bluuebunny/crossref_metadata_2025 huggingface dataset:
EP receptor subtypes implicated in the PGE2-induced sensitization of polymodal receptors in response to bradykinin and heat
Authors: Kumazawa T. , Mizumura K. , Koda H. , Fukusako H.
Published: December 2017

1. Our previous studies, in which we used in vitro canine testispermatic nerve preparations, showed that prostaglandin E2 (PGE2) augments both bradykinin (BK)- and heat-induced discharges of polymodal receptors. However, the PGE2 concentration required to augment the BK responses were 100 times lower than those necessary for the heat responses, suggesting that different receptors are involved in these phenomena. We studied which receptors for E series of prostaglandins (EP receptors) were responsible, using the antagonist and agonists for three subtypes of EP receptors. 2. PGE2-induced augmentation of the BK responses was unaffected when treated with an antagonist for the EP1 receptor, AH6809. 3. An agonist for the EP3 receptor, M&B28767, at > or = 10 nM, significantly augmented the BK responses in a concentration-dependent manner that mimics the PGE2-induced effect. An agonist for the EP1 receptor, 17-phenyl trinor PGE2 (17-phen PGE2), at the high concentrations of 0.1 and 1 microM, augmented the BK responses in two and four of nine cases tested, respectively. However, this augmentation was not suppressed by the antagonist for the EP1 receptor, AH6809. In addition, an agonist for the EP2 receptor, butaprost, did not affect the BK responses even when applied at 10 microM. 4. In contrast, butaprost at > or = 10 nM significantly augmented the heat responses in a concentration-dependent manner. M&B28767 and 17-phen PGE2, respectively, augmented the heat responses at higher concentrations of 100 nM and 1 microM. 5. These results indicate that the EP3 and EP2 receptor subtypesx are differentially implicated in the respective PGE2-induced augmentation of BK responses and heat responses of polymodal receptors.
Microstimulation of primate motor thalamus: somatotopic organization and differential distribution of evoked motor responses among subnuclei
Authors: Vitek J. L. , Ashe J. , DeLong M. R. , Kaneoke Y.
Published: December 2017

1. The functional organization of motor responses to microstimulation throughout the primate “motor” thalamus including nucleus ventralis lateralis, pars oralis (VLo); nucleus ventralis posterior lateralis, pars oralis (VPLo); nucleus ventralis lateralis, pars caudalis (VLc); and portions of ventralis anterior (VA) and area X, was systematically studied in awake monkeys. A total of 2,021 sites were examined for their response to microstimulation. Of these, 1,123 were histologically verified as to their location within the motor thalamus. At or near each site, isolated neurons were examined for their responses to somatosensory examination and active movement (n = 1,272). This study was carried out as part of a larger study examining the responses of neurons in the motor thalamus to somatosensory examination, torque-induced limb perturbations, and active movement in a visuomotor step-tracking task. 2. Microstimulation at < or = 40 microA evoked movements in the contralateral limbs, trunk, or face. Evoked movements of the limb were generally maximal about a single joint. 3. There was a differential response to microstimulation between subnuclei of the motor thalamus. In order of decreasing frequency, the percentages of sites within each subnucleus from which movements were evoked were as follows: VPLo, 93% (449 of 483); VLo, 21% (57 of 272); VLc, 11% (15 of 140); VA, 1% (1 of 85); and reticular nucleus, 0% (0 of 65). In VPLc, 44% (34 of 78) of sites examined were microexcitable. However, these were almost all within 500 microns of the border of VPLo, suggesting they may have occurred as a result of current spread to adjacent VPLo. Although area X was not sampled in its entirety, it did not appear to be microexcitable. 4. Microexcitable responses had a somatotopic organization, similar to that for neuronal responses to sensorimotor examination, with leg responses found most laterally and arm and face responses found progressively more medially. 5. Zones in VPLo generally ranging from 500 to 1,500 microns were found in which microstimulation resulted in the same motor response. These microexcitable zones resemble those described for the striatum and were termed thalamic microexcitable zones (TMZ). TMZs also resemble cortical efferent zones in that both are somatotopically organized, may affect a single muscle or group of muscles, have low thresholds for microstimulation with sharp boundaries that lie adjacent to other microexcitable zones with the opposite effects, and are of approximately the same dimension. 6. This study suggest that a fundamental unit of motor organization, i.e., single muscle or joint, is preserved at the thalamic level in the form of TMZs, and that these fundamental units of organization may contribute to the modular organization of the cortex.
Characterization of six voltage-gated K+ currents in adult rat sensory neurons
Authors: Gold M. S. , Shuster M. J. , Levine J. D.
Published: December 2017

1. Previously three voltage-gated K+ currents were described in neurons from mammalian sensory ganglia: two transient and one sustained. Because there is considerable variability in the gating properties of these three currents, we have investigated the possibility that this variability reflects the presence of additional currents in sensory neurons. 2. Using whole cell patch-clamp techniques, we provide evidence for the existence of six voltage-gated K+ currents in cultured dorsal root ganglion (DRG) neurons from the adult rat. The six currents were identified on the basis of distinct biophysical and pharmacological properties; three currents are transient (IAf, IAht, and IAs), and three are sustained (IKi, IKlt, and IKn). 3. In addition to possessing distinct biophysical and pharmacological properties, four of the six currents are differentially expressed among subpopulations of DRG neurons. IAht is selectively expressed in small-diameter neurons. IKi is expressed more frequently in neurons with an action-potential shoulder, and both IAht and IAs are selectively coexpressed in neurons that respond to the algogenic agent capsaicin. IAf is selectively expressed in large-diameter neurons and is the only current expressed more frequently in neurons without an action-potential shoulder. 4. It is likely that much of apparent variability in the properties of the three voltage-gated K+ currents reported previously in vertebrate sensory neurons can be accounted for by the existence of at least three additional voltage-gated K+ currents described in this report.
Coding of peripersonal space in inferior premotor cortex (area F4)
Authors: Fogassi L. , Gallese V. , Fadiga L. , Luppino G. , Matelli M. , Rizzolatti G.
Published: December 2017

1. We studied the functional properties of neurons in the caudal part of inferior area 6 (area F4) in awake monkeys. In agreement with previous reports, we found that the large majority (87%) of neurons responded to sensory stimuli. The responsive neurons fell into three categories: somatosensory neurons (30%); visual neurons (14%); and bimodal, visual and somatosensory neurons (56%). Both somatosensory and bimodal neurons typically responded to light touch of the skin. Their RFs were located on the face, neck, trunk, and arms. Approaching objects were the most effective visual stimuli. Visual RFs were mostly located in the space near the monkey (peripersonal space). Typically they extended in the space adjacent to the tactile RFs. 2. The coordinate system in which visual RFs were coded was studied in 110 neurons. In 94 neurons the RF location was independent of eye position, remaining in the same position in the peripersonal space regardless of eye deviation. The RF location with respect to the monkey was not modified by changing monkey position in the recording room. In 10 neurons the RF's location followed the eye movements, remaining in the same retinal position (retinocentric RFs). For the remaining six neurons the RF organization was not clear. We will refer to F4 neurons with RF independent of eye position as somatocentered neurons. 3. In most somatocentered neurons (43 of 60 neurons) the background level of activity and the response to visual stimuli were not modified by changes in eye position, whereas they were modulated in the remaining 17. It is important to note that eye deviations were constantly accompanied by a synergic increase of the activity of the ipsilateral neck muscles. It is not clear, therefore, whether the modulation of neuron discharge depended on eye position or was a consequence of changes in neck muscle activity. 4. The effect of stimulus velocity (20-80 cm/s) on neuron response intensity and RF extent in depth was studied in 34 somatocentered neurons. The results showed that in most neurons the increase of stimulus velocity produced an expansion in depth of the RF. 5. We conclude that space is coded differently in areas that control somatic and eye movements. We suggest that space coding in different cortical areas depends on the computational necessity of the effectors they control.
Mechanical states encoded by stretch-sensitive neurons in feline joint capsule
Authors: Khalsa P. S. , Hoffman A. H. , Grigg P.
Published: December 2017

1. The sensitivity of group II joint afferents innervating cat knee joint capsule to in-plane stretch was studied in vitro. Single afferents were recorded from teased filaments of the posterior articular nerve. The capsule was stretched by applying forces through tabs along the edges of the capsule (3 tabs/edge) with the use of an apparatus that allowed for independent control of each load. The relationships between the neural responses of these afferents and the local continuum mechanical state of the joint capsule have been investigated. By appropriately loading the tissue margins, it was possible to establish states of uniaxial and biaxial tension, including shear. 2. Plane stress was calculated from the loads along the tissue margins. Stress at the location of the mechanoreceptor ending was estimated by interpolation. Strain was calculated from deformations of the capsule measured by tracking markers on its surface. Full characterization of tissue stress and strain made it possible to determine strain energy density and the magnitudes of other coordinate invariant mechanical quantities. 3. Individual afferents (n = 15) exhibited pronounced selectivity to the direction of applied stress and strain. There was no overall preferred orientation across neurons, and simple correlation of individual stress or strain components with the neuronal response revealed no consistent relationship between neuronal response and any single tensor component. However, linear multiple regression of the combined stress and strain components with the neuronal response revealed high correlation (mean R = 0.91), indicating that the measured mechanical states strongly determine the neuronal response. There was a much stronger relationship between neuronal response and stress variables than with strain variables. Simple correlation of the first invariant of the stress tensor with neuronal response had the highest mean correlation of the tensor quantities (R = 0.51). On average, strain energy density was only modestly correlated with the neural response (R = 0.28). 4. These findings indicate that capsule mechanoreceptors are encoding the local continuum mechanical state in the joint capsule. The neural response of these mechanoreceptors is more strongly correlated to local stress than to local strain.
Regulation of synaptic facilitation by postsynaptic Ca2+/CaM pathways in hippocampal CA1 neurons
Authors: Wang J. H. , Kelly P. T.
Published: December 2017

1. Current- and voltage-clamp recordings with simultaneous field potential recordings were used to study the cellular and molecular mechanisms that contribute to synaptic facilitation at CA1 synapses in rat hippocampal slices. Microelectrodes used for intracellular recordings were also used to inject modulators of intracellular signal pathways into postsynaptic CA1 neurons. 2. Paired-pulse stimulation at constant stimulus intensity was used to analyze the relationship between the first evoked response (R1) and the absolute value of paired-pulse synaptic facilitation (R2-R1). The magnitudes of these two measures were inversely correlated. Compared with synapses that control motor functions, the synapses of CA1 pyramidal neurons did not exhibit accumulative synaptic facilitation during repetitive stimulation, which is often believed to be mediated by presynaptic residual Ca2+. 3. During studies on the cellular location of mechanisms contributing to synaptic facilitation, we observed that postsynaptic injections of 1,2-bis(2-aminophenoxy)-ethane-N,N,N',N'-tetra-acetic acid or [Ala286]CaMKII281-302 [a Ca2+/calmodulin-dependent protein kinase II (CaM-KII) inhibitor peptide] prevented the decreases in paired-pulse facilitation (PPF) and synaptic potentiation induced by elevating extracellular Ca2+. These results show that raising extracellular Ca2+ enhances synaptic transmission in part by activating postsynaptic Ca2+ signal pathways. 4. The injection of Ca2+/calmodulin (CaM) into postsynaptic neurons significantly decreased PPF in 50 of 57 experiments while inducing synaptic potentiation; the Ca2+/CaM-induced synaptic potentiation and PPF attenuation occluded subsequent high Ca(2+)-induced enhancements of synaptic transmission. The changes in PPF induced by postsynaptic injections of Ca2+/CaM were inversely correlated with R1 potentiation. 5. The decreases in PPF induced by postsynaptic Ca2+/CaM injections were prevented by coinjecting pseudosubstrate inhibitors or substrate peptides of CaM-KII and protein kinase C (PKC), and were reversed by subsequent application of cyclothiazide (a blocker of alpha-amino-3-hydroxy-5-methylisoxazole-4-proprionic acid receptor desensitization). 6. Our results reveal that postsynaptic Ca2+/CaM signal pathways can modulate synaptic facilitation in the CNS, and the activities of CaM-KII and PKC are involved in this modulation. The physiological significance of such modulation is that synaptic strength could be potentiated by activation of Ca2+/CaM pathways during integration of important sensory input (e.g., learning and memory), whereas decreases in synaptic facilitation may protect synaptic transmission during extreme stimulation so that neuronal signal mechanisms can more accurately code neural information.
Homomeric and heteromeric ion channels formed from the kainate-type subunits GluR6 and KA2 have very small, but different, unitary conductances
Authors: Howe J. R.
Published: December 2017

1. Patch-clamp methods were used to study recombinant glutamate receptor (GluR) ion channels expressed in human embryonic kidney cells (HEK 293) after transfection of the cells with cDNAs encoding kainate (KA)-type GluR subunits. Cells were transiently or stably transfected with the fully edited (R) version of GluR6 or they were contransfected with GluR6(R) and KA2. 2. Concentration-response data were obtained for KA and glutamate activation of homomeric GluR6(R) channels and fitted with Hill-type equations to give values for the agonist concentration at half-maximal activation (EC50), the Hill coefficient (nH), and the maximum current (Imax). Analysis of results obtained in seven cells with KA gave mean values of 0.47 microM and 1.47 for the EC50 and nH, respectively. The corresponding values for glutamate were 32 microM and 1.21 (n = 5). The Imax values obtained for KA and glutamate in the same cells were similar, suggesting that both KA and glutamate are full agonists at homomeric GluR6(R) channels. 3. Spectral density analysis of current noise evoked by KA and glutamate in GluR6(R)-expressing cells, or in outside-out patches from these cells, was used to obtain estimates of the apparent unitary conductance (gamma noise) of homomeric GluR6(R) channels. Results obtained with 10 microM KA in 15 cells gave a mean gamma noise value of 231 fS. The corresponding value from analysis of noise in outside-out patches was 259 fS (n = 4). Spectral density analysis of glutamate-evoked noise in six cells gave a mean gamma noise value of 264 fS. 4. Noise analysis of whole cell currents recorded in GluR6(R)/ KA2-expressing cell gave a mean gamma noise value of 572 fS (n = 9). Unlike homomeric GluR6(R) channels, GluR6(R)/KA2 heteromers were activated by alpha-amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid (AMPA) (0.25-5 mM). The mean EC50 for KA activation of GluR6(R)/KA2 channels was 1.62 microM (n = 6). 5. The results indicate that both homomeric GluR6(R) and heteromieric GluR6(R)/KA2 channels have a unitary conductance in the femtosiemen range. The coassembly of KA2 with GluR6(R) results in channels that have a different affinity for AMPA and KA and a two- to threefold larger unitary conductance.
Electrogenic pump and a Ca(2+)- dependent K+ conductance contribute to a posttetanic hyperpolarization in lamprey sensory neurons
Authors: Parker D. , Hill R. , Grillner S.
Published: December 2017

1. Tetanic stimulation of lamprey sensory dorsal cells resulted in a posttetanic hyperpolarization (PTH). The amplitude and duration of the PTH were dependent on the stimulus duration and frequency. The PTH was not reversed at membrane potentials negative to -100 mV, whereas the afterhyperpolarization following single action potentials reversed at approximately -85 mV. There was also a biphasic effect on the input resistance during the PTH, with an early reduction that recovered to control before the PTH had decayed. 2. The amplitude and duration of the PTH were increased in Ringer solution containing tetraethylammonium and 4-aminopyridine, both of which broadened single action potentials, but were reduced after intracellular injection of Cs+. Ca(2+)-free Ringer solution, Cd2+, and Co2+ also reduced the PTH, suggesting the involvement of a Ca(2+)-dependent K+ conductance. However, the PTH was not reduced in Ba2+ Ringer solution, or by the Ca(2+)-dependent K+ channel antagonists apamin and charybdotoxin. 3. The cardiac glycoside ouabain reduced the amplitude and duration of the PTH, as did substitution of Na+ with choline or Li+. K(+)-free Ringer solution also reduced the PTH, whereas high-K+ Ringer solution had more variable effects. The amplitude and duration of the PTH were also dependent on temperature. These results support the involvement of an ouabain-sensitive Na-K pump in the PTH. 4. The PTH was reduced by the tachykinins substance P and physalaemin, and by 5-hydroxytryptamine, which blocks apamin-sensitive Ca(2+)-dependent K+ channels in the lamprey. However, gamma-aminobutyric acid, which has been reported to reduce a Ca(2+)-dependent K+ conductance in the dorsal cells, did not reduce the PTH. 5. These results suggest that a Ca(2+)-dependent K+ conductance and an Na-K electrogenic pump underlie the PTH. The PTH reduces the excitability of the dorsal cells, suggesting that it may act as a mechanism to gate sensory information entering the spinal cord.
Associative synaptic plasticity in hippocampal CA1 neurons is not sensitive to unpaired presynaptic activity
Authors: Buonomano D. V. , Merzenich M. M.
Published: December 2017

1. Hebbian or associative synaptic plasticity has been proposed to play an important role in learning and memory. Whereas many behaviorally relevant stimuli are time-varying, most experimental and theoretical work on synaptic plasticity has focused on stimuli or induction protocols without temporal structure. Recent theoretical studies have suggested that associative plasticity sensitive to only the conjunction of pre- and postsynaptic activity is not an effective learning rule for networks required to learn time-varying stimuli. Our goal in the current experiment was to determine whether associative long-term potentiation (LTP) is sensitive to temporal structure. We examined whether the presentation of unpaired presynaptic pulses in addition to paired pre- and postsynaptic activity altered the induction of associative LTP. 2. By using intracellular recordings from CA1 pyramidal cells, associative long-term potentiation (LTP) was induced in a control pathway by pairing a single presynaptic pulse with postsynaptic depolarization every 5 s (50-70 x). The experimental pathway received the same training, with additional unpaired presynaptic pulses delivered in close temporal proximity, either after or before associative pairing. Five separate sets of experiments were performed with intervals of -200, -50, +50, +200, or +800 ms. Negative intervals indicate that the unpaired presynaptic pulse was presented before the depolarizing pulse. Our results showed that the presence of unpaired presynaptic pulses, occurring either before or after pairing, did not significantly alter the magnitude of LTP. 3. The experimental design permitted an analysis of whether changes in paired-pulse facilitation (PPF) occur as a result of associative LTP. The average degree of PPF was the same before and after LTP. However, there was a significant inverse correlation between the initial degree of PPF and the degree of PPF after LTP. There was no relationship between the change in PPF, and whether the first or second pulse had been paired with depolarization. 4. These results indicate that the presence of unpaired presynaptic pulses does not alter the induction of synaptic plasticity, suggesting that plasticity of the Schaffer collateral-CA1 synapse is primarily conjunctive rather than correlative.
Role of GABA in shaping frequency tuning and creating FM sweep selectivity in the inferior colliculus
Authors: Fuzessery Z. M. , Hall J. C.
Published: December 2017

1. We examined the role of gamma-aminobutyric acid (GABA)-mediated inhibition in shaping excitatory tuning curves and creating selectivity for frequency-modulated (FM) sweeps in 29 neurons in the central nucleus of the inferior colliculus (ICC) of the pallid bat, with the use of single-unit recording coupled with the iontophoretic application of bicuculline methiodide (BIC), an antagonist of GABAA receptors. 2. BIC increased response magnitude 2 to 6 times over pretreatment levels in > 80% of neurons tested, and converted > 50% of nonmonotonic intensity-rate functions to monotonic or plateaued functions, demonstrating that GABAergic input normally limited response magnitude and inhibited responses at higher intensities. BIC typically had little effect on response thresholds, except in more specialized neurons that normally responded poorly to tones. In these cases, BIC disinhibited the neurons' responses to tones and lowered excitatory thresholds as much as 25 dB. 3. We examined the effects of BIC application on both excitatory and inhibitory tuning curves (measured with simultaneous 2-tone inhibition) to determine whether inhibitory curves were GABA mediated and whether removal of this inhibition was accompanied by an expansion of the excitatory curve. BIC had variable effects on the width of excitatory curves. In most cases, excitatory curves were at least slightly broadened, and expanded into regions previously occupied by inhibitory curves. In most cases, excitatory curves were at least slightly broadened, and expanded into regions previously occupied by inhibitory curves. However, in a few cases, inhibitory curves could be eliminated without an expansion of the excitatory curve. The greatest effect was seen in neurons with closed excitatory tuning curves; blocking GABAergic input caused the curves to open, allowing the neurons to respond at higher intensities. 4. Approximately 50% of the neurons in the ICC tuned to the spectrum of the bat's downward FM sweeping biosonar pulse respond preferentially to downward FM sweeps and not to upward sweeps, tones, or noise. In all neurons tested, BIC at least partially destroyed selectivity for sweep direction. This destruction could occur, however, without a loss of response exclusivity; in some cases, the neurons still did not respond to tones or noise. These results suggest that response selectivity for a species-specific signal is created by GABAergic input to ICC neurons. These results are used to suggest a mechanism that creates selectivity for FM sweep direction.
A comparison of spontaneous EPSCs in layer II and layer IV-V neurons of the rat entorhinal cortex in vitro
Authors: Berretta N. , Jones R. S.
Published: December 2017

1. We have compared the characteristics of spontaneous excitatory postsynaptic currents (sEPSCs) in neurons of layer IV-V and layer II of the rat entorhinal cortex (EC) using whole cell voltage-clamp recordings in a slice preparation. 2. The frequency of sEPSCs was similar in the two layers, but the events in layer IV-V had a larger mean amplitude, faster rise time, and were faster to decay. The difference in amplitude could be attributed to the presence of a population of larger events in the layer IV-V neurons that were not present in layer II. 3. Electrotonic length was greater in layer II neurons, suggesting that the difference in kinetics of the sEPSCs may be explained partly by electrotonic attenuation. 4. The frequency of sEPSCs in both layers was reduced by tetrodotoxin (TTX) to a similar extent (15-20%). However, the amplitude distribution was unchanged in layer II, whereas in layer IV-V TTX abolished most of the larger amplitude sEPSCs. 5. 6-cyano-7-nitroquinoxaline-2,3-dione or 6-nitro-7-sulphamoylbenzo (f)-quinoxaline-2,3-dione, abolished most of the sEPSCs in neurons of both layers. However, even at negative holding potentials, a population of slower time-course sEPSCs remained in the presence of these antagonists. 6. The slow sEPSCs were more frequent in layer IV-V but had similar characteristics in both layers, being increased in amplitude at more positive holding potentials or in Mg2+-free medium, and blocked by 2-amino-5-phosphonovalerate (AP5). 7. AP5 alone (i.e., without addition of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid antagonists) reduced the peak amplitude and decay phase of sEPSCs in layer IV-V neurons but appeared to have little effect on amplitude and only a weak effect on decay phase in layer II. 8. Thus both layer IV-V and layer II neurons of the EC suffer continuous spontaneous excitation. However, layer IV-V neurons exhibit larger amplitude sEPSCs, probably mediated by release of multiple quanta of neurotransmitter. In addition, although both types of neurons display spontaneous excitation mediated by N-methyl-D-aspartate receptors, this component appears more pronounced in the deeper layers.
Soleus stretch reflex modulation during gait in humans
Authors: Sinkjaer T. , Andersen J. B. , Larsen B.
Published: December 2017

1. The modulation of the short-latency stretch reflex during walking at different walking speeds was investigated and compared with the stretch reflex during standing in healthy human subjects. 2. Ankle joint stretches were applied by a system able to rotate the human ankle joint during treadmill walking in any phase of the step cycle. The system consisted of a mechanical joint attached to the subject's ankle joint and connected to a motor placed beside the treadmill by means of bowden wires. The weight of the total system attached to the leg of the subject was 900 g. 3. The short-latency soleus stretch reflex was modulated during a step. In the stance phase, the amplitude equaled that found during standing at matched soleus background electromyogram (EMG). In the transition from stance to swing, the amplitude was 0 in all subjects. In late swing, the stretch reflex amplitude increased to 45 +/- 27% (mean +/- SD) of the maximal amplitude in the stance phase (stretch amplitude 8 degrees, stretch velocity 250 degrees/s). 4. The onset (42 +/- 3.2 ms) and peak latencies (59 +/- 2.5 ms) of the stretch reflex did not depend on the phase in the step cycle at which the reflex was elicited. 5. When the ankle joint is rotated, a change in torque can be measured. The torque measured over the first 35 ms after stretch onset (nonreflex torque) was at a maximum during late stance, when the leg supported a large part of the body's weight, and at a minimum during the swing phase. At heel contact the nonreflex torque was 50% of its maximal value. 6. During the stance phase the maximal EMG stretch reflex had a phase lead of approximately 120 ms with respect to the maximal background EMG and a phase lead of approximately 250 ms with respect to the maximal nonreflex torque. 7. The constant latency of the stretch reflex during a step implied that the ankle extensor muscle spindles are always taut during walking. 8. The relatively high amplitude of the stretch reflex in late swing and at heel contact made it likely that the stretch reflex contributed to the activation of the ankle extensor muscles in early stance phase.
GABAB receptors presynaptically modulate excitatory synaptic transmission in the rat supraoptic nucleus in vitro
Authors: Kombian S. B. , Zidichouski J. A. , Pittman Q. J.
Published: December 2017

1. The effect of gamma-aminobutyric acid-B (GABAB)-receptor activation on excitatory synaptic transmission in the rat supraoptic nucleus (SON) was examined using the nystatin perforated-patch whole cell recording technique in coronal hypothalamic slices. 2. Stimulation of the hypothalamic region dorso-medial to the SON elicited glutamate and GABAA-receptor-mediated synaptic responses in electrophysiologically identified magnocellular neurosecretory cells. 3. Bath application of the GABAB-receptor agonist, +/- -baclofen reversibly reduced pharmacologically isolated, glutamate-mediated excitatory postsynaptic currents (EPSCs) in a concentration-dependent manner. At the concentrations used, baclofen altered neither the postsynaptic conductances of these cells nor their response to bath applied alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA). 4. The baclofen-induced synaptic depression was accompanied by an increase in paired pulse facilitation (PPF). This increase in PPF, as well as the synaptic depression, was blocked by the GABAB-receptor antagonists CGP36742 and saclofen. 5. In addition to blocking the actions of baclofen in this nucleus, CGP36742 caused an increase in the evoked EPSC amplitude without altering postsynaptic cell conductances or responses induced by bath-applied AMPA. Contrary to the action of CGP36742, saclofen caused a baclofen-like depression of the evoked EPSC, suggesting that it may act as a partial GABAB receptor agonist. 6. These results indicate that the activation of presynaptic GABAB receptors reduces fast excitatory synaptic transmission in the SON. They further suggest that presynaptic GABAB receptors may be tonically activated in vitro. Thus GABAB receptors may influence the level of activity and excitation of SON neurons and hence modulate the secretion of the regulatory neuropeptides vasopressin and oxytocin.
Inward currents underlying action potentials in rat adrenal chromaffin cells
Authors: Hollins B. , Ikeda S. R.
Published: December 2017

1. Current- and voltage-clamp studies were conducted on isolated rat adrenal chromaffin cells to identify the voltage-dependent ion channels mediating inward currents. 2. Mean resting membrane potential of the isolated cells was -62 +/- 3 (SE) mV. Evoked action potentials were both Na+ and Ca2+ based, and whole cell voltage-clamp studies in normal saline revealed an inward-rectifier-type current. 3. Na+ channels were studied in isolation and showed a half-inactivation of -60 +/- 2 mV with a slope factor of -6 mV and a half-activation of -26.8 +/- 2 mV with a slope factor of 6.5 +/- 0.7 mV. 4. Isolated Ca2+ currents, elicited in 10 mM external Ca2+, revealed a T-type current in a subset of cells. Ca2+ currents were sensitive to both N- and L-type channel antagonists, and blockade of the current by the L-type channel antagonist nimodipine and the N-type channel antagonist omega-conotoxin GVIA revealed a third Ca2+-current component that was unaffected by the P-type channel antagonist omega-agatoxin IVA. 5. Ca2+ currents were facilitated 5-20% by a depolarizing prepulse, and facilitation was completely blocked by nimodipine. The effects of the dihydropyridine L-type channel agonist, (+)202-791 and depolarizing prepulses on the currents were additive. 6. The results of this study show that the properties of voltage-dependent ion channels in rat chromaffin cells differ from those reported in their counterparts in bovine chromaffin cells. Na+ channels differ in activation and inactivation properties and Ca2+ channels differ in activation, sensitivity to antagonists, and the magnitude of voltage-dependent facilitation.
Motor unit recruitment in a distributed model of extraocular muscle
Authors: Dean P.
Published: December 2017

1. Eye position commands frequently are treated as a lumped, single-valued variable that is related linearly to eye position. As a step toward investigating how system-level linearity might be achieved despite nonlinear components, a distributed model of motor units in the abducens nucleus and lateral rectus muscle was constructed. 2. Parameters in the model were estimated using data from three main sources: measurement of length-tension curves for eye muscle in people, electrophysiological recording of ocular motoneuron properties in monkeys, and investigations of oculomotor unit properties in cat. Units (n = 100) in the distributed model were assigned equal strengths and for a given fixation command, the force developed by each unit was calculated, and the sum of unit forces compared with the active force in the entire muscle as measured experimentally. 3. The properties of the active units then were adjusted to reduce the size of any resultant error in a manner related to gradient descent methods for neural-net training. Distributed models were "trained" in this fashion for a series of eye positions drawn at random from the oculomotor range until performance stabilized. The goal of the training procedure was to obtain a good match between the output of the model and the experimental data on muscle force as a function of eye position. 4. Plots of trained motor-unit strength against ocular motoneuron threshold revealed a U-shaped pattern with the strongest units being recruited at both extremes of the oculomotor range and the weakest units recruited in the middle. The pattern remained unaltered qualitatively over a range of assumptions about the distribution of ocular motoneuron parameters and the relation between motoneuron firing rate and unit force. 5. The right-hand limb of the U-shaped pattern is similar to that observed in spinal motoneurons, where stronger units tend to have higher recruitment thresholds. The left-hand limb may reflect the two specializations of eye muscle: the functional need for very precise control of eye position in the middle of the oculomotor range and the use of multiply innervated muscle fibers to provide ripple-free control of eye position at low firing frequencies.
Variability and interhemispheric asymmetry of single-whisker functional representations in rat barrel cortex
Authors: Chen-Bee C. H. , Frostig R. D.
Published: December 2017

1. The rat whisker-to-barrel system was used to investigate the variability and interhemispheric asymmetry in the functional organization of primary somatosensory cortex as assessed with intrinsic signal optical imaging. The areal extent of whisker D1 functional representation was determined for both the left and right barrel cortex of each of 10 adult male rats. The average size of whisker D1 functional representation and the amount of variability away from this average across animals were determined. In addition, interhemispheric asymmetry was addressed at both the population level and the individual level. The degree of side preference for thigmotactic scanning (typical whisker-related rodent behavior) was determined for each rat in an attempt to find a behavioral correlate for the degree of interhemispheric asymmetry in the size of whisker D1 functional representation. 2. The average areal extent of whisker D1 functional representation (defined as area at half-height) was large (1.95 +/- 0.14 mm2, mean +/- SE, N = 10 rats), suggesting that stimulation of a single whisker evokes activity over a large cortical area that includes other whisker representations. 3. The average size of whisker D1 functional representation was not significantly different between the left (1.86 +/- 0.21 mm2) and right (2.04 +/- 0.15 mm2) hemispheric side, suggesting that interhemispheric functional asymmetry of barrel cortex is not systematic toward a specific hemispheric side at the population level. 4. The degree of variability in the size of whisker D1 functional representation from the left hemisphere ranged between 54.6% smaller than to 50.6% larger than the left average areal extent. A large degree of variability was also observed for the right D1 representation, 37.6% smaller than to 34.9% larger than the right average areal extent. Thus it appears that a large variability in the size of unmanipulated single-whisker functional representations exists across animals from the same species and is not exclusive to a particular hemispheric side. 5. In 5 of 10 rats, the size of whisker D1 functional representation between the two hemispheres differed by > or = 25% within an individual animal. Of these five rats, four had a larger representation in their right hemisphere. The degree and direction of behavioral asymmetry was not linearly correlated with the interhemispheric asymmetry in the size of D1 functional representation (r = 0.494). 6. The large size of a single-whisker functional representation as defined with intrinsic signal optical imaging is discussed with respect to previous anatomic and 2-deoxyglucose autoradiography studies, whereas the large variability in this size across animals is discussed with respect to the individuality of each animal. In addition, the results of the present study have implications for projects that plan to investigate relative changes in the size of single-whisker functional representations.
Effects of red nucleus inactivation on burst discharge in turtle cerebellum in vitro: evidence for positive feedback
Authors: Keifer J.
Published: December 2017

1. In behaving animals the red nucleus produces sustained action potential discharge during movements of the limbs. These bursts are thought to encode parameters of movement and thereby represent motor commands. Similar bursts can be recorded in the in vitro brain stem-cerebellum from the turtle. In this preparation, sustained discharge of red nucleus neurons was postulated to be generated by N-methyl-D-aspartate-mediated cellular mechanisms acting in combination with positive feedback in a recurrent cerebellorubral network. The present study was designed to test this positive feedback hypothesis. During recording of sustained discharge in the deep cerebellar nuclei and cortex, the red nucleus was reversibly inactivated by microinjection. The positive feedback hypothesis would be supported if activity in the cerebellum was attenuated by inactivation of the red nucleus. A nonrecurrent source of excitation would have to be postulated if cerebellar activity was unaffected. 2. Extracellular single-unit recordings were made from neurons in the deep cerebellar nuclei, cerebellar cortex, and vestibular nuclei. Burst discharges were evoked by brief electrical stimuli applied to the spinal cord that activated sensory structures. During inactivation of the red nucleus, sensory projections to the cerebellum that may evoke burst discharge were unaffected. Pressure microinjections of cobalt, lidocaine, gamma-aminobutyric acid (GABA), or 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) were used to reversibly inactivate the red nucleus. Saline injections were also tested. 3. Sustained discharge of all neurons recorded in the lateral cerebellar nucleus was greatly attenuated or blocked completely by injection of the pharmacological agents into the red nucleus. These effects were reversible. Of the recordings in the cerebellar cortex, 63% of these were blocked. All four compounds tested were effective blockers of the bursts, although the effects of GABA were less potent than the others. Saline injections into the red nucleus showed no effect. Burst discharges of single units recorded in either the medial cerebellar nucleus or the vestibular complex, which do not receive input from the red nucleus, showed no effect of red nucleus inactivation. 4. The results showed that sustained discharge in the cerebellum was significantly attenuated by inactivation of the red nucleus even though sensory input that may trigger the bursts was intact. These data support the hypothesis that sustained discharge in the cerebellorubral circuit is generated by a distributed neuronal network that uses positive feedback. The results have implications for mechanisms underlying normal brain function and some motor disorders.
Role of ventral respiratory group bulbospinal expiratory neurons in vestibular-respiratory reflexes
Authors: Shiba K. , Siniaia M. S. , Miller A. D.
Published: December 2017

1. Activation of the vestibular system produces reflex modulation of expiratory muscle activity. The purpose of the present study was to investigate the possible role of bulbospinal expiratory (E) neurons located in the caudal ventral respiratory group (VRG) in mediating vestibulo-respiratory reflexes. Experiments were carried out in decerebrated, paralyzed, and artificially ventilated cats. 2. Electrical stimulation of the vestibular nerve (VN), using short trains of current pulses, elicited bilateral reflex responses on abdominal muscle nerves (ABDNs). This response was not affected by lesions of the cochlear nuclei made by kainic acid injections. The ABDN response typically consisted of a combination of short-latency excitation and long-latency inhibition on the ipsilateral side and, in contrast, a combination of short-latency inhibition and long-latency excitation on the contralateral side. 3. Extracellular recordings were made from 43 caudal VRG bulbospinal E neurons that were activated antidromically from the contralateral upper lumbar spinal cord. More than 80% of these neurons responded to either ipsi- and/or contralateral VN stimulation. The neuronal response consisted of either a combination of excitation and inhibition or only inhibition. The majority of neurons had response patterns appropriate to contribute to the response observed on the contralateral ABDN; however, the latency of the VRG E neuron response was too long to initiate the ABDN response. 4. To further evaluate the contribution of caudal VRG E neurons to the vestibulo-abdominal reflex, ABDN responses were compared before and after sectioning the axons of caudal VRG bulbospinal E neurons where they cross the midline between the obex and first cervical spinal segment. These midsagittal lesions abolished expiratory modulation of ABDN discharge. The lesions also decreased the amplitude of the vestibular-evoked ABDN response but could not abolish the response. The postlesion amplitude was decreased on average to approximately 70% of prelesion values. 5. In conclusion, although the present results indicate that the majority of caudal VRG bulbospinal E neurons respond appropriately to contribute to the vestibulo-abdominal reflex, the reflex largely is unaffected by the removal of caudal VRG E input. The additional descending inputs that are important for mediating the reflex remain to be investigated and may include vestibulospinal and/or reticulospinal tracts.
GABAA-receptor-mediated conductance and action potential waveform in cutaneous and muscle afferent neurons of the adult rat: differential expression and response to nerve injury
Authors: Oyelese A. A. , Kocsis J. D.
Published: December 2017

1. Whole cell patch-clamp recordings were obtained from identified cutaneous and muscle afferent neurons (33-60 microns diam) in dissociated L4 and L5 dorsal root ganglia (DRGs) from normal rats and from rats 2-3 wk after sciatic nerve ligation or crush injury. gamma-Aminobutyric acid (GABA)-induced conductance was compared in normal and injured neurons from both functional classes of sensory neurons. 2. Control cutaneous afferent neurons had a peak GABA-mediated conductance of 287 +/- 27 (SE) nS compared with 457 +/- 42 nS for control muscle afferent neurons. 3. An inflection on the downslope of the action potential was observed in 47% of cutaneous afferent neurons compared with 20% of muscle afferent neurons. 4. After ligation and transection of the sciatic nerve there was no change in the GABA-mediated conductance of muscle afferent neurons or in the action potential waveform (23% inflected). However, the cutaneous afferent neurons displayed a greater than two-fold increase in their GABA-mediated conductance and displayed a prominent reduction in the number of neurons with inflected action potentials (13% inflected). Input resistance was similar in cutaneous and muscle afferent neurons and decreased after ligation in cutaneous but not muscle afferents. Resting potential averaged from -50 to -56 mV in normal and ligated groups for both cutaneous and muscle afferent neurons. 5. After crush injury in cutaneous afferent neurons where the transected axons were allowed to regenerate into the distal nerve stump, GABAA-receptor-mediated conductance was elevated compared with controls. However, action potential waveform was not altered by crush injury, suggesting a differential regulation of these two properties in cutaneous afferent neurons. 6. These data indicate that injury-induced plasticity of GABAA-receptor-mediated conductance and action potential waveform occurs in cutaneous but not muscle afferent DRG neurons. It appears that peripherally derived influences are critical in maintaining the electrophysiological phenotype of cutaneous afferent neurons but not muscle afferent neurons.