ABSTRACT
OBJECTIVE: Using the gamma-butyrolactone (GBL) model of absence seizures in Long-Evans rats, this study investigated if gamma (30-160 Hz) activity were cross-frequency modulated by the 2-6 Hz slow-wave discharges induced by GBL in the limbic system. We hypothesized that inactivation of the nucleus reuniens (RE), which projects to frontal cortex (FC) and hippocampus, would affect the cross-frequency coupling of gamma (γ) in different brain regions. METHODS: Local field potentials were recorded by electrodes implanted in the FC, ventrolateral thalamus (TH), basolateral amygdala (BLA), nucleus accumbens (NAC), and dorsal hippocampus (CA1) of behaving rats. At each electrode, the coupling between the γ amplitude envelope to the phase of the 2-6 Hz slow-waves (SW) was measured by modulation index (MI) or cross-frequency coherence (CFC) of γ amplitude with SW. In separate experiments, the RE was infused with saline or GABAA receptor agonist, muscimol, before the injection of GBL. RESULTS: Following GBL injection, an increase in MI and CFC of SW to γ1 (30-58 Hz), γ2 (62-100 Hz) and γ3 (100-160 Hz) bands was observed at the FC, hippocampus and BLA, with significant increase in SW-γ1 and SW-γ3 coupling at TH, and increase in peak SW-γ1 CFC at NAC. Strong SW-γ modulation was also found during baseline immobility high-voltage spindles. Muscimol inactivation of RE, as compared to saline infusion, significantly decreased SW-γ1 CFC in the FC, and peak frequency of the SW-γ1 CFC in the thalamus, but did not significantly alter SW-γ CFCs in the hippocampus, BLA or NAC. SIGNIFICANCE: The paroxysmal 2-6 Hz SW discharges, a hallmark of absence seizure, significantly modulate γ activity in the hippocampus, BLA and NAC, suggesting a modulation of limbic functions. RE inactivation disrupted the SW modulation of FC and TH, partly supporting our hypothesis that RE participates in the modulation of SW discharges.
