Latency-Related Development of Functional Connections in Cultured Cortical Networks

To study plasticity, we cultured cortical networks on multi electrode arrays, enabling simultaneous re-cording from multiple neurons. We used conditional firing probabilities (CFPs) to describe functional network connections by their strength and latency. These are abstract representations of neuronal pathways, and may arise from direct pathways between two neurons, or from a common input. Functional connections based on direct pathways should reflect synaptic properties. Therefore, we searched for long term potentiaion (LTP; this mechanism occurs in vivo when presynaptic action po-tentials precede postsynaptic ones with interspike intervals up to ~20ms) in vitro. To investigate if the strength of functional connections showed a similar latency related development, we selected periods of monotonously increasing or decreasing strength. We observed increased incidence of short latencies (5-30ms) during strengthening, whereas these latencies rarely occurred during weakening. Further-more, we saw an increased incidence of 40-65ms latencies during weakening. Conversely, functional connections tended to strengthen in periods with short latency, whereas strengthening was significantly less than average during long latency. Our data suggests that functional connections contain information about synaptic connections, that CFP analysis is sensitive enough to detect it, and that a substantial fraction of all functional connec-tions is based on direct pathways.