Complexity of Epileptiform Activity in a Neuronal Network and Pharmacological Intervention

Neuronal outputs are complex signals of dynamically integrated excitatory and inhibitory components. Decreased synaptic inhibition in a neuronal network increases excitability and multiple spiking in neurons. Synchronized multiple spiking among a neuronal population further generates rhythmic field potentials and this epileptiform activity can propagate in the brain and cause seizures. Pharmacological interventions that reduce rhythmicity of epileptiform activity may have antiepileptic potentials. We evaluated the LempelZiv (LZ) complexity for identifying rhythmicity in population spikes recorded in granule cells of the murine dentate gyrus in vitro. Blocking synaptic inhibition by the GABAA receptor antagonist, bicuculline, caused epileptiform population spikes, and we found that the LZ complexity of the signal was significantly reduced. Moreover, the GABAB receptor agonist, baclofen, reduced the amplitude of the epileptiform population spike and we found that it increased LZ complexity. The results show that LZ complexity is sensitive to pharmacological interventions that apparently alter rhythmicity of neuronal outputs by desynchronizing neuronal population firing. This novel approach in neuronal signal processing may be used to identify new antiepileptic targets. Keywords— Lempel-Ziv complexity, epileptiform activity, dentate gyrus, excitation, synaptic inhibition