Response Properties of Cultured Cortical Networks As a Substrate for the Study of Learning in Vitro
Int. Conf. Cognitive and Neural Systems, Boston University, Boston, MA, 2002
Our lab pursues the study of learning in vitro by connecting neuronal cultures with simulated bodies in computer generated environments. We connect the output of a set of 60 electrodes embedded in a culture dish on which we grow dense networks of embryonic (E18) rat cortical neurons to the motor control of such artificial animals (or animats). Information from their sensory organs is sent back to the dish in a closed feedback loop by electrically stimulating through the same substrate electrodes. Our recording, processing and stimulation system can provide feedback with a delay of less than 100~ms.
As an essential step towards this goal, we have been studying the response properties of these living neuronal networks to simple electrical stimuli. In absense of stimulation, the cultures’ major mode of activity is global bursts, which show interesting dynamics at the timescale of minutes and large variability at the timescale of days to months. Responses to electrical stimuli consist of spikes in the first 20 ms post-stimulus timed with deep sub-millisecond precision, followed by less precisely timed spikes and occasional induced global bursts. These responses are typically stable over many days of continuous probing.
The study of short-latency responses became possible thanks to an algorithm we recently developed to suppress the very large artifacts that plague recordings shortly after stimulation. The algorithm locally fits polynomials to the shape of the artifact and can remove artifacts ten times the size of action potentials from the recorded trace in real-time on standard PC equipment.
We found that precisely timed responses, unlike other evoked activity, persist in the presence of NMDA and AMPA synapse channel blockers, indicating that they originate directly from the stimulated neuron. However, their reliability and latency do change as a result of blocking synapses, showing that synaptic influences are important. Non-monotonicities in response reliability vs stimulation voltage are further evidence for network influences.
These results will serve to help us to intelligently design sensory-motor mappings for our neurally controlled animats.
Work is currently underway to characterize the response to pairs of stimuli and the associated inter-pulse-interval dependence, which several groups have found to be of major significance in inducing synaptic plasticity.