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First published online May 26, 2006
Journal of Experimental Biology 209, 2312-2319 (2006)
Published by The Company of Biologists 2006
doi: 10.1242/jeb.02163

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Neuronal networks and synaptic plasticity: understanding complex system dynamics by interfacing neurons with silicon technologies

Michael A. Colicos^1,* and Naweed I. Syed²

¹ Department of Physiology and Biophysics, Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, T2N 4N1, Canada
² Department of Cell Biology and Anatomy, Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, T2N 4N1, Canada

View larger version (91K): [in a new window]   Fig. 1. Lymnaea neurons on a silicon chip paired in a soma–soma configuration. (a) A hybrid design depicting the relationship between neuronal connectivity and its interfacing with various chip components. G, gate; S, source; D, drain. (b) Photomicrograph of soma–soma paired presynaptic neurons visceral dorsal 4 (VD4-left) and its postsynaptic partner left pedal dorsal one (LPeD1 – larger cell) interfaced with silicon chip on a linear array of capacitors and transistors. Scale bar, 20 µm. Figure taken from (Kaul et al., 2004).

View larger version (19K): [in a new window]   Fig. 2. (A) Short-term synaptic plasticity between soma–soma paired Lymnaea neurons. Presynaptic neuron visceral dorsal 4 (VD4) and its postsynaptic partner left pedal dorsal 1 (LPeD1) were paired in a soma–soma configuration and cells allowed to develop synapses overnight. Simultaneous intracellular recordings revealed excitatory synapses where induced action potentials in VD4 (first open arrow) generated 1:1 excitatory postsynaptic potentials in LPeD1. Following a burst of action potentials in VD4 (at bar) the subsequent action potentials in the presynaptic cell (at closed arrow) induced 1:1 spikes in the postsynaptic cell. This short-term change in the postsynaptic cell's response to the presynaptic action potentials illustrates the plasticity in the system. (B) Synaptic potentiation on a silicon chip. Cells were soma–soma paired overnight and synaptic physiology studied through the chip. The upper traces show intracellular voltages in red, the lower traces represent capacitor stimuli (left) and transistor records (right) in black. (a) Control recordings. Capacitor stimulation of the presynaptic neuron VD4 generated action potentials that did not elicit a detectable response in the postsynaptic cell LPeD1 (right). (b) Stronger capacitive stimulation through the chip induced bursts of spikes in VD4. (c) Post-tetanic action potential in VD4 now induced 1:1 action potentials in LPeD1 (right). Figure taken from (Kaul et al., 2004).

View larger version (77K): [in a new window]   Fig. 3. Long-term stimulation of neuronal cultures. Rat hippocampal neurons were isolated from newborn pups and plated at high density on silicon wafers. After cultures were established (7 DIV) the chips were placed into parallel stimulation devices, the control chip receiving no stimulation whereas the second chip received periodic high frequency stimulation in a circular region at the center of the wafer. Following stimulation for 1–3 days, chips were removed from the device and fixed, and then processed for immunostaining with anti-bassoon antibody. Bassoon is a presynaptic active zone protein, allowing the visualization of synapses. Images are acquired at low magnification and joined together to span the entire chip. (A) Unstimulated network, (B) central region of stimulated chip. Several mathematical methods were used to analyze the synaptic distribution; the first steps in analysis include deconvolution, thresholding and watershed analysis of the synaptic distribution images. (C) Sample synaptic density profiles represented by density distribution, illustrating altered patterns that result from long-term stimulation. Pseudo-color scale represents regions of low to high synaptic density.

View larger version (90K): [in a new window]   Fig. 4. Analysis of heterogeneity. (A) Unstimulated and (B) stimulated example close-ups of different network configurations resulted from activity driven plasticity. A variety of methods can be used to analyze synaptic distribution, including analysis of heterogeneity, variance and clustering, as well as more sophisticated modeling of the spatial distribution, which incorporate techniques such as Fourier transforms. (C,D) Examples of a Delauney triangulation of regions of clustered synapses, induced following overnight stimulation of the network, illustrating how pattern analysis can be performed to address network development using this technology.

View larger version (69K): [in a new window]   Fig. 5. Directional heterogeneity analysis. In addition to analysis such as synaptic cluster distribution, direction mapping along paths of maximum entropy can be used to trace connectivity on a large-scale. The figure shows experimental software designed to follow connectivity patterns in a stimulated network.

View larger version (53K): [in a new window]   Fig. 6. Photoconductive electronics technology. By combining a massive array of transistor interface points, and the light-addressable specificity of photoconductive stimulation, a seamless interface with large neuronal ensembles can be achieved.