Precise Timing in Early Response to Electric Stimulation in Dense Cultures of Cortical Neurons
Proc. Mathematics in Molecular Biology, Santa Fe, NM, 2002
Using a novel algorithm for stimulation artifact suppression in micro-electrode array (MEA) recordings based on local regression to artifact shape [1], we are studying short latency responses to electrical stimulation in dense cultures of rat cortical neurons.
In the time window that was previously inaccessible due to artifacts, 1.5-20 ms post-stimulus, we observe spikes (extracellular action potentials) with timing precisions of 0.05-0.15 ms. These spikes are not abolished by blocking glutamatergic synapses, suggesting that they are the result of direct axonal propagation. Such directly evoked responses are observed on electrodes all the way across the array from the stimulation site (1.5 mm distant), and at latencies up to 15 ms. None of these response components are 100% reliable, but many occur in 50-75% of stimulation trials. Evoked responses on different electrode channels are mostly independent, and require different minimum stimulus voltages, indicating that several axons or somata are stimulated by the (single) stimulation electrode.
From 5 ms post-stimulus, spikes are also observed with timing precisions of 1-5 ms. Blocking glutamatergic synaptic transmission confirms that these are mostly postsynaptic from the stimulated neuron(s).
Blocking glutaminergic synapses does modify many of the precisely timed response components, even the very early ones, by sharpening up the timing, shifting the latency or changing the reliability. This indicates that ongoing synaptic activity plays an important modulatory role in the generation of directly evoked firing. We are currently investigating how patterned stimulation may be used to shape ongoing activity and thus to gain control over the modulation, which will be an important step towards realizing the computational capabilities of living neuronal networks [2].
[1] D. A. Wagenaar and S. M. Potter, Stimulus artifact suppression by local polynomial approximation, submitted.
[2] T. B. DeMarse, D. A. Wagenaar, A. W. Blau and S. M. Potter, The neurally controlled animat: biological brains acting with simulated bodies, Autonomous Robots 11 (2001), 305-310.