Physiology and Pharmacology Publications

Title

Kindled Seizure in the Prefrontal Cortex Activated Behavioral Hyperactivity and Increase in Accumbens Gamma Oscillations through the Hippocampus

Document Type

Article

Publication Date

1-5-2010

Journal

Behavioral Brain Research

Volume

206

Issue

1

First Page

68

Last Page

77

Abstract

In previous studies, we reported that a single afterdischarge (AD) or repeated ADs (kindling) in the hippocampus resulted in schizophrenia-like behaviors such as hyperactivity and loss of sensorimotor gating. Given that medial prefrontal cortex (PFC) dysfunction is also found in models of schizophrenia, we hypothesized that a single AD in the PFC induces postictal hyperactivity, and PFC kindling results in loss in prepulse inhibition (PPI). An AD was induced by stimulating the PFC with a 5s stimulus train of 60Hz frequency and 600-800muA intensity. An initial AD evoked in the PFC was not accompanied by clear postictal behavioral change. After partial kindling (11+/-2 ADs) of the PFC, the PFC-AD propagated into the hippocampus and nucleus accumbens (NAC) and postictal hyperactivity lasted >5min. The postictal hyperactivity was accompanied by increased gamma EEG oscillations in both PFC and NAC. A single AD in hippocampal CA1 also induced >5min of postictal hyperactivity and increased gamma oscillations in the NAC and the PFC, with a transient increase in hippocampus-NAC gamma coherence occurring 2-3min after a hippocampal AD. Electrolytic lesion or inactivation of the dorsal hippocampus abolished the behavioral hyperactivity and the NAC/PFC gamma wave increase induced by a PFC-AD. Kindling of the PFC (21 ADs) but not of the lateral frontal cortex resulted in a deficit of PPI to the acoustic startle response tested 3 days after the last AD. In summary, gamma waves in the NAC were found to accompany postictal hyperactivity induced by an AD in the PFC. Postictal gamma and hyperactivity required an intact hippocampus, perhaps through the hippocampal-NAC pathway. PFC kindling, similar to hippocampal CA1 kindling, resulted in a prolonged deficit in PPI.

Notes

Published in: Behavioural Brain Research, Volume 206, Issue 1, 5 January 2010, Pages 68-77. doi: 10.1016/j.bbr.2009.08.038