Abstract: Dissociated cortical neurons from rat embryos cultured onto micro-electrode arrays exhibit characteristic patterns of electrophysiological activity, ranging from isolated spikes in the first days of development to highly synchronized bursts after 3-4 weeks in vitro. In this work we analyzed these features by considering the approach proposed by the self-organized criticality theory: we found that networks of dissociated cortical neurons also generate spontaneous events of spreading activity, previously observed in cortical slices, in the form of neuronal avalanches. Choosing an appropriate time scale of observation to detect such neuronal avalanches, we studied the dynamics by considering the spontaneous activity during acute recordings in mature cultures and following the development of the network. We observed different behaviors, i.e. sub-critical, critical or super-critical distributions of avalanche sizes and durations, depending on both the age and the development of cultures. In order to clarify this variability, neuronal avalanches were correlated with other statistical parameters describing the global activity of the network. Criticality was found in correspondence to medium synchronization among bursts and high ratio between bursting and spiking activity. Then, the action of specific drugs affecting global bursting dynamics (i.e. acetylcholine and bicuculline) was investigated to confirm the correlation between criticality and regulated balance between synchronization and variability in the bursting activity. Finally, a computational model of neuronal network was developed in order to interpret the experimental results and understand which parameters (e.g. connectivity, excitability) influence the distribution of avalanches. In summary, cortical neurons preserve their capability to self-organize in an effective network even when dissociated and cultured in vitro. The distribution of avalanche features seems to be critical in those cultures displaying medium synchronization among bursts and poor random spiking activity, as confirmed by chemical manipulation experiments and modeling studies.
Abstract: The aim of this work is to present a new technique for defining interconnected sub-populations of cultured neurons on microelectrode arrays (MEAs). An automated microdrop delivery technique allows to design and realize spatially distributed neuronal ensembles by depositing sub-nanoliter volumes of adhesion molecules in which neurons grow and develop. Electrophysiological tests demonstrate that functionally interconnected clusters are obtained and experimental results (both spontaneous and stimulus evoked activity recordings) attesting the feasibility of the proposed approach are presented. By means of the automated system, different and specific architectures can be easily designed and functionally studied. In the presented system the speed of drop deposition is about 30 drops/min; the mean diameter is 147 microm; typical cell survival time is 4-5 weeks. By changing drop size and spacing, investigations about how the network dynamics is related to the network structure can be systematically carried out.
Abstract: Recent results indicate that cultures of cortical neurons exhibit large amounts of spontaneous modulation. It has even been suggested that results obtained earlier could be explained by spontaneous development, rather than to be due to the external manipulation. This stresses the importance of having detailed knowledge of how a culture responds to stimulation, in order to discern activity modulation from structural plasticity. In this paper we apply several promising techniques of electrical stimulation to describe global network modulation occurring in these preparations. The results allow to anticipate on integration of this work in goal-directed stimulus-induced plasticity.
Abstract: The purpose of this paper is to characterize the neuron-microelectrode junction, based on the equivalent electric-circuit approach. As a result, recording of action potentials can be simulated with a general-purpose circuit simulation program such as HSPICE. The response of the microelectrode was analyzed as a function of parameters such as sealing resistance and adhesion conditions. The models of the neuron and microelectrode implemented in HSPICE were first described. These models were used to simulate the behavior of the junction between a patch of neuronal membrane (described by the compartmental model) and a microelectrode.
Abstract: Purpose of this paper is to characterize the Ion-Sensitive Field-Effect Transistors (ISFET)-neuron junction, based on the equivalent electric-circuit approach. As a result, recording of action potentials can be simulated with a general-purpose circuit simulation program such as HSPICE. The neuronal electrical activity, extracellularly recorded by the ISFET, is analyzed as a function of the physical-chemical and geometric ISFET parameters, of the ionic currents in the neuron, and of the neuro-electronic junction parameters such as the sealing resistance, double-layer capacitance, and general adhesion conditions. The models of the neuron, of the coupling circuit, and of the ISFET implemented in HSPICE are first described. These models are then used to simulate the behavior of the junction between a patch of neuronal membrane (described by the compartmental model) and the ISFET.
