Long-lasting auditory gating deficit accompanied by GABA(B) receptor dysfunction in the hippocampus after early-life limbic seizures in rats

Autor: Melanie Crutchley, L. Stan Leung, Francis Boon, D.Peter Cain, Min Lan Tsai, Richard Boyce, Jingyi Ma
Rok vydání: 2012
Předmět:
Male
Startle Reaction
Reflex
Startle
Behavioral Neurobiology
Medical Physiology
Hippocampus
Water maze
Gating
GABA Antagonists
Behavioral Neuroscience
0302 clinical medicine
Limbic system
Receptors
Limbic System
0303 health sciences
Startle
Sensory Gating
medicine.anatomical_structure
Psychology
Intraventricular
Experimental and Cognitive Psychology
Hyperkinesis
Motor Activity
Injections
03 medical and health sciences
Developmental Neuroscience
Seizures
Limbic Encephalitis
Reflex
medicine
Animals
Rats
Long-Evans
Maze Learning
030304 developmental biology
Injections
Intraventricular
Sensory gating
Radial arm maze
GABA-B
Long-Evans
GABA receptor antagonist
Pharmacy and Pharmaceutical Sciences
Startle reaction
Phosphinic Acids
Electric Stimulation
Rats
nervous system
Acoustic Stimulation
Receptors
GABA-B
Nervous System Diseases
Neuroscience
030217 neurology & neurosurgery
Zdroj: Physiology and Pharmacology Publications
Popis: 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.
Databáze: OpenAIRE
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