. The rate of block by Mg2+ was similar in all groups. 4. Voltage and Mg2+ influenced primarily the shortest time constant of shut-time distributions. Longer components varied relatively little with voltage or [Mg2+]. The effects of voltage and [Mg2+] suggest that brief shuttings represent closed states in the absence of Mg2+ and primarily a Mg(2+)-blocked state in the presence of Mg2+. 5. The rate of unblocking by Mg2+ was similar in all groups. Thus the dissociation constant for Mg2+ binding (i.e., the ratio of the unblocking and blocking rates) also showed little variation. 6. NMDA-receptor channels in two regions of the hippocampus behaved in a qualitatively similar fashion both in neonates and 2-or 4-wk-old rats. These observations are inconsistent with previous studies obtained using other methods, which suggested that block of NMDA receptor channels by Mg2+ increases substantially with age. Nevertheless, subtle developmental and regional differences in other aspects of NMDA-receptor channel behavior were detected, perhaps reflecting variations in molecular structure tailored to specific functional requirements.
Nicotinic and muscarinic activation of motoneurons in the crayfish locomotor network
Authors: Cattaert D. , Araque A. , Buno W. , Clarac F.
Published: December 2017

1. We investigated the effects of acetylcholine (Ach) on identified motoneurons (MNs) using an in vitro preparation of the crayfish thoracic nervous system. Discontinuous current-clamp and single electrode voltage-clamp recordings from 50 MNs were performed along with micropipette pressure ejection of Ach (or agonists) close to the recording electrode. 2. Localized ejections of relatively large volumes (500–2,500 pl) of Ach (10(-2) M) or of the muscarinic agonist oxotremorine (Oxo, 10(-2)M) onto the MN neuropile region, usually (90% of the cases) induced a slow, alternating rhythmic activity in antagonistic MNs. In other cases (4 experiments), with similar deliveries of Ach or Oxo, MNs developed the ability to fire rhythmically but only when depolarized by sustained current injection. Pressure ejections of smaller volumes (50–200 pl) of Ach (10(-2)M) close to the recorded MN could give rise to a fast (1–2 s) large amplitude (< or = 20 mV) membrane depolarization (12%), a long-lasting (10 s to several minutes) and small (2–5 mV) depolarization (14%), and a combination of the two (74%). These responses appeared to involve different regions of the neurite because they changed when the drug-ejection pipette was displaced in the neuropile. Moreover, fast and long-lasting depolarizing components resulted from a direct effect of Ach onto the MNs because they persisted under tetrodotoxin (TTX, 10(-6)M) and cobalt (Co2+, 5 x 10(-3) M) superfusion. 3. Whereas the membrane resistance decreased during the fast Ach-induced depolarization, it increased during the long-lasting depolarization. The increase in membrane resistance was more pronounced at depolarized potentials more than -55 mV and involve a reduction in K+ conductance. 4. Superfusion with nicotinic and muscarinic antagonists revealed that the fast Ach-induced depolarization involved nicotinic receptors, muscarinic receptors, or both, whereas the slow depolarization was exclusively muscarinic. 5. The Ach-evoked inward currents were studied under voltage clamp. The fast nicotinic component (Inic) increased with hyperpolarizing holding potentials and decreased with depolarizing potentials, reversing at between 10 and 30 mV. The fast muscarinic current (Ifmus) displayed similar characteristics and reversed at about -10 mV. Whereas both fast components were voltage independent, the long-lasting muscarinic component (Ismus) was voltage dependent. The response grew with membrane depolarization, but when the holding potential was hyperpolarized below resting level, the response declined to disappear at about -60 mV and beyond.(ABSTRACT TRUNCATED AT 400 WORDS)
Calcium-dependent potassium channels play a critical role for burst termination in the locomotor network in lamprey
Authors: el Manira A. , Tegner J. , Grillner S.
Published: December 2017

1. The possible involvement of calcium-dependent potassium channels (KCa) in the termination of locomotor bursts was investigated by administration of a specific blocker, apamin, in the lamprey spinal cord in vitro. The effects were examined by recording the efferent activity in ventral roots and by intracellular recording from interneurons and motoneurons. During fictive locomotion induced by N-methyl-D-aspartate (NMDA), apamin was found to affect both the frequency of bursting and the regularity of the locomotor pattern. 2. At the single cell level, NMDA can induce pacemaker-like membrane potential oscillations in individual neurons after administration of tetrodotoxin. Apamin (2.5 microM) produced a marked increase of the duration of the depolarizing plateau phase occurring during these NMDA-induced oscillations; this shows that the repolarization of the plateau is initiated by a progressive activation of apamin-sensitive KCa-channels. 3. The action potential is followed by an afterhyperpolarization (AHP) with a fast and a slow phase (sAHP). The latter is known to be caused by apamin-sensitive KCa-channels. During repetitive firing, the interspike interval is dependent on the amplitude and the duration of the sAHP. Apamin caused a reduction of the spike frequency adaptation with a concomitant increase in the firing frequency. In some cells, apamin in addition reduced the threshold for the action potential. Apamin-sensitive KCa-channels thus will be involved in controlling both the onset and the duration of neuronal firing in the lamprey spinal cord. 4. During fictive locomotion induced by NMDA (40-200 microM), a blockade of KCa-channels by apamin produced an increase of the coefficient of variation (mean = 167%, n = 26), which was statistically significant in 21 out of 26 experiments. At 40-150 microM NMDA, an average increase in cycle duration was 77% and statistically significant in 15 out of 20 preparations. At 200 microM NMDA (corresponding to higher burst rate), on the other hand, the average increase was only 6% and the increase was statistically significant in only 1 out 6 cases. For a given experiment, the strength of the apamin effect depended on the level of NMDA drive used, being more pronounced at slow rhythms, when it often caused a complete disruption of the locomotor pattern. At high burst rates, however, the cycle duration was less affected and a disruption of the regular burst pattern did not occur.(ABSTRACT TRUNCATED AT 400 WORDS)
Properties of the sodium current in rat chromaffin cells exposed to nerve growth factor in vitro
Authors: Islas-Suarez L. , Gomez-Chavarin M. , Drucker-Colin R. , Hernandez-Cruz A.
Published: December 2017

1. This paper examines the electrophysiological properties of cultured rat adrenal chromaffin cells at different stages of neuron-like morphological differentiation in response to nerve growth factor (NGF). 2. Chromaffin cells display a large variability in the morphological changes after exposure to NGF. However, a marked tendency to neuronal phenotypic transformation prevails after two weeks in culture. 3. The voltage dependence of the macroscopic Na currents, judged by the current to voltage relationship, did not change significantly as a result of NGF treatment. Moreover, when kinetics, half-activation, and half-inactivation parameters of Na currents were compared between control and NGF-treated cells, no significant differences were observed. 4. Peak Na currents in control cells remained < 1 nA throughout the 17 d of observation, whereas currents > 1 nA became more frequent after the first week of NGF exposure. Cells with Na currents > 2 nA were found routinely in cultures exposed to NGF for > or = 15 d, but inadequate voltage control and neurite spiking prevented a thorough examination. Sodium current density in the population of NGF-treated chromaffin cells increased progressively over time, until an apparent plateau (3.5-fold increase) was reached by the end of the second week. No significant changes were observed in control, untreated cells. 5. The increase in Na channel density induced by NGF in chromaffin cells in compatible with the acquisition of the neuronal phenotype. Interestingly, the increase in Na channel expression occurs in slower time scale than in their neoplastic correlate, the PC12 cells. Na channels newly expressed by chromaffin cells after NGF treatment are functionally indistinguishable from those already present before treatment.
Extracellular alkaline transients mediated by glutamate receptors in the rat hippocampal slice are not due to a proton conductance
Authors: Paalasmaa P. , Taira T. , Voipio J. , Kaila K.
Published: December 2017

1. The ionic mechanism of extracellular alkaline transients mediated by alpha-amino-3-hydroxy-5-methylisoxazolate-4-propionic acid (AMPA) receptor channels was studied in the rat hippocampal slice (area CA1) by means of H(+)-, Ca(2+)- and Na(+)-selective microelectrodes. 2. Alkaline transients mediated by selective synaptic activation of AMPA receptors were coupled to a transient fall in extracellular Ca2+ ([Ca2+]o). 3. Removal of [Ca2+]o blocked the alkaline transient evoked by microinjection of AMPA, but had little effect on the simultaneous tetrodotoxin-resistant fall in extracellular Na+ ([Na+]o). 4. Alkaline transients evoked by microinjection of gamma-aminobutyric acid (GABA) were not affected by removal of [Ca2+]o. GABA had no effect on [Na+]o. 5. The present results indicate that activity-induced glutamatergic alkaline transients in the hippocampal slice are due to an influx of Ca2+, and not to a conductive movement of H+ ions across glutamate-gated cation channels.
A novel cholinergic induction of long-term potentiation in rat hippocampus
Authors: Auerbach J. M. , Segal M.
Published: December 2017

1. We studied long-term cholinergic effects on synaptic transmission in submerged hippocampal slices using intra- and extracellular recording techniques. 2. Bath application of submicromolar concentrations of carbachol (CCh) produced a gradually developing, long-lasting increase in the CA1 excitatory postsynaptic potential and population spike. This potentiation was blocked by atropine and, hence, named muscarinic long-term potentiation (LTPm). Application of DL-2-amino-5-phosphonovaleric acid had no effect on LTPm, indicating that this phenomenon is N-methyl-D-aspartate receptor independent. 3. These effects of CCh were not likely to be due to the blockade of one of several K+ conductances by the drug; the time and concentration dependence of LTPm were different from those associated with cholinergic blockade of K+ conductances. 4. Removal of extracellular calcium (Cao2+) from the bath blocked synaptic transmission. CCh added in calcium-free medium induced LTPm, which was revealed upon removal of the drug by washing with normal calcium-containing medium. Neither cutting CA1-CA3 connections nor cessation of synaptic stimulation interfered with LTPm induction. 5. Application of thapsigargin or H-7 together with CCh blocked LTPm, suggesting the involvement of intracellular calcium (Cai2+) stores and protein kinases, respectively, in the LTPm mechanism. 6. Subthreshold cholinergic stimulation coupled with subthreshold tetanic stimulation caused LTP. CCh had no effect when administered after the LTP mechanism had been saturated by repeated suprathreshold tetani. Tetanic stimulation failed to cause LTP when applied after LTPm had been induced by CCh. These experiments indicate that tetanus-induced potentiation and LTPm share a common mechanism and provide a direct link between ACh and mechanisms of synaptic plasticity.
Patterns of excitatory and inhibitory synaptic transmission in the rat neostriatum as revealed by 4-AP
Authors: Flores-Hernandez J. , Galarraga E. , Pineda J. C. , Bargas J.
Published: December 2017

1. Synaptic potentials induced by 4-aminopyridine (4-AP) were recorded intracellularly from rat neostriatal neurons in an in vitro slice preparation. EC50 for this 4-AP action was approximately 120 microM. The threshold for activation of synaptic potentials was 5 microM. 2. 4-AP-induced synaptic potentials appeared stochastically. Most were blocked by 1 microM tetrodotoxin or 400 microM Cd2+. Therefore they reflect a release of neurotransmitters dependent on both Ca2+ entry to the terminals and action potential firing. 3. Bicuculline (BIC) (< or = 10 microM), a gamma-aminobuturic acid-A (GABAA) antagonist, blocked about half of the 4-AP-induced synaptic potentials. This suggests that intrinsic inhibitory connections within the neostriatum are activated by 4-AP administration. 4. 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX; < or = 10 microM) plus D-2-amino-5-phosphonovaleric acid (D-APV; < or = 100 microM) blocked most of the BIC-resistant 4-AP-induced synaptic potentials. This suggests that 4-AP induced release of glutamate (GLU) from extrinsic glutamatergic afferents. As most glutamatergic afferents are extrinsic, these afferents then would be able to fire spikes and release transmitter for several hours after they are cut from their somata. 5. If CNQX plus D-APV were administered before BIC, neostriatal neurons responded in different ways. In one half of the neurons, all induced synaptic potentials were blocked. This suggests that most GABAergic intrinsic connections between neostriatal neurons are activated indirectly by 4-AP. 4-AP would first activate extrinsic glutamatergic afferents and these in turn would activate GABAergic intrinsic neurons and connections. 6. In the remaining half of the recorded neurons, administration of CNQX plus D-APV blocked most, but not all of the 4-AP-induced synaptic potentials. The synaptic potentials that remained had a characteristic pattern: they were high amplitude, rhythmic, bursts of synaptic potentials. They were blocked by BIC (5 microM) but not by mecamylamine (> 10 microM). This suggests that these bursts of synaptic potentials were GABAergic and generated by intrinsic neurons. Therefore these neurons would not innervate all neostriatal neurons equally but just a subset of them. 7. Records from an identified aspiny neostriatal interneuron, obtained from the same preparation, are shown. This interneuron fired in bursts and its morphologically and physiologically similar to the recently described, fast spiking, parvalbumin immunoreactive, GABAergic, aspiny interneuron is functional in the slice preparation.(ABSTRACT TRUNCATED AT 400 WORDS)
Neuronal responses in cat primary auditory cortex to electrical cochlear stimulation. I. Intensity dependence of firing rate and response latency
Authors: Raggio M. W. , Schreiner C. E.
Published: December 2017

1. Responses of neurons in primary auditory cortex (AI) of the barbiturate anesthetized adult cat were studied using cochlear stimulation with electrical and acoustic stimuli. Acoustic stimulation of the ear ipsilateral to the studied cortical hemisphere with brief biphasic clicks was compared with electrical stimulation of the contralateral cochlea with brief biphasic electrical pulses delivered via a feline cochlear prosthesis. The contralateral ear was deafened immediately before implantation of the cochlear prosthesis. The feline cochlear prosthesis consisted of four bipolar electrode pairs and was placed in the scala tympani. Two bipolar electrode conditions were used for stimulation: one near radial pair with electrode spacing of approximately 0.5 mm, and one longitudinal pair with electrode spacing of approximately 6 mm. 2. The firing rates obtained from single- and multiple-neuron recordings were measured as a function of stimulus intensity for single electrical and acoustic pulses. Resulting rate/level functions were characterized by a fast growing low-level segment and a more slowly growing, saturating, or decreasing high-level segment. The slopes of these two segments as well as the stimulus level and firing rate at the juncture of these two segments (the transition point) provide a complete characterization of the response magnitude behavior as a function of stimulus intensity. 3. The main characteristics of rate/level functions obtained with electrical and acoustic cochlear stimulation were quite similar. However, for any given neuron, differences in the primary growth behavior, such as monotonic or nonmonotonic growth, could be observed between the different stimulation modes. 4. Response latencies from single- and multiple-neuron recordings were obtained as a function of stimulus intensity for electrical and acoustic pulses. Resulting latency/level functions were characterized by a rapidly decreasing low-level segment and a more slowly decreasing high-level segment. The slopes of these two segments as well as the stimulus level and response latency at the juncture of these two segments (the transition point) provide a complete characterization of the response latency behavior as a function of stimulus intensity. Transition point levels for the rate/level function and the latency/level were nearly identical. 5. The characteristic latency behavior for each neuronal response was found to be very similar for acoustic and electrical stimulation. Correlation analysis revealed a close relationship between latency parameters of the two electrical stimulation conditions, a weaker relationship between the longitudinal electrical and the acoustic conditions, and the weakest relationship between the radial electrical and acoustic conditions. 6. Correlation analysis for rate and latency parameters revealed several relationships between these response aspects.(ABSTRACT TRUNCATED AT 400 WORDS)
Mechanosensitive properties of pelvic nerve afferent fibers innervating the urinary bladder of the rat
Authors: Sengupta J. N. , Gebhart G. F.
Published: December 2017

1. Single-unit activity was recorded from S1 dorsal root afferent fibers in pentobarbital-anesthetized rats. In 25 experiments, 245 afferent fibers were identified by electrical stimulation of the pelvic nerve. Fifty-two percent were C fibers (conduction velocity: 1.70 +/- 0.04 m/s; mean +/- SE) and 48% were A delta-fibers (conduction velocity: 11.07 +/- 0.95 m/s). 2. Of 245 pelvic nerve afferent fibers, 92 (38%) responded to noxious urinary bladder distension (UBD; 80 mmHg); 57 of these fibers were C fibers and 35 were A delta-fibers. Forty-four fibers responded to colorectal distension (CRD; 80 mmHg); 32 were C fibers and 12 were A delta-fibers. A total of 39 fibers were identified in the anal mucosa; 3 were C fibers and 36 were A delta-fibers. Seventy fibers (28%) in these experiments were unresponsive to either UBD or CRD or to probing of the anal mucosa; 32 were unmyelinated C fibers and 38 were A delta-fibers. 3. Reproducibility of responses to repeated UBD (80 mmHg, 20 s; 8 trials at 4-min intervals) was tested in 10 fibers. In nine fibers, responses to repeated distension did not change; one fiber exhibited a progressive decrease in response magnitude after the third trial. 4. Of the 92 afferent fibers that responded to UBD, 45 were further characterized for responses to graded intensities of UBD. Forty fibers had some resting activity (1.7 +/- 0.3 impulses/s) and five fibers exhibited no ongoing activity. The response to UBD adapted slowly during the 20-s period of phasic UBD or during slow isotonic filling of the bladder. 5. The stimulus-response function (SRF) of fibers (n = 45) to graded UBD was monotonic < or = 80 mmHg. Thresholds for responses were determined after extrapolation of the least-squares linear regression line to the ordinate, and varied between 0 and 45 mmHg. The frequency distribution profile of thresholds revealed two populations of pelvic nerve afferent fibers in the urinary bladder: a larger group (n = 36) of low-threshold (LT) fibers (5.7 +/- 1.0 mmHg) and a smaller group (n = 9) of high-threshold (HT) fibers (34 +/- 2.5 mmHg). 6. Responses of four LT fibers to graded UBD were tested before and 30 min after instillation of 0.5 ml of 0.5% acetic acid (pH 3) into the bladder. The mean threshold for response of these fibers before instillation of acetic acid (9.4 +/- 3.1 mmHg) more than doubled (to 22.3 +/- 6.7 mmHg) after instillation of acetic acid.(ABSTRACT TRUNCATED AT 400 WORDS)
Effects of 5-HT on thalamocortical synaptic transmission in the developing rat
Authors: Rhoades R. W. , Bennett-Clarke C. A. , Shi M. Y. , Mooney R. D.
Published: December 2017

1. Recent immunocytochemical and receptor binding data have demonstrated a transient somatotopic patterning of serotonin (5-HT)-immunoreactive fibers in the primary somatosensory cortex of developing rats and a transient expression of 5-HT1B receptors on thalamocortical axons from the ventral posteromedial thalamic nucleus (VPM). 2. These results suggest that 5-HT should strongly modulate thalamocortical synaptic transmission for a limited time during postnatal development. This hypothesis was tested in intracellular recording experiments carried out in thalamocortical slice preparations that included VPM, the thalamic radiations, and the primary somatosensory cortex. Effects of 5-HT and analogues were monitored on membrane potentials and input resistances of cortical neurons and on the amplitude of the synaptic potentials evoked in them by stimulation of VPM. 3. Results obtained from cortical neurons in slices taken from rats during the first 2 wk of life indicated that 5-HT strongly inhibited the VPM-evoked excitatory postsynaptic potential (EPSP) recorded from cortical neurons in a dose-dependent manner. In contrast, 5-HT had no significant effects on membrane potential, input resistance, or depolarizations induced by direct application of glutamic acid to cortical cells. 4. The effects of 5-HT were mimicked by the 5-HT1B receptor agonists 1-[3-(trifluoromethyl)phenyl]-piperazine (TFMPP) and 7-trifluoromethyl-4(4-methyl-1-piperazinyl)-pyrrolo[1,2-a]-quinoxaline maleate and antagonized by the 5-HT1B receptor antagonist (-)-pindolol. The 5-HT1A agonist [(+/-)8-hydroxydipropylaminotetralin HBr] (8-OH-DPAT) had less effect on the VPM-elicited EPSP, and the effects of 5-HT upon this response were generally not antagonized by either 1-(2-methoxyphenyl)-4-[4-(2- phthalimmido)butyl]piperazine HBr (a 5-HT1A antagonist) or ketanserine (a 5-HT2 antagonist) or spiperone (a 5-HT1A and 2 antagonist). 5. The ability of 5-HT to inhibit the VPM-evoked EPSP in cortical neurons was significantly reduced in slices from animals > 2 wk of age. The effectiveness of TFMPP in such animals was even more attenuated than that of 5-HT, and the effectiveness of 8-OH-DPAT was unchanged with age. These results are consistent with the disappearance of 5-HT1B receptors from thalamocortical axons after the second postnatal week and the maintenance of 5-HT1A receptors on some neurons. 6. All of the results obtained in this study are consistent with the conclusion that 5-HT has a profound, but developmentally transient, presynaptic inhibitory effect upon thalamocortical transmission in the rat's somatosensory cortex.
Retinal ganglion neurons express a toxin-resistant developmentally regulated novel type of high-voltage-activated calcium channel
Authors: Rothe T. , Grantyn R.
Published: December 2017

1. High-voltage-activated Ca2+ currents [ICa(HVA)] were studied in immunolabeled mouse retinal ganglion neurons (RGNs) to elucidate channel-specific components and their developmental changes in vitro. 2. Neurons were dissociated at postnatal day 5. RGNs were selected for electrophysiological measurements by vital labeling with an antibody against Thy-1.2. ICa(HVA) were recorded with patch electrodes in the whole cell configuration at a holding voltage (Vh) of -90 mV. 3. A total of 111 neurons was studied. On average, 13% of ICa(HVA) was reversibly blocked by 10 microM nifedipine, approximately 30% of the compound current displayed an irreversible block by 2.5 microM omega-conotoxin (omega-CTX) GVIA. The remainder current was resistant to both drugs, suggesting that the total ICa(HVA) was a mixture of at least three different components. 4. Developmental analysis revealed a significant increase of the omega-CTX-GVIA/nifedipine-resistant component of ICa(HVA) (31% at day in vitro (DIV) 0–2, 70% at DIV 18–26) mainly at the expense of the omega-CTX-GVIA-sensitive current. No significant change was found in the nifedipine-sensitive component of ICa(HVA). 5. To characterize the Ca2+ current component that was resistant to both omega-CTX-GVIA and nifedipine at Vh -90 mV, three tests were performed. The P channel antagonist omega-agatoxin IVA (omega-Aga-IVA, 200 nM) completely failed to block ICa(HVA) in mouse RGNs. The novel Ca2+ channel blocker omega-CTX-MVIIC (5 microM) decreased the ICa(HVA) remaining after omega-CTX-GVIA treatment by only approximately 10%.(ABSTRACT TRUNCATED AT 250 WORDS)
Cerebellar contribution to the spatial encoding of orienting gaze shifts in the head-free cat
Authors: Goffart L. , Pelisson D.
Published: December 2017

1. Cerebellar saccadic dysmetria may result from a disturbance in the processes that ensure correct execution of gaze displacement. Alternatively, an impairment in the preparatory processes that lead to the specification of the movement goal may also produce this deficit. 2. We report here on a pharmacologically induced dysmetria that suggests a cerebellar contribution to the neural processes encoding the location of the goal for orienting gaze shifts. 3. Shifts of gaze (eye-in-space) were recorded in the head-free cat after the GABA agonist muscimol was unilaterally injected into the caudal part of the fastigial nucleus. 4. Gaze saccades towards the inactivated side were hypermetric. These ipsiversive movements overshot the target by a constant error, regardless of target eccentricity and initial gaze position. 5. Gaze saccades directed away from the inactivated side undershot the target. The degree of hypometria increased when the amplitude of the required movement increased. 6. These results suggest a different contribution of the caudal fastigial nucleus to the accuracy of visually triggered gaze shifts, depending on the direction of the impending saccade. The systematic error of ipsiversive movements and the inappropriate movements evoked by presenting a target at the same physical location as gaze reveal that fastigial inactivation interfered with the processes that encode the location of a visual target.
Serotonin inhibits high-threshold Ca2+ channel currents in capsaicin-sensitive acutely isolated adult rat DRG neurons
Authors: Del Mar L. P. , Cardenas C. G. , Scroggs R. S.
Published: December 2017

1. The effect of serotonin (5HT) was studied on high-threshold Ca2+ channel currents in a subpopulation of acutely isolated rat dorsal root ganglion cell bodies that had long-duration action potentials, lacked IH current, were capsaicin-sensitive, and thus resembled C-type nociceptors. 2. In these neurons, 10 microM 5HT inhibited peak high-threshold Ca2+ channel currents by 61.5 +/- 6.9% (mean +/- SE), (n = 7). The effects of 5HT were mimicked by 1 microM (+)8-hydroxy-2-(di-n-propylamino)-tetralin HBr [(+)8-OH-DPAT] in five neurons tested, and the effects of 1 microM (+)8-OH-DPAT were antagonized by 100 nM 1-(2-methoxyphenyl)-4-[4-(2-phthalimmido)butyl]piperazine HBr (NAN-190) in six neurons tested. 3. The above data leads us to hypothesize that 5HT, released into the spinal cord by descending systems, may produce antinociception by inhibiting Ca2+ entry into afferent terminals of nociceptors via activation of 5HT1A receptors.
Uptake of potassium by nonmyelinating Schwann cells induced by axonal activity
Authors: Robert A. , Jirounek P.
Published: December 2017

1. The electrophysiological properties of the rabbit vagus nerve (membrane potential, compound action potentials, and afterpotentials) and potassium accumulation were measured simultaneously during low-frequency stimulation (LFS) (0.5 and 1 Hz) by using a modified sucrose-gap apparatus and potassium-sensitive microelectrodes (KSM). 2. During LFS at 0.5 and 1 Hz, the concentration of K+ in the extracellular space ([K+]c) increased in approximately 30 s to a maximal level that was 0.6 and 1.5 mM, respectively, above the resting concentration. Concomitantly the preparation developed an ouabain-sensitive hyperpolarization. 3. The compound action potential (CAP) was followed by a fast hyperpolarizing afterpotential (fHAP), a depolarizing afterpotential (DAP), and a slow hyperpolarizing afterpotential (sHAP). During LFS the characteristics of all these afterpotentials were profoundly modified. In parallel to the increase in [K+]e, the fHAP was decreased and the amplitude of the DAP was dramatically enhanced. Furthermore, the sHAP which had a duration of < 1 s when it followed a single CAP, turned into a ouabain-sensitive hyperpolarization (indicating that it was generated by the electrogenic Na(+)-K+ pump) that lasted several minutes. 4. The application of external Ba2+ produced a hyperpolarizing sag on the sHAP following a single isolated CAP. During LFS, Ba2+ enhanced the build-up of the DAP, raised the maximal level of [K+]e, and increased the activity-induced ouabain-sensitive hyperpolarization. 5. The increase by Ba2+ of the activity-induced hyperpolarization shifted the spikes from both myelinated and nonmyelinated fibers toward a more negative potential but did not increase their amplitude, indicating that this Ba(2+)-induced hyperpolarization originated from an extra-axonal source, presumably the Schwann cells. 6. It is proposed that the electrogenic activity of the Na(+)-K+ pump was enhanced in Schwann cells situated near active axons. This hyperpolarization was, however, not recorded in normal conditions because it was fully short-circuited by a K+ influx through Ba(2+)-sensitive channels. 7. Our results lead to the hypothesis that the Na(+)-K+ pump of the nonmyelinating Schwann cells is important in the mechanisms maintaining the homeostasis of K+ in the axonal microenvironment. They show that the Na(+)-K+ pump contributes to the K+ buffering not only by actively pumping K+ but also by generating a hyperpolarization that drives a passive K+ influx through Ba(2+)-sensitive K+ channels.