bluuebunny/crossref_metadata_2025 huggingface dataset:
Saccade Adaptation in Response to Altered Arm Dynamics
Authors: Nanayakkara Thrishantha , Shadmehr Reza
Published: May 2006

The delays in sensorimotor pathways pose a formidable challenge to the implementation of stable error feedback control, and yet the intact brain has little trouble maintaining limb stability. How is this achieved? One idea is that feedback control depends not only on delayed proprioceptive feedback but also on internal models of limb dynamics. In theory, an internal model allows the brain to predict limb position. Earlier we had found that during reaching, the brain estimates hand position in real-time in a coordinate system that can be used for generating saccades. Here we tested the idea that the estimate of hand position, as expressed through saccades, depends on an internal model that adapts to dynamics of the arm. We focused on the behavior of the eyes as perturbations were applied to the unseen hand. We found that when the hand was perturbed from stable posture with a 100-ms force pulse of random direction and magnitude, a saccade was generated on average at 182 ms postpulse onset to a position that was an unbiased estimate of real-time hand position. To test whether planning of saccades depended on an internal model of arm dynamics, arm dynamics were altered either predictably or unpredictably during the postpulse period. When arm dynamics were predictable, saccade amplitudes changed to reflect the change in the arm's behavior. We suggest that proprioceptive feedback from the arm is integrated into an adaptable internal model that computes an estimate of current hand position in eye-centered coordinates.
The Effects of Digital Anesthesia on Force Control Using a Precision Grip
Authors: Monzée Joël , Lamarre Yves , Smith Allan M.
Published: May 2006

A total of 20 right-handed subjects were asked to perform a grasp-lift-and-hold task using a precision grip. The grasped object was a one-degree-of-freedom manipuladum consisting of a vertically mounted linear motor capable of generating resistive forces to simulate a range of object weights. In the initial study, seven subjects (6 women, 1 man; ages 24–56 yr) were first asked to lift and hold the object stationary for 4 s. The object presented a metal tab with two different surface textures and offered one of four resistive forces (0.5, 1.0, 1.5, and 2.0 N). The lifts were performed both with and without visual feedback. Next, the subjects were asked to perform the same grasping sequence again after ring block anesthesia of the thumb and index finger with mepivacaine. The objective was to determine the degree to which an internal model obtained through prior familiarity might compensate for the loss of cutaneous sensation. In agreement with previous studies, it was found that all subjects applied significantly greater grip force after digital anesthesia, and the coordination between grip and load forces was disrupted. It appears from these data, that the internal model alone is insufficient to completely compensate for the loss of cutaneous sensation. Moreover, the results suggest that the internal model must have either continuous tonic excitation from cutaneous receptors or at least frequent intermittent reiteration to function optimally. A subsequent study performed with 10 additional subjects (9 women, 1 man; ages 24–49 yr) indicated that with unimpaired cutaneous feedback, the grasping and lifting forces were applied together with negligible forces and torques in other directions. In contrast, after digital anesthesia, significant additional linear and torsional forces appeared, particularly in the horizontal and frontal planes. These torques were thought to arise partially from the application of excessive grip force and partially from a misalignment of the two grasping fingers. These torques were further increased by an imbalance in the pressure exerted by the two opposing fingers. Vision of the grasping hand did not significantly correct the finger misalignment after digital anesthesia. Taken together, these results suggest that mechanoreceptors in the fingertips signal the source and direction of pressure applied to the skin. The nervous system uses this information to adjust the fingers and direct the pinch forces optimally for grasping and object manipulation.
A Modified Sindbis Vector for Prolonged Gene Expression in Neurons
Authors: Jeromin Andreas , Yuan Li-Lian , Frick Andreas , Pfaffinger Paul , Johnston Daniel
Published: May 2006

Sindbis viruses have been widely used in neurobiology to express a variety of genes in cultured neurons, in cultured slices, and in vivo. They provide fast onset and high levels of expression of foreign genes, but the expression is limited to a short time window due to a shut-off of host protein synthesis. We have used a mutation in an essential gene (nsP2) of the life cycle of Sindbis, which allows the functional analysis of changes in protein expression for ≥6 days after infection. This Sindbis mutant (nsP2) was used to express enhanced green fluorescent protein (EGFP) in hippocampal neurons in culture and in vivo without any sign of toxicity, based on two-photon imaging and electrophysiology. In addition, the EGFP mutant virus can be injected in vivo to visualize spines and other details of neuronal structure. The Sindbis mutant described here provides an improved tool in neurobiology with reduced cytotoxicity and a prolonged time window of expression for novel applications in imaging and behavior. In addition, the use of this vector for the functional expression of mammalian voltage-gated ion channels in organotypic slices is demonstrated.
The Time Course of Perisaccadic Receptive Field Shifts in the Lateral Intraparietal Area of the Monkey
Authors: Kusunoki Makoto , Goldberg Michael E.
Published: May 2006

Neurons in the lateral intraparietal area of the monkey (LIP) have visual receptive fields in retinotopic coordinates when studied in a fixation task. However, in the period immediately surrounding a saccade these receptive fields often shift, so that a briefly flashed stimulus outside the receptive field will drive the neurons if the eye movement will bring the spatial location of that vanished stimulus into the receptive field. This is equivalent to a transient shift of the retinal receptive field. The process enables the monkey brain to process a stimulus in a spatially accurate manner after a saccade, even though the stimulus appeared only before the saccade. We studied the time course of this receptive field shift by flashing a task-irrelevant stimulus for 100 ms before, during, or after a saccade. The stimulus could appear in receptive field as defined by the fixation before the saccade (the current receptive field) or the receptive field as defined by the fixation after the saccade (the future receptive field). We recorded the activity of 48 visually responsive neurons in LIP of three hemispheres of two rhesus monkeys. We studied 45 neurons in the current receptive field task, in which the saccade removed the stimulus from the receptive field. Of these neurons 29/45 (64%) showed a significant decrement of response when the stimulus appeared 250 ms or less before the saccade, as compared with their activity during fixation. The average response decrement was 38% for those cells showing a significant ( P < 0.05 by t-test) decrement. We studied 39 neurons in the future receptive field task, in which the saccade brought the spatial location of a recently vanished stimulus into the receptive field. Of these 32/39 (82%) had a significant response to stimuli flashed for 100 ms in the future receptive field, even 400 ms before the saccade. Neurons never responded to stimuli moved by the saccade from a point outside the receptive field to another point outside the receptive field. Neurons did not necessarily show any saccadic suppression for stimuli moved from one part of the receptive field to another by the saccade. Stimuli flashed <250 ms before the saccade-evoked responses in both the presaccadic and the postsaccadic receptive fields, resulting in an increase in the effective receptive field size, an effect that we suggest is responsible for perisaccadic perceptual inaccuracies.
Active Dendritic Integration of Inhibitory Synaptic Inputs In Vivo
Authors: Kuo Jason J. , Lee Robert H. , Johnson Michael D. , Heckman Heather M. , Heckman C. J.
Published: May 2006

Synaptic integration in vivo often involves activation of many afferent inputs whose firing patterns modulate over time. In spinal motoneurons, sustained excitatory inputs undergo enormous enhancement due to persistent inward currents (PICs) that are generated primarily in the dendrites and are dependent on monoaminergic neuromodulatory input from the brain stem to the spinal cord. We measured the interaction between dendritic PICs and inhibition generated by tonic electrical stimulation of nerves to antagonist muscles during voltage clamp in motoneurons in the lumbar spinal cord of the cat. Separate samples of cells were obtained for two different states of monoaminergic input: standard (provided by the decerebrate preparation, which has tonic activity in monoaminergic axons) and minimal (the chloralose anesthetized preparation, which lacks tonic monoaminergic input). In the standard state, steady inhibition that increased the input conductance of the motoneurons by an average of 38% reduced the PIC by 69%. The range of this reduction, from <10% to >100%, was proportional to the magnitude of the applied inhibition. Thus nearly linear integration of synaptic inhibition may occur in these highly active dendrites. In the minimal state, PICs were much smaller, being approximately equal to inhibition-suppressed PICs in the standard state. Inhibition did not further reduce these already small PICs. Overall, these results demonstrate that inhibition from local spinal circuits can oppose the facilitation of dendritic PICs by descending monoaminergic inputs. As a result, local inhibition may also suppress active dendritic integration of excitatory inputs.
Ion Conductances in Supporting Cells Isolated From the Mouse Vomeronasal Organ
Authors: Ghiaroni Valeria , Fieni Francesca , Tirindelli Roberto , Pietra Pierangelo , Bigiani Albertino
Published: May 2006

The vomeronasal organ (VNO) is a chemosensory structure involved in the detection of pheromones in most mammals. The VNO sensory epithelium contains both neurons and supporting cells. Data suggest that vomeronasal neurons represent the pheromonal transduction sites, whereas scarce information is available on the functional properties of supporting cells. To begin to understand their role in VNO physiology, we have characterized with patch-clamp recording techniques the electrophysiological properties of supporting cells isolated from the neuroepithelium of the mouse VNO. Supporting cells were distinguished from neurons by their typical morphology and by the lack of immunoreactivity for Gγ8 and OMP, two specific markers for vomeronasal neurons. Unlike glial cells in other tissues, VNO supporting cells exhibited a depolarized resting potential (about −29 mV). A Goldman-Hodgkin-Katz analysis for resting ion permeabilities revealed indeed an unique ratio of PK: PNa: PCl= 1:0.23:1.4. Supporting cells also possessed voltage-dependent K+and Na+conductances that differed significantly in their biophysical and pharmacological properties from those expressed by VNO neurons. Thus glial membranes in the VNO can sustain significant fluxes of K+and Na+, as well as Cl−. This functional property might allow supporting cells to mop-up and redistribute the excess of KCl and NaCl that often occurs in certain pheromone-delivering fluids, like urine, and that could blunt the sensitivity of VNO neurons to pheromones. Therefore vomeronasal supporting cells could affect chemosensory transduction in the VNO by regulating the ionic strength of the pheromone-containing medium.
Convulsant and Anticonvulsant Effects on Spontaneous CA3 Population Bursts
Authors: Yee Audrey S. , Longacher J. Mark , Staley Kevin J.
Published: May 2006

This paper analyzes the effects of a convulsant and an anticonvulsant manipulation on spontaneous bursts in CA3 pyramidal cells in the in vitro slice preparation under conditions of low (3.3 mM [K+]o) and high (8.5 mM [K+]o) burst probability. When burst probability was low, the anticonvulsant, pentobarbital, produced the anticipated effects: the burst duration decreased and interburst interval increased. However, when burst probability was high, both anticonvulsant and convulsant manipulations decreased the interburst interval and the burst duration. To reconcile these findings, we utilized a model in which CA3 burst duration is limited by activity-dependent depression of CA3 excitatory recurrent collateral synapses and the interburst interval is determined by the time required to recover from this depression. We defined the burst end threshold as the level of synaptic depression at which bursts terminate, and the burst start threshold as the level of synaptic depression at which burst initiation is possible. Synapses were considered to oscillate between these thresholds. When average burst duration and interburst interval data were fit using this model, the paradoxically similar effects of the convulsant and anticonvulsant manipulations could be quantitatively interpreted. The convulsant maneuver decreased both the burst start and end thresholds. The start threshold decreased more than the end threshold, so that the thresholds were closer together. This decreased the time needed to transition from one threshold to the other, i.e., the interburst interval and burst duration. The anticonvulsant manipulation primarily increased the burst end threshold. This also decreased the difference between thresholds, decreasing both interburst interval and burst duration. This model resolves the paradoxical proconvulsant effects of pentobarbital in the CA3 preparation and provides insights into the effects of anticonvulsants on epileptiform discharges in the human EEG.
A Computational Model of Muscle Recruitment for Wrist Movements
Authors: Fagg Andrew H. , Shah Ashvin , Barto Andrew G.
Published: May 2006

To execute a movement, the CNS must appropriately select and activate the set of muscles that will produce the desired movement. This problem is particularly difficult because a variety of muscle subsets can usually be used to produce the same joint motion. The motor system is therefore faced with a motor redundancy problem that must be resolved to produce the movement. In this paper, we present a model of muscle recruitment in the wrist step-tracking task. Muscle activation levels for five muscles are selected so as to satisfy task constraints (moving to the designated target) while also minimizing a measure of the total effort in producing the movement. Imposing these constraints yields muscle activation patterns qualitatively similar to those observed experimentally. In particular, the model reproduces the observed cosine-like recruitment of muscles as a function of movement direction and also appropriately predicts that certain muscles will be recruited most strongly in movement directions that differ significantly from their direction of action. These results suggest that the observed recruitment behavior may not be an explicit strategy employed by the nervous system, but instead may result from a process of movement optimization.
Computational Diversity in the Cochlear Nucleus Angularis of the Barn Owl
Authors: Köppl Christine , Carr Catherine E.
Published: May 2006

The cochlear nucleus angularis (NA) is widely assumed to form the starting point of a brain stem pathway for processing sound intensity in birds. Details of its function are unclear, however, and its evolutionary origin and relationship to the mammalian cochlear-nucleus complex are obscure. We have carried out extracellular single-unit recordings in the NA of ketamine-anesthetized barn owls. The aim was to re-evaluate the extent of heterogeneity in NA physiology because recent studies of cellular morphology had established several distinct types. Extensive characterization, using tuning curves, phase locking, peristimulus time histograms and rate-level functions for pure tones and noise, revealed five major response types. The most common one was a primary-like pattern that was distinguished from auditory-nerve fibers by showing lower vector strengths of phase locking and/or lower spontaneous rates. Two types of chopper responses were found (chopper-transient and a rare chopper-sustained), as well as onset units. Finally, we routinely encountered a complex response type with a pronounced inhibitory component, similar to the mammalian typeIV. Evidence is presented that this range of response types is representative for birds and that earlier conflicting reports may be due to methodological differences. All five response types defined were similar to well-known types in the mammalian cochlear nucleus. This suggests convergent evolution of neurons specialized for encoding different behaviorally relevant features of the auditory stimulus. It remains to be investigated whether the different response types correlate with morphological types and whether they establish different processing streams in the auditory brain stem of birds.
On the Persistent Sodium Current in Squid Giant Axons
Authors: Clay John R.
Published: May 2006

R. F. Rakowski, D. C. Gadsby, and P. DeWeer have reported a persistent, tetrodotoxin-sensitive sodium ion current ( INaP) in squid giant axons having a low threshold (-90 mV) and a maximal inward amplitude of −4 μA/cm2at −50 mV. This report makes the case that most of INaPis attributable to an ion channel mechanism distinct from the classical rapidly activating and inactivating sodium ion current, INa, which is also tetrodotoxin sensitive. The analysis of the contribution of INato INaPis critically dependent on slow inactivation of INa. The results of this gating process reported here demonstrate that inactivation of INais complete in the steady-state for V > −40 mV, thereby making it unlikely that INaPin this potential range is attributable to INa. Moreover, −90 mV is well below INathreshold, as demonstrated by the C. A. Vandenberg and F. Bezanilla model of INagating in squid giant axons. Their model predicts a persistent current having a threshold of −60 mV and a peak amplitude of −25 μA/cm2at −20 mV. Modulation of this component by the slow inactivation process predicts a persistent current that is finite in the −60- to −40-mV range having a peak amplitude of −1μA/cm-2at −50 mV. Subtraction of this current from the INaPmeasurements yields the portion of INaPthat appears to be attributable to an ion channel mechanism distinct from INa.
Changes in Electrophysiological Properties of Lamprey Spinal Motoneurons During Fictive Swimming
Authors: Martin Michelle M.
Published: May 2006

Electrophysiological properties of lamprey spinal motoneurons were measured to determine whether their cellular properties change as the spinal cord goes from a quiescent state to the active state of fictive swimming. Intracellular microelectrode recordings of membrane potential were made from motoneurons in the isolated spinal cord preparation. Electrophysiological properties were first characterized in the quiescent spinal cord, and then fictive swimming was induced by perfusion with d-glutamate and the measurements were repeated. During the depolarizing excitatory phase of fictive swimming, the motoneurons had significantly reduced rheobase and significantly increased input resistance compared with the quiescent state, with no significant changes in these parameters during the repolarizing inhibitory phase of swimming. Spike threshold did not change significantly during fictive swimming compared with the quiescent state. During fictive swimming, the slope of the spike frequency versus injected current ( F-I) relationship decreased significantly as did spike-frequency adaptation and the amplitude of the slow after-spike hyperpolarization (sAHP). Serotonin is known to be released endogenously from the spinal cord during fictive swimming and is known to reduce the amplitude of the sAHP. Therefore the effects of serotonin on cellular properties were tested in the quiescent spinal cord. It was found that, in addition to reducing the sAHP amplitude, serotonin also reduced the slope of the F-I relationship and reduced spike-frequency adaptation, reproducing the changes observed in these parameters during fictive swimming. Application of spiperone, a serotonin antagonist, significantly increased the sAHP amplitude during fictive swimming but had no significant effect on F-I slope or adaptation. Because serotonin may act in part through reduction of calcium currents, the effect of calcium-free solution (cobalt substituted for calcium) was tested in the quiescent spinal cord. Similar to fictive swimming and serotonin application, the calcium-free solution significantly reduced the sAHP amplitude, the slope of the F-I relationship, and spike-frequency adaptation. These results suggest that there are significant changes in the firing properties of motoneurons during fictive swimming compared with the quiescent state, and it is possible that these changes may be attributed in part to the endogenous release of serotonin acting via reduction of calcium currents.
Cerebral CBm1 Neuron Contributes to Synaptic Modulation Appearing During Rejection of Seaweed inAplysia kurodai
Authors: Narusuye Kenji , Nagahama Tatsumi
Published: May 2006

The Japanese species Aplysia kurodai feeds well on Ulva but rejects Gelidium with distinctive rhythmic patterned movements of the jaws and radula. We have previously shown that the patterned jaw movements during the rejection of Gelidium might be caused by long-lasting suppression of the monosynaptic transmission from the multiaction MA neurons to the jaw-closing (JC) motor neurons in the buccal ganglia and that the modulation might be directly produced by some cerebral neurons. In the present paper, we have identified a pair of catecholaminergic neurons (CBm1) in bilateral cerebral M clusters. The CBm1, probably equivalent to CBI-1 in A. californica, simultaneously produced monosynaptic excitatory postsynaptic potentials (EPSPs) in the MA and JC neurons. Firing of the CBm1 reduced the size of the inhibitory postsynaptic currents (IPSCs) in the JC neuron, evoked by the MA spikes, for >100 s. Moreover, the application of dopamine mimicked the CBm1 modulatory effects and pretreatment with a D1 antagonist, SCH23390, blocked the modulatory effects induced by dopamine. It could also largely block the modulatory effects induced by the CBm1 firing. These results suggest that the CBm1 may directly modulate the synaptic transmission by releasing dopamine. Moreover, we explored the CBm1 spike activity induced by taste stimulation of the animal lips with seaweed extracts by the use of calcium imaging. The calcium-sensitive dye, Calcium Green-1, was iontophoretically loaded into a cell body of the CBm1 using a microelectrode. Application of either Ulva or Gelidium extract to the lips increased the fluorescence intensity, but the Gelidium extract always induced a larger change in fluorescence compared with the Ulva extract, although the solution used induced the maximum spike responses of the CBm1 for each of the seaweed extracts. When the firing frequency of the CBm1 activity after taste stimulation was estimated, the Gelidium extract induced a spike activity of ∼30 spikes/s while the Ulva extract induced an activity of ∼20 spikes/s, consistent with the effective firing frequency (>25 spikes/s) for the synaptic modulation. These results suggest that the CBm1 may be one of the cerebral neurons contributing to the modulation of the basic feeding circuits for rejection induced by the taste of seaweeds such as Gelidium.
Functional Analysis of Whole Cell Currents From Hair Cells of the Turtle Posterior Crista
Authors: Goldberg Jay M. , Brichta Alan M.
Published: May 2006

Controlled currents were used to study possible functions of voltage-sensitive, outwardly rectifying conductances. Results were interpreted with linearized Hodgkin-Huxley theory. Because of their more hyperpolarized resting potentials and lower impedances, type I hair cells require larger currents to be depolarized to a given voltage than do type II hair cells. “Fast” type II cells, so-called because of the fast activation of their outward currents, show slightly underdamped responses to current steps with resonant (best) frequencies of 40–85 Hz, well above the bandwidth of natural head movements. Reflecting their slower activation kinetics, type I and “slow” type II cells have best frequencies of 15–30 Hz and are poorly tuned, being critically damped or overdamped. Linearized theory identified the factors responsible for tuning quality. Our fast type II hair cells show only modestly underdamped responses because their steady-state I-V curves are not particularly steep. The even poorer tuning of our type I and slow type II cells can be attributed to their slow activation kinetics and large conductances. To study how ionic currents shape response dynamics, we superimposed sinusoidal currents of 0.1–100 Hz on a small depolarizing steady current intended to simulate resting conditions in vivo. The steady current resulted in a slow inactivation, most pronounced in fast type II cells and least pronounced in type I cells. Because of inactivation, fast type II cells have nearly passive response dynamics with low-frequency gains of 500–1,000 MΩ. In contrast, type I and slow type II cells show active components in the vestibular bandwidth and low-frequency gains of 20–100 and 100–500 MΩ, respectively. As there are no differences in the responses to sinusoidal currents for fast type II cells from the torus and planum, voltage-sensitive currents are unlikely to be responsible for the large differences in gains and response dynamics of afferents innervating these two regions of the peripheral zone. The low impedances and active components of type I cells may be related to the low gains and modestly phasic response dynamics of calyx-bearing afferents.
Differential Sensitization of Amygdala Neurons to Afferent Inputs in a Model of Arthritic Pain
Authors: Neugebauer Volker , Li Weidong
Published: May 2006

Pain is associated with negative affect such as anxiety and depression. The amygdala plays a key role in emotionality and has been shown to undergo neuroplastic changes in models of affective disorders. Many neurons in the central nucleus of the amygdala (CeA) are driven by nociceptive inputs, but the role of the amygdala in persistent pain states is not known. This study is the first to address nociceptive processing by CeA neurons in a model of prolonged pain. Extracellular single-unit recordings were made from 41 CeA neurons in anesthetized rats. Each neuron's responses to brief mechanical stimulation of joints, muscles, and skin and to cutaneous thermal stimuli were recorded. Background activity, receptive field size, and threshold were mapped, and stimulus-response functions were constructed. These parameters were measured repeatedly before and after induction of arthritis in one knee by intraarticular injections of kaolin and carrageenan. Multireceptive (MR) amygdala neurons ( n = 20) with excitatory input from the knee joint responded more strongly to noxious than to innocuous mechanical stimuli of deep tissue ( n = 20) and skin ( n = 11). After induction of arthritis, 18 of 20 MR neurons developed enhanced responses to mechanical stimuli and expansion of receptive field size. These changes occurred with a biphasic time course (early peak: 1–1.5 h; persistent plateau phase: after 3–4 h). Responses to thermal stimuli did not change (7 of 7 neurons), but background activity (16 of 18 neurons) and electrically evoked orthodromic activity (11 of 12 neurons) increased in the arthritic state. Nociceptive-specific (NS) neurons ( n = 13) showed no changes of their responses to mechanical, thermal, and electrical stimulation after induction of arthritis. A third group of neurons did not respond to somesthetic stimuli under control conditions (noSOM neurons; n = 8) but developed prolonged responses to mechanical, but not thermal, stimuli in arthritis (5 of 8 neurons). These data suggest that prolonged pain is accompanied by enhanced responsiveness of a subset of CeA neurons. Their sensitization to mechanical, but not thermal, stimuli argues against a nonspecific state of hyperexcitability. MR neurons could serve to integrate and evaluate information in the context of prolonged pain. Recruitment of noSOM neurons increases the gain of amygdala processing. NS neurons preserve the distinction between nociceptive and nonnociceptive inputs.
Single-Pulse Transcranial Magnetic Stimulation of Parietal and Prefrontal Areas in a Memory Delay Arm Pointing Task
Authors: Smyrnis Nikolaos , Theleritis Christos , Evdokimidis Ioannis , Müri Rene M. , Karandreas Nikos
Published: May 2006

Fifteen healthy volunteers performed a memory-pointing task using their right arm while single-pulse transcranial magnetic stimulation (TMS) above motor threshold was applied over the posterior parietal or prefrontal cortex of the left or right hemisphere in four blocks of trials. The stimulation was randomly delivered at one of three time intervals during the 3-s delay period (early: 300 ms, intermediate: 1,500 ms, late: 2,700 ms). A separate block with no stimulation was used as control. Only early left parietal stimulation resulted in an increase in the variance of movement amplitude but not direction for all targets in two-dimensional space (both hemifields). The results point to the significance of the contralateral posterior parietal cortex early on during the memorization of the target for an upcoming movement. Taking into consideration the limitations of TMS and those imposed by the particular task, the lack of specific effects of prefrontal stimulation provides evidence that these areas might not be involved in the performance of simple memorized arm movements.
Asymmetry in the Pitch Control System of the Lamprey Caused by a Unilateral Labyrinthectomy
Authors: Pavlova E. L. , Deliagina T. G.
Published: May 2006

A postural control system in the lamprey is driven by vestibular input and maintains a definite orientation of the animal during swimming. After a unilateral labyrinthectomy (UL), the lamprey continuously rolls toward the damaged side. Important elements of the postural network are the reticulospinal (RS) neurons that are driven by vestibular input and transmit commands for postural corrections to the spinal cord. We characterized the effect of UL on vestibular responses in RS neurons elicited by rotation of the animal in the pitch plane. The activity of RS neurons was recorded from their axons in the spinal cord before and after UL. The neurons can be classified into the Up and Down groups activated preferentially with nose-up or nose-down rotation, respectively. After UL, vestibular responses in the group Up changed only slightly on the damaged side and disappeared almost completely on the opposite side. In the group Down, responses on both sides persisted after UL. These results indicate that the left and right subgroups of the group Up neurons receive excitatory input mainly from the contralateral labyrinth. In contrast, the group Down neurons receive excitatory input from both labyrinths. We conclude that the UL-induced changes in vestibular responses to pitch tilt will disturb the normal activity of the postural control system. The UL-induced asymmetry in the bilateral activity of the group Up neurons seems to be an important factor contributing to the loss of equilibrium in UL animals and to their rotation during swimming.
KChIP1 and Frequenin Modify shal-Evoked Potassium Currents in Pyloric Neurons in the Lobster Stomatogastric Ganglion
Authors: Zhang Y. , MacLean J. N. , An W. F. , Lanning C. C. , Harris-Warrick R. M.
Published: May 2006

The transient potassium current ( I A) plays an important role in shaping the firing properties of pyloric neurons in the stomatogastric ganglion (STG) of the spiny lobster, Panulirus interruptus. The shal gene encodes I A in pyloric neurons. However, when we over-expressed the lobster Shal protein by shal RNA injection into the pyloric dilator (PD) neuron, the increased I A had somewhat different properties from the endogenous I A. The recently cloned K-channel interacting proteins (KChIPs) can modify vertebrate Kv4 channels in cloned cell lines. When we co-expressed hKChIP1 with lobster shal in Xenopusoocytes or lobster PD neurons, they produced A-currents resembling the endogenous I A in PD neurons; compared with currents evoked by shal alone, their voltage for half inactivation was depolarized, their kinetics of inactivation were slowed, and their recovery from inactivation was accelerated. We also co-expressed shal in PD neurons with lobster frequenin, which encodes a protein belonging to the same EF-hand family of Ca2+ sensing proteins as hKChIP. Frequenin also restored most of properties of the shal-evoked currents to those of the endogenous A-currents, but the time course of recovery from inactivation was not corrected. These results suggest that lobster shal proteins normally interact with proteins in the KChIP/frequenin family to produce the transient potassium current in pyloric neurons.
Independent Neuronal Oscillators of the Rat Globus Pallidus
Authors: Stanford I. M.
Published: May 2006

In vivo, neurons of the globus pallidus (GP) and subthalamic nucleus (STN) resonate independently around 70 Hz. However, on the loss of dopamine as in Parkinson's disease, there is a switch to a lower frequency of firing with increased bursting and synchronization of activity. In vitro, type A neurons of the GP, identified by the presence of Ih and rebound depolarizations, fire at frequencies (≤80 Hz) in response to glutamate pressure ejection, designed to mimic STN input. The profile of this frequency response was unaltered by bath application of the GABAA antagonist bicuculline (10 μM), indicating the lack of involvement of a local GABA neuronal network, while cross-correlations of neuronal pairs revealed uncorrelated activity or phase-locked activity with a variable phase delay, consistent with each GP neuron acting as an independent oscillator. This autonomy of firing appears to arise due to the presence of intrinsic voltage- and sodium-dependent subthreshold membrane oscillations. GABAA inhibitory postsynaptic potentials are able to disrupt this tonic activity while promoting a rebound depolarization and action potential firing. This rebound is able to reset the phase of the intrinsic oscillation and provides a mechanism for promoting coherent firing activity in ensembles of GP neurons that may ultimately lead to abnormal and pathological disorders of movement.
Excitatory Inputs to CA1 Interneurons Show Selective Synaptic Dynamics
Authors: Wierenga Corette J. , Wadman Wytse J.
Published: May 2006

The dynamic properties of synapses between neurons in the hippocampal CA1 area are important for the frequency-dependent signal transfer of the network. We have examined the synaptic dynamics of excitatory inputs to CA1 interneurons and pyramidal cells using whole cell voltage-clamp recordings. The CA1 network was activated using extracellular stimulation electrodes at the Schaffer collaterals (feedforward activation) or at the Alveus (activation of the feedback loop). The dynamic properties of input from the Schaffer collaterals to CA1 interneurons (basket and bistratified cells) were different from the synaptic dynamics of input from the Alveus. Synaptic input from the Schaffer collaterals to CA1 interneurons showed facilitation for most frequencies. After 10 stimuli the synaptic response reached a plateau level that was ∼150% of the first response in the train. In contrast, the plateau levels of Alveus inputs to interneurons were not different from the first responses for frequencies ≤40 Hz. Paired-pulse facilitation of Schaffer input was stronger than for Alveus input. Cells in stratum oriens with horizontal dendritic trees appeared to be a special group of interneurons because Alveus input to these cells showed strong facilitation with plateau levels of 200% of the first responses. Schaffer input to CA1 basket and bistratified cells showed similar synaptic dynamics compared with Schaffer input to pyramidal cells for frequencies ≤80 Hz. The synaptic dynamics of Schaffer and Alveus input depended only weakly on the stimulus intensity. The difference between the dynamics of Alveus and Schaffer input to CA1 interneurons implies that the relative contribution of feedforward and -back inhibition to network activity depends on the frequency of the input signal at the afferent fibers, adding a level of complexity to transient responses.
Perception of Self-Motion From Peripheral Optokinetic Stimulation Suppresses Visual Evoked Responses to Central Stimuli
Authors: Thilo Kai V. , Kleinschmidt Andreas , Gresty Michael A.
Published: May 2006

In a previous functional neuroimaging study we found that early visual areas deactivated when a rotating optical flow stimulus elicited the illusion of self-motion (vection) compared with when it was perceived as a moving object. Here, we investigated whether electrical cortical responses to an independent central visual probe stimulus change as a function of whether optical flow stimulation in the periphery induces the illusion of self-motion or not. Visual-evoked potentials (VEPs) were obtained in response to pattern-reversals in the central visual field in the presence of a constant peripheral large-field optokinetic stimulus that rotated around the naso-occipital axis and induced intermittent sensations of vection. As control, VEPs were also recorded during a stationary peripheral stimulus and showed no difference than those obtained during optokinetic stimulation. The VEPs during constant peripheral stimulation were then divided into two groups according to the time spans where the subjects reported object- or self-motion, respectively. The N70 VEP component showed a significant amplitude reduction when, due to the peripheral stimulus, subjects experienced self-motion compared to when the peripheral stimulus was perceived as object-motion. This finding supplements and corroborates our recent evidence from functional neuroimaging that early visual cortex deactivates when a visual flow stimulus elicits the illusion of self-motion compared with when the same sensory input is interpreted as object-motion. This dampened responsiveness might reflect a redistribution of sensorial and attentional resources when the monitoring of self-motion relies on a sustained and veridical processing of optic flow and may be compromised by other sources of visual input.
Both Electrical and Chemical Synapses Mediate Fast Network Oscillations in the Olfactory Bulb
Authors: Friedman Daniel , Strowbridge Ben W.
Published: May 2006

Odor perception depends on a constellation of molecular, cellular, and network interactions in olfactory brain areas. Recently, there has been better understanding of the cellular and molecular mechanisms underlying the odor responses of neurons in the olfactory epithelium, the first-order olfactory area. In higher order sensory areas, synchronized activity in networks of neurons is known to be a prominent feature of odor processing. The perception and discrimination of odorants is associated with fast (20–70 Hz) electroencephalographic oscillations. The cellular mechanisms underlying these fast network oscillations have not been defined. In this study, we show that synchronous fast oscillations can be evoked by brief electrical stimulation in the rat olfactory bulb in vitro, partially mimicking the natural response of this brain region to sensory input. Stimulation induces periodic inhibitory synaptic potentials in mitral cells and prolonged spiking in GABAergic granule cells. Repeated stimulation leads to the persistent enhancement in both granule cell activity and mitral cell inhibition. Prominent oscillations in field recordings indicate that stimulation induces high-frequency activity throughout networks of olfactory bulb neurons. Network synchronization results from chemical and electrical synaptic interactions since both glutamate-receptor antagonists and gap junction inhibitors block oscillatory intracellular and field responses. Our results demonstrate that the olfactory bulb can generate fast oscillations autonomously through the persistent activation of networks of inhibitory interneurons. These local circuit interactions may be critically involved in odor processing in vivo.
Synapse Formation Between Isolated Axons Requires Presynaptic Soma and Redistribution of Postsynaptic AChRs
Authors: Meems Ryanne , Munno David , van Minnen Jan , Syed Naweed I.
Published: May 2006

The involvement of neuronal protein synthetic machinery and extrinsic trophic factors during synapse formation is poorly understood. Here we determine the roles of these processes by reconstructing synapses between the axons severed from identified Lymnaea neurons in cell culture, either in the presence or absence of trophic factors. We demonstrate that, although synapses are maintained between isolated pre- and postsynaptic axons for several days, the presynaptic, but not the postsynaptic, cell body, however, is required for new synapse formation between soma–axon pairs. The formation of cholinergic synapses between presynaptic soma and postsynaptic axon requires gene transcription and protein synthesis solely in the presynaptic neuron. We show that this synaptogenesis is contingent on extrinsic trophic factors present in brain conditioned medium (CM). The CM-induced excitatory synapse formation is mediated through receptor tyrosine kinases. We further demonstrate that, although the postsynaptic axon does not require new protein synthesis for synapse formation, its contact with the presynaptic cell in CM, but not in defined medium (no trophic factors), differentially alters its responsiveness to exogenously applied acetylcholine at synaptic compared with extrasynaptic sites. Together, these data suggest a synergetic action of cell–cell signaling and trophic factors to bring about specific changes in both pre- and postsynaptic neurons during synapse formation.
Simulations to Derive Membrane Resistivity in Three Phenotypes of Guinea Pig Sympathetic Postganglionic Neuron
Authors: Jamieson John , Boyd Hugh D. , McLachlan Elspeth M.
Published: May 2006

The electrotonic behavior of three phenotypes of sympathetic postganglionic neuron has been analyzed to assess whether their distinct cell input capacitances simply reflect differences in morphology. Because the distribution of membrane properties over the soma and dendrites is unknown, compartmental models incorporating cell morphology were used to simulate hyperpolarizing responses to small current steps. Neurons were classified as phasic (Ph), tonic (T), or long-afterhyperpolarizing (LAH) by their discharge pattern to threshold depolarizing current steps and filled with biocytin to determine their morphology. Responses were simulated in models with the average morphology of each cell class using the program NEURON. Specific membrane resistivity, R m, was derived in each model. Fits were acceptable when specific membrane capacitance, C m, and specific resistivity of the axoplasm, R i, were varied within realistic limits and when underestimation of membrane area due to surface irregularities was accounted for. In all models with uniform R m, solutions for R m that were the same for all classes could not be found unless C m or R i were different for each class, which seems unrealistic. Incorporation of a small somatic shunt conductance yielded values for R m for each class close to those derived assuming isopotentiality ( R m approximately 40, 27, and 15 kΩcm2 for T, Ph, and LAH neurons, respectively). It is concluded that R mis distinct between neuron classes. Because Ph and LAH neurons relay selected preganglionic inputs directly, R m generally affects function only in T neurons that integrate multiple subthreshold inputs and are modulated by peptidergic transmitters.
Morphological Correlates of Intrinsic Electrical Excitability in Neurons of the Deep Cerebellar Nuclei
Authors: Aizenman Carlos D. , Huang Eric J. , Linden David J.
Published: May 2006

To what degree does neuronal morphology determine or correlate with intrinsic electrical properties within a particular class of neuron? This question has been examined using microelectrode recordings and subsequent neurobiotin filling and reconstruction of neurons in the deep cerebellar nuclei (DCN) of brain slices from young rats (P13–16). The neurons reconstructed from these recordings were mostly large and multipolar (17/21 cells) and were likely to represent glutamatergic projection neurons. Within this class, there was considerable variation in intrinsic electrical properties and cellular morphology. Remarkably, in a correlation matrix of 18 electrophysiological and 6 morphological measures, only one morphological characteristic was predictive of intrinsic excitability: neurons with more spines had a significantly slower basal firing rate. To address the possibility that neurons with fewer spines represented a slowly maturing subgroup, recordings and reconstructions were also made from neurons at a younger age (P6–9). While P6–9 neurons were morphologically indistinguishable from P13 to 16 neurons, they were considerably less excitable: P6–9 neurons had a lower spontaneous spiking rate, larger fast AHPs, higher resting membrane potentials, and smaller rebound depolarizations. Thus while the large projection neurons of the DCN are morphologically mature by P6–9, they continue to mature electrophysiologically through P13–16 in a way that renders them more responsive to the burst-and-pause pattern that characterizes Purkinje cell inhibitory synaptic drive.
The Rat Lumbosacral Spinal Cord Adapts to Robotic Loading Applied During Stance
Authors: Timoszyk W. K. , de Leon R. D. , London N. , Roy R. R. , Edgerton V. R. , Reinkensmeyer D. J.
Published: May 2006

Load-related afferent information modifies the magnitude and timing of hindlimb muscle activity during stepping in decerebrate animals and spinal cord–injured humans and animals, suggesting that the spinal cord mediates load-related locomotor responses. In this study, we found that stepping on a treadmill by adult rats that received complete, midthoracic spinal cord transections as neonates could be altered by loading the hindlimbs using a pair of small robotic arms. The robotic arms applied a downward force to the lower shanks of the hindlimbs during the stance phase and measured the position of the lower shank during stepping. No external force was applied during the swing phase of the step. When applied bilaterally, this stance force field perturbed the hindlimb trajectories so that the ankle position was shifted downward during stance. In response to this perturbation, both the stance and step cycle durations decreased. During swing, the hindlimb initially accelerated toward the normal, unperturbed swing trajectory and then tracked the normal trajectory. Bilateral loading increased the magnitude of the medial gastrocnemius electromyographic (EMG) burst during stance and increased the amplitude of the semitendinosus and rectus femoris EMG bursts. When the force field was applied unilaterally, stance duration decreased in the loaded hindlimb, while swing duration was decreased in the contralateral hindlimb, thereby preserving interlimb coordination. These results demonstrate the feasibility of using robotic devices to mechanically modulate afferent input to the injured spinal cord during weight-supported locomotion. In addition, these results indicate that the lumbosacral spinal cord responds to load-related input applied to the lower shank during stance by modifying step timing and muscle activation patterns, while preserving normal swing kinematics and interlimb coordination.