ABSTRACT
In a previous study, we reported a rat model of early-life limbic seizures which resulted in a loss of GABA(B) receptor inhibition in the hippocampus. Since gating of auditory evoked potentials in the hippocampus (auditory gating) requires GABA(B) receptors and spatial behaviors depend on the hippocampus, we hypothesize that rats with early-life limbic seizures manifest deficits of auditory gating and spatial behaviors. Seizure rats were given a single injection of GABA(B) receptor antagonist CGP56999A (1-1.2 mg/kg i.p.) on postnatal day (PND) 15, which induced multiple limbic seizures in 8h; control rats were given saline injection. When tested at 3-9 weeks after seizure/control treatment, seizure as compared to control rats showed no difference in finding a hidden platform in the water maze, but were deficient in learning and maintaining consecutive criterion performance in the 8-arm radial arm maze. Auditory gating, as measured by paired-click (conditioning followed by test click) average auditory evoked potentials in the hippocampus, revealed a significant difference between seizure rats and controls. Seizure as compared to control rats showed an increased ratio of the test to conditioning click response as adolescents (50 days old) or adults (70 days old). Heterosynaptic electric paired-pulse depression of hippocampal population excitatory postsynaptic potential in freely moving rats, a measure of hippocampal GABA(B)-receptor mediated inhibition, was decreased in seizure as compared to control rats. Seizure as compared to control rats showed increased locomotor activity in a novel open field for the first 10 min, and decreased activity at 15-60 min. However, auditory prepulse inhibition, a measure of sensorimotor gating, revealed no difference between seizure and control rats. In conclusion, early-life limbic seizures induced a long-lasting deficit in auditory gating, likely caused by GABA(B) receptor-mediated inhibition loss in the hippocampus. Auditory gating loss is a symptom of schizophrenia, and thus GABA(B) receptor inhibition loss in the hippocampus provides a mechanism linking early-life seizures to a psychiatric symptom.
Subject(s)
Hippocampus/physiopathology , Limbic Encephalitis/physiopathology , Receptors, GABA-B/physiology , Seizures/physiopathology , Sensory Gating/physiology , Acoustic Stimulation , Animals , Electric Stimulation , GABA Antagonists/administration & dosage , GABA Antagonists/pharmacology , Hyperkinesis/physiopathology , Injections , Injections, Intraventricular , Limbic System , Male , Maze Learning/physiology , Motor Activity/physiology , Phosphinic Acids/administration & dosage , Phosphinic Acids/pharmacology , Rats , Rats, Long-Evans , Receptors, GABA-B/drug effects , Reflex, Startle/physiologyABSTRACT
We used an off-line story continuation task and an online ERP reading task to investigate coreferential processing following sentences that portrayed transfer-of-possession events as either ongoing or completed, using imperfective and perfective verb aspect (e.g., Amanda was shifting/shifted some poker chips to Scott). The story continuation task demonstrated that people were more likely to begin continuations with references to the Goal than to the Source, but that perfective aspect strengthened this bias. In the ERP task we probed expectations for Source and Goal referents by employing pronouns that matched one of the referents in gender. The ERP results were consistent with the biases revealed in the story continuation task and demonstrate that the difference in Goal bias for the two forms of aspect was manifested differently in the brain. These results provide novel behavioral and neurocognitive evidence that verb aspect influences the construction of situation models during language comprehension.
