title: Inhibition of long-term potentiation in the schaffer-CA1 pathway by repetitive high-intensity sound stimulation.
abstract: High-intensity sound can induce seizures in susceptible animals. After repeated acoustic stimuli changes in behavioural seizure repertoire and epileptic EEG activity might be seen in recruited limbic and forebrain structures, a phenomenon known as audiogenic kindling. It is postulated that audiogenic kindling can produce synaptic plasticity events leading to the spread of epileptogenic activity to the limbic system. In order to test this hypothesis, we investigated if long-term potentiation (LTP) of hippocampal Schaffer-CA1 synapses and spatial navigation memory are altered by a repeated high-intensity sound stimulation (HISS) protocol, consisting of one-minute 120 dB broadband noise applied twice a day for 10 days, in normal Wistar rats and in audiogenic seizure-prone rats (Wistar Audiogenic Rats - WARs). After HISS all WARs exhibited midbrain seizures and 50% of these animals developed limbic recruitment, while only 26% of Wistar rats presented midbrain seizures and none of them had limbic recruitment. In naïve animals, LTP in hippocampal CA1 neurons was induced by 50- or 100-Hz high-frequency stimulation of Schaffer fibres in slices from both Wistar and WAR animals similarly. Surprisingly, HISS suppressed LTP in CA1 neurons in slices from Wistar rats that did not present any seizure, and inhibited LTP in slices from Wistar rats with only midbrain seizures. However HISS had no effect on LTP in CA1 neurons from slices of WARs. Interestingly HISS did not alter spatial navigation and memory in both strains. These findings show that repeated high-intensity sound stimulation prevent LTP of Schaffer-CA1 synapses from Wistar rats, without affecting spatial memory. This effect was not seen in hippocampi from audiogenic seizure-prone WARs. In WARs the link between auditory stimulation and hippocampal LTP seems to be disrupted which could be relevant for the susceptibility to seizures in this strain.
authors.affiliation: Department of Physiology, FMRP, University of São Paulo, Ribeirão Preto-SP, Brazil.
authors.forename: A O S
authors.initials: AO
authors.lastname: Cunha
authors.affiliation: Department of Physiology, FMRP, University of São Paulo, Ribeirão Preto-SP, Brazil.
authors.forename: J A C
authors.initials: JA
authors.lastname: de Oliveira
authors.affiliation: Departament of Psychology, FFCLRP, University of São Paulo, Ribeirão Preto-SP, Brazil.
authors.forename: S S
authors.initials: SS
authors.lastname: Almeida
authors.affiliation: Department of Physiology, FMRP, University of São Paulo, Ribeirão Preto-SP, Brazil. Electronic address: ngcairas@fmrp.usp.br.
authors.forename: N
authors.initials: N
authors.lastname: Garcia-Cairasco
authors.affiliation: Department of Physiology, FMRP, University of São Paulo, Ribeirão Preto-SP, Brazil. Electronic address: leaor@fmrp.usp.br.
authors.forename: R M
authors.initials: RM
authors.lastname: Leão
mesh_terms: D000161:Acoustic Stimulation / Q000009:adverse effects*; D000818:Animals; D056547:CA1 Region, Hippocampal / Q000502:physiology*; D004195:Disease Models, Animal; D004558:Electric Stimulation; D004594:Electrophysiology; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D066298:In Vitro Techniques; D007696:Kindling, Neurologic / Q000235:genetics / Q000473:pathology; D017774:Long-Term Potentiation / Q000235:genetics / Q000502:physiology*; D008297:Male; D018782:Maze Learning / Q000502:physiology; D008568:Memory / Q000502:physiology; D009433:Neural Inhibition / Q000502:physiology*; D009434:Neural Pathways / Q000502:physiology*; D011571:Psychoacoustics; D051381:Rats; D017208:Rats, Wistar; D012640:Seizures / Q000473:pathology / Q000503:physiopathology
keywords: LTP; audiogenic seizure; epilepsy; kindling; synapse; synaptic plasticity