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Changes in Nonlinear Signal Processing in Rat Hippocampus Associated with Loss of Paired‐Pulse Inhibition or Epileptogenesis
Author(s) -
Naylor David
Publication year - 2002
Publication title -
epilepsia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.687
H-Index - 191
eISSN - 1528-1167
pISSN - 0013-9580
DOI - 10.1046/j.1528-1157.43.s.5.37.x
Subject(s) - epileptogenesis , hippocampus , neuroscience , pulse (music) , medicine , psychology , physics , detector , optics
Summary:  Purpose: To study acute and chronic physiological effects of perforant path stimulation using paired‐pulse and nonlinear signal analysis techniques (Wiener kernel analysis). Methods: Two to 3‐month‐old Wistar rats were implanted with stimulating electrodes in the perforant path and recording electrodes in the granule cell layer. Loss of paired‐pulse inhibition was produced with 2 Hz continuous and 20 Hz (10 s/min) intermittent stimulation for periods of 1–15 min (0.1 ms, 20 v pulses). Some animals received 30–60 min of stimulation, a model for status epilepticus/epileptogenesis. Responses to paired‐pulse or white noise inputs were recorded sequentially. Results: Loss of inhibition with brief 1–3 min of stimulation, measured by increase paired‐pulse ratio (P2/P1 ISI 40 ms) from 0.25 (±0.27) pre‐ to 1.02 (±0.18) post‐stimulation (p < 0.001), lasted 43 (±15) min. For 30–60 min of stimulation, the paired‐pulse ratios were 0.088 (±0.11), 1.59 (±0.036), 0.06 (±0.11), 0.82 (±0.22) for pre‐, immediate post‐, 1 week post‐, and 1 month poststimulation, respectively (p < 0.025). Compared to prestimulation values, Wiener kernel amplitudes for immediate, 1 week, and 1 month poststimulation were 24% (±13%), 72% (±17%), and 31% (±21%), respectively (p < 0.05). Wiener kernels 1 month poststimulation showed response prolongation with increased opportunity for excitatory interactions of inputs (particularly those separated by 4 ms). Conclusions: Brief perforant path stimulation causes sustained loss of inhibition in the dentate, possibly an early event in the transition to status epilepticus. Stimulation for 30–60 min causes chronic changes in paired‐pulse and white noise (Wiener kernel) responses. Transient recovery occurs by 1 week, but later new features appear (including delayed/late inhibition and potential excitatory cross‐talk) that might favor epileptic seizures.

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