Frequency bands and spatiotemporal dynamics of beta burst stimulation induced afterdischarges in hippocampus in vivo

Temporal and spatial characteristics of hippocampal neuronal network activation are modified during epileptiform afterdischarges. We developed a beta burst stimulation protocol to investigate subregional variations and substrates of rhythmic population spike discharges in vivo in urethane anesthetized Wistar rat hippocampus with a 14-electrode recording array and extracellular single electrode recordings. Our 64 pulse beta burst stimulation protocol was constructed from electrical pulses delivered at intervals corresponding to beta (14-25 Hz), Delta (2 Hz), and slow (0.5 Hz) frequencies. In each experiment these interleaved pulses were all repeated four times with unchanged intervals. Stimulation of either perforant path or fimbria fornix induced a prolonged afterdischarge pattern peaking at 200 Hz fast, 20 Hz beta, and 2 Hz Delta frequencies. Analysis of variance confirmed that the response pattern of the discharges remained constant regardless of the stimulation beta frequency. Within the afterdischarge the fast frequencies were restricted to independent hippocampal subfields whereas beta and slow frequencies correlated across the subfields. Current source density (CSD) analysis revealed that the original signal propagation through subfields of the hippocampus was compromised during the beta burst stimulation induced afterdischarge. In addition, the CSD profile of the epileptiform afterdischarge was consistently similar across the different experiments. Time-frequency analysis revealed that the beta frequency afterdischarge was initiated and terminated at higher gamma (30-80 Hz) frequencies. However, the alterations in the CSD profile of the hippocampus coincided with the beta frequency dominated discharges. We propose that hippocampal epileptiform activity at fast, beta and Delta frequencies represents coupled oscillators at respectively increasing spatial scales in the hippocampal neuronal network in vivo.