Frequency dependent signal transfer in neuron transistors

Nerve cells are attached to open, metal-free gates of field-effect transistors submersed in electrolyte. The intracellular voltage is modulated by small ac signals from 0.1 Hz to 5000 Hz using a patch-clamp technique. The source-drain current is affected in amplitude and phase through a modulation of the extracellular voltage in the cleft between transistor and cell. The ac-signal transfer is evaluated on the basis of linear response theory. We use the model of a planar two-dimensional cable which consists of the core of an electrolyte sandwiched between the coats of a cell membrane and silicon dioxide of the transistor surface. Comparing experiment and model we obtain the resistances of core and coat, i.e., of the seal of cell and surface and of the attached membrane. The resistance of the membrane varies in different junctions. It may be lowered by two orders of magnitude as compared with the free membrane. This drop of the membrane resistance correlates with an enhancement of the seal resistance, i.e., with closer adhesion. The linear ac-transfer functions are used to compute the signal transfer of an action potential. The computed response is in good agreement with the observations of excited nerve cells on transistors

ANNINE-6plus, a voltage-sensitive dye with good solubility, strong membrane binding and high sensitivity

We present a novel voltage-sensitive hemicyanine dye ANNINE-6plus and describe its synthesis, its properties and its voltage-sensitivity in neurons. The dye ANNINE-6plus is a salt with a double positively charged chromophore and two bromide counterions. It is derived from the zwitterionic dye ANNINE-6. While ANNINE-6 is insoluble in water, ANNINE-6plus exhibits a high solubility of around 1 mM. Nonetheless, it displays a strong binding to lipid membranes. In contrast to ANNINE-6, the novel dye can be used to stain cells from aqueous solution without surfactants or organic solvents. In neuronal membranes, ANNINE-6plus exhibits the same molecular Stark effect as ANNINE-6. As a consequence, a high voltage-sensitivity is achieved with illumination and detection in the red end of the excitation and emission spectra, respectively. ANNINE-6plus will be particularly useful for sensitive optical recording of neuronal excitation when organic solvents and surfactants must be avoided as with intracellular or extracellular staining of brain tissue

Axonal Transmission in the Retina Introduces a Small Dispersion of Relative Timing in the Ganglion Cell Population Response

Background: Visual stimuli elicit action potentials in tens of different retinal ganglion cells. Each ganglion cell type responds with a different latency to a given stimulus, thus transforming the high-dimensional input into a temporal neural code. The timing of the first spikes between different retinal projection neurons cells may further change along axonal transmission. The purpose of this study is to investigate if intraretinal conduction velocity leads to a synchronization or dispersion of the population signal leaving the eye. Methodology/Principal Findings: We 'imaged' the initiation and transmission of light-evoked action potentials along individual axons in the rabbit retina at micron-scale resolution using a high-density multi-transistor array. We measured unimodal conduction velocity distributions (1.3 +/- 0.3 m/sec, mean +/- SD) for axonal populations at all retinal eccentricities with the exception of the central part that contains myelinated axons. The velocity variance within each piece of retina is caused by ganglion cell types that show narrower and slightly different average velocity tuning. Ganglion cells of the same type respond with similar latency to spatially homogenous stimuli and conduct with similar velocity. For ganglion cells of different type intraretinal conduction velocity and response latency to flashed stimuli are negatively correlated, indicating that differences in first spike timing increase (up to 10 msec). Similarly, the analysis of pair-wise correlated activity in response to white-noise stimuli reveals that conduction velocity and response latency are negatively correlated. Conclusion/Significance: Intraretinal conduction does not change the relative spike timing between ganglion cells of the same type but increases spike timing differences among ganglion cells of different type. The fastest retinal ganglion cells therefore act as indicators of new stimuli for postsynaptic neurons. The intraretinal dispersion of the population activity will not be compensated by variability in extraretinal conduction times, estimated from data in the literature

Saxifraga decipiens Ehrh.

Von Fromher

Transistor Probes Local Potassium Conductances in the Adhesion Region of Cultured Rat Hippocampal Neurons

to et al., 1997). Until now, however, it was not possible to measure the local electrophysiological properties of the cell membrane in a region of adhesion. With respect to the complex cell -- cell and cell -- extracellular matrix contacts in vivo, neurons cultured on a coated solid substrate represent a simple model in which the membrane interacts with known adhesion molecules. In the present paper we examine the following question: are there different ion conductances on the upper and lower membrane of a neuron in culture that are exposed, respectively, to the culture medium on one side and in contact with the substrate on the other side? To answer the question, the membrane conductance of the attached membrane of a cultured neuron was studied without disturbing its adhesion to the substrate. We took advantage of the novel method of transistor recording (Fromherz et al., 1991; Fromherz, 1999). There a field-effect transistor is integrated in a silicon substrate bene