bluuebunny/crossref_metadata_2025 huggingface dataset:
Excitatory Synaptic Currents in Lumbosacral Parasympathetic Preganglionic Neurons Evoked by Stimulation of the Dorsal Commissure
Authors: Miura Akira , Kawatani Masahito , De Groat William C.
Published: May 2006

Excitatory pathways from the dorsal commissure (DCM) to L6–S1 parasympathetic preganglionic neurons (PGN) were examined using whole-cell patch-clamp recording techniques in spinal cord slices from neonatal rats. PGN were identified by retrograde axonal transport of a fluorescent dye injected into the intraperitoneal space. Excitatory postsynaptic currents (EPSCs) were evoked in PGN by stimulation of DCM in the presence of bicuculline methiodide (10 μM) and strychnine (1 μM) to block inhibitory pathways. Electrical stimulation of DCM evoked two types of inward currents. In the majority of PGN ( n = 66), currents (mean amplitude, 47.9 ± 4.7 pA) occurred at a short and relatively constant latency (3.8 ± 0.1 ms) and presumably represent monosynaptic EPSCs (Type 1). However, in other neurons ( n = 20), a different type of EPSC (Type 2) was noted, consisting of a fast monosynaptic component followed by a prolonged inward current with superimposed fast transients presumably representing excitatory inputs mediated by polysynaptic pathways. Type 1 EPSCs were pharmacologically dissected into two components. A fast component was blocked by 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 5μM) and a slowly decaying component was blocked by 2-amino-5-phosphonovalerate (APV, 50 μM). The fast component of Type 1 EPSCs had a linear current-voltage relationship and reversed at a membrane potential of −7.6 ± 1.3 mV ( n = 5). The fast component of Type 2 EPSCs was also blocked by 5 μM CNQX and the remaining slower component was blocked by 50 μM APV. When the DCM was stimulated in the presence of 50 μM APV, the time to peak and decay time constant in Type 1 EPSCs were 1.9 ± 0.2 and 4.1 ± 0.8 ms, respectively. Examination of the NMDA receptor-mediated component of the EPSCs in the presence of 5 μM CNQX revealed a current-voltage relationship that had a region of negative slope conductance (from −20 to −80 mV), which was abolished in Mg2+-free external solution. The time to peak and decay time constant of this component were 14.2 ± 2.0 and 91.0 ± 12.4 ms, respectively. Type 1 EPSCs in some PGN responded in an all-or-none manner and presumably represented unitary synaptic responses; whereas Type 2 EPSCs always exhibited a graded stimulus intensity–response relationship. Paired-pulse facilitation (50-ms interstimulus intervals; 141 ± 5.6% increase, n = 8) of EPSCs was observed. These results indicate that PGN receive monosynaptic and polysynaptic glutamatergic excitatory inputs from neurons and/or axonal pathways in the DCM.
Static and Dynamic Membrane Properties of Lateral Vestibular Nucleus Neurons in Guinea Pig Brain Stem Slices
Authors: Uno Atsuhiko , Idoux Erwin , Beraneck Mathieu , Vidal Pierre-Paul , Moore Lee E. , Wilson Victor J. , Vibert Nicolas
Published: May 2006

In vitro intracellular recordings of central vestibular neurons have been restricted so far to the medial vestibular nucleus (MVN). We performed intracellular recordings of large Deiters' neurons in the lateral vestibular nucleus (LVN) to determine their static and dynamic membrane properties, and compare them with those of type A and type B neurons identified in the MVN. Unlike MVN neurons (MVNn), the giant-size LVN neurons (LVNn) form a homogeneous population of cells characterized by sharp spikes, a low-amplitude, biphasic after-hyperpolarization like type B MVNn, but also an A-like rectification like type A MVNn. In accordance with their lower membrane resistance, the sensitivity of LVNn to current injection was lower than that of MVNn over a large range of frequencies. The main difference between LVNn and MVNn was that the Bode plots showing the sensitivity of LVNn as a function of stimulation frequency were flatter than those of MVNn, and displayed a weaker resonance. Furthermore, most LVNn did not show a gradual decrease of their firing rate modulation in the frequency range where it was observed in MVNn. LVNn synchronized their firing with the depolarizing phase of high-frequency sinusoidal current injections. In vivo studies have shown that the MVN would be mainly involved in gaze control, whereas the giant LVNn that project to the spinal cord are involved in the control of posture. We suggest that the difference in the membrane properties of LVNn and MVNn may reflect their specific physiological roles.
Modulation ofIACurrents by Capsaicin in Rat Trigeminal Ganglion Neurons
Authors: Liu L. , Simon S. A.
Published: May 2006

When capsaicin, the pungent compound in hot pepper, is applied to epithelia it produces pain, allodynia, and hyperalgesia. We investigated, using whole cell path clamp, whether some of these responses induced by capsaicin could be a consequence of capsaicin blocking IAcurrents, a reduction in which, such as occurs in injury, increases neuronal excitability. In capsaicin-sensitive (CS) rat trigeminal ganglion (TG) neurons, capsaicin inhibited IAcurrents in a dose-dependent manner. IAcurrents were reduced 49% by 1 μM capsaicin. In capsaicin-insensitive (CIS) rat TG neurons, or small-diameter mouse VR1−/− neurons, 1 μM capsaicin inhibited IAcurrents 9 and 3%, respectively. These data suggest that in CS neurons the vast majority of the capsaicin-induced inhibition of IAcurrents occurs as a consequence of the activation of vanilloid receptors. Capsaicin (1 μM) did not alter the IAconductance-voltage relationship but shifted the inactivation-voltage curve about 15 mV to hyperpolarizing voltages, thereby increasing the number of inactivated IAchannels at the resting potential. IAcurrents were relatively unaffected by 1 mM CTP-cAMP or 500 nM phorbol-12, 13-dibuterate (a protein kinase C agonist) but were inhibited by 20–30% with either 1 mM CTP-cGMP or 25 μM N-(6-aminohexyl)-5-chloro-1-napthalenesulfonamide HCl (a calcium-calmodulin kinase inhibitor). In the presence of 0.5 μM KT5823, an inhibitor of protein kinase G (PKG) pathways, 1 μM capsaicin inhibited IAby only 26%. In summary, in CS neurons, capsaicin decreases IAcurrents through the activation of vanilloid receptors. That activation, partially through the activation of cGMP-PKG and calmodulin-dependent pathways should result in increased excitability of capsaicin-sensitive nociceptors.
Investigation of the Neuronal Aggregate Generating Seizures in the Rat Tetanus Toxin Model of Epilepsy
Authors: Finnerty G. T. , Jefferys J.G.R.
Published: May 2006

A key question in epilepsy is the organization and size of the neuronal networks necessary for generating seizures. Hypotheses include: a single focal neuronal network drives seizure discharges across the brain, which may or may not be identical with the circuits that generate interictal spikes; or multiple neuronal networks link together in re-entrant loops or other long-range networks. It remains unclear whether any of these hypotheses apply to spontaneous seizures in freely moving animals. We used the tetanus toxin chronic model of epilepsy to test the different predictions made by each hypothesis about the propagation and interaction of epileptic discharges during seizures. Seizures could start in either the injected or noninjected dorsal hippocampus, suggesting that seizures have multifocal onsets in the tetanus toxin model. During seizures, individual bursts propagated in either direction, both between the right and left dorsal hippocampi, and between CA3 and the dentate gyrus in the same hippocampus. These findings argue against one site “driving” seizures or seizures propagating around a limbic loop. Specifically, the side leading each burst switched a median of three times during the first 20 s of a seizure. Analysis of bursts during seizures suggested that the network at each recording site acted like a neuronal oscillator. Coupling of population spikes in right and left CA3 increased during the early part of seizures, but the cross-correlation of their whole-discharge waveforms changed little over the same period. Furthermore, the polarity of the phase difference between population spikes did not follow the phase difference for complete discharges. We concluded that the neuronal aggregate necessary for seizures in our animals comprises multiple spatially distributed neuronal networks and that the increased synchrony of the output (population spike firing) of these networks during the early part of seizures may contribute to seizure generation.
NMDA and AMPA Receptors Contribute to the Nicotinic Cholinergic Excitation of CA1 Interneurons in the Rat Hippocampus
Authors: Alkondon Manickavasagom , Pereira Edna F.R. , Albuquerque Edson X.
Published: May 2006

In the hippocampus, glutamatergic inputs to pyramidal neurons and interneurons are modulated by α7* and α3β4* nicotinic acetylcholine receptors (nAChRs), respectively, present in glutamatergic neurons. This study examines how nicotinic AMPA, and NMDA receptor nAChR activities are integrated to regulate the excitability of CA1 stratum radiatum (SR) interneurons in rat hippocampal slices. At resting membrane potentials and in the presence of extracellular Mg2+(1 mM), nicotinic agonists triggered in SR interneurons excitatory postsynaptic currents (EPSCs) that had two components: one mediated by AMPA receptors, and the other by NMDA receptors. As previously shown, nicotinic agonist–triggered EPSCs resulted from glutamate released by activation of α3β4* nAChRs in glutamatergic neurons/fibers synapsing directly onto the neurons under study. The finding that CNQX caused more inhibition of nicotinic agonist–triggered EPSCs than expected from the blockade of postsynaptic AMPA receptors indicated that this nicotinic response also depended on the AMPA receptor activity in the glutamatergic neurons synapsing onto the interneuron under study. Nicotinic agonists always triggered action potentials in CA1 SR interneurons. In most interneurons, these action potentials resulted from activation of somatodendritic AMPA receptors and α7* nAChRs. In interneurons expressing somatodendritic α4β2* nAChRs, activation of these receptors caused sufficient membrane depolarization to remove the Mg2+-induced block of somatodendritic NMDA receptors; in these neurons, nicotinic agonist–triggered action potentials were partially dependent on NMDA receptor activation. Removing extracellular Mg2+or clamping the neuron at positive membrane potentials revealed the existence of a tonic NMDA current in SR interneurons that was unaffected by nAChR activation or inhibition. Thus integration of the activities of nAChRs, NMDA, and AMPA receptors in different compartments of CA1 neurons contributes to the excitability of CA1 SR interneurons.
Dopamine Modulates Synaptic Transmission in the Nucleus of the Solitary Tract
Authors: Kline David D. , Takacs Kristin N. , Ficker Eckhard , Kunze Diana L.
Published: May 2006

10.1152/jn.00224.2002. Dopamine (DA) modulates the cardiorespiratory reflex by peripheral and central mechanisms. The aim of this study was to examine the role of DA in synaptic transmission of the nucleus tractus solitarius (NTS), the major integration site for cardiopulmonary reflexes. To examine DA's role, we used whole cell, voltage-clamp recordings in a rat horizontal brain stem slice. Solitary tract stimulation evoked excitatory postsynaptic currents (EPSCs) that were reduced to 70 ± 5% of control by DA (100 μM). The reduction in EPSCs by DA was accompanied by a decrease in the paired pulse depression ratio with little or no change in input resistance or EPSC decay, suggesting a presynaptic mechanism. The D1-like agonist SKF 38393 Br (30 μM) did not alter EPSC amplitude, whereas the D2-like agonist, quinpirole HCl (30 μM), depressed EPSCs to 73 ± 4% of control. The D2-like receptor antagonist, sulpiride (20 μM), abolished DA modulation of EPSCs. Most importantly, sulpiride alone increased EPSCs to 131 ± 10% of control, suggesting a tonic D2-like modulation of synaptic transmission in the NTS. Examination of spontaneous EPSCs revealed DA reversibly decreased the frequency of events from 9.4 ± 2.2 to 6.2 ± 1.4 Hz. Sulpiride, however, did not alter spontaneous events. Immunohistochemistry of NTS slices demonstrated that D2 receptors colocalized with synaptophysin and substance P, confirming a presynaptic distribution. D2 receptors also localized to cultured petrosal neurons, the soma of presynaptic afferent fibers. In the petrosal neurons, D2 was found in cells that were TH-immunopositive, suggesting they were chemoreceptor afferent fibers. These results demonstrate that DA tonically modulates synaptic activity between afferent sensory fibers and secondary relay neurons in the NTS via a presynaptic D2-like mechanism.
Effects of Echo Intensity on Doppler-Shift Compensation Behavior in Horseshoe Bats
Authors: Smotherman Michael , Metzner Walter
Published: May 2006

Echolocating horseshoe bats respond to flight-speed induced shifts in echo frequency by adjusting the frequency of subsequent calls. Under natural conditions, Doppler effects may force the frequency of a returning echo several kilohertz above the original emission frequency. By lowering subsequent call frequencies, the bat can return echo frequencies to within a narrow spectral bandwidth to which its highly specialized auditory system is most sensitive. While Doppler-shift compensation (DSC) behavior specifically refers to frequency compensation, other parameters of the returning echo, such as delay, duration, and interaural time and intensity differences have been shown to influence DSC performance. Understanding the nature of these influences has already led to a better appreciation of the neurophysiology of DSC. Here we provide a quantitative analysis of the effects of a prominent feature of the returning echo, its intensity, on DSC performance in horseshoe bats. Although DSC performance generally tolerates echo attenuation up to approximately 40 dB relative to the outgoing emission intensity, a systematic decline in DSC performance can be observed over this range. Generally, the effects of echo attenuation are characterized by a reduction in 1) the overall amount of compensation relative to the size of the shift in echo frequency and 2) the rate at which the bat responds to perceived echo shifts. These effects appear to be the consequence of a systematic shift in the range of echo frequencies capable of inducing DSC behavior. In particular, the reference frequency (the minimum shift in echo frequency that will elicit DSC behavior) appears to be highly sensitive to echo intensity. Every 10-dB reduction in echo intensity shifts the reference upward nearly 250 Hz. Our results indicate that, even at the highest intensity levels, relatively minor changes in echo intensity critically influence frequency compensation during normal DSC. We conclude with a discussion of how these results might impact echolocation behavior of horseshoe bats under natural and experimental conditions.
Modulation of Cortical Activity During Different Imitative Behaviors
Authors: Koski Lisa , Iacoboni Marco , Dubeau Marie-Charlotte , Woods Roger P. , Mazziotta John C.
Published: May 2006

Imitation is a basic form of motor learning during development. We have a preference to imitate the actions of others as if looking in a mirror (specular imitation: i.e., when the actor moves the left hand, the imitator moves the right hand) rather than with the anatomically congruent hand (anatomic imitation: i.e., actor and imitator both moving the right hand). We hypothesized that this preference reflects changes in activity in previously described frontoparietal cortical areas involved in directly matching observed and executed actions (mirror neuron areas). We used functional magnetic resonance imaging to study brain activity in normal volunteers imitating left and right hand movements with their right hand. Bilateral inferior frontal and right posterior parietal cortex were more active during specular imitation compared with anatomic imitation and control motor tasks. Furthermore this same pattern of activity was also observed in the rostral part of the supplementary motor area (SMA-proper) of the right hemisphere. These findings suggest that the degree of involvement of frontoparietal mirror areas in imitation depends on the nature of the imitative behavior, ruling out a linguistic mediation of these areas in imitation. Moreover, activity in the SMA appears to be tightly coupled to frontoparietal mirror areas when subjects copy the actions of others.
Electrophysiological Evidence of Monosynaptic Excitatory Transmission Between Granule Cells After Seizure-Induced Mossy Fiber Sprouting
Authors: Scharfman Helen E. , Sollas Anne L. , Berger Russell E. , Goodman Jeffrey H.
Published: May 2006

Mossy fiber sprouting is a form of synaptic reorganization in the dentate gyrus that occurs in human temporal lobe epilepsy and animal models of epilepsy. The axons of dentate gyrus granule cells, called mossy fibers, develop collaterals that grow into an abnormal location, the inner third of the dentate gyrus molecular layer. Electron microscopy has shown that sprouted fibers from synapses on both spines and dendritic shafts in the inner molecular layer, which are likely to represent the dendrites of granule cells and inhibitory neurons. One of the controversies about this phenomenon is whether mossy fiber sprouting contributes to seizures by forming novel recurrent excitatory circuits among granule cells. To date, there is a great deal of indirect evidence that suggests this is the case, but there are also counterarguments. The purpose of this study was to determine whether functional monosynaptic connections exist between granule cells after mossy fiber sprouting. Using simultaneous recordings from granule cells, we obtained direct evidence that granule cells in epileptic rats have monosynaptic excitatory connections with other granule cells. Such connections were not obtained when age-matched, saline control rats were examined. The results suggest that indeed mossy fiber sprouting provides a substrate for monosynaptic recurrent excitation among granule cells in the dentate gyrus. Interestingly, the characteristics of the excitatory connections that were found indicate that the pathway is only weakly excitatory. These characteristics may contribute to the empirical observation that the sprouted dentate gyrus does not normally generate epileptiform discharges.
Contrast Dependence of Response Normalization in Area MT of the Rhesus Macaque
Authors: Heuer Hilary W. , Britten Kenneth H.
Published: May 2006

Contrast normalization is a process whereby responses of neurons are scaled according to the total amount of contrast in a region of the image nearby the receptive field of a neuron. This process allows neurons to code for informative scene or object attributes in a manner unaffected by changes in illumination. Evidence for normalization is seen in striate and extrastriate cortex from experiments where multiple stimuli are presented with a single receptive field (RF). Neuronal responses in such experiments are smaller than that predicted by linear summation, revealing the presence of normalization. While the presence of normalization is often clear, its mechanism is less so. To study the mechanism of normalization, we measured the interaction between pairs of brief local stimuli (spatial Gabor functions) within the RFs of cells in the middle temporal (MT or V5) area of monkeys and varied both the location and contrast of the stimuli. We found response summed approximately linearly when contrast was low but rapidly became normalized as stimulus contrast increased. The rapid transition to effective normalization at low contrasts suggested cooperativity in the normalization, and a model embodying such a cooperative step provided a good account of our data.
Vasoactive Intestinal Peptide Selectively Depolarizes Thalamic Relay Neurons and Attenuates Intrathalamic Rhythmic Activity
Authors: Lee Sang-Hun , Cox Charles L.
Published: May 2006

The reciprocal synaptic relationship between the relay thalamus and surrounding thalamic reticular nucleus can lead to the generation of various rhythmic activities that are associated with different levels of behavioral states as well as certain pathophysiological conditions. Intrathalamic rhythmic activities may be attenuated by numerous neuromodulators that arise from a variety of brain stem nuclei. This study focuses on the potential role of a particular neuropeptide, vasoactive intestinal peptide (VIP). VIP and its receptors are localized within the thalamic circuit and thus may serve as an endogenous modulator of the rhythmic activity. Using extracellular multiple-unit recording techniques, we found that VIP strongly attenuated the slow, 2- to 4-Hz intrathalamic rhythm. This rhythm is similar to that observed during slow wave sleep and certain pathophysiological conditions such as generalized absence epilepsy. Using intracellular recording techniques, we found that VIP selectively depolarized relay neurons in the ventrobasal nucleus but had negligible actions on neurons in thalamic reticular nucleus. The VIP-mediated depolarization is produced via an enhancement of the nonselective cation conductance, Ih. The antioscillatory actions of VIP likely occur by shifting the membrane potential to decrease the probability of burst discharge by relay neurons, a requirement to maintain the rhythmic activity. Not only does VIP alter the intrathalamic rhythmic activity, this peptide that is endogenous to the thalamic circuit may also play a significant role in the regulation of information transfer through the thalamocortical circuit.
Gravity-Specific Adaptation of the Angular Vestibuloocular Reflex: Dependence on Head Orientation With Regard to Gravity
Authors: Yakushin Sergei B. , Raphan Theodore , Cohen Bernard
Published: May 2006

The gain of the vertical angular vestibuloocular reflex (aVOR) was adaptively altered by visual-vestibular mismatch during rotation about an interaural axis, using steps of velocity in three head orientations: upright, left-side down, and right-side down. Gains were decreased by rotating the animal and visual surround in the same direction and increased by visual and surround rotation in opposite directions. Gains were adapted in one head position (single-state adaptation) or decreased with one side down and increased with the other side down (dual-state adaptation). Animals were tested in darkness using sinusoidal rotation at 0.5 Hz about an interaural axis that was tilted from horizontal to vertical. They were also sinusoidally oscillated from 0.5 to 4 Hz about a spatial vertical axis in static tilt positions from yaw to pitch. After both single- and dual-state adaptation, gain changes were maximal when the monkeys were in the position in which the gain had been adapted, and the gain changes progressively declined as the head was tilted away from that position. We call this gravity-specific aVOR gain adaptation. The spatial distribution of the specific aVOR gain changes could be represented by a cosine function that was superimposed on a bias level, which we called gravity-independent gain adaptation. Maximal gravity-specific gain changes were produced by 2–4 h of adaptation for both single- and dual-state adaptations, and changes in gain were similar at all test frequencies. When adapted while upright, the magnitude and distribution of the gravity-specific adaptation was comparable to that when animals were adapted in side-down positions. Single-state adaptation also produced gain changes that were independent of head position re gravity particularly in association with gain reduction. There was no bias after dual-state adaptation. With this difference, fits to data obtained by altering the gain in separate sessions predicted the modulations in gain obtained from dual-state adaptations. These data show that the vertical aVOR gain changes dependent on head position with regard to gravity are continuous functions of head tilt, whose spatial phase depends on the position in which the gain was adapted. From their different characteristics, it is likely that gravity-specific and gravity-independent adaptive changes in gain are produced by separate neural processes. These data demonstrate that head orientation to gravity plays an important role in both orienting and tuning the gain of the vertical aVOR.
Neurons in Parafoveal Areas V1 and V2 Encode Vertical and Horizontal Disparities
Authors: Durand Jean-Baptiste , Zhu Shiping , Celebrini Simona , Trotter Yves
Published: May 2006

Stereoscopic vision mainly relies on binocular horizontal disparity (HD), and its cortical encoding is well established in the foveal representation of the visual field. The role of vertical disparity (VD) is more controversial. Thus far, in the monkey, very few studies have investigated the HD sensitivity beyond 5° of retinal eccentricity and no evidence of a real encoding of VD exists in the parafoveal representation of areas V1 and V2. Using dynamic random dot stereograms, we have tested both HD and VD selectivities in the parafoveal representation of V1 (calcarine V1) and V2 (eccentricities > 10°) in a behaving monkey. HD and VD selectivities have been characterized using fitting with Gabor function. A large proportion of the tested cells were both HD and VD selective (47%) and, to a lesser extent, HD selective only (8%) or VD selective only (23%). We found a real encoding of VD, with the same diversity in the tuning profiles as described for HD, that cannot be assimilated to a simple perturbation of the HD matching process. Moreover, the VD encoding had a finer scale than the HD one, which is coherent with the smaller range of naturally occurring VD. For the HD encoding, both the percentage of selective cells and the tuning parameters were close to those reported in foveal V1. These results show that, at parafoveal eccentricities in V1 and V2, disparity detectors are tuned to both horizontal and vertical dimensions of the positional disparity existing between matched features in both retinas.
Activation of δ-Opioid Receptors Excites Spinally Projecting Locus Coeruleus Neurons Through Inhibition of GABAergic Inputs
Authors: Pan Yu-Zhen , Li De-Pei , Chen Shao-Rui , Pan Hui-Lin
Published: May 2006

Stimulation of the noradrenergic nucleus locus coeruleus (LC) releases norepinephrine in the spinal cord, which inhibits dorsal horn neurons and produces analgesia. Activation of this descending noradrenergic pathway also contributes to the analgesic action produced by systemic opioids. The δ-opioid receptors are present presynaptically in the LC. However, their functional role in the control of the activity of spinally projecting LC neurons remains uncertain. In this study, we tested the hypothesis that activation of presynaptic δ-opioid receptors excites spinally projecting LC neurons through inhibition of GABA release. Spinally projecting LC neurons were retrogradely labeled by a fluorescent dye, DiI, injected into the spinal dorsal horn of rats. Whole cell voltage- and current-clamp recordings were performed on DiI-labeled LC neurons in brain slices in vitro. Retrogradely labeled LC noradrenergic neurons were demonstrated by dopamine-β-hydroxylase immunofluorescence. [d-Pen2,d-Pen5]-enkephalin (DPDPE, 1 μM) significantly decreased the frequency of GABA-mediated miniature inhibitory postsynaptic currents (IPSCs) of nine DiI-labeled LC neurons from 2.1 ± 0.5 to 0.7 ± 0.2 Hz without altering their amplitude and the kinetics. On the other hand, the miniature excitatory postsynaptic currents (EPSC) of nine DiI-labeled LC neurons were not significantly altered by DPDPE. Furthermore, DPDPE significantly inhibited the amplitude of evoked IPSC but not EPSC in eight DiI-labeled LC neurons. Under the current-clamp condition, the firing activity in 9 of 11 DiI-labeled LC neurons was significantly increased by 1 μM DPDPE from 4.6 ± 0.7 to 6.2 ± 1.0 Hz. Bicuculline (20 μM) also significantly increased the firing frequency in 13 of 20 neurons from 1.8 ± 0.5 to 2.8 ± 0.6 Hz. Additionally, the excitatory effect of DPDPE on LC neurons was diminished in the presence of bicuculline. Collectively, these data strongly suggest that activation of presynaptic δ-opioid receptors by DPDPE excites a population of spinally projecting LC neurons by preferential inhibition of GABA release. Thus presynaptic δ-opioid receptors likely play an important role in the regulation of the excitability of spinally projecting LC neurons and the descending noradrenergic inhibitory system.
Voltage-Gated Outward K Currents in Frog Saccular Hair Cells
Authors: Catacuzzeno Luigi , Fioretti Bernard , Franciolini Fabio
Published: May 2006

A biophysical analysis of the voltage-gated K (Kv) currents of frog saccular hair cells enzymatically isolated with bacterial protease VIII was carried out, and their contribution to the cell electrical response was addressed by a modeling approach. Based on steady-state and kinetic properties of inactivation, two distinct Kvcurrents were found: a fast inactivating IAand a delayed rectifier IDRK. IAexhibited a strongly hyperpolarized inactivation V1/2(-83 mV), a relatively rapid single exponential recovery from inactivation (τrecof ∼100 ms at -100 mV), and fast activation and deactivation kinetics. IDRKshowed instead a less-hyperpolarized inactivation V1/2(-48 mV), a slower, double-exponential recovery from inactivation (τrec1∼ 490 ms and τrec2∼ 4,960 ms at -100 mV), and slower activation and deactivation kinetics. Steady-state activation gave a V1/2and a k of -46.2 and 8.2 mV for IAand -48.3 and 4.2 mV for IDRK. Both currents were not appreciably blocked by bath application of 10 mM TEA, but were inhibited by 4-AP, with IDRKdisplaying a higher sensitivity. IDRKalso showed a relatively low affinity to linopirdine, being half blocked at ∼50 μM. Steady-state and kinetic properties of IDRKand IAwere described by 2nd- and 3rd-order Hodgkin–Huxley models, respectively. The goodness of our quantitative description of the Kvcurrents was validated by including IAand IDRKin a theoretical model of saccular hair cell electrical activity and by comparing the simulated responses with those obtained experimentally. This thorough description of the IDRKand IAwill contribute toward understanding the role of these currents in the electrical response on this preparation.
Distribution and Function of GABABReceptors in Spider Peripheral Mechanosensilla
Authors: Panek Izabela , Meisner Shannon , Torkkeli Päivi H.
Published: May 2006

The mechanosensilla in spider exoskeleton are innervated by bipolar neurons with their cell bodies close to the cuticle and dendrites attached to it. Numerous efferent fibers synapse with peripheral parts of the mechanosensory neurons, with glial cells surrounding the neurons, and with each other. Most of these efferent fibers are immunoreactive to γ-aminobutyric acid (GABA), and the sensory neurons respond to agonists of ionotropic GABA receptors with a rapid and complete inhibition. In contrast, little is known about metabotropic GABABreceptors that may mediate long-term effects. We investigated the distribution of GABABreceptors on spider leg mechanosensilla using specific antibodies against 2 proteins needed to form functional receptors and an antibody that labels the synaptic vesicles on presynaptic sites. Both anti-GABABreceptor antibodies labeled the distal parts of the sensory cell bodies and dendrites but anti-GABABR1 immunoreactivity was also found in the axons and proximal parts of the cell bodies and some glial cells. The fine efferent fibers that branch on top of the sensory neurons did not show GABABreceptor immunoreactivity but were densely labeled with anti-synapsin and indicated synaptic vesicles on presynaptic locations to the GABABreceptors. Intracellular recordings from sensory neurons innervating the slit sensilla of the spider legs revealed that application of GABABreceptor agonists attenuated voltage-activated Ca2+current and enhanced voltage-activated outward K+current, providing 2 possible mechanisms for controlling the neurons' excitability. These findings support the hypothesis that GABABreceptors are present in the spider mechanosensilla where their activation may modulate information transmission.
Regulation of Inhibitory Synaptic Transmission by Vasoactive Intestinal Peptide (VIP) in the Mouse Suprachiasmatic Nucleus
Authors: Itri Jason , Colwell Christopher S.
Published: May 2006

Circadian rhythmicity in mammals is generated by a pair of nuclei in the anterior hypothalamus known as the suprachiasmatic nuclei (SCN), whose neurons express a variety of neuropeptides that are thought to play an important role in the circadian timing system. To evaluate the influence of VIP on inhibitory synaptic transmission between SCN neurons, we used whole cell patch-clamp recording in an acute brain slice preparation of mouse SCN. Baseline spontaneous GABAergic inhibitory postsynaptic currents (IPSCs) varied significantly between regions and across phases, with a greater frequency of IPSCs observed in the dorsomedial region during the early night. Bath-applied VIP caused a significant increase in the frequency of spontaneous inhibitory postsynaptic currents (sIPSC) in a reversible and dose-dependent manner with no effect on the mean amplitude or kinetic parameters. The effect of VIP was widespread throughout the SCN and observed in both ventrolateral (VL) and dorsomedial (DM) regions. In the presence of tetrodotoxin, VIP increased the frequency of miniature IPSCs without affecting the mean magnitude or kinetic parameters. The magnitude of the enhancement by VIP was significantly larger during the day than during the night. Pretreatment with the VIP-PACAP receptor antagonist [Ac-Tyr1, D-Phe2]-GHRF 1-29 or the selective VPAC2receptor antagonist PG 99-465 completely blocked the VIP-induced enhancement. The effect of VIP appears to be mediated by a cAMP/PKA-dependent mechanism as forskolin mimics, while the PKA antagonist H-89 blocks the observed enhancement of GABA currents. Our data suggest that VIP activates presynaptic VPAC2receptors to regulate inhibitory synaptic transmission within the SCN and that this effect varies from day to night.
Single-Unit Activity Related to Bimanual Arm Movements in the Primary and Supplementary Motor Cortices
Authors: Donchin O. , Gribova A. , Steinberg O. , Mitz A. R. , Bergman H. , Vaadia E.
Published: May 2006

Single units were recorded from the primary motor (MI) and supplementary motor (SMA) areas of Rhesus monkeys performing one-arm (unimanual) and two-arm (bimanual) proximal reaching tasks. During execution of the bimanual movements, the task related activity of about one-half the neurons in each area (MI: 129/232, SMA: 107/206) differed from the activity during similar displacements of one arm while the other was stationary. The bulk of this “bimanual-related” activity could not be explained by any linear combination of activities during unimanual reaching or by differences in kinematics or recorded EMG activity. The bimanual-related activity was relatively insensitive to trial-to-trial variations in muscular activity or arm kinematics. For example, trials where bimanual arm movements differed the most from their unimanual controls did not correspond to the ones where the largest bimanual neural effects were observed. Cortical localization established by using a mixture of surface landmarks, electromyographic recordings, microstimulation, and sensory testing suggests that the recorded neurons were not limited to areas specifically involved with postural muscles. By rejecting this range of alternative explanations, we conclude that neural activity in MI as well as SMA can reflect specialized cortical processing associated with bimanual movements.
Hyperpolarization-Activated Current Ih Disconnects Somatic and Dendritic Spike Initiation Zones in Layer V Pyramidal Neurons
Authors: Berger Thomas , Senn Walter , Lüscher Hans-R.
Published: May 2006

Layer V pyramidal cells of the somatosensory cortex operate with two spike initiation zones. Subthreshold depolarizations are strongly attenuated along the apical dendrite linking the somatic and distal dendritic spike initiation zones. Sodium action potentials, on the other hand, are actively back-propagating from the axon hillock into the apical tuft. There they can interact with local excitatory input leading to the generation of calcium action potentials. We investigated if and how back-propagating sodium action potentials alone, without concomitant excitatory dendritic input, can initiate calcium action potentials in the distal dendrite. In acute slices of the rat somatosensory cortex, layer V pyramidal cells were studied under current-clamp with simultaneous recordings from the soma and the apical dendrite. A train of four somatic action potentials had to reach high frequencies to induce calcium action potentials in the dendrite (“critical frequency,” CF ∼100 Hz). Depolarization in the dendrite reduced the CF, while hyperpolarization increased it. The CF depended on the presence of the hyperpolarization-activated current Ih: blockade with 20 μM 4-( N-ethyl- N-phenylamino)-1,2-dimethyl-6-(methylamino) pyridinium chloride (ZD7288) reduced the CF to 68% of control. If the neurons were stimulated with noisy current injections, leading to in-vivo-like irregular spiking, no calcium action potentials were induced in the dendrite. However, after Ih channel blockade, calcium action potentials were frequently seen. These data suggest that Ih prevents initiation of the dendritic calcium action potential by proximal input alone. Dendritic calcium action potentials may therefore represent a unique signature for coincident somatic and dendritic activation.
Long-Term Depression of Synaptic Inhibition Is Expressed Postsynaptically in the Developing Auditory System
Authors: Chang Eric H. , Kotak Vibhakar C. , Sanes Dan H.
Published: May 2006

Inhibitory transmission is critically involved in the functional maturation of neural circuits within the brain. However, the mechanisms involved in its plasticity and development remain poorly understood. At an inhibitory synapse of the developing auditory brain stem, we used whole cell recordings to determine the site of induction and expression of long-term depression (LTD), a robust activity-dependent phenomenon that decreases inhibitory synaptic gain and is postulated to underlie synapse elimination. Recordings were obtained from lateral superior olivary (LSO) neurons, and hyperpolarizing inhibitory potentials were evoked by stimulation of the medial nucleus of the trapezoid body (MNTB). Both postsynaptic glycine and GABAA receptors could independently display LTD when isolated pharmacologically. Focal application of GABA, but not glycine, on the postsynaptic LSO neuron was sufficient to induce depression of the amino acid–evoked response, or MNTB-evoked inhibitory postsynaptic potentials. This GABA-mediated depression, in the absence of MNTB stimulation, was blocked by a GABAB receptor antagonist. To assess whether a change in neurotransmitter release is associated with the LTD, the polyvalent cation, ruthenium red, was used to increase the frequency of miniature inhibitory synaptic events. Consistent with a postsynaptic locus of expression, we found that the mean amplitude of miniature events decreased after LTD with no change in their frequency of occurrence. Furthermore, there was no change in the paired-pulse ratio or release kinetics of evoked inhibitory responses. Together, these results provide direct evidence that activity-dependent LTD of inhibition has a postsynaptic locus of induction and alteration, and that GABA but not glycine plays a pivotal role.
Differential Adaptation of the Linear and Nonlinear Components of the Horizontal Vestibuloocular Reflex in Squirrel Monkeys
Authors: Clendaniel Richard A. , Lasker David M. , Minor Lloyd B.
Published: May 2006

Previous work in squirrel monkeys has demonstrated the presence of linear and nonlinear components to the horizontal vestibuloocular reflex (VOR) evoked by high-acceleration rotations. The nonlinear component is seen as a rise in gain with increasing velocity of rotation at frequencies more than 2 Hz (a velocity-dependent gain enhancement). We have shown that there are greater changes in the nonlinear than linear component of the response after spectacle-induced adaptation. The present study was conducted to determine if the two components of the response share a common adaptive process. The gain of the VOR, in the dark, to sinusoidal stimuli at 4 Hz (peak velocities: 20–150°/s) and 10 Hz (peak velocities: 20 and 100°/s) was measured pre- and postadaptation. Adaptation was induced over 4 h with ×0.45 minimizing spectacles. Sum-of-sines stimuli were used to induce adaptation, and the parameters of the stimuli were adjusted to invoke only the linear or both linear and nonlinear components of the response. Preadaptation, there was a velocity-dependent gain enhancement at 4 and 10 Hz. In postadaptation with the paradigms that only recruited the linear component, there was a decrease in gain and a persistent velocity-dependent gain enhancement (indicating adaptation of only the linear component). After adaptation with the paradigm designed to recruit both the linear and nonlinear components, there was a decrease in gain and no velocity-dependent gain enhancement (indicating adaptation of both components). There were comparable changes in the response to steps of acceleration. We interpret these results to indicate that separate processes drive the adaptation of the linear and nonlinear components of the response.
Contribution of Synaptic Depression to Phase Maintenance in a Model Rhythmic Network
Authors: Manor Yair , Bose, Amitabha , Booth Victoria , Nadim, Farzan
Published: May 2006

In many rhythmic neuronal networks that operate in a wide range of frequencies, the time of neuronal firing relative to the cycle period (the phase) is invariant. This invariance suggests that when frequency changes, firing time is precisely adjusted either by intrinsic or synaptic mechanisms. We study the maintenance of phase in a computational model in which an oscillator neuron (O) inhibits a follower neuron (F) by comparing the dependency of phase on cycle period in two cases: when the inhibitory synapse is depressing and when it is nondepressing. Of the numerous ways of changing the cycle period, we focus on three cases where either the duration of the active state, the inactive state, or the duty cycle of neuron O remains constant. In each case, we measure the phase at which neuron F fires with respect to the onset of firing in neuron O. With a nondepressing synapse, this phase is generally a monotonic function of cycle period except in a small parameter range in the case of the constant inactive duration. In contrast, with a depressing synapse, there is always a parameter regime in which phase is a cubic function of cycle period: it decreases at short cycle periods, increases in an intermediate range, and decreases at long cycle periods. This complex shape for the phase-period relationship arises because of the interaction between synaptic dynamics and intrinsic properties of the postsynaptic neuron. By choosing appropriate parameters, the cubic shape of the phase-period curve results in a small variation in phase for a large interval of periods. Consequently, we find that although a depressing synapse does not produce perfect phase maintenance, in most cases it is superior to a nondepressing synapse in promoting a constant phase difference.
Glycine Receptors and Glycinergic Synaptic Transmission in the Deep Cerebellar Nuclei of the Rat: A Patch-Clamp Study
Authors: Kawa Kazuyoshi
Published: May 2006

To clarify possible glycinergic transmission in the cerebellum, principal neurons in deep cerebellar nuclei (DCN) of sliced cerebella (200 μm in thickness) from rats (aged 2–14 days) were studied using whole cell patch-clamp techniques. When glycine (100 μM) was applied to the DCN neurons from a “Y tube,” large outward currents were induced (average peak amplitude of about 600 pA at -40 mV). The currents were blocked by strychnine (1 μM) and showed a reversal potential of -62 mV, which was approximately the estimated Cl- equilibrium potential. The dose-response relation of the currents showed an apparent dissociation constant of 170 μM for glycine and Hill coefficient of 1.6. In the presence of 6-cyano-7-nitroquinoziline-2, 3-dione (CNQX), d-(-)-2-amino-5-phosphonovaleric acid (APV) and bicuculline, which antagonize amino-3-hydroxy-5-methyl-isoxazol-propionate (APMA), N-methyl-d-aspartate (NMDA), and GABAA receptors, respectively, postsynaptic currents sensitive to strychnine (1 μM) were induced in DCN neurons by external perfusion of 20 mM K+ saline. Electrical stimulation of surrounding tissues in DCN evoked definite inhibitory postsynaptic currents (IPSCs) in these neurons. The IPSCs had a reversal potential of -62 mV and showed sensitivities to strychnine and tetrodotoxin. Thus this study has revealed that strychnine-sensitive glycine receptors are expressed in neurons of the DCN of rats and that glycinergic transmission mediated by these receptors is functional in these neurons from stages immediately after birth. The glycinergic innervations are presumably supplied by small interneurons located in the DCN.
Scleral Search Coils Influence Saccade Dynamics
Authors: Frens M. A. , Van der Geest J. N.
Published: May 2006

The scleral search coil technique is commonly used for recording eye movements. The goal of this paper is to investigate to what extent the placement of scleral search coils onto the eyes influences the kinematics of saccades. To that end saccadic eye movements of human subjects were recorded with an infrared video system, while they wore coils and we compared the main sequence properties with recordings in which no coils were mounted on the eyes. It was found that saccades last longer (by about 8%) and become slower (by about 5%) when both eyes wear coils. This is truly due to the fact that the coils are on the eyes and not due to other factors that are part of this method, such as the scleral anesthesia. The influence of coils in both eyes was also observed when one coil was mounted on one eye only. Therefore the effect that the coils have on the eye movements cannot be attributed to purely mechanical factors, such as inertial load on the eyeball or increased friction. Rather the coils appear to change the oculomotor command signals that drive the saccadic eye movements.
Functional Organization of the Cat Visual Cortex in Relation to the Representation of a Uniform Surface
Authors: Tani Toshiki , Yokoi Isao , Ito Minami , Tanaka Shigeru , Komatsu Hidehiko
Published: May 2006

Neuronal activity in the early visual cortex has been extensively studied from the standpoint of contour representation. On the other hand, representation of the interior of a surface surrounded by a contour is much less well understood. Several studies have identified neurons activated by a uniform surface covering their receptive fields, but their distribution within the cortex is not yet known. The aim of the present study was to obtain a better understanding of the distribution of such neurons in the visual cortex. Using optical imaging of intrinsic signals, we found that there are a group of surface-responsive regions located in area 18, along the area 17/18 border, that tend to overlap the singular points of the orientation-preference map. Extracellular recordings confirmed that neurons responsive to uniform plane stimuli are accumulated in these regions. Such neurons also existed outside the surface-responsive regions around the singular points. These results suggest that there exists a functional organization related to the representation of a uniform surface in the early visual cortex.