bluuebunny/crossref_metadata_2025 huggingface dataset:
Pattern Generation for Walking and Searching Movements of a Stick Insect Leg. II. Control of Motoneuronal Activity
Authors: Schmidt Joachim , Fischer Hanno , Büschges Ansgar
Published: December 2017

In the stick insect, Cuniculina impigra, intracellular recordings from mesothoracic motoneurons that control flexion and extension of the tibia and depression and levation of the trochantero-femur were made while the leg performed walking-like movements on a treadband or stereotyped rhythmic searching movements. We were interested in how synaptic input and intrinsic properties contribute to form the activity pattern of motoneurons during rhythmic leg movements without sensory feedback from other legs. During searching and walking, motoneurons expressed a rhythmic bursting pattern that was formed by a depolarizing input followed by a hyperpolarizing input in the inter-burst interval. This basic pattern was similar in all fast, semi-fast, and slow motoneurons that were recorded. Hyperpolarizations were in synchrony with activity in the antagonistic motoneurons. De- and hyperpolarizations were associated with a decrease in input resistance. All motoneurons showed spike frequency adaptation when depolarized by current injection to a membrane potential similar to that observed during walking. In the hyperpolarizing phase of fast flexor motoneurons, the initial maximum hyperpolarization was followed by a sag in potential toward more depolarized values. Consistent with this observation, only fast flexor motoneurons developed a depolarizing sag potential when hyperpolarized by injection of constant negative current.
Activity of Cardiorespiratory Networks Revealed by Transsynaptic Virus Expressing GFP
Authors: Irnaten Mustapha , Neff Robert A. , Wang Jijiang , Loewy Arthur D. , Mettenleiter Thomas C. , Mendelowitz David
Published: December 2017

A fluorescent transneuronal marker capable of labeling individual neurons in a central network while maintaining their normal physiology would permit functional studies of neurons within entire networks responsible for complex behaviors such as cardiorespiratory reflexes. The Bartha strain of pseudorabies virus (PRV), an attenuated swine alphaherpesvirus, can be used as a transsynaptic marker of neural circuits. Bartha PRV invades neuronal networks in the CNS through peripherally projecting axons, replicates in these parent neurons, and then travels transsynaptically to continue labeling the second- and higher-order neurons in a time-dependent manner. A Bartha PRV mutant that expresses green fluorescent protein (GFP) was used to visualize and record from neurons that determine the vagal motor outflow to the heart. Here we show that Bartha PRV-GFP-labeled neurons retain their normal electrophysiological properties and that the labeled baroreflex pathways that control heart rate are unaltered by the virus. This novel transynaptic virus permits in vitro studies of identified neurons within functionally defined neuronal systems including networks that mediate cardiovascular and respiratory function and interactions. We also demonstrate superior laryngeal motorneurons fire spontaneously and synapse on cardiac vagal neurons in the nucleus ambiguus. This cardiorespiratory pathway provides a neural basis of respiratory sinus arrhythmias.
Identified Serotonergic Neurons in the TritoniaSwim CPG Activate Both Ionotropic and Metabotropic Receptors
Authors: Clemens Stefan , Katz Paul S.
Published: December 2017

Although G-protein-coupled (metabotropic) receptors are known to modulate the production of motor patterns, evidence from the escape swim central pattern generator (CPG) of the nudibranch mollusk, Tritonia diomedea, suggests that they might also participate in the generation of the motor pattern itself. The dorsal swim interneurons (DSIs), identified serotonergic neurons intrinsic to the Tritonia swim CPG, evoke dual component synaptic potentials onto other CPG neurons and premotor interneurons. Both the fast and slow components were previously shown to be due to serotonin (5-HT) acting at distinct postsynaptic receptors. We find that blocking or facilitating metabotropic receptors in a postsynaptic premotor interneuron differentially affects the fast and slow synaptic responses to DSI stimulation. Blocking G-protein activation by iontophoretically injecting the GDP-analogue guanosine 5′- O-(2-thiodiphosphate) (GDP-β-S) did not significantly affect the DSI-evoked fast excitatory postsynaptic potential (EPSP) but decreased the amplitude of the slow component more than 50%. Injection of the GTP analogues guanosine 5′- O-(3-thiotriphosphate) (GTP-γ-S) and 5′-guanylyl-imidodiphosphate, to prolong G-protein activation, had mixed effects on the fast component but increased the amplitude and duration of the slow component of the DSI-evoked response and, with repeated DSI stimulation, led to a persistent depolarization. These results indicate that the fast component of the biphasic synaptic potential evoked by a serotonergic CPG neuron onto premotor interneurons is mediated by ionotropic receptors (5-HT-gated ion channels), whereas the slow component is mediated by G-protein-coupled receptors. A similar synaptic activation of metabotropic receptors might also be found within the CPG itself, where it could exert a direct influence onto motor pattern generation.
Direct Depolarization and Antidromic Action Potentials Transiently Suppress Dendritic IPSPs in Hippocampal CA1 Pyramidal Cells
Authors: Morishita Wade , Alger Bradley E.
Published: December 2017

Whole-cell current-clamp recordings were made from distal dendrites of rat hippocampal CA1 pyramidal cells. Following depolarization of the dendritic membrane by direct injection of current pulses or by back-propagating action potentials elicited by antidromic stimulation, evoked γ-aminobutyric acid-A (GABAA) receptor-mediated inhibitory postsynaptic potentials (IPSPs) were transiently suppressed. This suppression had properties similar to depolarization-induced suppression of inhibition (DSI): it was enhanced by carbachol, blocked by dendritic hyperpolarization sufficient to prevent action potential invasion, and reduced by 4-aminopyridine (4-AP) application. Thus DSI or a DSI-like process can be recorded in CA1 distal dendrites. Moreover, localized application of TTX to stratum pyramidale blocked somatic action potentials and somatic IPSPs, but not dendritic IPSPs or DSI induced by direct dendritic depolarization, suggesting DSI is expressed in part in the dendrites. These data extend the potential physiological roles of DSI.
The Role of Sensory Signals From the Insect Coxa-Trochanteral Joint in Controlling Motor Activity of the Femur-Tibia Joint
Authors: Akay Turgay , Bässler Ulrich , Gerharz Petra , Büschges Ansgar
Published: December 2017

Interjoint coordination in multi-jointed limbs is essential for the generation of functional locomotor patterns. Here we have focused on the role that sensory signals from the coxa-trochanteral (CT) joint play in patterning motoneuronal activity of the femur-tibia (FT) joint in the stick insect middle leg. This question is of interest because when the locomotor system is active, movement signals from the FT joint are known to contribute to patterning of activity of the central rhythm-generating networks governing the CT joint. We investigated the influence of femoral levation and depression on the activity of tibial motoneurons. When the locomotor system was active, levation of the femur often induced a decrease or inactivation of tibial extensor activity while flexor motoneurons were activated. Depression of the femur had no systematic influence on tibial motoneurons. Ablation experiments revealed that this interjoint influence was not mediated by signals from movement and/or position sensitive receptors at the CT joint, i.e., trochanteral hairplate, rhombal hairplate, or internal levator receptor organ. Instead the influence was initiated by sensory signals from a field of campaniform sensillae, situated on the proximal femur (fCS). Selective stimulation of these fCS produced barrages of inhibitory postsynaptic potentials (IPSPs) in tibial extensor motoneurons and activated tibial flexor motoneurons. During pharmacologically activated rhythmic activity of the otherwise isolated mesothoracic ganglion (pilocarpine, 5 × 10−4M), deafferented except for the CT joint, levation of the femur as well had an inhibitory influence on tibial extensor motoneurons. However, the influence of femoral levation on the rhythm generated was rather labile and only sometimes a reset of the rhythm was induced. In none of the preparations could entrainment of rhythmicity by femoral movement be achieved, suggesting that sensory signals from the CT joint only weakly affect central rhythm-generating networks of the FT joint. Finally, we analyzed the role of sensory signals from the fCS during walking by recording motoneuronal activity in the single middle leg preparation with fCS intact and after their removal. These experiments showed that fCS activity plays an important role in generating tibial motoneuron activity during the stance phase of walking.
Excitatory Synaptic Input to Granule Cells Increases With Time After Kainate Treatment
Authors: Wuarin Jean-Pierre , Dudek F. Edward
Published: December 2017

Temporal lobe epilepsy is usually associated with a latent period and an increased seizure frequency following a precipitating insult. After kainate treatment, the mossy fibers of the dentate gyrus are hypothesized to form recurrent excitatory circuits between granule cells, thus leading to a progressive increase in the excitatory input to granule cells. Three groups of animals were studied as a function of time after kainate treatment: 1–2 wk, 2–4 wk, and 10–51 wk. All the animals studied 10–51 wk after kainate treatment were observed to have repetitive spontaneous seizures. Whole cell patch-clamp recordings in hippocampal slices showed that the amplitude and frequency of spontaneous excitatory postsynaptic currents (EPSCs) in granule cells increased with time after kainate treatment. This increased excitatory synaptic input was correlated with the intensity of the Timm stain in the inner molecular layer (IML). Flash photolysis of caged glutamate applied in the granule cell layer evoked repetitive EPSCs in 10, 32, and 66% of the granule cells at the different times after kainate treatment. When inhibition was reduced with bicuculline, photostimulation of the granule cell layer evoked epileptiform bursts of action potentials only in granule cells from rats 10–51 wk after kainate treatment. These data support the hypothesis that kainate-induced mossy fiber sprouting in the IML results in the progressive formation of aberrant excitatory connections between granule cells. They also suggest that the probability of occurrence of electrographic seizures in the dentate gyrus increases with time after kainate treatment.
Zinc-Induced Augmentation of Excitatory Synaptic Currents and Glutamate Receptor Responses in Hippocampal CA3 Neurons
Authors: Lin Dean D. , Cohen Akiva S. , Coulter Douglas A.
Published: December 2017

Zinc is found throughout the CNS at synapses co-localized with glutamate in presynaptic terminals. In particular, dentate granule cells' (DGC) mossy fiber (MF) axons contain especially high concentrations of zinc co-localized with glutamate within vesicles. To study possible physiological roles of zinc, visualized slice-patch techniques were used to voltage-clamp rat CA3 pyramidal neurons, and miniature excitatory postsynaptic currents (mEPSCs) were isolated. Bath-applied zinc (200 μM) enhanced median mEPSC peak amplitudes to 153.0% of controls, without affecting mEPSC kinetics. To characterize this augmentation further, rapid agonist application was performed on perisomatic outside-out patches to coapply zinc with glutamate extremely rapidly for brief (1 ms) durations, thereby emulating release kinetics of these substances at excitatory synapses. When zinc was coapplied with glutamate, zinc augmented peak glutamate currents (mean ± SE, 116.6 ± 2.8% and 143.8 ± 9.8% of controls at 50 and 200 μM zinc, respectively). This zinc-induced potentiation was concentration dependent, and pharmacological isolation of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor–mediated currents (AMPAR currents) gave results similar to those observed with glutamate application (mean, 115.0 ± 5.4% and 132.5 ± 9.1% of controls at 50 and 200 μM zinc, respectively). Inclusion of the AMPAR desensitization blocker cyclothiazide in the control solution, however, abolished zinc-induced augmentation of glutamate-evoked currents, suggesting that zinc may potentiate AMPAR currents by inhibiting AMPAR desensitization. Based on the results of the present study, we hypothesize that zinc is a powerful modulator of both excitatory synaptic transmission and glutamate-evoked currents at physiologically relevant concentrations. This modulatory role played by zinc may be a significant factor in enhancing excitatory neurotransmission and could significantly regulate function at the mossy fiber-CA3 synapse.
Enhancement of Short-Term Synaptic Plasticity by Prior Environmental Stress
Authors: Barclay J. W. , Robertson R. M.
Published: December 2017

All chemical synapses can rapidly up- or downregulate the strength of their connections to reshape the postsynaptic signal, thereby stressing the informational importance of specific neural pathways. It is also true that an organism's environment can exert a powerful influence on all aspects of neural circuitry. We investigated the effect of a prior high-temperature stress on the short-term plasticity of a neuromuscular synapse in the hindleg tibial extensor muscle of Locusta migratoria. We found that the prior stress acted to precondition the synapse by increasing the upper temperature limit for synaptic transmission during a subsequent stressful exposure. As well, preexposure to a stressful high-temperature environment increased short-term facilitation of excitatory junction potentials concurrent with a decrease in excitatory junction potential amplitude and a reduction in its temporal parameters. We conclude that a stressful environment can modify synaptic physiological properties resulting in an enhancement of short-term plasticity of the synapse.
Dopaminergic Substantia Nigra Neurons Express Functional NMDA Receptors in Postnatal Rats
Authors: Lin John Yu-Luen , Lipski Janusz
Published: December 2017

Activation of N-methyl-d-aspartate (NMDA) receptors in the Substantia Nigra zona compacta (SNc) may determine the degree of physiological apoptosis during the early postnatal period. However, the expression of these receptors during this stage of development is uncertain, as a recent study failed to detect responses to NMDA in unidentified SNc neurons isolated from 2-wk-old rats. Using conventional or perforated-patch whole cell recordings, we examined the presence of NMDA-evoked responses in SNc neurons acutely dissociated from P4 to P16 rats, applying strict criteria for identification of these neurons as nigrostriatal and dopaminergic. The SNc neurons were identified by retrograde labeling after striatal injection of Fluoro-Gold; the presence of I hcurrent; and the inhibition of firing by dopamine (50 μM). NMDA (100 μM, V hold = −60 mV) evoked inward, APV-sensitive currents (56.4 ± 8.6 pA) in all tested neurons ( n = 29). Strong depolarizing responses were observed under current-clamp. These results indicate that NMDA receptors play a functional role in SNc neurons during the first two postnatal weeks.
RPCH Modulation of a Multi-Oscillator Network: Effects on the Pyloric Network of the Spiny Lobster
Authors: Dickinson Patsy S. , Hauptman Jane , Hetling John , Mahadevan Anand
Published: December 2017

The neuropeptide red pigment concentrating hormone (RPCH), which we have previously shown to activate the cardiac sac motor pattern and lead to a conjoint gastric mill-cardiac sac pattern in the spiny lobster Panulirus, also activates and modulates the pyloric pattern. Like the activity of gastric mill neurons in RPCH, the pattern of activity in the pyloric neurons is considerably more complex than that seen in control saline. This reflects the influence of the cardiac sac motor pattern, and particularly the upstream inferior ventricular (IV) neurons, on many of the pyloric neurons. RPCH intensifies this interaction by increasing the strength of the synaptic connections between the IV neurons and their targets in the stomatogastric ganglion. At the same time, RPCH enhances postinhibitory rebound in the lateral pyloric (LP) neuron. Taken together, these factors largely explain the complex pyloric pattern recorded in RPCH in Panulirus.
Functional Characteristics of the Parallel SI- and SII-Projecting Neurons of the Thalamic Ventral Posterior Nucleus in the Marmoset
Authors: Zhang H. Q. , Murray G. M. , Coleman G. T. , Turman A. B. , Zhang S. P. , Rowe M. J.
Published: December 2017

The functional organization of the primate somatosensory system at thalamocortical levels has been a matter of controversy, in particular, over the extent to which the primary and secondary somatosensory cortical areas, SI and SII, are organized in parallel or serial neural networks for the processing of tactile information. This issue was investigated for the marmoset monkey by recording from 55 single tactile-sensitive neurons in the lateral division of the ventral posterior nucleus of the thalamus (VPL) with a projection to either SI or SII, identified with the use of the antidromic collision technique. Neurons activated from the hand and distal forearm were classified according to their peripheral source of input and characterized in terms of their functional capacities to determine whether the directthalamic input can account for tactile processing in both SI and SII. Both the SI- and SII-projecting samples contained a slowly adapting (SA) class of neurons, sensitive to static skin displacement, and purely dynamically sensitive tactile neurons that could be subdivided into two classes. One was most sensitive to high-frequency (≥100 Hz) cutaneous vibration whose input appeared to be derived from Pacinian sources, while the other was sensitive to lower frequency vibration (≤100 Hz) or trains of rectangular mechanical pulse stimuli, that appeared to receive its input from rapidly adapting (RA) afferent fibers presumed to be associated with intradermal tactile receptors. There appeared to be no systematic differences in functional capacities between SI- and SII-projecting neurons of each of these three classes, based on receptive field characteristics, on the form of stimulus-response relations, and on measures derived from these relations. These measures included threshold and responsiveness values, bandwidths of vibrational sensitivity, and the capacity for responding to cutaneous vibrotactile stimuli with phase-locked, temporally patterned impulse activity. The analysis indicates that low-threshold, high-acuity tactile information is conveyed directly to both SI and SII from overlapping regions within the thalamic VP nucleus. This direct confirmation of a parallel functional projection to both SI and SII in the marmoset is consistent with our separate studies at the cortical level that demonstrate first, that tactile responsiveness in SII largely survives the SI inactivation and second,that SI responsiveness is largely independent of SII. It therefore reinforces the evidence that SI and SII occupy a hierarchically equivalent network for tactile processing.
Lack of Effect of Mossy Fiber-Released Zinc on Granule Cell GABAAReceptors in the Pilocarpine Model of Epilepsy
Authors: Molnár Péter , Nadler J. Victor
Published: December 2017

The recurrent mossy fiber pathway of the dentate gyrus expands dramatically in the epileptic brain and serves as a mechanism for synchronization of granule cell epileptiform activity. It has been suggested that this pathway also promotes epileptiform activity by inhibiting GABAAreceptor function through release of zinc. Hippocampal slices from pilocarpine-treated rats were used to evaluate this hypothesis. The rats had developed status epilepticus after pilocarpine administration, followed by robust recurrent mossy fiber growth. The ability of exogenously applied zinc to depress GABAAreceptor function in dentate granule cells depended on removal of polyvalent anions from the superfusion medium. Under these conditions, 200 μM zinc reduced the amplitude of the current evoked by applying muscimol to the proximal portion of the granule cell dendrite (23%). It also reduced the mean amplitude (31%) and frequency (36%) of miniature inhibitory postsynaptic currents. Nevertheless, repetitive mossy fiber stimulation (10 Hz for 1 s, 100 Hz for 1 s, or 10 Hz for 5 min) at maximal intensity did not affect GABAAreceptor-mediated currents evoked by photorelease of GABA onto the proximal portion of the dendrite, where recurrent mossy fiber synapses were located. These results could not be explained by stimulation-induced depletion of zinc from the recurrent mossy fiber boutons. Negative results were obtained even during exposure to conditions that promoted transmitter release and synchronized granule cell activity (6 mM [K+]o, nominally Mg2+-free medium, 33°C). These results suggest that zinc released from the recurrent mossy fiber pathway did not reach a concentration at postsynaptic GABAAreceptors sufficient to inhibit agonist-evoked activation.
Natural Waking and Sleep States: A View From Inside Neocortical Neurons
Authors: Steriade M. , Timofeev I. , Grenier F.
Published: December 2017

In this first intracellular study of neocortical activities during waking and sleep states, we hypothesized that synaptic activities during natural states of vigilance have a decisive impact on the observed electrophysiological properties of neurons that were previously studied under anesthesia or in brain slices. We investigated the incidence of different firing patterns in neocortical neurons of awake cats, the relation between membrane potential fluctuations and firing rates, and the input resistance during all states of vigilance. In awake animals, the neurons displaying fast-spiking firing patterns were more numerous, whereas the incidence of neurons with intrinsically bursting patterns was much lower than in our previous experiments conducted on the intact-cortex or isolated cortical slabs of anesthetized cats. Although cortical neurons displayed prolonged hyperpolarizing phases during slow-wave sleep, the firing rates during the depolarizing phases of the slow sleep oscillation was as high during these epochs as during waking and rapid-eye-movement sleep. Maximum firing rates, exceeding those of regular-spiking neurons, were reached by conventional fast-spiking neurons during both waking and sleep states, and by fast-rhythmic-bursting neurons during waking. The input resistance was more stable and it increased during quiet wakefulness, compared with sleep states. As waking is associated with high synaptic activity, we explain this result by a higher release of activating neuromodulators, which produce an increase in the input resistance of cortical neurons. In view of the high firing rates in the functionally disconnected state of slow-wave sleep, we suggest that neocortical neurons are engaged in processing internally generated signals.
Chronotropic Effect of Angiotensin II via Type 2 Receptors in Rat Brain Neurons
Authors: Zhu Mingyan , Sumners Colin , Gelband Craig H. , Posner Philip
Published: December 2017

Previously, we determined that angiotensin II (Ang II) elicits an Ang II type 2 (AT2) receptor–mediated increase of neuronal delayed rectifier K+( I KV) current in neuronal cultures from newborn rat hypothalamus and brain stem. This requires generation of lipoxygenase (LO) metabolites of arachidonic acid (AA) and activation of serine/threonine phosphatase type 2A (PP-2A). Enhancement of I KV results in a decrease in net inward current during the action potential (AP) upstroke as well as shortening of the refractory period, which may lead to alterations in neuronal firing rate. Thus, in the present study, we used whole-cell current clamp recording methods to investigate the AT2 receptor–mediated effects of Ang II on the firing rate of cultured neurons from the hypothalamus and brain stem. At room temperature, these neurons exhibited spontaneous APs with an amplitude of 77.72 ± 2.7 mV ( n = 20) and they fired at a frequency of 0.8 ± 0.1 Hz ( n = 11). Most cells had a prolonged early after-depolarization that followed an initial fully developed AP. Superfusion of Ang II (100 nM) plus losartan (LOS, 1 μM) to block Ang II type 1 receptors elicited a significant chronotropic effect that was reversed by the AT2 receptor inhibitor PD 123,319 (1 μM). LOS alone had no effect on any of the parameters measured. The chronotropic effect of Ang II was reversed by the general LO inhibitor 5,8,11,14-eicosatetraynoic acid (10 μM) or by the selective PP-2A inhibitor okadaic acid (1 nM) and was mimicked by the 12-LO metabolite of AA 12-(S)-hydroxy-(5Z, 8Z, 10E, 14Z)-eicosatetraynoic acid. These data indicate that Ang II elicits an AT2 receptor–mediated increase in neuronal firing rate, an effect that involves generation of LO metabolites of AA and activation of PP-2A.
Kindling Induces Transient NMDA Receptor–Mediated Facilitation of High-Frequency Input in the Rat Dentate Gyrus
Authors: Behr Joachim , Heinemann Uwe , Mody Istvan
Published: December 2017

To elucidate the gating mechanism of the epileptic dentate gyrus on seizure-like input, we investigated dentate gyrus field potentials and granule cell excitatory postsynaptic potentials (EPSPs) following high-frequency stimulation (10–100 Hz) of the lateral perforant path in an experimental model of temporal lobe epilepsy (i.e., kindled rats). Although control slices showed steady EPSP depression at frequencies greater than 20 Hz, slices taken from animals 48 h after the last seizure presented pronounced EPSP facilitation at 50 and 100 Hz, followed by steady depression. However, 28 days after kindling, the EPSP facilitation was no longer detectable. Using the specific N-methyl-d-aspartate (NMDA) and RS-α-amino-3-hydroxy-5-methyl-4-isoxazoleproponic acid (AMPA) receptor antagonists 2-amino-5-phosphonovaleric acid and SYM 2206, we examined the time course of alterations in glutamate receptor–dependent synaptic currents that parallel transient EPSP facilitation. Forty-eight hours after kindling, the fractional AMPA and NMDA receptor–mediated excitatory postsynaptic current (EPSC) components shifted dramatically in favor of the NMDA receptor–mediated response. Four weeks after kindling, however, AMPA and NMDA receptor–mediated EPSCs reverted to control-like values. Although the granule cells of the dentate gyrus contain mRNA-encoding kainate receptors, neither single nor repetitive perforant path stimuli evoked kainate receptor–mediated EPSCs in control or in kindled rats. The enhanced excitability of the kindled dentate gyrus 48 h after the last seizure, as well as the breakdown of its gating function, appear to result from transiently enhanced NMDA receptor activation that provides significantly slower EPSC kinetics than those observed in control slices and in slices from kindled animals with a 28-day seizure-free interval. Therefore, NMDA receptors seem to play a critical role in the acute throughput of seizure activity and in the induction of the kindled state but not in the persistence of enhanced seizure susceptibility.
Acute Adaptation of the Vestibuloocular Reflex: Signal Processing by Floccular and Ventral Parafloccular Purkinje Cells
Authors: Hirata Y. , Highstein S. M.
Published: December 2017

The gain of the vertical vestibuloocular reflex (VVOR), defined as eye velocity/head velocity was adapted in squirrel monkeys by employing visual-vestibular mismatch stimuli. VVOR gain, measured in the dark, could be trained to values between 0.4 and 1.5. Single-unit activity of vertical zone Purkinje cells was recorded from the flocculus and ventral paraflocculus in alert squirrel monkeys before and during the gain change training. Our goal was to evaluate the site(s) of learning of the gain change. To aid in the evaluation, a model of the vertical optokinetic reflex (VOKR) and VVOR was constructed consisting of floccular and nonfloccular systems divided into subsystems based on the known anatomy and input and output parameters. Three kinds of input to floccular Purkinje cells via mossy fibers were explicitly described, namely vestibular, visual (retinal slip), and efference copy of eye movement. The characteristics of each subsystem (gain and phase) were identified at different VOR gains by reconstructing single-unit activity of Purkinje cells during VOKR and VVOR with multiple linear regression models consisting of sensory input and motor output signals. Model adequacy was checked by evaluating the residual following the regressions and by predicting Purkinje cells' activity during visual-vestibular mismatch paradigms. As a result, parallel changes in identified characteristics with VVOR adaptation were found in the prefloccular/floccular subsystem that conveys vestibular signals and in the nonfloccular subsystem that conveys vestibular signals, while no change was found in other subsystems, namely prefloccular/floccular subsystems conveying efference copy or visual signals, nonfloccular subsystem conveying visual signals, and postfloccular subsystem transforming Purkinje cell activity to eye movements. The result suggests multiple sites for VVOR motor learning including both flocculus and nonflocculus pathways. The gain change in the nonfloccular vestibular subsystem was in the correct direction to cause VOR gain adaptation while the change in the prefloccular/floccular vestibular subsystem was incorrect (anti-compensatory). This apparent incorrect directional change might serve to prevent instability of the VOR caused by positive feedback via the efference copy pathway.
Electrophysiological Characteristics of Rat Gustatory Cyclic Nucleotide–Gated Channel Expressed in Xenopus Oocytes
Authors: Lee Han Mi , Park Young Sun , Kim Wonjae , Park Chul-Seung
Published: December 2017

The complementary DNA encoding gustatory cyclic nucleotide–gated ion channel (or gustCNG channel) cloned from rat tongue epithelial tissue was expressed in Xenopus oocytes, and its electrophysiological characteristics were investigated using tight-seal patch-clamp recordings of single and macroscopic channel currents. Both cGMP and cAMP directly activated gustCNG channels but with markedly different affinities. No desensitization or inactivation of gustCNG channel currents was observed even in the prolonged application of the cyclic nucleotides. Single-channel conductance of gustCNG channel was estimated as 28 pS in 130 mM of symmetric Na+. Single-channel current recordings revealed fast open-close transitions and longer lasting closure states. The distribution of both open and closed events could be well fitted with two exponential components and intracellular cGMP increased the open probability ( P o) of gustCNG channels mainly by increasing the slower opening rate. Under bi-ionic conditions, the selectivity order of gustCNG channel among divalent cations was determined as Na+ ∼ K+ > Rb+ > Li+ > Cs+ with the permeability ratio of 1:0.95:0.74:0.63:0.49. Magnesium ion blocked Na+ currents through gustCNG channels from both intracellular and extracellular sides in voltage-dependent manners. The inhibition constants ( K is) of intracellular Mg2+ were determined as 360 ± 40 μM at 70 mV and 8.2 ± 1.5 mM at −70 mV with zδ value of 1.04, while K is of extracellular Mg2+ were as 1.1 ± 0.3 mM at 70 mV and 20.0 ± 0.1 μM at −70 mV with zδ of 0.94. Although 100 μM l- cis-diltiazem blocked significant portions of outward Na+ currents through both bovine rod and rat olfactory CNG channels, the gustCNG channel currents were minimally affected by the same concentration of the drug.
Differential Modulation of Nicotinic Acetylcholine Receptor Subtypes and Synaptic Transmission in Chick Sympathetic Ganglia by PGE2
Authors: Du Chuang , Role Lorna W.
Published: December 2017

The diversity of neuronal nicotinic acetylcholine receptors (nAChRs) is likely an important factor in the modulation of synaptic transmission by acetylcholine and nicotine. We have tested whether postsynaptic nAChRs are modulated in a subtype-specific manner by prostaglandin E2(PGE2), a regulator of neuronal excitability in both the central and peripheral nervous systems, and examined the effects of PGE2 on nicotinic transmission. Somatodendritic nAChRs in chick lumbar sympathetic ganglia include four nAChR subtypes distinguished on the basis of conductance and kinetic profile. Nanomolar PGE2 applied to the extrapatch membrane differentially regulates opening probability (Po), frequency and the opening duration of each nAChR channel subtype in cell-attached patches. PGE2 decreases the Po of the predominant nAChR subtype (36 pS) and significantly increases Po and open duration of the 23 pS subtype. The 23 pS subtype is gated by the α7-selective agonist choline, and choline-gated currents are inhibited by α-bungarotoxin. To examine whether PGE2modulates nAChRs at synaptic sites, we studied the effects of PGE2 on amplitude and decay of synaptic currents in visceral motoneuron-sympathetic neuron co-cultures. PGE2 significantly decreases the amplitude of miniature excitatory postsynaptic currents (mEPSCs), consistent with the predominant inhibition by PGE2 of all but the 23 pS subtype. The time constant of mEPSCs at PGE2-treated synapses is prolonged, which is also consistent with an increased contribution of the longer open duration of the 23 pS nAChR subtype with PGE2 treatment. To examine the presynaptic effect of PGE2, nanomolar nicotine was used. Nicotine induces facilitation of synaptic transmission by increasing mEPSC frequency, an action thought to involve presynaptic, α7-containing nAChRs. In the presence of PGE2, nicotine-induced synaptic facilitation persists. Thus the net effect of PGE2 is to alter the profile of nAChRs contributing to synaptic transmission from larger conductance, briefer opening channels to smaller conductance, longer opening events. This subtype-specific modulation of nAChRs by PGE2 may provide a mechanism for selective activation and suppression of synaptic pathways mediated by different nAChR subtype(s) at both pre- and postsynaptic sites.
Ankle Muscle Stiffness in the Control of Balance During Quiet Standing
Authors: Winter David A. , Patla Aftab E. , Rietdyk Shirley , Ishac Milad G.
Published: December 2017

This research presents new data and reanalyzed information to refute the criticisms of our model of stiffness control during quiet standing. A re-review of their references to biomechanical research on muscle ankle stiffness confirmed muscle stiffness estimates of the ankle series elastic elements that agreed closely with our estimates. A new technique is presented that directly estimates the muscle stiffness from the ankle moment (N · m) and sway angle (deg). The linear regression of 10 subjects standing quietly for 10 s estimated the stiffness (N · m/deg) to be safely above the gravitational spring. The R 2 scores for this linear regression averaged 0.92, confirming how closely the model approached a perfect spring that would have an R 2 = 1. These results confirm our model of a simple muscle stiffness control and refutes the criticisms.
A Novel Ca2+Influx Pathway in Mammalian Primary Sensory Neurons Is Activated by Caffeine
Authors: Hoesch Robert E. , Weinreich Daniel , Kao Joseph P. Y.
Published: December 2017

Single-cell microfluorimetry and electrophysiology techniques were used to identify and characterize a novel Ca2+influx pathway in adult rabbit vagal sensory neurons. Acutely dissociated nodose ganglion neurons (NGNs) exhibit robust Ca2+-induced Ca2+release (CICR) that can be triggered by 10 mM caffeine, the classic agonist of CICR. A caffeine-induced increase in cytosolic-free Ca2+concentration ([Ca2+]i) is considered diagnostic evidence of the existence of CICR. However, when CICR was disabled through depletion of intracellular Ca2+stores or pharmacological blockade of intracellular Ca2+release channels (ryanodine receptors), caffeine still elicited a significant rise in [Ca2+]iin ∼50% of NGNs. The same response was not elicited by pharmacological agents that elevate cyclic nucleotide concentrations. Moreover, extracellular Ca2+was obligatory for such caffeine-induced [Ca2+]irises in this population of NGNs, suggesting that Ca2+influx is responsible for this rise. Simultaneous microfluorimetry with whole cell patch-clamp studies showed that caffeine activates an inward current that temporally parallels the rise in [Ca2+]i. The inward current had a reversal potential of +8.1 ± 6.1 (SE) mV ( n = 4), a mean peak amplitude of −126 ± 24 pA ( n = 4) at Em= −50 mV, and a slope conductance of 1.43 ± 0.79 nS ( n= 4). Estimated EC50values for caffeine-induced CICR and for caffeine-activated current were 1.5 and ∼0.6 mM, respectively. These results indicate that caffeine-induced rises in [Ca2+]i, in the presence of extracellular Ca2+, can no longer be interpreted as unequivocal diagnostic evidence for CICR in neurons. These results also indicate that sensory neurons possess a novel Ca2+influx pathway.
Effects of Apomorphine on Subthalamic Nucleus and Globus Pallidus Internus Neurons in Patients With Parkinson's Disease
Authors: Levy R. , Dostrovsky J. O. , Lang A. E. , Sime E. , Hutchison W. D. , Lozano A. M.
Published: December 2017

This study examines the effect of apomorphine (APO), a nonselective D1- and D2-dopamine receptor agonist, on the firing activity of neurons in the subthalamic nucleus (STN) and internal segment of the globus pallidus (GPi) in patients with Parkinson's disease (PD). Single-unit microelectrode recordings were conducted in 13 patients undergoing implantation of deep brain stimulation electrodes in STN and 6 patients undergoing a pallidotomy. Doses of APO (2.5–8 mg) were sufficient to produce anon state, but not intended to induce dyskinetic movements. Following baseline recordings from a single neuron, APO was administered and the activity of the neuron followed for an average of 15 min. The spontaneous discharge of neurons encountered before ( n = 309), during ( n = 146, 10–60 min), and after the effect of APO had waned ( n = 127, >60 min) was also sampled, and the response to passive joint movements was noted. In both nuclei, APO increased the overall proportion of spikes in burst discharges (as detected with Poisson “surprise” analysis), and a greater proportion of cells with an irregular discharge pattern was observed. APO significantly decreased the overall firing rates of GPi neurons ( P < 0.01), but there was no change in the overall firing rate of neurons in the STN ( P = 0.68). However, the mean firing rates of STN neurons during APO-induced movements (choreic or dystonic dyskinesias) that occurred in four patients were significantly lower thanoff-period baseline values ( P < 0.05). Concurrent with a reduction in limb tremor, the percentage of cells with tremor-related activity (TCs) was found to be significantly reduced from 19 to 6% in the STN and 14 to 0% in the GPi following APO administration. APO also decreased the firing rate of STN TCs ( P < 0.05). During the off state, more than 15% of neurons tested (STN = 93, GPi = 63) responded to passive movement of two or more joints. After APO, this proportion decreased significantly to 7% of STN cells and 4% of GPi cells (STN = 28, GPi = 26). These findings suggest that the APO-induced amelioration of parkinsonian symptoms is not solely due to a decrease in overall activity in the GPi or STN as predicted by the current model of basal ganglia function in PD.
Spectrotemporal Organization of Excitatory and Inhibitory Receptive Fields of Cat Posterior Auditory Field Neurons
Authors: Loftus William C. , Sutter Mitchell L.
Published: December 2017

The excitatory and inhibitory frequency/intensity response areas (FRAs) and spectrotemporal receptive fields (STRFs) of posterior auditory cortical field (PAF) single neurons were investigated in barbiturate anesthetized cats. PAF neurons' pure-tone excitatory FRAs (eFRAs) exhibited a diversity of shapes, including some with very broad frequency tuning and some with multiple distinct excitatory frequency ranges (i.e., multipeaked eFRAs). Excitatory FRAs were analyzed after selectively excluding spikes on the basis of spike response times relative to stimulus onset. This analysis indicated that spikes with shorter response times were confined to narrow regions of the eFRAs, while spikes with longer response times were more broadly distributed over the eFRA. First-spike latencies in higher threshold response peaks of multipeaked eFRAs were ∼10 ms longer, on average, than latencies in lower threshold response peaks. STRFs were constructed to examine the dynamic frequency tuning of neurons. More than half of the neurons (51%) had STRFs with “sloped” response maxima, indicating that the excitatory frequency range shifted with time. A population analysis demonstrated that the median first-spike latency varied systematically as a function of frequency with a median slope of ∼12 ms per octave. Inhibitory frequency response areas were determined by simultaneous two-tone stimulation. As in primary auditory cortex (A1), a diversity of inhibitory band structures was observed. The largest class of neurons (25%) had an inhibitory band flanking each eFRA edge, i.e., one lower and one upper inhibitory band in a “center-surround” organization. However, in comparison to a previous report of inhibitory structure in A1 neurons, PAF exhibited a higher incidence of neurons with more complex inhibitory band structure (for example, >2 inhibitory bands). As was the case with eFRAs, spikes with longer response times contributed to the complexity of inhibitory FRAs. These data indicate that PAF neurons integrate temporally varying excitatory and inhibitory inputs from a broad spectral extent and, compared with A1, may be suited to analyzing acoustic signals of greater spectrotemporal complexity than was previously thought.
GABAA and 5-HT3 Receptors Are Involved in Dorsal Root Reflexes: Possible Role in Periaqueductal Gray Descending Inhibition
Authors: Peng Yuan Bo , Wu Jing , Willis William D. , Kenshalo Daniel R.
Published: December 2017

The dorsal root reflex (DRR) is a measure of the central excitability of presynaptic inhibitory circuits in the spinal cord. Activation of the periaqueductal gray (PAG), a center for descending inhibition of spinal cord nociceptive transmission, induces release of variety of neurotransmitters in the spinal cord, including GABA and serotonin (5-HT). GABA has been shown to be involved in generation of DRRs. In this study, pharmacological agents that influence DRRs and their possible mechanisms were investigated. DRRs were recorded in anesthetized rats from filaments teased from the cut central stump of the left L4or L5 dorsal root, using a monopolar recording electrode. Stimulating electrodes were placed either on the left sciatic nerve or transcutaneously in the left foot. Animals were paralyzed and maintained by artificial ventilation. Drugs were applied topically to the spinal cord. A total of 64 units were recorded in 34 Sprague-Dawley rats. Peripheral receptive fields were found for nine of these units. In these units, DRRs were evoked by brush, pressure, and pinch stimuli. Nine units were tested for an effect of electrical stimulation in the periaqueductal gray on the DRRs. In eight cases, DRR responses were enhanced following PAG stimulation. The background activity was 4.2 ± 1.9 spikes/s (mean ± SE; range: 0–97.7; n = 57). The responses to agents applied to the spinal cord were (in spikes/s): artificial cerebrospinal fluid, 7.1 ± 3.6 (range: 0–86.9; n = 25); 0.1 mM GABA, 16.8 ± 8.7 (range: 0–191.0; n = 22); 1.0 mM GABA, 116.0 ± 26.5 (range: 0.05–1001.2; n = 50); and 1.0 mM phenylbiguanide (PBG), 68.1 ± 25.3 (range: 0–1,073.0; n = 49). Bicuculline (0.5 mM, n = 27) and ondansetron (1.0 mM, n = 10) blocked the GABA and PBG effects, respectively ( P < 0.05). Significant cross blockade was also observed. It is concluded that GABAA receptors are likely to play a key role in the generation of DRRs, but that 5-HT3 receptors may also contribute. DRRs can be modulated by supraspinal mechanisms through descending systems.
Transition From GABAergic to Glycinergic Synaptic Transmission in Newly Formed Spinal Networks
Authors: Gao Bao-Xi , Stricker Christian , Ziskind-Conhaim Lea
Published: December 2017

The role of glycinergic and GABAergic systems in mediating spontaneous synaptic transmission in newly formed neural networks was examined in motoneurons in the developing rat spinal cord. Properties of action potential–independent miniature inhibitory postsynaptic currents (mIPSCs) mediated by glycine and GABAA receptors (GlyR and GABAAR) were studied in spinal cord slices of 17- to 18-day-old embryos ( E17–18) and 1- to 3-day-old postnatal rats ( P1–3). mIPSC frequency and amplitude significantly increased after birth, while their decay time decreased. To determine the contribution of glycinergic and GABAergic synapses to those changes, GlyR- and GABAAR-mediated mIPSCs were isolated based on their pharmacological properties. Two populations of pharmacologically distinct mIPSCs were recorded in the presence of glycine or GABAA receptors antagonists: bicuculline-resistant, fast-decaying GlyR-mediated mIPSCs, and strychnine-resistant, slow-decaying GABAAR-mediated mIPSCs. The frequency of GABAAR-mediated mIPSCs was fourfold higher than that of GlyR-mediated mIPSCs at E17–18, indicating that GABAergic synaptic sites were functionally dominant at early stages of neural network formation. Properties of GABAAR-mediated mIPSC amplitude fluctuations changed from primarily unimodal skewed distribution at E17–18 to Gaussian mixtures with two to three discrete components at P1–3. A developmental shift from primarily long-duration GABAergic mIPSCs to short-duration glycinergic mIPSCs was evident after birth, when the frequency of GlyR-mediated mIPSCs increased 10-fold. This finding suggested that either the number of glycinergic synapses or the probability of vesicular glycine release increased during the period studied. The increased frequency of GlyR-mediated mIPSCs was associated with more than a twofold increase in their mean amplitude, and in the number of motoneurons in which mIPSC amplitude fluctuations were best fitted by multi-component Gaussian curves. A third subpopulation of mIPSCs was apparent in the absence of glycine and GABAA receptor antagonists: mIPSCs with both fast and slow decaying components. Based on their dual-component decay time and their suppression by either strychnine or bicuculline, we assumed that these were generated by the activation of co-localized postsynaptic glycine and GABAA receptors. The contribution of mixed glycine-GABA synaptic sites to the generation of mIPSCs did not change after birth. The developmental switch from predominantly long-duration GABAergic inhibitory synaptic currents to short-duration glycinergic currents might serve as a mechanism regulating neuronal excitation in the developing spinal networks.