Idit Tamir1, Moshe Daninos2, Yoel Yaari2. 1. Department of Medical Neurobiology, IMRIC, Hebrew University-Hadassah School of Medicine, Jerusalem 91120, Israel. Electronic address: iditt@hadassah.org.il. 2. Department of Medical Neurobiology, IMRIC, Hebrew University-Hadassah School of Medicine, Jerusalem 91120, Israel.
Abstract
OBJECTIVE: In experimental models of temporal lobe epilepsy (TLE), brain neurons manifest multiple changes in intrinsic excitability that contribute to neuronal network hyperexcitability. We have investigated whether the intrinsic firing response gain, quantified by the slope of the function relating the number of evoked spikes (Ns) to input excitatory current intensity (I), is modified in principal rat hippocampal neurons in the pilocarpine-status epilepticus (SE) model of TLE. METHODS: Intracellular recordings were made in CA3 and CA1 pyramidal cells (PCs) and dentate granule cells (GCs) in acute hippocampal slices obtained 7-36days after pilocarpine-SE. Firing response gains were determined empirically from Ns/I relationships and compared to other measured neuronal properties. RESULTS: The firing response gain in all three types of principal neurons, particularly in CA3 PCs, was markedly multiplied following pilocarpine-SE. Analyses of persistent changes in active and passive properties of CA3 PCs suggested that this increase is multifactorial in origin, the major factors being a reduction in amplitude of the slow afterhyperpolarization and an increase in the fraction of bursting neurons. SIGNIFICANCE: Here we show that pilocarpine-SE causes multiplication of the firing response gain in the three principal neurons in the hippocampal trisynaptic pathway. This alteration undoubtedly would contribute to hippocampal hyperexcitability in SE-induced TLE.
OBJECTIVE: In experimental models of temporal lobe epilepsy (TLE), brain neurons manifest multiple changes in intrinsic excitability that contribute to neuronal network hyperexcitability. We have investigated whether the intrinsic firing response gain, quantified by the slope of the function relating the number of evoked spikes (Ns) to input excitatory current intensity (I), is modified in principal rat hippocampal neurons in the pilocarpine-status epilepticus (SE) model of TLE. METHODS: Intracellular recordings were made in CA3 and CA1 pyramidal cells (PCs) and dentate granule cells (GCs) in acute hippocampal slices obtained 7-36days after pilocarpine-SE. Firing response gains were determined empirically from Ns/I relationships and compared to other measured neuronal properties. RESULTS: The firing response gain in all three types of principal neurons, particularly in CA3 PCs, was markedly multiplied following pilocarpine-SE. Analyses of persistent changes in active and passive properties of CA3 PCs suggested that this increase is multifactorial in origin, the major factors being a reduction in amplitude of the slow afterhyperpolarization and an increase in the fraction of bursting neurons. SIGNIFICANCE: Here we show that pilocarpine-SE causes multiplication of the firing response gain in the three principal neurons in the hippocampal trisynaptic pathway. This alteration undoubtedly would contribute to hippocampal hyperexcitability in SE-induced TLE.