We report the design and application of a Micro Electro Mechanical Systems (MEMs) device that permits investigators to create arbitrary network topologies. With this device investigators can manipulate the degree of functional connectivity among distinct neural populations by systematically altering their geometric connectivity in vitro. Each polydimethylsilxane (PDMS) device was cast from molds and consisted of two wells each containing a small neural population of dissociated rat cortical neurons. Wells were separated by a series of parallel micrometer scale tunnels that permitted passage of axonal processes but not somata; with the device placed over an 8 × 8 microelectrode array, action potentials from somata in wells and axons in microtunnels can be recorded and stimulated. In our earlier report we showed that a one week delay in plating of neurons from one well to the other led to a filling and blocking of the microtunnels by axons from the older well resulting in strong directionality (older to younger) of both axon action potentials in tunnels and longer duration and more slowly propagating bursts of action potentials between wells. Here we show that changing the number of tunnels, and hence the number of axons, connecting the two wells leads to changes in connectivity and propagation of bursting activity. More specifically, the greater the number of tunnels the stronger the connectivity, the greater the probability of bursting propagating between wells, and shorter peak-to-peak delays between bursts and time to first spike measured in the opposing well. We estimate that a minimum of 100 axons are needed to reliably initiate a burst in the opposing well. This device provides a tool for researchers interested in understanding network dynamics who will profit from having the ability to design both the degree and directionality connectivity among multiple small neural populations.

A polydimethylsiloxane (PDMS) microtunnel device with two wells is aligned and attached on top of a multi-electrode-array (MEA). Neurons are grown first in one well and allowed to propagate axons through the tunnels into a second well. After ten days cells are plated in the second well, with much lower likelihood of extending axons back to the first well, with the intent of creating unidirectional connectivity between populations of neurons in the two wells. Here we report electrophysiological evidence that supports the hypothesis that the dominant information flow is in the desired direction. This was done by measuring the propagation speed and direction of individual action potentials, with the result that 84% of the spikes propagated in the desired direction. Further, we recorded globally synchronized burst activity on each of the electrodes, identified the timing of the first spike on each electrode, recorded locally synchronized burst activity which is found only in the second well and does not propagate back to the first well, and concluded that this measure of burst propagation supports the hypothesis of a unidirectionally connected network. Two hypotheses are discussed for mechanism underlying the activity pattern of the particular neural networks.

When extracellular action potentials (spikes) from cultured neurons are recorded using microelectrode arrays in open wells, their amplitudes are usually quite small (often below the noise level) despite the extracellular currents originating from the relatively large surface area of neural cell somata. In this paper rat cortical neurons were seeded into one well of a two well system separated by 3×10 μm microtunnels and then 7 days later into the second well forming a feed-forward network between two small neuronal assemblies. In contrast to measurements in the open well spikes recorded from axons within the restricted volumes imposed by the microtunnels are often several orders of magnitude larger than in the open well, with high signal to noise ratio, despite the currents originating in the much smaller surface area of the axon. Average signal amplitudes exceeding 250 μV are typical, with some signals as large as 4.5 mV (signal-to-noise ratio up to 450), twenty times greater than the maximum recorded from electrodes in adjacent but open wells. We confirm the dependence of signal amplitude on the impedance of the microtunnel and discuss possible reasons for the phenomenon.

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