Biomedical subjects

John Rinzel

Publications and source records attributed to John Rinzel.

12 recordsLinked to original sources

PubMed2005

Modeling spontaneous activity in the developing spinal cord using activity-dependent variations of intracellular chloride.

We investigated how spontaneous activity is generated in developing, hyperexcitable networks. We focused our study on the embryonic chick spinal cord, a preparation that exhibits rhythmic discharge on multiple timescales: slow episodes (lasting minutes) and faster intraepisode cycling (approximately 1 Hz frequency). For this purpose, we developed a mean field model of a recurrent network with slow chloride dynamics and a fast depression variable. We showed that the model, in addition to providing a biophysical mechanism for the slow dynamics, was able to account for the experimentally observed activity. The model made predictions on how interval and duration of episodes are affected when changing chloride-mediated synaptic transmission or chloride flux across cell membrane. These predictions guided experiments, and the model results were compared with experimental data obtained with electrophysiological recordings. We found agreement when transmission was affected through changes in synaptic conductance and good qualitative agreement when chloride flux was varied through changes in external chloride concentration or in the rate of the Na+-K+-2Cl- cotransporter. Furthermore, the model made predictions about the time course of intracellular chloride concentration and chloride reversal potential and how these are affected by changes in synaptic conductance. Based on the comparison between modeling and experimental results, we propose that chloride dynamics could be an important mechanism in rhythm generation in the developing chick spinal cord.

2-Amino-5-phosphonovalerate↗

PubMed2005

Background-activity-dependent properties of a network model for working memory that incorporates cellular bistability.

In models of working memory, transient stimuli are encoded by feature-selective persistent neural activity. Network models of working memory are also implicitly bistable. In the absence of a brief stimulus, only spontaneous, low-level, and presumably nonpatterned neural activity is seen. In many working-memory models, local recurrent excitation combined with long-range inhibition (Mexican hat coupling) can result in a network-induced, spatially localized persistent activity or "bump state" that coexists with a stable uniform state. There is now renewed interest in the concept that individual neurons might have some intrinsic ability to sustain persistent activity without recurrent network interactions. A recent visuospatial working-memory model (Camperi and Wang 1998) incorporates both intrinsic bistability of individual neurons within a firing rate network model and a single population of neurons on a ring with lateral inhibitory coupling. We have explored this model in more detail and have characterized the response properties with changes in background synaptic input I(o) and stimulus width. We find that only a small range of I(o) yields a working-memory-like coexistence of bump and uniform solutions that are both stable. There is a rather larger range where only the bump solution is stable that might correspond instead to a feature-selective long-term memory. Such a network therefore requires careful tuning to exhibit working-memory-like function. Interestingly, where bumps and uniform stable states coexist, we find a continuous family of stable bumps representing stimulus width. Thus, in the range of parameters corresponding to working memory, the model is capable of capturing a two-parameter family of stimulus features including both orientation and width.

Action Potentials↗

PubMed2005

Electrical coupling induces bistability of rhythms in networks of inhibitory spiking neurons.

Information processing in higher brain structures is thought to rely on the synchronization of spiking neurons. Increasing evidence indicates that, within these structures, inhibitory neurons are linked by both chemical and electrical synapses. However, how synchronized states may emerge from such circuits is not fully understood. Using snail neurons interconnected through a dynamic-clamp system, we show that networks of spiking neurons linked by both reciprocal inhibition and electrical coupling can express two coexisting coordination patterns of different rhythms. One of these patterns consists of antiphase firing of the network partners whereas, in the other, neurons fire synchronously. Switching between patterns may be evoked immediately by transient stimuli, demonstrating bistability of the network. Thus electrical coupling can provide a potent way for instantaneous reconfiguration of activity patterns in inhibitory spiking networks without alteration of intrinsic network properties by modulatory processes.

Algorithms↗

PubMed2004

Sodium along with low-threshold potassium currents enhance coincidence detection of subthreshold noisy signals in MSO neurons.

Voltage-dependent membrane conductances support specific neurophysiological properties. To investigate the mechanisms of coincidence detection, we activated gerbil medial superior olivary (MSO) neurons with dynamic current-clamp stimuli in vitro. Spike-triggered reverse-correlation analysis for injected current was used to evaluate the integration of subthreshold noisy signals. Consistent with previous reports, the partial blockade of low-threshold potassium channels (I(KLT)) reduced coincidence detection by slowing the rise of current needed on average to evoke a spike. However, two factors point toward the involvement of a second mechanism. First, the reverse correlation currents revealed that spike generation was associated with a preceding hyperpolarization. Second, rebound action potentials are 45% larger compared to depolarization-evoked spikes in the presence of an I(KLT) antagonist. These observations suggest that the sodium current (I(Na)) was substantially inactivated at rest. To test this idea, I(Na) was enhanced by increasing extracellular sodium concentration. This manipulation reduced coincidence detection, as reflected by slower spike-triggering current, and diminished the hyperpolarization phase in the reverse-correlation currents. As expected, a small outward bias current decreased the pre-spike hyperpolarization phase, and TTX blockade of I(Na) nearly eliminated the hyperpolarization phase in the reverse correlation current. A computer model including Hodgkin-Huxley type conductances for spike generation and for I(KLT) showed reduction in coincidence detection when I(KLT) was reduced or when I(Na) was increased. We hypothesize that desirable synaptic signals first remove some inactivation of I(Na) and reduce activation of I(KLT) to create a brief temporal window for coincidence detection of subthreshold noisy signals.

Action Potentials↗

PubMed2003

Subthreshold outward currents enhance temporal integration in auditory neurons.

Many auditory neurons possess low-threshold potassium currents ( I(KLT)) that enhance their responsiveness to rapid and coincident inputs. We present recordings from gerbil medial superior olivary (MSO) neurons in vitro and modeling results that illustrate how I(KLT) improves the detection of brief signals, of weak signals in noise, and of the coincidence of signals (as needed for sound localization). We quantify the enhancing effect of I(KLT) on temporal processing with several measures: signal-to-noise ratio (SNR), reverse correlation or spike-triggered averaging of input currents, and interaural time difference (ITD) tuning curves. To characterize how I(KLT), which activates below spike threshold, influences a neuron's voltage rise toward threshold, i.e., how it filters the inputs, we focus first on the response to weak and noisy signals. Cells and models were stimulated with a computer-generated steady barrage of random inputs, mimicking weak synaptic conductance transients (the "noise"), together with a larger but still subthreshold postsynaptic conductance, EPSG (the "signal"). Reduction of I(KLT) decreased the SNR, mainly due to an increase in spontaneous firing (more "false positive"). The spike-triggered reverse correlation indicated that I(KLT) shortened the integration time for spike generation. I(KLT) also heightened the model's timing selectivity for coincidence detection of simulated binaural inputs. Further, ITD tuning is shifted in favor of a slope code rather than a place code by precise and rapid inhibition onto MSO cells (Brand et al. 2002). In several ways, low-threshold outward currents are seen to shape integration of weak and strong signals in auditory neurons.

Animals↗

PubMed2003

Auditory system.

Explore the source record for details and available documents.

Animals↗

PubMed2003

Short duty cycle destabilizes a half-center oscillator, but gap junctions can restabilize the anti-phase pattern.

Mutually inhibitory pacemaker neurons with duty cycle close to 50% operate as a half-center oscillator (anti-phase coordination, i.e., 180 degrees out of phase), even in the presence of weak to modest gap junctional coupling. For electrical coupling strength above a critical value synchronization occurs. But, as shown here with modeling studies, the effects of electrical coupling depend critically on a cell's duty cycle. Instead of oscillating either in-phase or anti-phase, model cells with short duty cycle express additional rhythmic patterns, and different transitions between them, depending on electrical coupling strength. For weak or no electrical coupling, cells do not oscillate in anti-phase but instead exhibit almost in-phase activity. Strengthening this weak coupling leads to stable anti-phase activity. With yet stronger electrical coupling stable inphase (synchrony) emerges but it coexists with the anti-phase pattern. Thus the network shows bistability for an intermediate range of coupling strength. For sufficiently strong electrical coupling synchrony is the network's only attracting rhythmic state. Our results, numerical and analytical (phase plane analysis), are based on a minimal but biophysically motivated pacemaker model for the slowly oscillating envelope of bursting neurons. However, illustrations for an Hodgkin-Huxley model suggest that some of our results for short duty cycle may extend to patterning of repetitive spikes. In particular, electrical coupling of intermediate strength may promote anti-phase activity and provide bistability of anti-phase and in-phase spiking.

Biological Clocks↗

PubMed2003

Influence of subthreshold nonlinearities on signal-to-noise ratio and timing precision for small signals in neurons: minimal model analysis.

Subthreshold voltage- and time-dependent conductances can subserve different roles in signal integration and action potential generation. Here, we use minimal models to demonstrate how a non-inactivating low-threshold outward current (I(KLT)) can enhance the precision of small-signal integration. Our integrate-and-fire models have only a few biophysical parameters, enabling a parametric study of I(KLT) effects. I(KLT) increases the signal-to-noise ratio (SNR) for firing when a subthreshold 'signal' EPSP is delivered in the presence of weak random input. The increased SNR is due to the suppression of spontaneous firings to random input. In accordance, SNR grows as the EPSP amplitude increases. SNR also grows as the unitary synaptic current's time constant increases, leading to more effective suppression of spontaneous activity. Spike-triggered reverse correlation of the injected current indicates that, to reach spike threshold, a cell with I(KLT) requires a briefer time course of injected current. Consistent with this narrowed integration time window, I(KI.T) enhances phase-locking. measured as vector strength, to a weak noisy and periodically modulated stimulus. Thus subthreshold negative feedback mediated by I(KLT) enhances temporal processing. An alternative suppression mechanism is voltage- and time-dependent inactivation of a low-threshold inward current. This feature in an integrate-and-fire model also shows SNR enhancement, in comparison with a case when the inward current is non-inactivating. Small-signal detection can be significantly improved in noisy neuronal systems by subthreshold negative feedback, serving to suppress false positives.

Analysis of Variance↗

PubMed2002

Enhancement of signal-to-noise ratio and phase locking for small inputs by a low-threshold outward current in auditory neurons.

Neurons possess multiple voltage-dependent conductances specific for their function. To investigate how low-threshold outward currents improve the detection of small signals in a noisy background, we recorded from gerbil medial superior olivary (MSO) neurons in vitro. MSO neurons responded phasically, with a single spike to a step current injection. When bathed in dendrotoxin (DTX), most cells switched to tonic firing, suggesting that low-threshold potassium currents (I(KLT)) participated in shaping these phasic responses. Neurons were stimulated with a computer-generated steady barrage of random inputs, mimicking weak synaptic conductance transients (the "noise"), together with a larger but still subthreshold postsynaptic conductance, EPSG (the "signal"). DTX reduced the signal-to-noise ratio (SNR), defined as the ratio of probability to fire in response to the EPSG and the probability to fire spontaneously in response to noise. The reduction was mainly attributable to the increase of spontaneous firing in DTX. The spike-triggered reverse correlation indicated that, for spike generation, the neuron with I(KLT) required faster inward current transients. This narrow temporal integration window contributed to superior phase locking of firing to periodic stimuli before application of DTX. A computer model including Hodgkin-Huxley type conductances for spike generation and for I(KLT) (Rathouz and Trussell, 1998) showed similar response statistics. The dynamic low-threshold outward current increased SNR and the temporal precision of integration of weak subthreshold signals in auditory neurons by suppressing false positives.

Animals↗

PubMed2002

Thalamocortical bursts trigger recurrent activity in neocortical networks: layer 4 as a frequency-dependent gate.

Sensory information reaches the cortex via thalamocortical (TC) synapses in layer 4. Thalamic relay neurons that mediate information flow to cortex operate in two distinct modes, tonic and burst firing. Burst firing has been implicated in enhancing reliability of information flow between individual neurons. However, little is known about how local networks of neocortical neurons respond to different temporal patterns of TC activity. We studied cortical activity patterns evoked by stimulating TC afferents at different frequencies, using a combination of electrophysiology and calcium imaging in TC slices that allowed for the reconstruction of spatiotemporal activity with single-cell resolution. Stimulation of TC axons at low frequencies triggered action potentials in only a small number of layer 4 neurons. In contrast, brief high-frequency stimulus trains triggered widespread recurrent activity in populations of neurons in layer 4 and then spread into adjacent layers 2/3 and 5. Recurrent activity had a clear threshold, typically lasted 300 msec, and could be evoked repetitively at frequencies up to 0.5 Hz. Moreover, the spatial extent of recurrent activity was controlled by the TC pattern of activity. Recurrent activity triggered within the highly interconnected networks of layer 4 might act to selectively amplify and redistribute transient high-frequency TC inputs, filter out low-frequency inputs, and temporarily preserve a record of past sensory activity.

Action Potentials↗

PubMed2002

Adaptation and inhibition underlie responses to time-varying interaural phase cues in a model of inferior colliculus neurons.

A mathematical model was developed for exploring the sensitivity of low-frequency inferior colliculus (IC) neurons to interaural phase disparity (IPD). The formulation involves a firing-rate-type model that does not include spikes per se. The model IC neuron receives IPD-tuned excitatory and inhibitory inputs (viewed as the output of a collection of cells in the medial superior olive). The model cell possesses cellular properties of firing rate adaptation and postinhibitory rebound (PIR). The descriptions of these mechanisms are biophysically reasonable, but only semi-quantitative. We seek to explain within a minimal model the experimentally observed mismatch between responses to IPD stimuli delivered dynamically and those delivered statically (McAlpine et al. 2000; Spitzer and Semple 1993). The model reproduces many features of the responses to static IPD presentations, binaural beat, and partial range sweep stimuli. These features include differences in responses to a stimulus presented in static or dynamic context: sharper tuning and phase shifts in response to binaural beats, and hysteresis and "rise-from-nowhere" in response to partial range sweeps. Our results suggest that dynamic response features are due to the structure of inputs and the presence of firing rate adaptation and PIR mechanism in IC cells, but do not depend on a specific biophysical mechanism. We demonstrate how the model's various components contribute to shaping the observed phenomena. For example, adaptation, PIR, and transmission delay shape phase advances and delays in responses to binaural beats, adaptation and PIR shape hysteresis in different ranges of IPD, and tuned inhibition underlies asymmetry in dynamic tuning properties. We also suggest experiments to test our modeling predictions: in vitro simulation of the binaural beat (phase advance at low beat frequencies, its dependence on firing rate), in vivo partial range sweep experiments (dependence of the hysteresis curve on parameters), and inhibition blocking experiments (to study inhibitory tuning properties by observation of phase shifts).

Acoustic Stimulation↗

PubMedDate not supplied

Dynamics of spiking neurons connected by both inhibitory and electrical coupling.

We study the dynamics of a pair of intrinsically oscillating leaky integrate-and-fire neurons (identical and noise-free) connected by combinations of electrical and inhibitory coupling. We use the theory of weakly coupled oscillators to examine how synchronization patterns are influenced by cellular properties (intrinsic frequency and the strength of spikes) and coupling parameters (speed of synapses and coupling strengths). We find that, when inhibitory synapses are fast and the electrotonic effect of the suprathreshold portion of the spike is large, increasing the strength of weak electrical coupling promotes synchrony. Conversely, when inhibitory synapses are slow and the electrotonic effect of the suprathreshold portion of the spike is small, increasing the strength of weak electrical coupling promotes antisynchrony (see Fig. 10). Furthermore, our results indicate that, given a fixed total coupling strength, either electrical coupling alone or inhibition alone is better at enhancing neural synchrony than a combination of electrical and inhibitory coupling. We also show that these results extend to moderate coupling strengths.

Action Potentials↗