Microstimulation reveals anesthetic state-dependent effective connectivity of neurons in cerebral cortex.

Introduction: Complex neuronal interactions underlie cortical information processing that can be compromised in altered states of consciousness. Here intracortical microstimulation was applied to investigate anesthetic state-dependent effective connectivity of neurons in rat visual cortex Methods: Extracellular activity was recorded at 32 sites in layers 5/6 while stimulating with charge-balanced discrete pulses at each electrode in random order. The same stimulation pattern was applied at three levels of anesthesia with desflurane and in wakefulness. Spikes were sorted and classified by their waveform features as putative excitatory and inhibitory neurons. Network motifs were identified in graphs of effective connectivity constructed from monosynaptic cross-correlograms. Results: Microstimulation caused early (<10 ms) increase followed by prolonged (11-100 ms) decrease in spiking of all neurons throughout the electrode array. The early response of excitatory but not inhibitory neurons decayed rapidly with distance from the stimulation site over 1 mm. Effective connectivity of neurons with significant stimulus response was dense in wakefulness and sparse under anesthesia. The number of network motifs, especially those of higher order, increased rapidly as the anesthesia was withdrawn indicating a substantial increase in network connectivity as the animals woke up. Conclusion: The results illuminate the impact of anesthesia on functional integrity of local cortical circuits affecting the state of consciousness.