Biomedical subjects

Steve M Potter

Publications and source records attributed to Steve M Potter.

8 recordsLinked to original sources

PubMed2006

Searching for plasticity in dissociated cortical cultures on multi-electrode arrays.

We attempted to induce functional plasticity in dense cultures of cortical cells using stimulation through extracellular electrodes embedded in the culture dish substrate (multi-electrode arrays, or MEAs). We looked for plasticity expressed in changes in spontaneous burst patterns, and in array-wide response patterns to electrical stimuli, following several induction protocols related to those used in the literature, as well as some novel ones. Experiments were performed with spontaneous culture-wide bursting suppressed by either distributed electrical stimulation or by elevated extracellular magnesium concentrations as well as with spontaneous bursting untreated. Changes concomitant with induction were no larger in magnitude than changes that occurred spontaneously, except in one novel protocol in which spontaneous bursts were quieted using elevated extracellular magnesium concentrations.

Animals↗

PubMed2006

Persistent dynamic attractors in activity patterns of cultured neuronal networks.

Three remarkable features of the nervous system--complex spatiotemporal patterns, oscillations, and persistent activity--are fundamental to such diverse functions as stereotypical motor behavior, working memory, and awareness. Here we report that cultured cortical networks spontaneously generate a hierarchical structure of periodic activity with a strongly stereotyped population-wide spatiotemporal structure demonstrating all three fundamental properties in a recurring pattern. During these "superbursts," the firing sequence of the culture periodically converges to a dynamic attractor orbit. Precursors of oscillations and persistent activity have previously been reported as intrinsic properties of the neurons. However, complex spatiotemporal patterns that are coordinated in a large population of neurons and persist over several hours--and thus are capable of representing and preserving information--cannot be explained by known oscillatory properties of isolated neurons. Instead, the complexity of the observed spatiotemporal patterns implies large-scale self-organization of neurons interacting in a precise temporal order even in vitro, in cultures usually considered to have random connectivity.

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PubMed2006

An extremely rich repertoire of bursting patterns during the development of cortical cultures.

BACKGROUND: We have collected a comprehensive set of multi-unit data on dissociated cortical cultures. Previous studies of the development of the electrical activity of dissociated cultures of cortical neurons each focused on limited aspects of its dynamics, and were often based on small numbers of observed cultures. We followed 58 cultures of different densities--3000 to 50,000 neurons on areas of 30 to 75 mm2--growing on multi-electrode arrays (MEAs) during the first five weeks of their development. RESULTS: Plating density had a profound effect on development. While the aggregate spike detection rate scaled linearly with density, as expected from the number of cells in proximity to electrodes, dense cultures started to exhibit bursting behavior earlier in development than sparser cultures. Analysis of responses to electrical stimulation suggests that axonal outgrowth likewise occurred faster in dense cultures. After two weeks, the network activity was dominated by population bursts in most cultures. In contrast to previous reports, development continued with changing burst patterns throughout the observation period. Burst patterns were extremely varied, with inter-burst intervals between 1 and 300 s, different amounts of temporal clustering of bursts, and different firing rate profiles during bursts. During certain stages of development bursts were organized into tight clusters with highly conserved internal structure. CONCLUSION: Dissociated cultures of cortical cells exhibited a much richer repertoire of activity patterns than previously reported. Except for the very sparsest cultures, all cultures exhibited globally synchronized bursts, but bursting patterns changed over the course of development, and varied considerably between preparations. This emphasizes the importance of using multiple preparations--not just multiple cultures from one preparation--in any study involving neuronal cultures. These results are based on 963 half-hour-long recordings. To encourage further investigation of the rich range of behaviors exhibited by cortical cells in vitro, we are making the data available to other researchers, together with Matlab code to facilitate access.

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PubMed2005

Controlling bursting in cortical cultures with closed-loop multi-electrode stimulation.

One of the major modes of activity of high-density cultures of dissociated neurons is globally synchronized bursting. Unlike in vivo, neuronal ensembles in culture maintain activity patterns dominated by global bursts for the lifetime of the culture (up to 2 years). We hypothesize that persistence of bursting is caused by a lack of input from other brain areas. To study this hypothesis, we grew small but dense monolayer cultures of cortical neurons and glia from rat embryos on multi-electrode arrays and used electrical stimulation to substitute for afferents. We quantified the burstiness of the firing of the cultures in spontaneous activity and during several stimulation protocols. Although slow stimulation through individual electrodes increased burstiness as a result of burst entrainment, rapid stimulation reduced burstiness. Distributing stimuli across several electrodes, as well as continuously fine-tuning stimulus strength with closed-loop feedback, greatly enhanced burst control. We conclude that externally applied electrical stimulation can substitute for natural inputs to cortical neuronal ensembles in transforming burst-dominated activity to dispersed spiking, more reminiscent of the awake cortex in vivo. This nonpharmacological method of controlling bursts will be a critical tool for exploring the information processing capacities of neuronal ensembles in vitro and has potential applications for the treatment of epilepsy.

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PubMed2005

Effects of random external background stimulation on network synaptic stability after tetanization: a modeling study.

We constructed a simulated spiking neural network model to investigate the effects of random background stimulation on the dynamics of network activity patterns and tetanus induced network plasticity. The simulated model was a "leaky integrate-and-fire" (LIF) neural model with spike-timing-dependent plasticity (STDP) and frequency-dependent synaptic depression. Spontaneous and evoked activity patterns were compared with those of living neuronal networks cultured on multi-electrode arrays. To help visualize activity patterns and plasticity in our simulated model, we introduced new population measures called Center of Activity (CA) and Center of Weights (CW) to describe the spatio-temporal dynamics of network-wide firing activity and network-wide synaptic strength, respectively. Without random background stimulation, the network synaptic weights were unstable and often drifted after tetanization. In contrast, with random background stimulation, the network synaptic weights remained close to their values immediately after tetanization. The simulation suggests that the effects of tetanization on network synaptic weights were difficult to control because of ongoing synchronized spontaneous bursts of action potentials, or "barrages." Random background stimulation helped maintain network synaptic stability after tetanization by reducing the number and thus the influence of spontaneous barrages. We used our simulated network to model the interaction between ongoing neural activity, external stimulation and plasticity, and to guide our choice of sensory-motor mappings for adaptive behavior in hybrid neural-robotic systems or "hybrots."

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PubMed2004

Effective parameters for stimulation of dissociated cultures using multi-electrode arrays.

Electrical stimulation through multi-electrode arrays is used to evoke activity in dissociated cultures of cortical neurons. We study the efficacies of a variety of pulse shapes under voltage control as well as current control, and determine useful parameter ranges that optimize efficacy while preventing damage through electrochemistry. For any pulse shape, stimulation is found to be mediated by negative currents. We find that positive-then-negative biphasic voltage-controlled pulses are more effective than any of the other pulse shapes tested, when compared at the same peak voltage. These results suggest that voltage-control, with its inherent control over limiting electrochemistry, may be advantageous in a wide variety of stimulation scenarios, possibly extending to in-vivo experiments.

2-Amino-5-phosphonovalerate↗

PubMed2004

A versatile all-channel stimulator for electrode arrays, with real-time control.

Over the last few decades, technology to record through ever increasing numbers of electrodes has become available to electrophysiologists. For the study of distributed neural processing, however, the ability to stimulate through equal numbers of electrodes, and thus to attain bidirectional communication, is of paramount importance. Here, we present a stimulation system for multi-electrode arrays which interfaces with existing commercial recording hardware, and allows stimulation through any electrode in the array, with rapid switching between channels. The system is controlled through real-time Linux, making it extremely flexible: stimulation sequences can be constructed on-the-fly, and arbitrary stimulus waveforms can be used if desired. A key feature of this design is that it can be readily and inexpensively reproduced in other labs, since it interfaces to standard PC parallel ports and uses only off-the-shelf components. Moreover, adaptation for use with in vivo multi-electrode probes would be straightforward. In combination with our freely available data-acquisition software, MeaBench, this system can provide feedback stimulation in response to recorded action potentials within 15 ms.

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PubMed2002

Real-time multi-channel stimulus artifact suppression by local curve fitting.

We describe an algorithm for suppression of stimulation artifacts in extracellular micro-electrode array (MEA) recordings. A model of the artifact based on locally fitted cubic polynomials is subtracted from the recording, yielding a flat baseline amenable to spike detection by voltage thresholding. The algorithm, SALPA, reduces the period after stimulation during which action potentials cannot be detected by an order of magnitude, to less than 2 ms. Our implementation is fast enough to process 60-channel data sampled at 25 kHz in real-time on an inexpensive desktop PC. It performs well on a wide range of artifact shapes without re-tuning any parameters, because it accounts for amplifier saturation explicitly and uses a statistic to verify successful artifact suppression immediately after the amplifiers become operational. We demonstrate the algorithm's effectiveness on recordings from dense monolayer cultures of cortical neurons obtained from rat embryos. SALPA opens up a previously inaccessible window for studying transient neural oscillations and precisely timed dynamics in short-latency responses to electric stimulation.

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