Abstracts

Seizures have been called [quot]hypersynchronous[quot] events, but recent work indicates that neurons may receive more synchronous inputs at seizure termination. We describe the dynamics of synaptic activity and spike output in CA1 pyramidal-pyramidal and pyramidal-interneuron cell pairs before, during, and after [italic]in vitro[/italic] seizures. Simultaneous dual (n=40) and triple (n=5) whole-cell and extracellular recordings of network activity were performed in CA1 using transverse hippocampal slice preparations of juvenile rats (P18-P30). Inhibitory interneurons (fast spiking, burst firing, stuttering, and regular spiking) from the CA1 strata were distinguished from pyramidal cells by differential infrared contrast microscopy, membrane firing properties, and [italic]post-hoc[/italic] morphological analysis of neurobiotin histochemistry. To induce seizures, neurons were held at resting membrane potentials in current-clamp and bathed in 50-250[mu]M 4-Amino Pyridine. Seizures here are defined as sustained long-lasting ([gt]10s) paroxysmal network events accompanied by a substantial extracellular negative DC shift and clear initiation, body, and termination phases (Fig.1, A). Synchrony was assessed using a unique approach involving separate correlation analyses of output spikes, synaptic inputs, and the complete signals between each pair of neuronal subtypes. 43% of all cell pairs showed multiple repetitive seizures. Synaptic input correlation was complex and varied greatly. Pyramidal cell pairs showed a small decrease in synaptic correlation in the seizure body and an increase during the termination. During seizures, depolarization block of interneurons was common and interleaved with pyramidal spiking sequences (Fig 1, A). Pyramidal cell pair spike output exhibited strong correlation (may be required for seizure propagation [italic]en route[/italic] to cortex). Spike output between pyramidal cells and interneurons revealed a complex interplay between these networks. The interactions between different neurons (pyramidal-pyramidal and interneuron-pyramidal) in seizures are complex and cannot be described simply by [quot]synchrony[quot]. The interactions between neurons can be qualitatively different when characterized by either synaptic input current or output spike correlation. The dynamical interplay between inhibitory and excitatory networks appears to orchestrate the initiation, persistence, and termination of these seizure events.[figure1] (Supported by NIH: K02MH01493, K25MH01963, and RO1MH50006)