bluuebunny/crossref_metadata_2025 huggingface dataset:
Modulation of Lower Limb Withdrawal Reflexes During Gait: A Topographical Study
Authors: Spaich Erika G. , Arendt-Nielsen Lars , Andersen Ole K.
Published: January 2004

The aim of this study was to investigate the modulation and topography of the nociceptive withdrawal reflex elicited by painful electrical stimulation of the foot sole during gait. Fifteen healthy volunteers participated in this study. Cutaneous electrical stimulation was delivered on five locations of the foot sole after heel-contact, during foot-flat, after heel-off, and during the mid-swing phase of the gait cycle during treadmill walking. Reflexes were recorded from muscles of the ipsilateral and contralateral legs. Furthermore, the kinematic responses in the sagittal plane of the ipsilateral ankle, knee, and hip joints were recorded. Reflexes in the distal muscles showed a site-dependant modulation. The largest responses in tibialis anterior were evoked at the arch of the foot and the smallest at the heel ( P < 0.05). The largest soleus responses were also elicited at the arch of the foot ( P < 0.04). The EMG responses in flexors and extensors of the knee and extensors of the contralateral leg were generally not dependent on the stimulation site. The response at the three joints showed site dependency, especially during the swing phase where maximal flexion was obtained by stimulation at the arch of the foot ( P < 0.05). The withdrawal reflex was modulated during the gait cycle and presented distinctive characteristics for the different muscles studied. Minimal kinematic responses were observed during stance in contrast to swing phase. Modulation of the reflex probably ensures an appropriate withdrawal but primarily secures balance and continuity of movement.
Stiffness of the Gerbil Basilar Membrane: Radial and Longitudinal Variations
Authors: Emadi Gulam , Richter Claus-Peter , Dallos Peter
Published: January 2004

Experimental data on the mechanical properties of the tissues of the mammalian cochlea are essential for understanding the frequency- and location-dependent motion patterns that result in response to incoming sound waves. Within the cochlea, sound-induced vibrations are transduced into neural activity by the organ of Corti, the gross motion of which is dependent on the motion of the underlying basilar membrane. In this study we present data on stiffness of the gerbil basilar membrane measured at multiple positions within a cochlear cross section and at multiple locations along the length of the cochlea. A basic analysis of these data using relatively simple models of cochlear mechanics reveals our most important result: the experimentally measured longitudinal stiffness gradient at the middle of the pectinate zone of the basilar membrane (4.43 dB/mm) can account for changes of best frequency along the length of the cochlea. Furthermore, our results indicate qualitative changes of stiffness-deflection curves as a function of radial position; in particular, there are differences in the rate of stiffness growth with increasing tissue deflection. Longitudinal coupling within the basilar membrane/organ of Corti complex is determined to have a space constant of 21 μm in the middle turn of the cochlea. The bulk of our data was obtained in the hemicochlea preparation, and we include a comparison of this set of data to data obtained in vivo.
GCP II (NAALADase) Inhibition Suppresses Mossy Fiber-CA3 Synaptic Neurotransmission by a Presynaptic Mechanism
Authors: Garrido Sanabria Emilio R. , Wozniak Krystyna M. , Slusher Barbara S. , Keller Asaf
Published: January 2004

We tested the hypothesis that endogenous N-acetylaspartylglutamate (NAAG) presynaptically inhibits glutamate release at mossy fiber-CA3 synapses. For this purpose, we made use of 2-(3-mercaptopropyl)pentanedioic acid (2-MPPA), an inhibitor of glutamate carboxypeptidase II [GCP II; also known as N-acetylated alpha-linked acidic dipeptidase (NAALADase)], the enzyme that hydrolyzes NAAG into N-acetylaspartate and glutamate. Application of 2-MPPA (1–20 μM) had no effect on intrinsic membrane properties of CA3 pyramidal neurons recorded in vitro in whole cell current- or voltage-clamp mode. Bath application of 10 μM 2-MPPA suppressed evoked excitatory postsynaptic current (EPSC) amplitudes. Attenuation of EPSC amplitudes was accompanied by a significant increase in paired-pulse facilitation (50-ms interpulse intervals), suggesting that a presynaptic mechanism is involved. The group II metabotropic glutamate receptor (mGluR) antagonist 2 S-2-amino-2-(1 S,2 S-2-carboxycyclopropyl-1-yl)-3-(xanth-9-y l) propanoic acid (LY341495) prevented the 2-MPPA-dependent suppression of EPSC amplitudes. 2-MPPA reduced the frequencies of TTX-insensitive miniature EPSCs (mEPSC), without affecting their amplitudes, further supporting a presynaptic action for GCP II inhibition. 2-MPPA-induced reduction of mEPSC frequencies was prevented by LY341495, reinforcing the role of presynaptic group II mGluR. Because GCP II inhibition is thought to increase NAAG levels, these results suggest that NAAG suppresses synaptic transmission at mossy fiber-CA3 synapses through presynaptic activation of group II mGluRs.
Differential Roles of mGluR1 and mGluR5 in Brief and Prolonged Nociceptive Processing in Central Amygdala Neurons
Authors: Li Weidong , Neugebauer Volker
Published: January 2004

The laterocapsular division of the central nucleus of the amygdala (CeA) is now defined as the “nociceptive amygdala” because of its high content of neurons that respond to painful stimuli. The majority of these neurons become sensitized in a model of arthritis pain. Here we address the role of G protein–coupled group I metabotropic glutamate receptor subtypes mGluR1 and mGluR5 in nociceptive processing under normal conditions and in pain-related sensitization. Extracellular single-unit recordings were made from 65 CeA neurons in anesthetized rats. Each neuron's responses to brief mechanical stimuli, background activity, receptive field size, and threshold were measured before and after induction of the kaolin/carrageenan mono-arthritis in one knee and before and during applications of agonists and antagonists into the CeA by microdialysis. All neurons received excitatory input from the knee(s) and responded most strongly to noxious stimuli. Before arthritis, a group I mGluR1 and mGluR5 agonist (DHPG, n = 10) potentiated the responses to innocuous and noxious stimuli. This effect was mimicked by an mGluR5 agonist (CHPG, n = 15). In the arthritis pain state (>6 h after induction), the facilitatory effects of DHPG ( n = 9), but not CHPG ( n = 7), increased. An mGluR1 antagonist (CPCCOEt) had no effect before arthritis ( n = 12) but inhibited the responses of sensitized neurons in the arthritis pain state ( n = 8). An mGluR5 antagonist (MPEP) inhibited brief nociceptive responses under normal conditions ( n = 19) and prolonged nociception in arthritis ( n = 8). These data suggest a change of mGluR1 function and activation in the amygdala in pain-related sensitization, whereas mGluR5 is involved in brief as well as prolonged nociception.
Is Spontaneous High-Voltage Rhythmic Spike Discharge in Long Evans Rats an Absence-Like Seizure Activity?
Authors: Shaw Fu-Zen
Published: January 2004

A distinct high-voltage rhythmic spike (HVRS) discharge characterized by a barrage of negative spikes oscillating at 5–12 Hz was observed in chronically implanted Long Evans rats. Spontaneous HVRS discharges were exhibited in 90% of 40 Long Evans rats and occurred during sudden arrest of ongoing behavior (immobility) with occasional facial/whisker twitching. However, the function of HVRS discharges in Long Evans rats remains inconclusive to date and has been associated with alpha tremor/mu rhythm, attentive mu wave, and absence seizure. To elucidate the function of HVRS discharges in Long Evans rats, several experiments were performed. In a 6-h recording session (12:00–18:00), HVRS activities primarily occurred in several specific vigilance states, being particularly abundant in a short-lasting period before vigilance changes. Several characteristics, such as durations, oscillatory frequencies, and interspike intervals (ISIs) of HVRS discharges, were altered during wake-sleep states. Oscillatory frequencies were negatively correlated with durations of HVRS segments. In addition, ISIs of a HVRS episode exhibited a crescendo-decrescendo pattern. These variable ISIs could explain why a negative correlation was found between oscillatory frequencies and durations of HVRS episodes. Moreover, HVRS discharges were demonstrated to have widespread and near-synchronous distribution to bilateral cortical areas. In addition, innocuous electrical stimuli were unable to stop ongoing HVRS discharges. By contrast, noxious stimuli elicited behavioral arousal and immediately terminated most HVRS discharges. Cortical-evoked potentials in response to mild electrical stimulation under HVRS discharges were different from those under waking state but resemble those under slow-wave sleep with a smaller magnitude. Moreover, the temporal and spectral characteristics of spontaneous HVRS activities were analogous to those of seizure activities induced by penicillin and pentylenetetrazol. The incidence of spontaneous HVRS discharges was significantly decreased by ethosuximide administration. Based on these results, HVRS discharge might not be associated with a voluntary mu-rhythm behavior, instead it behaves as an absence-like seizure activity. These results were also collaborated using other genetic absence-seizure rats, such as WAG/Rij and GAERS rats. Possible mechanisms for the generation and termination of paroxysmal HVRS discharges are also discussed.
Basal Forebrain Cholinergic System Is Involved in Rapid Nerve Growth Factor (NGF)-Induced Plasticity in the Barrel Cortex of Adult Rats
Authors: Prakash Neal , Cohen-Cory Susana , Penschuck Silke , Frostig Ron D.
Published: January 2004

We have previously reported that topical application of nerve growth factor (NGF) to the barrel cortex of an adult rat rapidly augmented a whisker functional representation (WFR) by increasing its area and height within minutes after NGF application. In addition, we found that TrkA, the high-affinity NGF receptor, was only found on fibers projecting into the barrel cortex. Here we use a combination of techniques including chronic intrinsic signal optical imaging, neuronal fiber tracking and immunohistological techniques, to test the hypothesis that NGF-induced rapid cortical plasticity is mediated by the cortical projections of the basal forebrain cholinergic system (BFCS). Our studies localize the source of the cells in the BFCS that project to a single WFR and also demonstrate that TrkA-immunoreactive fibers in the cortex are also cholinergic and likely arise from the BFCS. In addition, by selectively lesioning the BFCS cortical fibers with the immunotoxin 192 IgG-saporin, we show that NGF-induced WFR-cortical plasticity is eliminated. These results, taken together with our previously reported imaging results that demonstrated that agonists of the cholinergic system (particularly nicotine) showed transient NGF-like augmentations of a WFR, implicate the BFCS cortical projections as necessary for NGF's rapid plasticity in the adult rat somatosensory cortex.
The Moving Platform Aftereffect: Limited Generalization of a Locomotor Adaptation
Authors: Reynolds R. F. , Bronstein A. M.
Published: January 2004

We have recently described a postural after-effect of walking onto a stationary platform previously experienced as moving, which occurs despite full knowledge that the platform will no longer move. This experiment involves an initial baseline period when the platform is kept stationary (BEFORE condition), followed by a brief adaptation period when subjects learn to walk onto the platform moving at 1.2 m/s (MOVING condition). Subjects are clearly warned that the platform will no longer move and asked to walk onto it again (AFTER condition). Despite the warning, they walk toward the platform with a velocity greater than that observed during the BEFORE condition, and a large forward sway of the trunk is observed once they have landed on the platform. This aftereffect, which disappears within three trials, represents dissociation of knowledge and action. In the current set of experiments, to gain further insight into this phenomenon, we have manipulated three variables, the context, location, and method of the walking task, between the MOVING and AFTER conditions, to determine how far the adaptation will generalize. It was found that when the gait initiation cue was changed from beeps to a flashing light, or vice versa, there was no difference in the magnitude of the aftereffect, either in terms of walking velocity or forward sway of the trunk. Changing the leg with which gait was initiated, however, reduced sway magnitude by approximately 50%. When subjects changed from forward walking to backward walking, the aftereffect was abolished. Similarly, walking in a location other than the mobile platform did not produce any aftereffect. However, in these latter two experiments, the aftereffect reappeared when subjects reverted to the walking pattern used during the MOVING condition. Hence, these results show that a change in abstract context had no influence, whereas any deviation from the way and location in which the moving platform task was originally performed profoundly reduced the size of the aftereffect. Although the moving platform aftereffect is an example of inappropriate generalization by the motor system across time, these results show that this generalization is highly limited to the method and location in which the original adaptation took place.
Dynamic Regulation of Sensorimotor Integration in Human Postural Control
Authors: Peterka Robert J. , Loughlin Patrick J.
Published: January 2004

Upright stance in humans is inherently unstable, requiring corrective action based on spatial-orientation information from sensory systems. One might logically predict that environments providing access to accurate orientation information from multiple sensory systems would facilitate postural stability. However, we show that, after a period in which access to accurate sensory information was reduced, the restoration of accurate information disrupted postural stability. In eyes-closed trials, proprioceptive information was altered by rotating the support surface in proportion to body sway (support surface “sway-referencing”). When the support surface returned to a level orientation, most subjects developed a transient 1-Hz body sway oscillation that differed significantly from the low-amplitude body sway typically observed during quiet stance. Additional experiments showed further enhancement of the 1-Hz oscillation when the surface transitioned from a sway-referenced to a reverse sway-referenced motion. Oscillatory behavior declined with repetition of trials, suggesting a learning effect. A simple negative feedback-control model of the postural control system predicted the occurrence of this 1-Hz oscillation in conditions where too much corrective torque is generated in proportion to body sway. Model simulations were used to distinguish between two alternative explanations for the excessive corrective torque generation. Simulation results favor an explanation based on the dynamic reweighting of sensory contributions to postural control rather than a load-compensation mechanism that scales torque in proportion to a fixed combination of sensory-orientation information.
Heartbeat Control in Leeches. I. Constriction Pattern and Neural Modulation of Blood Pressure in Intact Animals
Authors: Wenning Angela , Cymbalyuk Gennady S. , Calabrese Ronald L.
Published: January 2004

Two tubular hearts propel blood through the closed circulatory system of the medicinal leech. The hearts are myogenic but are driven by a centrally generated motor pattern that controls heart rate and intersegmental coordination. In two consecutive papers, we address the question of how the motor pattern is translated into the pattern of diastole and systole of leech hearts. We imaged the constriction patterns of the hearts in quiescent intact animals. In one heart, systole progresses rear-to-front (peristaltic coordination mode), whereas systole occurs nearly simultaneously in the other heart (synchronous coordination mode) with regular switches between these two coordination modes. Intersegmental phase relations between heart segments do not vary with changes in the heartbeat period. The peristaltic heart drives blood forward through itself and then rearward through the other longitudinal vessels. The synchronous heart does not seem to contribute to rearward flow along the body axis and may support segmental circulation instead. Simultaneous monitoring of heart motor neuron discharge and the constriction of the corresponding heart segment in innervated, reduced preparations enabled us later to meld the constriction pattern with the fictive motor pattern described in the following paper. Current injections into one heart modulatory neuron while monitoring intravascular pressure from the corresponding heart showed that these neurons can acutely change diastolic and systolic pressure. However, they do not determine the different systolic pressure profiles associated with the two coordination modes, which appear to result from the constriction pattern.
Comparison of Responses of Primate Spinothalamic Tract Neurons to Pruritic and Algogenic Stimuli
Authors: Simone Donald A. , Zhang Xijing , Li Jun , Zhang Jun-Ming , Honda Christopher N. , LaMotte Robert H. , Giesler Glenn J.
Published: January 2004

We investigated the role of mechanosensitive spinothalamic tract (STT) neurons in mediating 1) the itch evoked by intradermal injection of histamine, 2) the enhanced sense of itch evoked by innocuous stroking (alloknesis), and 3) the enhanced pain evoked by punctate stimulation (hyperalgesia) of the skin surrounding the injection site. Responses to intradermal injections of histamine and capsaicin were compared in STT neurons recorded in either the superficial or the deep dorsal horn of the anesthetized monkey. Each neuron was identified by antidromic activation from the ventral posterior lateral nucleus of thalamus and classified by its initial responses to mechanical stimuli as wide dynamic range (WDR) or high-threshold (HT). Approximately half of the WDRs and one of the HTs responded weakly to histamine, some with a duration > 5 min, the maximal time allotted. WDRs but not HTs exhibited a significant increase in response to punctate stimulation after histamine consistent with their possible role in mediating histamine-induced hyperalgesia. Neither type of neuron exhibited significant changes in response to stroking, consistent with their unlikely role in mediating alloknesis. Furthermore, nearly all STT neurons exhibited vigorous and persistent responses to capsaicin, after which they became sensitized to stroking and to punctate stimulation. We conclude that the STT neurons in our sample are more likely to contribute to pain, allodynia, and hyperalgesia than to itch and alloknesis.
Heartbeat Control in Leeches. II. Fictive Motor Pattern
Authors: Wenning Angela , Hill Andrew A. V. , Calabrese Ronald L.
Published: January 2004

The rhythmic beating of the tube-like hearts in the medicinal leech is driven and coordinated by rhythmic activity in segmental heart motor neurons. The motor neurons are controlled by rhythmic inhibitory input from a network of heart interneurons that compose the heartbeat central pattern generator. In the preceding paper, we described the constriction pattern of the hearts in quiescent intact animals and showed that one heart constricts in a rear-to-front wave (peristaltic coordination mode), while the other heart constricts in near unison over its length (synchronous coordination mode) and that they regularly switch coordination modes. Here we analyze intersegmental and side-to-side-coordination of the fictive motor pattern for heartbeat in denervated nerve cords. We show that the intersegmental phase relations among heart motor neurons in both coordination modes are independent of heartbeat period. This finding enables us to combine data from different experiments to form a detailed analysis of the relative phases, duty cycle, and intraburst spike frequency of the bursts of the segmental heart motor neurons. The fictive motor pattern and the constriction pattern seen in intact leeches closely match in their intersegmental and side-to-side coordination, indicating that sensory feedback is not necessary for properly phased intersegmental coordination. Moreover, the regular switches in coordination mode of the fictive motor pattern mimic those seen in intact animals indicating that these switches likely arise by a central mechanism.
Angular Tuning and Velocity Sensitivity in Different Neuron Classes Within Layer 4 of Rat Barrel Cortex
Authors: Lee Soo-Hyun , Simons Daniel J.
Published: January 2004

Local circuitry within layer IV whisker-related barrels is preferentially sensitive to thalamic population firing synchrony, and neurons respond most vigorously to stimuli, such as high-velocity whisker deflections, that evoke it. Field potential recordings suggest that thalamic barreloid neurons having similar angular preferences fire synchronously. To examine whether angular tuning of cortical neurons might also be affected by thalamic firing synchrony, we characterized responses of layer IV units to whisker deflections that varied in angular direction and velocity. Barrel regular-spike units (RSUs) became more tuned for deflection angle with slower whisker movements. Deflection amplitude had no affect. Barrel fast-spike units (FSUs) were poorly tuned for deflection angle, and their responses remained constant with different deflection velocity. The dependence of angular tuning on deflection velocity among barrel RSUs appears to reflect the same underlying response dynamics that determine their velocity sensitivity and receptive field focus. Unexpectedly, septal RSUs and FSUs are largely similar to their barrel counterparts despite available evidence suggesting that they receive different afferent inputs and are embedded within different local circuits.
Influence of Ionic Conductances on Spike Timing Reliability of Cortical Neurons for Suprathreshold Rhythmic Inputs
Authors: Schreiber Susanne , Fellous Jean-Marc , Tiesinga Paul , Sejnowski Terrence J.
Published: January 2004

Spike timing reliability of neuronal responses depends on the frequency content of the input. We investigate how intrinsic properties of cortical neurons affect spike timing reliability in response to rhythmic inputs of suprathreshold mean. Analyzing reliability of conductance-based cortical model neurons on the basis of a correlation measure, we show two aspects of how ionic conductances influence spike timing reliability. First, they set the preferred frequency for spike timing reliability, which in accordance with the resonance effect of spike timing reliability is well approximated by the firing rate of a neuron in response to the DC component in the input. We demonstrate that a slow potassium current can modulate the spike timing frequency preference over a broad range of frequencies. This result is confirmed experimentally by dynamic-clamp recordings from rat prefrontal cortical neurons in vitro. Second, we provide evidence that ionic conductances also influence spike timing beyond changes in preferred frequency. Cells with the same DC firing rate exhibit more reliable spike timing at the preferred frequency and its harmonics if the slow potassium current is larger and its kinetics are faster, whereas a larger persistent sodium current impairs reliability. We predict that potassium channels are an efficient target for neuromodulators that can tune spike timing reliability to a given rhythmic input.
Hereditary Cerebellar Ataxia Progressively Impairs Force Adaptation During Goal-Directed Arm Movements
Authors: Maschke Matthias , Gomez Christopher M. , Ebner Timothy J. , Konczak Jürgen
Published: January 2004

We investigated how humans with hereditary cerebellar degeneration [spinocerebellar ataxia (SCA) type 6 and 8, n = 9] and age- and sex-matched healthy controls ( n = 9) adapted goal-directed arm movements to an unknown external force field. We tested whether learning could be generalized to untrained regions in the workspace, an aspect central to the idea of an internal model, and if any learning could be retained. After removal of the force field, SCA patients showed little or no learning-related aftereffects indicating that repeated force-field exposure never led to successful force compensation. In contrast, healthy control subjects quickly adapted their movements to the new force field. The difference in force adaptation was significant for movements to targets that required both the shoulder and elbow joint ( P < 0.001). Moreover, the generalization of learned movements to targets outside the learned workspace was prevented by the cerebellar degeneration ( P < 0.01). Retention of force adaptation was significantly lower in SCA patients ( P = 0.003). The severity of ataxia in SCA patients correlated negatively with the extent of learning ( r = –0.84, P = 0.004). Our findings imply that progressive loss of cerebellar function gradually impairs force adaptation. The failure to generalize learning suggests that cerebellar degeneration prevents the formation of an internal representation of the limb dynamics.
Implementation of a Fast 16-Bit Dynamic Clamp Using LabVIEW-RT
Authors: Kullmann Paul H. M. , Wheeler Diek W. , Beacom Joshua , Horn John P.
Published: January 2004

The dynamic-clamp method provides a powerful electrophysiological tool for creating virtual ionic conductances in living cells and studying their influence on membrane potential. Here we describe G-clamp, a new way to implement a dynamic clamp using the real-time version of the Lab-VIEW programming environment together with a Windows host, an embedded microprocessor that runs a real-time operating system and a multifunction data-acquisition board. The software includes descriptions of a fast voltage-dependent sodium conductance, delayed rectifier, M-type and A-type potassium conductances, and a leak conductance. The system can also read synaptic conductance waveforms from preassembled data files. These virtual conductances can be reliably implemented at speeds ≤43 kHz while simultaneously saving two channels of data with 16-bit precision. G-clamp also includes utilities for measuring current-voltage relations, synaptic strength, and synaptic gain. Taking an approach built on a commercially available software/hardware platform has resulted in a system that is easy to assemble and upgrade. In addition, the graphical programming structure of LabVIEW should make it relatively easy for others to adapt G-clamp for new experimental applications.
Synaptic Strength Between Motoneurons and Terminals of the Dorsolateral Funiculus Is Regulated by GABA Receptors in the Turtle Spinal Cord
Authors: Delgado-Lezama Rodolfo , Aguilar Justo , Cueva-Rolón Rafael
Published: January 2004

The role of GABAA and GABAB receptors in modulation of excitatory synaptic transmission between motoneurons and terminals from dorsolateral funiculus (DLF) was studied in in vitro spinal cord slices of adult turtles. Muscimol—a GABAA receptor agonist— depressed the monosynaptic excitatory postsynaptic potential (EPSP) induced by stimulation of the DLF and shortened its duration. The input resistance and the membrane time constant also were strongly reduced. The input membrane resistance, the amplitude, and the half-width of the EPSP were reduced at the same rate in the presence of muscimol. Bicuculline—a GABAA receptor antagonist—increased the EPSPs amplitude and the input membrane resistance. The EPSP amplitude ratio elicited by a paired-pulse protocol did not change significantly. Our results suggest that muscimol acts mainly by activation of postsynaptic GABAA receptors located on the motoneuron and the synaptic strength on motoneurons may be modulated by tonic activation of postsynaptic GABAA receptors. Baclofen—a GABAB receptor agonist—also depressed DLF-motoneuron synaptic transmission. However, it did not affect the falling phase of the EPSPs or the motoneuron membrane time constant but induced a small decrement in input resistance. In the presence of baclofen, the amplitude ratio produced by a paired-pulse protocol increased significantly. This suggests that baclofen decreased the synaptic strength by inhibition of neurotransmitter release from the DLF terminals via activation of presynaptic GABAB receptors.
Relationships Between Intracellular Calcium and Afterhyperpolarizations in Neocortical Pyramidal Neurons
Authors: Abel H. J. , Lee J.C.F. , Callaway J. C. , Foehring R. C.
Published: January 2004

We examined the effects of recent discharge activity on [Ca2+]iin neocortical pyramidal cells. Our data confirm and extend the observation that there is a linear relationship between plateau [Ca2+]iand firing frequency in soma and proximal apical dendrites. The rise in [Ca2+] activates K+channels underlying the afterhyperpolarization (AHP), which consists of 2 Ca2+-dependent components: the medium AHP (mAHP) and the slow AHP (sAHP). The mAHP is blocked by apamin, indicating involvement of SK-type Ca2+-dependent K+channels. The identity of the apamin-insensitive sAHP channel is unknown. We compared the sAHP and the mAHP with regard to: 1) number and frequency of spikes versus AHP amplitude; 2) number and frequency of spikes versus [Ca2+]i; 3) IAHPversus [Ca2+]i. Our data suggest that sAHP channels require an elevation of [Ca2+]iin the cytoplasm, rather than at the membrane, consistent with a role for a cytoplasmic intermediate between Ca2+and the K+channels. The mAHP channels appear to respond to a restricted Ca2+domain.
Spatiotemporal Tuning of Motor Cortical Neurons for Hand Position and Velocity
Authors: Paninski Liam , Fellows Matthew R. , Hatsopoulos Nicholas G. , Donoghue John P.
Published: January 2004

A pursuit-tracking task (PTT) and multielectrode recordings were used to investigate the spatiotemporal encoding of hand position and velocity in primate primary motor cortex (MI). Continuous tracking of a randomly moving visual stimulus provided a broad sample of velocity and position space, reduced statistical dependencies between kinematic variables, and minimized the nonstationarities that are found in typical “step-tracking” tasks. These statistical features permitted the application of signal-processing and information-theoretic tools for the analysis of neural encoding. The multielectrode method allowed for the comparison of tuning functions among simultaneously recorded cells. During tracking, MI neurons showed heterogeneity of position and velocity coding, with markedly different temporal dynamics for each. Velocity-tuned neurons were approximately sinusoidally tuned for direction, with linear speed scaling; other cells showed sinusoidal tuning for position, with linear scaling by distance. Velocity encoding led behavior by about 100 ms for most cells, whereas position tuning was more broadly distributed, with leads and lags suggestive of both feedforward and feedback coding. Individual cells encoded velocity and position weakly, with comparable amounts of information about each. Linear regression methods confirmed that random, 2-D hand trajectories can be reconstructed from the firing of small ensembles of randomly selected neurons (3-19 cells) within the MI arm area. These findings demonstrate that MI carries information about evolving hand trajectory during visually guided pursuit tracking, including information about arm position both during and after its specification. However, the reconstruction methods used here capture only the low-frequency components of movement during the PTT. Hand motion signals appear to be represented as a distributed code in which diverse information about position and velocity is available within small regions of MI.
Response Properties of Single Neurons in the Zebra Finch Auditory Midbrain: Response Patterns, Frequency Coding, Intensity Coding, and Spike Latencies
Authors: Woolley Sarah M. N. , Casseday John H.
Published: January 2004

The avian mesencephalicus lateralis, dorsalis (MLd) is the auditory midbrain nucleus in which multiple parallel inputs from lower brain stem converge and through which most auditory information passes to reach the forebrain. Auditory processing in the MLd has not been investigated in songbirds. We studied the tuning properties of single MLd neurons in adult male zebra finches. Pure tones were used to examine tonotopy, temporal response patterns, frequency coding, intensity coding, spike latencies, and duration tuning. Most neurons had no spontaneous activity. The tonotopy of MLd is like that of other birds and mammals; characteristic frequencies (CFs) increase in a dorsal to ventral direction. Four major response patterns were found: 1) onset (49% of cells); 2) primary-like (20%); 3) sustained (19%); and 4) primary-like with notch (12%). CFs ranged between 0.9 and 6.1 kHz, matching the zebra finch hearing range and the power spectrum of song. Tuning curves were generally V-shaped, but complex curves, with multiple peaks or noncontiguous excitatory regions, were observed in 22% of cells. Rate-level functions indicated that 51% of nononset cells showed monotonic relationships between spike rate and sound level. Other cells showed low saturation or nonmonotonic responses. Spike latencies ranged from 4 to 40 ms, measured at CF. Spike latencies generally decreased with increasing sound pressure level (SPL), although paradoxical latency shifts were observed in 16% of units. For onset cells, changes in SPL produced smaller latency changes than for cells showing other response types. Results suggest that auditory midbrain neurons may be particularly suited for processing temporally complex signals with a high degree of precision.
Role of the Tectorial Membrane Revealed by Otoacoustic Emissions Recorded From Wild-Type and Transgenic TectaΔENT/ΔENT Mice
Authors: Lukashkin Andrei N. , Lukashkina Victoria A. , Legan P. Kevin , Richardson Guy P. , Russell Ian J.
Published: January 2004

Distortion product otoacoustic emissions (DPOAE) were recorded from wild-type mice and mutant TectaΔ ENT/Δ ENT mice with detached tectorial membranes (TM) under combined ketamine/xylaxine anesthesia. In TectaΔ ENT/Δ ENT mice, DPOAEs could be detected above the noise floor only when the levels of the primary tones exceeded 65 dB SPL. DPOAE amplitude decreased with increasing frequency of the primaries in TectaΔ ENT/Δ ENT mice. This was attributed to hair cell excitation via viscous coupling to the surrounding fluid and not by interaction with the TM as in the wild-type mice. Local minima and corresponding phase transitions in the DPOAE growth functions occurred at higher DPOAE levels in wild-type than in TectaΔ ENT/Δ ENT mice. In less-sensitive TectaΔ ENT/Δ ENT mice, the position of the local minima varied nonsystematically with frequency or no minima were observed. A bell-like dependence of the DPOAE amplitude on the ratio of the primaries was recorded in both wild-type and TectaΔ ENT/Δ ENT mice. However, the pattern of this dependence was different in the wild-type and TectaΔ ENT/Δ ENT mice, an indication that the bell-like shape of the DPOAE was produced by a combination of different mechanisms. A nonlinear low-frequency resonance, revealed by nonmonotonicity of the phase behavior, was seen in the wild-type but not in TectaΔ ENT/Δ ENT mice.
Hyperosmolar Solutions Selectively Block Action Potentials in Rat Myelinated Sensory Fibers: Implications for Diabetic Neuropathy
Authors: Matsuka Yoshizo , Spigelman Igor
Published: January 2004

Diabetic neuropathy is a common complication of diabetes mellitus patients. It is a wide range of abnormalities affecting proximal and distal peripheral sensory and motor nerves. Although plasma hyperosmolality is a common finding in diabetes mellitus, the effects of hyperosmolality on conduction of various sensory signal components have not been addressed in detail. Here we show that in rat dorsal root ganglion (DRG) preparations from normal rats, hyperosmolar solutions (360 mmol/kg, containing increased glucose, sucrose, NaCl, or mannitol) produce a selective block of signal propagation in myelinated sensory A-fibers. In compound action potential (CAP) recordings with suction electrodes, peak A-fiber CAP amplitude was selectively decreased (20%), while the C-fiber peak remained intact or was slightly increased. Hyperosmolar solutions had smaller effects on conduction velocity (CV) of both A- and C-fibers (approximately 5% decrease). Hyperosmolality-induced CAP changes could not be observed during recordings from isolated spinal nerves but were evident during recordings from desheathed spinal nerves. In intracellular recordings, hyperosmolar solutions produced a block of spinal nerve-evoked action potential invasion into the somata of some A-fiber neurons. Removal of extracellular calcium completely prevented the hyperosmolality-induced CAP decreases. Based on these data, we propose that the decreased CAP amplitudes recorded in human patients and in animal models of diabetes are in part due to the effects of hyperosmolality and would depend on the extracellular osmolality at the time of sensory testing. We also hypothesize that hyperosmolality may contribute to both the sensory abnormalities (paresthesias) and the chronic pain symptoms of diabetic neuropathy.
Integration of Temporal Order and Object Information in the Monkey Lateral Prefrontal Cortex
Authors: Ninokura Yoshihisa , Mushiake Hajime , Tanji Jun
Published: January 2004

Generation of information about the temporal order of events is essential for the control of memory-based behavioral tasks. We studied cellular activity in the lateral prefrontal cortex (LPFC) in two monkeys that were required to remember the temporal order in which visual objects were presented. In this report, we focus on cellular activity in response to the sequential appearance of three different objects. We identified cells that responded selectively to physical properties (color and shape) of objects (23%) in the ventral part of the LPFC and cells for which activity was selective for the numerical position (rank order) of objects (44%) in the dorsal part of the LPFC. We also identified cells for which activity was selective for both the physical properties and rank order of objects (30%). The third type of cells, distributed in the ventral LPFC, seems of importance in integrating the two categories of information, i.e., physical and temporal information about the occurrences of objects to construct sequential order information. Furthermore, we identified a distinct group of cells that exhibited selectivity for the sequence of presentation of the three objects. Our findings suggest that LPFC cells are involved in encoding temporal sequences of events when such information is required for planning forthcoming motor behavior.
Novel Form of LTD Induced by Transient, Partial Inhibition of the Na,K-Pump in Rat Hippocampal CA1 Cells
Authors: Reich Christian G. , Mason Susanne E. , Alger Bradley E.
Published: January 2004

We tested the hypothesis that transient, partial inhibition of the Na,K-pumps could produce lasting effects on synaptic efficacy in brain tissue by applying a low concentration of the ouabain analogue, dihydroouabain (DHO), to hippocampal slices for 15 min and studying the effects on field excitatory postsynaptic potentials (fEPSPs). DHO caused a suppression of fEPSPs during the application period, but this recovered only partially, to ∼80% of control levels, after washout lasting as long as 2 h. The lasting suppression had several properties in common with low-frequency stimulation induced long-term depression (LFS-LTD), including an ability to depotentiate long-term potentiated responses. However, DHO-LTD was insensitive to blockade of N-methyl-d-aspartate or mGlu receptors or to inhibitors of protein kinase C or p38 MAP kinase. DHO-LTD did not co-occlude with LFS-LTD and therefore appears to represent a novel form of LTD. Interestingly, DHO-LTD could be prevented by pretreating slices with iberiotoxin, the selective blocker of large, Ca2+-dependent K+channels (“big K,” BK channels), although this toxin did not affect basal fEPSPs. Certain pathological conditions, including hypoxia and ischemia, are associated with a decrease in Na,K-pump activity and hence DHO-LTD may serve as a model for the effects on neuronal function in these conditions.
Microstimulation of the Frontal Eye Field and Its Effects on Covert Spatial Attention
Authors: Moore Tirin , Fallah Mazyar
Published: January 2004

Many studies have established that the strength of visual perception and the strength of visual representations within visual cortex vary according to the focus of covert spatial attention. While it is clear that attention can modulate visual signals, the source of this modulation remains unknown. We have examined the possibility that saccade related mechanisms provide a source of spatial attention by studying the effects of electrical microstimulation of the frontal eye fields (FEF) on spatial attention. Monkeys performed a task in which they had to detect luminance changes of a peripheral target while ignoring a flashing distracter. The target luminance change could be preceded by stimulation of the FEF at current levels below that which evoked saccadic eye movements. We found that when the target change was preceded by stimulation of FEF, the monkey could detect smaller changes in target luminance. The increased sensitivity to the target change only occurred when the target was placed in the part of the visual field represented by neurons at the stimulation site. The magnitude of improvement depended on the temporal asynchrony of the stimulation onset and the target event. No significant effect of stimulation was observed when long intervals (>300 ms) between stimulation and the target event were used, and the magnitude of the increased sensitivity decreased systematically with increasing asynchrony. At the shortest asynchrony, FEF stimulation temporally overlapped the target event and the magnitude of the improvement was comparable to that of removing the distracter from the task. These results demonstrate that transient, but potent improvements in the deployment of covert spatial attention can be obtained by microstimulation of FEF sites from which saccadic eye movements are also evoked.
Long-Lasting Activation of Rhythmic Neuronal Activity by a Novel Mechanosensory System in the Crustacean Stomatogastric Nervous System
Authors: Beenhakker Mark P. , Blitz Dawn M. , Nusbaum Michael P.
Published: January 2004

Sensory neurons enable neural circuits to generate behaviors appropriate for the current environmental situation. Here, we characterize the actions of a population (about 60) of bilaterally symmetric bipolar neurons identified within the inner wall of the cardiac gutter, a foregut structure in the crab Cancer borealis. These neurons, called the ventral cardiac neurons (VCNs), project their axons through the crab stomatogastric nervous system to influence neural circuits associated with feeding. Brief pressure application to the cardiac gutter transiently modulated the filtering motor pattern (pyloric rhythm) generated by the pyloric circuit within the stomatogastric ganglion (STG). This modulation included an increased speed of the pyloric rhythm and a concomitant decrease in the activity of the lateral pyloric neuron. Furthermore, 2 min of rhythmic pressure application to the cardiac gutter elicited a chewing motor pattern (gastric mill rhythm) generated by the gastric mill circuit in the STG that persisted for ≤30 min. These sensory actions on the pyloric and gastric mill circuits were mimicked by either ventral cardiac nerve or dorsal posterior esophageal nerve stimulation. VCN actions on the STG circuits required the activation of projection neurons in the commissural ganglia. A subset of the VCN actions on these projection neurons appeared to be direct and cholinergic. We propose that the VCN neurons are mechanoreceptors that are activated when food stored in the foregut applies an outward force, leading to the long-lasting activation of projection neurons required to initiate chewing and modify the filtering of chewed food.
Dual Sensory-Motor Function for a Molluskan Statocyst Network
Authors: Levi R. , Varona P. , Arshavsky Y. I. , Rabinovich M. I. , Selverston A. I.
Published: January 2004

In mollusks, statocyst receptor cells (SRCs) interact with each other forming a neural network; their activity is determined by both the animal's orientation in the gravitational field and multimodal inputs. These two facts suggest that the function of the statocysts is not limited to sensing the animal's orientation. We studied the role of the statocysts in the organization of search motion during hunting behavior in the marine mollusk, Clione limacina. When hunting, Clione swims along a complex trajectory including numerous twists and turns confined within a definite space. Search-like behavior could be evoked pharmacologically by physostigmine; application of physostigmine to the isolated CNS produced “fictive search behavior” monitored by recordings from wing and tail nerves. Both in behavioral and in vitro experiments, we found that the statocysts are necessary for search behavior. The motor program typical of searching could not be produced after removing the statocysts. Simultaneous recordings from single SRCs and motor nerves showed that there was a correlation between the SRCs activity and search episodes. This correlation occurred even though the preparation was fixed and, therefore the sensory stimulus was constant. The excitation of individual SRCs could in some cases precede the beginning of search episodes. A biologically based model showed that, theoretically, the hunting search motor program could be generated by the statocyst receptor network due to its intrinsic dynamics. The results presented support for the idea that the statocysts are actively involved in the production of the motor program underlying search movements during hunting behavior.
Telencephalic Input to the Pretectum of Pigeons: An Electrophysiological and Pharmacological Inactivation Study
Authors: Crowder Nathan A. , Dickson Clayton T. , Wylie Douglas R.W.
Published: January 2004

The pretectal nucleus lentiformis mesencephali (LM) and the nucleus of the basal optic root (nBOR) of the avian accessory optic system (AOS) are retinal-recipient visual nuclei involved in the analysis of optic flow that results from self-motion, and in the generation of the optokinetic response. Neurons in these nuclei show direction selectivity in response to large-field motion and are tuned in the spatiotemporal domain. In addition to retinal afferentation, both the nBOR and LM receive afferents from the Wulst, which is thought to be the avian homolog of the primary visual cortex. We examined the effects of Wulst electrical stimulation on the activity of LM neurons and recorded the directional and spatiotemporal tuning of LM neurons in pigeons before, during, and after the Wulst was temporarily inactivated by lidocaine injection. In response to Wulst electrical stimulation, LM neurons showed either short-latency excitation followed by longer-latency inhibition (W+ cells), or only a longer-latency inhibition (W– cells). The average response latencies for W+ and W– cells were 13.5 and 28.3 ms, respectively. The effects of Wulst stimulation did not correlate with either the directional or spatiotemporal tuning of the LM neurons. Injection of lidocaine into the nBOR reduced the longer-latency oscillations of W+ and W– cells. When the Wulst was temporarily inactivated by lidocaine neither the directional nor spatiotemporal response properties of LM neurons were affected. The possible functions of the projection from the Wulst to the LM are discussed.