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Variations in the ensemble of potassium currents underlying resonance in turtle hair cells.

1. Potassium currents were characterized in turtle cochlear hair cells by whole-cell voltage clamp during superfusion with the potassium channel antagonists, tetraethylammonium (TEA) and 4-aminopyridine (4-AP). The estimated resonant frequency, f0, was inferred from tau, the time constant of deactivation of outward current upon repolarization to -50 mV, according to the empirical relation, f0 = k1 tau-1/2 + k2. 2. Dose-response relations for TEA and 4-AP were obtained by exposing single cells to ten concentrations exponentially distributed over four orders of magnitude. Potassium current in cells tuned to low frequencies was carried by a single class of channels with an apparent affinity constant, K1, for TEA of 35.9 mM. Half-blocking concentrations of 4-AP were correlated with the time constant of deactivation and varied between 26.2 and 102 microM. In cells tuned to higher frequencies, K+ current was carried by a single class of channels with high affinity for TEA (K1 = 0.215 mM) and low affinity for 4-AP (K1 = 12.3 mM). This pharmacological profile suggests that K+ current in low frequency cells is purely voltage gated and in high frequency cells, it is gated by both Ca2+ and voltage. 3. For each current type, the voltage dependence of activation was determined from tail current amplitude at -50 mV. The purely voltage-gated current, IK(V), was found to increase e-fold in 4.0 +/- 0.3 mV (n = 3) in low frequency cells exposed to TEA (25 mM). The Ca(2+)- and voltage-gated current, IK(Ca), was more steeply voltage dependent, increasing e-fold in 1.9 mV (n = 2) in high frequency cells exposed to 4-AP (0.8 mM). 4. IK(V) was found to inactivate slowly during prolonged voltage steps (approximately 10 s). Steady-state inactivation increased with depolarization from -70 mV and was incomplete such that on average IK(v) did not fall below approximately 0.39 of its maximum value. 5. Superfusion of 4-AP (0.8 mM) reversibly depolarized a low frequency cell and eliminated steady voltage oscillations, while TEA (6 mM) had no effect. In a high frequency cell, voltage oscillations were abolished by TEA, but not by 4-AP. 6. The differential pharmacology of IK(V) and IK(Ca) was used to measure their contribution to K+ current in cells tuned to different frequencies. Both currents exhibited a frequency-dependent increase in maximum conductance. IK(V) accounted for nearly all K+ current in cells tuned to less than 60 Hz, while IK(Ca) was the dominant current in higher frequency cells. 7. Mapping resonant frequency onto epithelial position suggests an exponential relation between K+ current size and position. IK(V) appeared to be limited to the apical or low frequency portion of the basilar papilla and coincided with maximal expression of a K(+)-selective inward rectifier, IK(IR). This finding is consistent with the notion that low frequency resonance is produced by interaction of IK(V) and IK(IR) with the voltage-gated Ca2+ current, ICa, and the cell's capacitance. The ionic events underlying higher frequency resonance are dominated by the action of IK(Ca) and ICa and include a contribution from IK(IR).

4-Aminopyridine↗

Independent codes for spatial and episodic memory in hippocampal neuronal ensembles.

Hippocampal neurons were recorded under conditions in which the recording chamber was varied but its location remained unchanged versus conditions in which an identical chamber was encountered in different places. Two forms of neuronal pattern separation occurred. In the variable cue-constant place condition, the firing rates of active cells varied, often over more than an order of magnitude, whereas the location of firing remained constant. In the variable place-constant cue condition, both location and rates changed, so that population vectors for a given location in the chamber were statistically independent. These independent encoding schemes may enable simultaneous representation of spatial and episodic memory information.

Animals↗

Conserved P-loop GTPases of unknown function in bacteria: an emerging and vital ensemble in bacterial physiology.

Establishing the roles of conserved gene products in bacteria is of fundamental importance to our understanding of the core protein complement necessary to sustain cellular life. P-loop GTPases and related ATPases represent an abundant and remarkable group of proteins in bacteria that, in many cases, have evaded characterization. Here, efforts aimed at understanding the cellular function of a group of 8 conserved, poorly characterized genes encoding P-loop GTPases, era, obg, trmE, yjeQ, engA, yihA, hflX, ychF, and a related ATPase, yjeE, are reviewed in considerable detail. While concrete cellular roles remain elusive for all of these genes and considerable pleiotropy has plagued their study, experiments to date have frequently implicated the ribosome. In the case of era, obg, yjeQ, and engA, the evidence is most consistent with roles in ribosome biogenesis, though the prediction is necessarily putative. While the protein encoded in trmE clearly has a catalytic function in tRNA modification, the participation of its GTPase domain remains obscure, as do the functions of the remaining proteins. A full understanding of the cellular functions of all of these important proteins remains the goal of ongoing studies of cellular phenotype and protein biochemistry.

Bacteria↗

One sequence, four folds: transitions between an ensemble of metastable folds for the N-terminal domain of CD2.

Recombinant forms of the N-terminal domain of the cell adhesion receptor CD2 adopt a variety of olds by exchange of beta-sheets between adjacent polypeptide chains. Although these interdigitated forms are normally metastable, we have used site-directed mutagenesis to alter the kinetics of formation and relative stabilities of these states, leading to spontaneous formation of monomeric, dimeric, trimeric and tetrameric intertwined folded states. A characteristic feature of these fold-disorder-alternative fold transitions is the independence of each domain folding event, as deduced from kinetic analysis of folding data. Structures for fully interdigitated trimeric and tetrameric forms have been modelled, consistent with both the crystallographic and kinetic data. Although the biological role of these alternative folded states remains unclear, these structures form a remarkable demonstration of the fluidity of structure generated from a single polypeptide chain.

Amino Acid Sequence↗

Ensemble discharge from Golgi tendon organs of cat peroneus tertius muscle.

1. The responses of individual tendon organs of the cat peroneus tertius muscle to motor-unit contractions were recorded in anesthetized cats during experiments in which all the Ib-afferent fibers from the muscle had been prepared for recording in dorsal root filaments. This was possible because the cat peroneus tertius only contains a relatively small complement of approximately 10 tendon organs. 2. Motor units of different physiological types were tested for their effects on the whole population of tendon organs in the muscle. Effects of unfused tetanic contractions were tested under both isometric and anisometric conditions. Each motor unit activated at least one tendon organ, and each tendon organ was activated by at least one motor unit. Individual slow-type units were found to act on a single or two receptors, whereas a fast-type unit could activate up to six tendon organs. 3. In one experiment, the effects of 8 motor units on 10 tendon organs were examined. One fast-twitch, fatigue resistant (FR)-type unit acted on six tendon organs, of which four were also activated by another FR unit. The contraction of each unit, on its own, elicited a range of individual responses, from weak to strong. The discharge frequencies of individual responses displayed no clear relation with the strength of contraction, nor did they accurately represent the shape of force profiles. But when all the discharges were pooled, a fairly good correspondence appeared between variations of contractile force and variations of averaged discharge frequencies.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Neural ensemble coding in inferior temporal cortex.

1. Isolated, single-neuron extracellular potentials were recorded sequentially in area TE of the inferior temporal cortex (IT) of two macaque monkeys (n = 58 and n = 41 neurons). Data were obtained while the animals were performing a paired-associate task. The task utilized five stimuli and eight stimulus pairings (4 correct and 4 incorrect). Data were evaluated as average spike rate during experimental epochs of 100 or 400 ms. Single-unit and population characteristics were measured using a form of linear discriminant analysis and information theoretic measures. To evaluate the significance of covariance on population code measures, additional data consisting of simultaneous recordings from < or = 8 isolated neurons (n = 37) were obtained from a third macaque monkey that was passively viewing visual stimuli. 2. On average, 43% of IT neurons were activated by any of the stimuli used (60% if those inhibited also are included). Yet the neurons were rather unique in the relative magnitude of their responses to each stimulus in the test set. These results suggest that information may be represented in IT by the pattern of activity across neurons and that the representation is not sparsely coded. It is further suggested that the representation scheme may have similarities to DNA or computer codes wherein a coding element is not a local parametric descriptor. This is a departure from the V1 representation, which appears to be both local and parametric. It is also different from theories of IT representation that suggest a constructive basis set or "alphabet". From this view, determination of stimulus discrimination capacity in IT should be evaluated by measures of population activity patterns. 3. Evaluation of small groups of simultaneously recorded neurons obtained during a fixation task suggests that little information about visual stimuli is conveyed by covariance of activity in IT when a 100-ms time scale is used as in this study. This finding is consistent with a prior report, by Gochin et al., which used a 1-ms time scale and failed to find neural activity coherence or oscillations dependent on stimuli. 4. Population-stimulus-discrimination capacity measures were influenced by the number of neurons and to some extent the number and type of stimuli. 5. Information conveyed by individual neurons (mutual information) averaged 0.26 bits. The distribution of information values was unimodal and is therefore more consistent with a distributed than a local coding scheme.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Sensorimotor-correlated discharge recorded from ensembles of cerebellar Purkinje cells varies across the estrous cycle of the rat.

1. In the present study, locomotor-correlated activity of cerebellar Purkinje cells, recorded using arrays of microwires chronically implanted in adult female rats, was examined across estrous-cycle-associated fluctuations in endogenous sex steroids. Ongoing studies from this laboratory have shown that systemic and local administration of the sex steroid 17 beta-estradiol (E2) augments excitatory responses of cerebellar Purkinje cells to iontophoretically applied glutamate, recorded in vivo from anesthetized female rats. In addition, this steroid potentiated discharge correlated with limb movement. For the present study, extracellular single-unit activity was recorded from as many as 5-11 Purkinje cells simultaneously during treadmill locomotion paradigms. Motor modulation of activity was recorded across three to five consecutive estrous cycles from behaviorally identified cohorts of neurons to test the hypothesis that fluctuations in endogenous sex steroids alter motor modulation of Purkinje cell discharge. 2. Locomotor-associated discharge correlated with treadmill locomotion was increased by a mean of 47% on proestrus, when E2 levels are elevated, relative to diestrus 1. These changes in discharge rate during treadmill locomotion were of significantly greater magnitude than corresponding cyclic alterations in discharge during stationary periods. 3. Correlations with the circadian cycle were also significant, because peak levels of locomotor-associated discharge on the night of behavioral estrus, following elevations in circulating E2, were on average 67% greater than corresponding discharge recorded during the light (proestrus). 4. Alterations in the step cycle were also observed across the estrous cycle: significant decreases in the duration of the flexion phase (by 265 ms, P < 0.05) were noted on estrus compared with diestrus. 5. When recorded on estrus, Purkinje cell discharge correlated with the stance or flexion phase of the step cycle was greater in magnitude and preceded the event by an average of 130 ms, compared with values determined on diestrus. 6. On estrus, responses of Purkinje neurons to iontophoretically applied quisqualate were enhanced fourfold after administration of exogenous E2, assessed in urethan-anesthetized female rats. 7. In addition, systemic administration of E2 (30 ng iv) potentiated responses of cerebellar Purkinje cells to electrical stimulation of the forepaw by an average of 150%, recorded in anesthetized female rats. 8. These results are consistent with the hypothesis that elevations in circulating E2 are associated with enhanced discharge of cerebellar Purkinje cells in response to pharmacological or electrical stimuli or associated with locomotor behavior.

Animals↗

Two-channel polarization analyzer in the sustaining fiber-dimming fiber ensemble of crayfish visual system.

Polarization sensitivity (PS) was examined in two classes of neurons, sustaining fibers and dimming fibers, in the medulla externa (second optic neuropile) of the crayfish, Pacifasticus leniusculus. Visual responses were recorded intracellularly and extracellularly. The influence of e-vector orientation (theta) was probed in steady-state responses, with brief flashes and with a rotating polarizer. The results indicate that the entire sustaining fiber population appears to be maximally sensitive to vertically polarized light. Although the evidence is less complete for dimming fibers, they appear to be maximally inhibited by vertically polarized light and excited by horizontally polarized light. Thus the sustaining fibers and dimming fibers form a two-channel polarization analyzer that captures the main features of the polarization system established in photoreceptors and lamina monopolar cells. The available evidence suggests that this two-channel system has the same characteristics across most or all of the retinula. Lateral inhibition in sustaining fibers is differentially sensitive to theta. Inhibition is substantial at theta = 90 degrees (horizontal) and essentially absent at theta = 0 degrees. The details of the sustaining fiber polarization response closely follow features established in more peripheral neurons, including the magnitude of PS, enhanced responsiveness to a changing e-vector, and modest directionality to a changing e-vector in approximately 40% of the cells.

Animals↗

Position reconstruction from an ensemble of hippocampal place cells: contribution of theta phase coding.

Previous analysis of the firing of individual rat hippocampal place cells has shown that their firing rate increases when they enter a place field and that their phase of firing relative to the ongoing theta oscillation (7-12 Hz) varies systematically as the rat traverses the place field, a phenomenon termed the theta phase precession. To study the relative contribution of phased-coded and rate-coded information, we reconstructed the animal's position on a linear track using spikes recorded simultaneously from 38 hippocampal neurons. Two previous studies of this kind found no evidence that phase information substantially improves reconstruction accuracy. We have found that reconstruction is improved provided epochs with large, systematic errors are first excluded. With this condition, use of both phase and rate information improves the reconstruction accuracy by >43% as compared with the use of rate information alone. Furthermore, it becomes possible to predict the rat's position on a 204-cm track with very high accuracy (error of <3 cm). The best reconstructions were obtained with more than three phase divisions per theta cycle. These results strengthen the hypothesis that information in rat hippocampal place cells is encoded by the phase of theta at which cells fire.

Action Potentials↗

A tripeptidyl ensemble perspective of interactive control of growth hormone secretion.

Current investigational tools in molecular biology, biochemistry and integrative physiology have revealed an increasing array of signals that influence growth hormone (GH) secretion. The present perspective combines these factors under a simplified final-common pathway model of threefold joint control by GH-releasing hormone, GH-releasing peptide/ghrelin and somatostatin. This concept is highlighted from the viewpoint of sex steroid- and age-dependent modulation of the peptide trilogy listed above.

Aging↗

Optimizing a linear algorithm for real-time robotic control using chronic cortical ensemble recordings in monkeys.

Previous work in our laboratory has demonstrated that a simple linear model can be used to translate cortical neuronal activity into real-time motor control commands that allow a robot arm to mimic the intended hand movements of trained primates. Here, we describe the results of a comprehensive analysis of the contribution of single cortical neurons to this linear model. Key to the operation of this model was the observation that a large percentage of cortical neurons located in both frontal and parietal cortical areas are tuned for hand position. In most neurons, hand position tuning was time-dependent, varying continuously during a 1-sec period before hand movement onset. The relevance of this physiological finding was demonstrated by showing that maximum contribution of individual neurons to the linear model was only achieved when optimal parameters for the impulse response functions describing time-varying neuronal position tuning were selected. Optimal parameters included impulse response functions with 1.0- to 1.4-sec time length and 50- to 100-msec bins. Although reliable generalization and long-term predictions (60-90 min) could be achieved after 10-min training sessions, we noticed that the model performance degraded over long periods. Part of this degradation was accounted by the observation that neuronal position tuning varied significantly throughout the duration (60-90 min) of a recording session. Altogether, these results indicate that the experimental paradigm described here may be useful not only to investigate aspects of neural population coding, but it may also provide a test bed for the development of clinically useful cortical prosthetic devices aimed at restoring motor functions in severely paralyzed patients.

Action Potentials↗

A simple neural network exhibiting selective activation of neuronal ensembles: from winner-take-all to winners-share-all.

A neuroecological equation of the Lotka-Volterra type for mean firing rate is derived from the conventional membrane dynamics of a neural network with lateral inhibition and self-inhibition. Neural selection mechanisms employed by the competitive neural network receiving external inputs are studied with analytic and numerical calculations. A remarkable findings is that the strength of lateral inhibition relative to that of self-inhibition is crucial for determining the steady states of the network among three qualitatively different types of behavior. Equal strength of both types of inhibitory connections leads the network to the well-known winner-take-all behavior. If, however, the lateral inhibition is weaker than the self-inhibition, a certain number of neurons are activated in the steady states or the number of winners is in general more than one (the winners-share-all behavior). On the other hand, if the self-inhibition is weaker than the lateral one, only one neuron is activated, but the winner is not necessarily the neuron receiving the largest input. It is suggested that our simple network model provides a mathematical basis for understanding neural selection mechanisms.

Algorithms↗