bluuebunny/crossref_metadata_2025 huggingface dataset:
Odor-induced currents in Xenopus olfactory receptor cells measured with perforated-patch recording
Authors: Zhainazarov A. B. , Ache B. W.
Published: December 2017

1. Odor-evoked currents were recorded in Xenopus laevis olfactory receptor neurons (ORNs) by the use of conventional, as well as nystatin and gramicidin-perforated, whole cell recording. The odor-evoked current ran down quickly in conventional, but not in perforated, whole cell recording. All three types of recording gave similar values for the amplitude, latency, time-to-peak, recovery time, and reversal potential of the odor-evoked current. 2. A secondary Cl current comprised a significant part of the odor-evoked current (55-65%). ECl measured by gramicidin perforation, which does not alter [Cl-]i, was -2.3 +/- 5.0 (SE) mV, indicating that these neurons maintain a high [Cl-]i and that the secondary Cl current plays an excitatory role in olfactory transduction.
Regional heterogeneity of pathophysiological alterations in CA1 and dentate gyrus in a chronic model of temporal lobe epilepsy
Authors: Rempe D. A. , Mangan P. S. , Lothman E. W.
Published: December 2017

1. Extracellular and intracellular recording techniques were employed in brain slice preparations to characterize responses of hippocampal tissue in the post-self sustaining limbic status epilepticus (post-SSLSE) model of chronic temporal lobe epilepsy (TLE) as compared with responses in slices from control animals. Experiments were performed > or = 1 mo, and up to 7 mo, after status epilepticus. Two regions of the hippocampal formation linked to different aspects of epileptogenesis, the CA1 region and the dentate gyrus (DG), were studied. In any given experiment, CA1 and DG were examined in different slices from the same animal. 2. Pyramidal cells in CA1 were activated by means of electrodes positioned over fiber bundles that monosynaptically project to these cells, either those located in the stratum lacunosum/moleculare or those in the stratum radiatum. Granule cells were similarly activated by electrodes positioned in the perforant path. Full input-output curves were determined by varying stimulus strength and charting the amplitudes of population spikes (PSs). 3. Two indexes, stimulus sensitivity and responsiveness, were quantified in control tissue and in post-SSLSE tissue by means of input-output curves to provide comparisons between normal and epileptic tissue. There were no changes in stimulus sensitivity, defined as the stimulus intensity required to evoke comparable responses in input-output curves, between control and post-SSLSE tissue. However, responsiveness, defined as the number of extracellular PSs or intracellular action potentials (APs) elicited by a stimulus strength giving rise to maximal-amplitude PSs, proved a reliable method for identifying and categorizing epileptic responses. This index allowed for comparisons between anatomic regions within an experiment as well as among experiments for the same region. Both CA1 pyramidal cells and DG granule cells from post-SSLSE tissue showed hyperresponsiveness relative to control tissue. 4. Control tissue never exhibited > 2 PSs in either CA1 or DG in response to stimuli that produced maximal-amplitude PSs. Therefore a criterion of > or = 3 PSs was adopted to delineate tissue as hyperresponsive on the basis of extracellular responses. In CA1 about one half of the post-SSLSE slices displayed > or = 3 PSs with stimuli giving maximal-amplitude PSs, meeting the criterion for hyperresponsiveness; in DG about one fifth of the slices showed hyperresponsiveness. 5. CA1 and DG differed with respect to the spectrum of hyperresponsiveness they exhibited, this being more robust in CA1. The two regions studied also showed heterogeneity with respect to maximal PS amplitudes.(ABSTRACT TRUNCATED AT 400 WORDS)
Nitric oxide is used as an orthograde cotransmitter at identified histaminergic synapses
Authors: Jacklet J. W.
Published: December 2017

1. Nitric oxide (NO) is produced by the enzyme nitric oxide synthase (NOS) and serves as an interneuronal messenger. Here, an identified histaminergic neuron (C2) in the mollusk Aplysia californica is shown to contain NOS with the use of NADPH diaphorase staining, suggesting that NO and histamine are used as cotransmitters by neuron C2. 2. The NOS containing neuron, C2, evokes a very slow excitatory postsynaptic potential in two of its identified postsynaptic follower neurons that are insensitive to H1 and H2 histamine receptor antagonists. 3. The very slow excitatory postsynaptic potential is blocked by inhibitors of NOS, such as nitroarginine methyl ester, and suppressed by the NO scavenger reduced hemoglobin. 4. Treatments with compounds that release NO, such as nitrosocysteine, mimic the membrane depolarization and the decrease in membrane conductance in the follower that are characteristic of the very slow excitatory postsynaptic potential induced normally by the presynaptic C2 neuron. 5. These results indicate that NO is used as an orthograde synaptic cotransmitter at synapses between histaminergic neuron C2 and its followers that receive the very slow excitatory postsynaptic potential.
Differences in inhibitory synaptic input between layer II-III and layer V neurons of the cat neocortex
Authors: van Brederode J. F. , Spain W. J.
Published: December 2017

1. The goal of this study was to compare the relative effectiveness of intrinsic inhibitory synaptic inputs in different layers of the cat motor cortex. Postsynaptic potentials (PSPs) were evoked in neurons located in the superficial (layer II-III) or deep layers (layer V) by local extracellular stimulation in vitro. Electrophysiological properties and intracellular filling indicated that the recorded neurons were pyramidal cells. 2. The shape and time course of the evoked PSPs differed. Layer II-III cells showed stereotyped triphasic PSPs consisting of a fast excitatory PSP (fEPSP) and a fast and slow inhibitory PSP (fIPSP and sIPSP, respectively). PSPs in layer V cells, in contrast, were much more variable, mainly depolarizing at resting membrane potential, and lacked a hyperpolarizing IPSP in 84% of neurons tested at rest. 3. Blockade of glutaminergic neurotransmission with 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) and D-2-amino-5-phosphonovaleric acid (AP5) revealed that fIPSPs could be evoked in all layer V cells by local stimulation of the superficial or deep layers, even in those that showed small or no IPSPs in control perfusate. Small (< 1 mV) isolated sIPSPs were evoked in only one-fifth of layer V cells when the deep layers were stimulated, and in about one-half of the layer V cells when the superficial layers were stimulated. In layer II-III cells, stimulation of the superficial layers always resulted in fIPSP-sIPSP combinations. No IPSPs could be evoked in layer II-III neurons by stimulating the deep layers after glutaminergic blockade. Selective blockade of gamma-aminobutyric acid-A (GABAA) or GABAB receptor-mediated neurotransmission showed that in both cell types fIPSPs were due to GABAA receptor stimulation, whereas sIPSPs were mediated by GABAB receptors. 4. Isolated fIPSPs were recorded in perfusate containing CNQX, AP5, and the GABAB antagonist CGP 35348. The rise and decay times of the fIPSPs in layer II-III cells were significantly longer than those in layer V cells. Rise and decay times normalized for differences in membrane time constant were not significantly different, however, suggesting that the intrinsic membrane properties of the postsynaptic membrane account for the difference in time course of the fIPSPs in these two cell types. 5. Selective blockade of the inward rectifier current Ih with extracellular Cs+ showed that this conductance functions to shorten and attenuate fIPSPs in layer V cells. In contrast, Ih is absent or small in layer II-III cells, and, consequently, Cs+ had little or no effect on the fIPSPs evoked in these cells.(ABSTRACT TRUNCATED AT 400 WORDS)
G alpha o1 decapeptide modulates the hippocampal 5-HT1A potassium current
Authors: Oleskevich S.
Published: December 2017

1. The serotonin1A (5-HT1A) receptor is coupled to an inwardly rectifying potassium current (IKir) via a G protein. The identity of the G-protein subtype was investigated with 2 10-amino acid peptides derived from the carboxyl (C) terminus of the alpha-subunits of the Go1 and Gi2 proteins (G alpha o1 and G alpha i2). The synthetic decapeptides were applied by intracellular perfusion during whole cell recording from dentate granule cells in the hippocampal slice preparation. 2. Bath application of 5-HT produced an IKir, which was blocked by the selective 5-HT1A receptor antagonist, pindobind5-HT1A. The G alpha o1 peptide inhibited the 5-HT1A IKir by 60 +/- 7% (mean +/- SE; t = 30 min), whereas the G alpha i2 peptide had no effect. The G alpha o1 peptide produced a slowly developing outward current that was not observed in the absence of peptide or in the presence of the G alpha i2 peptide. 3. The results indicate that G alpha o1 and not G alpha i2 modulates the 5-HT1A IKir in hippocampal granule cells. They also suggest that G alpha o1 occludes the 5-HT1A response by direct activation of the IKir. The intracellular perfusion of synthetic G alpha peptides provides a new approach to identify the G-protein subtype(s) in a receptor-mediated electrophysiological response.
Primate striate and prestriate cortical neurons during discrimination. II. separable temporal codes for color and pattern
Authors: McClurkin J. W. , Zarbock J. A. , Optican L. M.
Published: December 2017

1. In the previous paper we reported our analysis of the responses of neurons in cortical areas V1, V2, and V4 to a set of stimuli that consisted of all 36 combinations of six colors and six patterns. Neurons in all three cortical areas simultaneously encoded information about both the color and pattern of the stimulus in the number and temporal distribution of spikes in their responses. To account for this ability, we propose that a neuron's response consists of separable temporal codes representing the color and pattern of the stimulus that are multiplexed together. 2. We used nonlinear regression to fit the model parameters to the data. We used the responses to 30 of the 36 stimuli as a training set to estimate the parameters of the model and the responses to the remaining 6 stimuli as a test set. After training, the model fitted the responses to stimuli in the training sets very well and predicted the responses to stimuli in the test sets. Thus neuronal responses to colored patterns contain separate temporal codes representing color and pattern. 3. After establishing the model parameters, we obtained the waveforms that represented each neuron's temporal codes for the six colors and six patterns of our stimulus set. We then proceeded with a series of analyses to determine whether these waveforms were viable candidates for neuronal codes. Cluster analysis revealed that there were only a few different classes of waveforms representing each color and pattern, and there were many neurons in each class. Further, neurons that used similar waveforms to represent one color or pattern also tended to use similar waveforms to represent other colors or patterns. The waveforms representing five of the six colors and three of the six patterns were similar in the two monkeys used in this study. 4. We compared the shapes of the code waveforms across cortical areas and found no differences among areas in the shapes of the waveforms representing four of the six colors. In contrast, we found that there were differences among areas in the shapes of the waveforms representing all six patterns. These results suggest that messages about color are encoded at an early level and are then propagated upward, but that messages about pattern are altered in each successive cortical area. 5. Our results offer a neurophysiological explanation for the psychophysical evidence that color and form are processed by different channels. We propose that the psychophysical channels for color and pattern arise from the separability of the temporal codes for color and pattern in the responses of single neurons. This hypothesis implies that psychophysical channels correspond to classes of temporal codes rather than to classes of neurons.
Activation of type-identified motor units during centrally evoked contractions in the cat medial gastrocnemius muscle. III. Muscle-unit force modulation
Authors: Tansey K. E. , Yee A. K. , Botterman B. R.
Published: December 2017

1. The aim of this study was to examine the extent of muscle-unit force modulation due to motoneuron firing-rate variation in type-identified motor units of the cat medial gastrocnemius (MG) muscle, and to investigate the contribution of muscle-unit force modulation to whole-muscle force regulation. The motoneuron discharge patterns recorded from 8 pairs of motor units during 12 smoothly graded muscle contractions evoked by stimulation of the mesencephalic locomotor region (MLR) were used to reactivate those units in isolation to estimate what their force profiles would have been like during the evoked whole-muscle contractions. 2. For most motor units, muscle-unit force modulation was similar to motoneuron firing-rate modulation, in that muscle-unit force increased over a limited range (120-600 g) of increasing whole-muscle tension and was then maintained at a near maximal (> 70%) output level as muscle force continued to rise. Most muscle units also decreased their force outputs over a slightly larger range of declining whole-muscle force before relaxing. This second finding was best explained by the counterclockwise hysteresis recorded in the motor units' frequency-tension (f-t) relationships. 3. In those instances when whole-muscle force fluctuated just above the recruitment threshold of a motor unit, a substantial percentage (10-25%) of the change in whole-muscle force could be accounted for by force modulation in that motor unit alone. This finding suggested that few motor units in the pool were simultaneously simultaneously undergoing force modulation. To evaluate this possibility, the extent of parallel muscle-unit force modulation within the 8 pairs of simultaneously active motor units was evaluated. As with parallel motoneuron firing-rate modulation, the extent of parallel muscle-unit force modulation was limited to unit pairs of the same physiological type and recruitment threshold. In several instances, pairs of motor units displayed parallel motoneuron firing-rate modulation but did not show parallel muscle-unit force modulation because of the nature of the motor units' f-t relationships. 4. The limited extent of parallel muscle-unit force modulation seen in these experiments implies that the major strategy for force modulation in the cat MG muscle, involving contractions estimated to reach 30-40% of maximum, may be motor-unit recruitment rather than motor-unit firing-rate variation with resulting force modulation. Given, however, that the majority of motor units are already recruited at these output levels (< 40%), it is proposed that motor-unit firing-rate variation with resulting force modulation may take over as the major muscle force modulating strategy at higher output levels.
Presynaptic GABAB receptors modulate IPSPs evoked in neurons of deep cerebellar nuclei in vitro
Authors: Mouginot D. , Gahwiler B. H.
Published: December 2017

1. Recording from deep cerebellar nuclei neurons, we investigated the role of presynaptic gamma-aminobutyric acid-B (GABAB) receptors in the modulation of monosynaptic inhibitory postsynaptic potentials (IPSPs) evoked by stimulation of Purkinje cells in rat slice cultures. 2. Bath application of the GABAB receptor agonist, baclofen (10 and 100 microM) induced two effects in cerebellar nuclei neurons: a postsynaptic hyperpolarization of 4.2 +/- 1.7 (SD) mV and a reduction in the amplitude of evoked IPSPs (30 +/- 10%). 3. When the postsynaptic GABAB response was blocked by filling the electrode with cesium methanesulfonate (2 M), or with a solution containing QX 314 (50 mM), bath application of baclofen (10 microM) reversibly depressed the evoked IPSPs by 36.7 +/- 18.7% and 42 +/- 20.3%, respectively. Under these experimental conditions, baclofen (10 microM) also reduced the amplitude of spontaneous IPSPs (10.2 +/- 9.5%) and decreased their frequency by 45.6 +/- 8.8%, suggesting a presynaptic site of action. 4. The presynaptic action of baclofen was not due to activation of receptors on the somata of Purkinje cells: baclofen (100 microM) failed to alter membrane holding current in Purkinje cells, and it had no effect on the rate of spontaneous action-potential discharge in Purkinje cells in the presence of ionotropic glutamate receptor antagonists (6-cyano-7-nitroquinoxaline-2,3-dione, 20 microM; D-2-amino-5-phosphonovalerate, 40 microM). 5. IPSPs could be evoked by extracellular stimulation of the Purkinje cell layer or by direct stimulation of the fiber bundle connecting Purkinje cells to deep cerebellar neurons. In both situations, baclofen (10 microM) reduced the amplitude of evoked IPSPs by 32.7 +/- 8.8% and 31.2 +/- 10.2%, respectively. 6. These results demonstrate that GABAB receptors are present on the terminals of Purkinje cells. Their activation causes a decrease in the amplitude of evoked IPSPs recorded in deep cerebellar nuclei and also reduces the frequency of spontaneous inhibitory events.
Relation between rise times and amplitudes of GABAergic postsynaptic currents
Authors: Bier M. , Kits K. S. , Borst J. G.
Published: December 2017

1. We recorded rise times and amplitudes of spontaneous GABAergic inhibitory postsynaptic currents (IPSCs) in melanotropes of Xenopus laevis. Average rise times did not vary with amplitude, but the rise times of larger IPSCs were less variable. A simple linear one-step Markov model for channel opening following the binding of a transmitter molecule can quantitatively account for the average rise time and its coefficient of variation as a function of amplitude. Our results indicate that the observed variations in the rise times are not due to variations in transmitter concentrations, but result from stochastic variations in the opening of the receptor channels.
Capsaicin-induced rapid receptive field reorganization in cuneate neurons
Authors: Pettit M. J. , Schwark H. D.
Published: December 2017

1. To determine whether activity in unmyelinated or thinly myelinated primary afferents affects the organization of cutaneous receptive fields (RFs) in the cuneate nucleus, subcutaneous injections of capsaicin were made into the RFs of cuneate neurons in anesthetized cats. The effects of capsaicin injection on RF size and position, response properties, and spontaneous firing rates were determined during single-unit recordings. 2. Subcutaneous injection of capsaicin (10% dissolved in 70% ethanol) into peripheral RFs produced rapid RF reorganization in all neurons tested (n = 20), even when the original RF remained responsive to tactile stimulation. RF reorganization was marked by the appearance of newly responsive RFs. These RFs appeared as either contiguous expansions of the original RF or as new, noncontiguous fields. Control injections of the vehicle alone never produced RF reorganization (n = 9). RF reorganization was not related to changes in spontaneous activity. 3. Following capsaicin-induced RF reorganization, subcutaneous injections of lidocaine were made into the original RFs (n = 8). These injections produced no additional RF reorganization in seven of the eight neurons, even though in each case the lidocaine injections produced at least partial blocks of responsiveness from within the original RF. 4. In approximately one-half of the neurons (9 of 20), the reorganized RFs had response properties that were different from those of the original RF. This result suggests that, for neurons in the dorsal column nuclei (DCN), physiological mechanisms that normally mask inputs and restrict RF size can give rise to response specificity. 5. The results of these experiments demonstrate that capsaicin-induced RF reorganization, which has been reported previously in ventrobasal thalamus and primary somatosensory cortex, can arise within the dorsal column-medial lemniscal system, at the level of the DCN. The present results also provide evidence that rapid RF reorganization in cuneate neurons can be produced by blockade of a subset of peripheral afferents that are sensitive to capsaicin.
Hyperosmotic regulation of voltage-gated calcium currents in rat anterior pituitary cells
Authors: Matzner O. , Ben-Tabou S. , Nussinovitch I.
Published: December 2017

1. The sensitivity of voltage-gated calcium currents to hyperosmotic media containing mannitol or sucrose (373-723 mOsm) and to the dihydropyridine (DHP) calcium channel agonist Bay K 8644 was examined in enriched populations of rat anterior pituitary somatotrophs by using the whole cell mode of the patch-clamp technique. 2. Hyperosmotic media reduced the amplitude of voltage-gated calcium currents. With a 61.9% increase in extracellular medium osmolarity (523 mOsm), low voltage-activated (LVA) calcium currents were reduced to 67.9 +/- 17.8% of control size and high voltage-activated (HVA) calcium currents were reduced to 57.0 +/- 5.7% (mean +/- SD) of control size. The hyperosmotic suppression of HVA calcium currents was usually accompanied with a negative shift of 6.0 +/- 2.9 mV (mean +/- SD) in the activation curve of HVA currents. 3. The DHP calcium-channel agonist Bay K 8644 (10 microM), which stimulates hormone secretion from somatotrophs, increased the amplitude of HVA calcium currents to 212.6 +/- 67.2% of their control size, prolonged their tail currents, and negatively shifted the activation curve of HVA calcium currents by 6.2 +/- 2.8 mV. 4. Hyperosmotic media reduced the amplitude of DHP-sensitive HVA calcium currents and their associated prolonged tail currents, thus providing direct evidence for hyperosmotic suppression of DHP-sensitive currents. 5. Hence, exposure of pituitary cells to hyperosmotic media reduced voltage-sensitive calcium influx through LVA and DHP-sensitive HVA calcium channels. The inhibition of calcium influx through DHP-sensitive channels, which are implicated in regulation of hormone secretion in these cells, suggests that inhibitory hyperosmotic effects on hormone secretion from pituitary cells may stem from inhibition of calcium influx, before the exocytotic process. These results may also be relevant to effects of hypertonicity on neurosecretion in the nervous system.
Cloning of a novel component of A-type K+ channels operating at subthreshold potentials with unique expression in heart and brain
Authors: Serodio P. , Vega-Saenz de Miera E. , Rudy B.
Published: December 2017

1. Proteins of the Kv4 or Shal-related subfamily are key components of transient K+ channels (A channels) operating at subthreshold values of the membrane potential. We have cloned and characterized a new mammalian Kv4 or Shal-related cDNA (Kv4.3) that predicts a protein with strong sequence conservation with the other known members of this subfamily. 2. Injection of Kv4.3 transcripts into Xenopus oocytes generates an A type K+ current, with small but physiologically significant differences from the currents expressed by Kv4.2 and Kv4.1 mRNAs. Kv4.3 currents can be modified to resemble native A currents by coinjection with a low molecular weight mRNA fraction from rat brain which does not express detectable currents on its own. Particularly striking is a 7-to-10-fold increase in the rate of recovery from inactivation, a 5- to 10-fold increase in current magnitude and a 3- to 4-fold increase in sensitivity to 4-amino pyridine (4-AP). 3. In situ hybridization histochemistry was used to compare the expression of the three known Kv4 genes. Kv4.2 and Kv4.3 (but not Kv4.1) are abundant in the adult rat brain, with each displaying a specific, but sometimes overlapping pattern of expression. Moreover, a reciprocal gradient of expression of Kv4.2 and Kv4.3 transcripts is seen in some brain areas, such as in the pyramidal cell layers of the hippocampus and the granule cell layer of the cerebellum. Therefore Kv4 proteins may form heteromultimeric channels of distinct subunit composition in different neurons. Moreover, the results suggest that neurons such as pyramidal cells in the hippocampus and granule cells in the cerebellum represent heterogeneous cell populations in terms of their ISA, and hence in their firing patterns. Kv4.2 and Kv4.3 also display complementary expression in the heart, with Kv4.3 being more abundant in atria and Kv4.2 in ventricle. The existence of multiple Kv4 proteins forming channels of variable subunit combinations helps explain the diversity of ISA channels in neurons.
Characterization of TTX-resistant persistent Na+ current underlying pacemaker potentials of fish gonadotropin-releasing hormone (GnRH) neurons
Authors: Oka Y.
Published: December 2017

1. Endogenous pacemaker activities are important for the putative neuromodulator functions of the gonadotropin-releasing hormone (GnRH)-immunoreactive terminal nerve (TN) cells. Previously we have shown by current-clamp analysis that a tetrodotoxin (TTX)-resistant persistent Na+ current, INa(slow), plays an important role in the generation of pacemaker potentials of TN-GnRH cells. The present study investigates electrophysiological characteristics of INa(slow) by using the whole cell patch-clamp technique in in vitro whole-brain preparation of a small fish brain. 2. TN-GnRH cells lie immediately beneath the ventral meningeal membrane; the cells could thus be exposed and visualized by gently removing the meningeal membrane. INa(slow) currents were isolated pharmacologically by blocking K+ currents, Ca2+ currents, and conventional fast Na+ currents. 3. INa(slow) was characterized by resistance to TTX blockade, dependence on external Na+, slow activation, very slow and little inactivation, and wide overlap of activation and inactivation curves near the resting potential. These characteristics are distinct from those of conventional fast Na+ current, and are relevant for the generation of persistent inward currents necessary for the pacemaker activity of TN-GnRH cells.
Noise-enhanced information transmission in rat SA1 cutaneous mechanoreceptors via aperiodic stochastic resonance
Authors: Collins J. J. , Imhoff T. T. , Grigg P.
Published: December 2017

1. Aperiodic stochastic resonance (ASR) is a phenomenon wherein the response of a nonlinear system to a weak aperiodic input signal is optimized by the presence of a particular, nonzero level of noise. Our objective was to demonstrate ASR experimentally in mammalian cutaneous mechanoreceptors. 2. Experiments were performed on rat slowly adapting type 1 (SA1) afferents. Each neuron was subjected to a perithreshold aperiodic stimulus plus noise. The variance of the noise was varied between trials. The coherence between the aperiodic input stimulus and the response of each SA1 afferent was computed. 3. Of the 12 neurons tested, 11 showed clear ASR behavior: as input noise variance was increased, the stimulus-response coherence rapidly increased to a peak and then slowly decreased. These findings were in contrast with those for the average firing rate, which increased monotonically as a function of input noise variance. 4. This work shows that noise can serve to enhance the response of a sensory neuron to a perithreshold aperiodic input signal. These results suggest a possible functional role for input noise in sensory systems. These findings also indicate that it may be possible to introduce noise artificially into sensory neurons to improve their abilities to detect arbitrary weak signals.
Presynaptic inhibition of exteroceptive afferents by proprioceptive afferents in the terminal abdominal ganglion of the crayfish
Authors: Newland P. L. , Aonuma H. , Sato M. , Nagayama T.
Published: December 2017

1. Exteroceptive hairs that are sensitive to water displacement and touch are distributed over the surface of the tailfan of crayfish. We show that the sensory neurons innervating these hairs receive a primary afferent depolarization (PAD) from sensory neurons innervating a proprioceptor that monitors movements of the endopodite and protopodite of the tailfan. This PAD occurs only during high-velocity movements of the exopodite, which are similar to those that occur during swimming. The effects that the proprioceptor mediate are widespread, so that afferents in four sensory nerve roots of the terminal abdominal ganglion, innervating hairs on the protopodite, exopodite, endopodite, and telson, receive a PAD. The PAD is unlikely to be mediated through monosynaptic pathways because there is no anatomic overlap between the central projections of chordotonal afferents and many of the exteroceptive afferents. The depolarization is associated with a conductance increase and can be increased by the injection of hyperpolarizing current or reversed (approximately 10 mV above resting potential) by injection of depolarizing current. The properties of the presynaptic input are, therefore, consistent with being mediated through chemical synapses. This is supported by the observation in the electron microscope that the exteroceptive afferents receive chemical input synapses. The depolarization is mimicked by gamma-aminobutyric acid and reduced by bath application of picrotoxin or bicuculline, suggesting that it is a depolarizing inhibitory postsynaptic potential. The PAD reduces the amplitude of exteroceptive afferent spikes, an action that is thus likely to reduce transmitter release and the efficacy of synaptic transmission.
NMDA-receptor-mediated synaptic currents in guinea pig laterodorsal tegmental neurons in vitro
Authors: Sanchez R. , Leonard C. S.
Published: December 2017

1. Whole cell voltage-clamp techniques were used to record glutamate-receptor-mediated synaptic currents from neurons of the laterodorsal tegmental nucleus (LDT). The principal cells of the LDT contain acetylcholine and nitric oxide synthase, and are believed to be involved in the control of sleep-waking behavior via widespread projections to the thalamus and brain stem. LDT cells were recorded from slices of mature guinea pig brain stem with patch pipette solutions containing cesium as the primary cation. 2. Application of N-methyl-D-aspartate (NMDA) elicited currents that were strongly voltage dependent with a mean reversal potential of +16.3 mV. Peak currents occurred near -15 mV, and a region of negative slope conductance was seen at more negative potentials. Application of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid evoked currents that exhibited a nearly linear current-voltage relation with a mean reversal potential of -3.4 mV. 3. Electrical stimulation of local afferents elicited dual-component excitatory postsynaptic currents (EPSCs) with decays that were well fitted by the sum of two exponentials. Mean decay time constants at -60 mV were 8.77 ms for the faster component and 129.4 ms for the slower component. The faster component displayed a linear current-voltage relation and was blocked by 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) or 6,7-dinitroquinoxaline-2,3-dione, indicating that it was mediated by non-NMDA receptors, whereas the slower component displayed a voltage dependence similar to that for NMDA-evoked currents and was blocked by 2-amino-5-phosphonopentanoic acid (AP-5), indicating its mediation by NMDA receptors. 4. The fractional contribution of NMDA receptors to the EPSC was estimated from double-exponential curve fits to the decay phases. With this method, NMDA receptors were estimated on average to carry 10.1% of the total peak EPSC at -60 mV. Blockade of the non-NMDA-receptor-mediated component with CNQX revealed a residual EPSC whose amplitude was 14.4% of the control value, whereas AP-5 alone reduced the control EPSC peak by 16.1%, both values were comparable with those obtained from curve fit estimates. 5. Previous work has shown that the presence of 4-aminopyridine-sensitive, A-like transient current in LDT cells is correlated with the cholinergic phenotype. The majority of cells in this study exhibited A-like transient currents that were blocked by 4-amino-pyridine, suggesting that the majority of the data were obtained from the cholinergic and NOS-containing neurons of the LDT nucleus. 6. These experiments demonstrate the synaptic activation of functional NMDA and non-NMDA receptors in LDT neurons, and indicate that NMDA receptors contribute to fast excitatory transmission in these cells. The results suggest that afferents releasing excitatory amino acids may play an important role in controlling the state-dependent activity of LDT neurons.
Central modulation of stretch receptor neurons during fictive locomotion in lamprey
Authors: Vinay L. , Barthe J. Y. , Grillner S.
Published: December 2017

1. In lamprey, stretch receptor neurons (SRNs), also referred to as edge cells, are located along the lateral margin of the spinal cord. They sense the lateral movements occurring in each swim cycle during locomotion. The isolated lamprey spinal cord in vitro was used to investigate the activity of SRNs during fictive locomotion induced by bath-applied N-methyl-D-aspartate (NMDA). Intracellular recordings with potassium acetate filled electrodes showed that 63% of SRNs had a clear locomotor-related modulation of their membrane potential. 2. Of the modulated SRNs, two-thirds had periods of alternating excitation and inhibition occurring during the ipsilateral and the contralateral ventral root bursts, respectively. The phasic hyperpolarization could be reversed into a depolarizing phase after the injection of chloride ions into the cells; this revealed a chloride-dependent synaptic drive. The remaining modulated SRNs were inhibited phasically during ipsilateral motor activity. 3. Experiments with barriers partitioning the recording chamber with the spinal cord into three pools, allowed an inactivation of the locomotor networks within one pool by washing out NMDA from the pool in which the SRN was recorded. This resulted in a marked reduction, but not an abolishment, of the amplitude of the membrane potential oscillations. Both the excitatory and the inhibitory phases were reduced, resulting from removal of input from inhibitory and excitatory interneurons projecting from the adjacent pools. If the glycine receptor antagonist strychnine (1 microM) was applied in one pool, the phasic hyperpolarizing phase disappeared without affecting the excitatory phase. 4. Bath application of the gamma-aminobutyric acid (GABA)A receptor antagonist, bicuculline (50-100 microM) blocked the spontaneous large unitary inhibitory postsynaptic potentials, which occurred without a clear phasic pattern. Bicuculline had no significant effect on the peak to peak amplitude of the locomotor-related membrane potential oscillations. The inhibition in SRNs therefore has a dual origin: glycinergic interneurons provide phasic inhibition, while the GABA system can exert a tonic inhibition via GABAA receptors. 5. These data show that, in addition to the stretch-evoked excitation, which SRNs receive during each locomotor cycle, most of them also receive excitation from the central pattern generator network during the ipsilateral contraction, which may ensure a maintained high level of sensitivity to stretch during the shortening phase of the locomotor cycle. This arrangement is analogous to the efferent control of muscle spindles exerted by gamma-motoneurons in mammals, which as a rule are coactivated with alpha-motoneurons to the same muscle (alpha-gamma linkage).
Utriculoocular reflex arc of the cat
Authors: Uchino Y. , Sasaki M. , Sato H. , Imagawa M. , Suwa H. , Isu N.
Published: December 2017

1. Intracellular recordings of synaptic potentials in extraocular motoneurons were studied to determine the connectivities between the utricular nerve and the extraocular motoneurons in cats. 2. Stimulating electrodes were placed within the left utricular nerve, while other branches of the vestibular nerve were removed. Subsequently, the N1 field potentials evoked by utricular nerve stimulation were recorded in the vestibular nuclei. The potential typically grew until reaching a plateau (submaximal stimulation). Stimulus spread to the other nerve branches appeared as an additional increase in N1 amplitude after the plateau discontinued (supramaximal stimulation). 3. Intracellular recordings were made from 200 identified motoneurons in the bilateral III, IV, and VI cranial nuclei. 4. Stimulation of the utricular nerve at submaximal intensity evoked a longer latency depolarizing and hyperpolarizing potentials in contra- and ipsilateral medial rectus motoneurons, respectively. Complex potentials with longer latencies also were recorded in ipsilateral inferior oblique and contralateral trochlear motoneurons after stimulation of the utricular nerve at a submaximal intensity. Monosynaptic and disynaptic connections between the utricular nerve and ipsilateral abducens motoneurons and interneurons were recorded as described previously. 5. The results of the present study confirm our initial findings that a disynaptic pathway from the utricular nerve to contralateral trochlear motoneurons is absent or very poorly developed, whereas polysynaptic circuits from the utricular nerve to inferior oblique and trochlear motoneurons may play a role in eye rotation during head tilt.
Distinct synaptic loci of Ca2+/calmodulin-dependent protein kinase II necessary for long-term potentiation and depression
Authors: Stanton P. K. , Gage A. T.
Published: December 2017

1. Extracellular bath application of the selective Ca2+/calmodulin-dependent kinase II (CaMKII) inhibitor KN-62 to hippocampal slices in vitro blocked the induction of long-term depression (LTD) by low-frequency Schaffer collateral stimulation (1 Hz/15 min) of the same concentration as has been shown previously to prevent induction of long-term potentiation (LTP) at these synapses. 2. In contrast, postsynaptic intracellular infusion of KN-62 into single CA1 pyramidal neurons did not prevent induction of LTD, although it was quite effective in blocking LTP. 3. We conclude that there is a presynaptic CaMKII that must be activated to induce LTD, whereas postsynaptic CaMKII stimulation is needed to evoke LTP. 4. Bath application of KN-62 also blocked depotentiation by low-frequency stimuli of previously induced LTP, suggesting that induction of depotentiation and de novo LTD may require the same CaMKII-dependent mechanisms.
Gq/11 and PLC-beta 1 mediate the substance P-induced inhibition of an inward rectifier K+ channel in brain neurons
Authors: Takano K. , Yasufuku-Takano J. , Kozasa T. , Singer W. D. , Nakajima S. , Nakajima Y.
Published: December 2017

1. Substance P (SP) induces a slow neuronal excitation in cholinergic neurons from the nucleus basalis by suppressing an inwardly rectifying K+ current (Kir). We have determined which G protein alpha-subunit mediates this SP effect. 2. After intracellularly injecting antibody against each alpha-subunit of G proteins (Gq alpha/11 alpha, G12 alpha, and G13 alpha) with an Eppendorf microinjector, we examined, by using the whole cell patch-clamp and the ON-cell mode of single-channel recording, the effect of SP on Kir in cultured neurons of the nucleus basalis. The effect of SP on Kir was substantially reduced in neurons injected with antibodies to Gq alpha/11 alpha but not with antibodies to G12 alpha or G13 alpha. 3. The effects of antibodies against three isozymes of phospholipase C (PLC-beta 1, PLC-beta 2, and PLC-beta 3) were tested. The SP-induced suppression of Kir was reduced by antibody against PLC-beta 1 but not by antibodies against PLC-beta 2 or PLC-beta 3. 4. We conclude that the SP-induced inhibition of Kir in nucleus basalis neurons is mediated by Gq/11 and PLC-beta 1.
Spontaneous and stimulation-induced synchronized burst afterdischarges in the isolated CA1 of kainate-treated rats
Authors: Meier C. L. , Dudek F. E.
Published: December 2017

1. Kainate treatment preferentially kills dentate hilar neurons and CA3 pyramidal cells and ultimately leads to a chronic epileptic state. Bicuculline-induced epileptiform bursts were studied to test the hypothesis that multiple kainate injections and consequent status epilepticus would lead-after weeks to months of recovery-to prolonged synchronous afterdischarges in the isolated CA1 area of rat hippocampal slices, as would be expected if new recurrent excitatory circuits had formed. 2. Synaptic responses evoked in CA1 pyramidal cells of rats injected subcutaneously with kainate (10 hourly injections, 5 mg/kg each) 24-316 days before the slice experiment were compared with responses in slices from untreated and saline-injected controls. The maximal response to stratum radiatum stimulation in normal solution consisted of two to eight population spikes. 3. When gamma-aminobutyric acid-A receptor-mediated inhibition was reduced with bicuculline, synchronized burst afterdischarges after the initial stimulation-evoked burst, similar to the type of activity described in area CA3 under conditions where inhibition is impaired, occurred in 23% of slices. 4. The prolonged synchronized burst afterdischarges in the isolated CA1 area of kainate-treated rats were associated with large excitatory postsynaptic potentials (EPSPs). These prolonged bursts were not graded with the stimulus intensity; rather, they were triggered in an all-or-none manner, even though there was some variability across bursts. The bursts of population spikes also were correlated with subthreshold EPSPs. 5. Slices that had synchronized burst afterdischarges had significantly more damage in area CA3 than slices without afterdischarges. 6. The data indicate that kainate-induced damage in CA3 can lead to prolonged synchronous afterdischarges, even after CA1 is surgically isolated from the CA3 area. Because the repetitive bursts during the prolonged and synchronous afterdischarges were associated with large EPSPs, these data suggest that kainate-induced damage to CA3 and subsequent degeneration of synaptic terminals in the CA1 area causes the formation of new recurrent excitatory circuits that could be involved in the development of chronic epilepsy.
Voltage-dependent facilitation of calcium channels in rat neostriatal neurons
Authors: Song W. J. , Surmeier D. J.
Published: December 2017

1. Voltage-dependent facilitation of Ca2+ channels was studied in acutely isolated adult rat neostriatal neurons. Particular attention was paid to the facilitation of L-type channels. 2. In the absence of neuromodulators, the current-voltage relationship for whole cell Ba2+ currents was enhanced by a prepulse to +100 mV. The median enhancement at -20 mV was nearly 60%. The voltage dependence and kinetics of the processes underlying the facilitation were similar to those reported in other neurons. N-, P-, Q-, and L-type currents contributed to the observed facilitation. 3. Voltage-dependent facilitation of L-type currents was studied by subtracting nifedipine-insensitive currents from control currents. Although the kinetics were similar to those of the whole cell currents, the half-activation voltage for facilitation of L-type currents [half-activation voltage (Vh) = -0.6 mV, slope factors (Vc) = 11.8 mV, [n = 5] was significantly less depolarized than that of the pooled currents (Vh = 47.3 mV, Vc = 12.3 mV, n = 7). 4. Repetitive depolarization with spikelike waveforms was also able to induce facilitation of L-type currents, suggesting that facilitation was not simply a consequence of a modal shift in gating like that induced by Bay K 8644. 6. Combined whole cell recording and single-cell reverse transcription-polymerase chain reaction amplification revealed that neostriatal medium spiny neurons expressed detectable levels of either class C or class D L-type channel alpha 1, subunit mRNA. Both neurons expressing class C L-type channels and neurons expressing class D L-type channels exhibited voltage-dependent facilitation.
Two functional muscle groupings during postural equilibrium tasks in standing cats
Authors: Jacobs R. , Macpherson J. M.
Published: December 2017

1. This study examined the relation between electromyographic (EMG) activation and the contact force and joint torques of the left hindlimb during postural equilibrium tasks in the standing cat. It is the appropriate application of force by the limbs against the support surface that allows the animal to control its center of mass and maintain equilibrium. 2. Cats were trained to stand quietly on a moveable force platform. During quiet stance, the cat was perturbed by a platform translation in each of 12 directions evenly spaced in the horizontal plane. EMG activity of mono- and biarticular thigh muscles, three-dimensional ground reaction force under the paw (contact force), and kinematics of the hindlimb segments were recorded Net joint torques were computed using inverse dynamics. The analysis focused on the functional organization of the rapid, automatic postural response in relation to the sagittal plane contact force and joint torques. 3. The muscles of the thigh were subdivided into two functional groups, based on the relationship of the evoked response to the various components of the sagittal plane contact force or joint torques. The first group, consisting of the monoarticular and some biarticular muscles, was correlated with the vertical force component, Fz. The second group, consisting of a separate group of biarticular muscles, was correlated with the difference between knee and hip torque. This torque difference is a function of both sagittal plane force components, Fz and Fy, and is related to contact force direction. 4. It is suggested that this subdivision of muscle activations reflects a neural strategy of parallel control of the two muscle groups in relation to their influence on Fz and Fy. Such a control mechanism could be a strategy for simplifying the control of the multisegmented limb in contact force tasks such as maintaining postural equilibrium.