Systemic injection of kainic acid differently affects LTP magnitude depending on its epileptogenic efficiency

• Published in: PloS one 2012-10, Vol.7 (10), p.e48128
• Main Authors: Suárez, Luz M, Cid, Elena, Gal, Beatriz, Inostroza, Marion, Brotons-Mas, Jorge R, Gómez-Domínguez, Daniel, de la Prida, Liset Menéndez, Solís, José M
• Format: Article
• Language: English
• Subjects: Acids; Animals; Biology; Brain; Brain slice preparation; Brain-derived neurotrophic factor; Chronic Disease; Disease Resistance; Efficiency; Electroencephalography; Epilepsy; Group dynamics; Hippocampal plasticity; Hippocampus; Hippocampus - drug effects; Hippocampus - pathology; Hippocampus - physiopathology; In Vitro Techniques; Injection; Kainic Acid; Kindling; Laboratories; Long-term effects; Long-term potentiation; Long-Term Potentiation - drug effects; Male; Medicine; Memory; Memory tasks; Mental task performance; Neurosciences; Object recognition; Oscillations; Paired-pulse facilitation; Pattern recognition; Physiological aspects; Physiology; Plasticity; Presynaptic Terminals - physiology; Rats; Rats, Sprague-Dawley; Rats, Wistar; Recognition (Psychology) - drug effects; Rodents; Sclerosis; Seizing; Seizures; Seizures (Medicine); Spatial analysis; Spatial memory; Status Epilepticus - chemically induced; Status Epilepticus - physiopathology; Status Epilepticus - psychology; Synaptic plasticity; Synaptic Transmission - drug effects; Theta Rhythm
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0048128

Seizures have profound impact on synaptic function and plasticity. While kainic acid is a popular method to induce seizures and to potentially affect synaptic plasticity, it can also produce physiological-like oscillations and trigger some forms of long-term potentiation (LTP). Here, we examine whether induction of LTP is altered in hippocampal slices prepared from rats with different sensitivity to develop status epilepticus (SE) by systemic injection of kainic acid. Rats were treated with multiple low doses of kainic acid (5 mg/kg; i.p.) to develop SE in a majority of animals (72-85% rats). A group of rats were resistant to develop SE (15-28%) after several accumulated doses. Animals were subsequently tested using chronic recordings and object recognition tasks before brain slices were prepared for histological studies and to examine basic features of hippocampal synaptic function and plasticity, including input/output curves, paired-pulse facilitation and theta-burst induced LTP. Consistent with previous reports in kindling and pilocapine models, LTP was reduced in rats that developed SE after kainic acid injection. These animals exhibited signs of hippocampal sclerosis and developed spontaneous seizures. In contrast, resistant rats did not become epileptic and had no signs of cell loss and mossy fiber sprouting. In slices from resistant rats, theta-burst stimulation induced LTP of higher magnitude when compared with control and epileptic rats. Variations on LTP magnitude correlate with animals' performance in a hippocampal-dependent spatial memory task. Our results suggest dissociable long-term effects of treatment with kainic acid on synaptic function and plasticity depending on its epileptogenic efficiency.