Excitatory synaptic potentials in kainic acid-denervated rat CA1 pyramidal neurons

Abstract

Intracellular recordings were performed in the CA1 region of the rat hippocampus following an ipsilateral intraventricular injection of kainic acid. Seven days postlesion, graded bursts of up to four action potentials could be evoked by stimulation of the stratum radiatum. The evoked EPSPs underlying these bursts showed a prolonged 10–90% rise time and half-width compared to control EPSPs, an absence of a significant inhibitory phase, and an increase in magnitude and duration at depolarized resting levels. The evoked EPSPs also exhibited a significant decrease in amplitude and time course in response to D-APV (D-2-amino-5-phosphonovaleric acid; 1–20 microM), though this effect was variable from cell to cell. The prolonged time course, voltage sensitivity, and response to a selective NMDA antagonist confirmed that the major component of the EPSP in neurons from lesioned slices was mediated by NMDA receptors. The partial denervation of the CA1 area induced by the kainic acid led to both an enhanced NMDA-mediated excitatory phase and a decrease in postsynaptic inhibition, resulting in the pronounced hyperexcitability noted in the lesioned slices.

Restoration of calbindin after fetal hippocampal CA3 cell grafting into the injured hippocampus in a rat model of temporal lobe epilepsy

“…The reductions in GABA-ergic interneuron numbers following ICV KA-induced injury have been observed in both dentate gyrus and CA1 and CA3 subfields of the hippocampus (Shetty and Turner, 2001), which is consistent with loss of functional inhibition observed in this model (Wheal, 1989;Turner and Wheal, 1991;Chen et al, 1999). However, these reductions appeared to be due to loss of glutamate decarboxylase (synthesizing enzyme of GABA) rather than interneuron degeneration per se (Shetty and Turner, 2001).…”

“…Thus, though the precise reason for calbindin loss following hippocampal injury or during epilepsy is still unclear, the loss of calbindin in dentate granule cells and CA1 pyramidal cells after the KA-induced CA3-region injury implies the existence of hyperexcitability in both dentate gyrus and CA1 subfield. Indeed, physiological studies report the presence of hyperexcitability in both of these regions following CA3 region injury (Tauck and Nadler, 1985;Turner and Wheal, 1991;Perez et al, 1996). The mechanisms responsible for persistent hyperexcitability in the dentate gyrus and the CA1 subfield of the CA3-lesioned hippocampus likely include an aberrant reorganization of the disrupted circuitry, decreased afferent circuitry leading to interneurons, loss of the physiological efficacy of interneurons, and reductions in the number of GABA synthesizing interneurons (Mathern et al, 1993;Mello et al, 1993;Dudek et al, 1994;Okazaki et al, 1995;Shetty andTurner, 2000, 2001;Wuarin and Dudek, 2001;Buckmaster et al, 2002;Scharfman et al, 2003;Shetty et al, 2005) Therefore, strategies that facilitate appropriate reorganization of the disrupted circuitry may be critical for easing hyperexcitability in the injured hippocampus.…”

LTD Induction in Adult Visual Cortex: Role of Stimulus Timing and Inhibition

“…(1) DNDS-Cs does not completely block inhibition in some cells but rather attenuates it, and 2) some PSPs in the control group exhibit a very weak or absent inhibitory One way to evaluate the contribution of inhibition to compound PSPs is with the half-width measure of the PSP. This measure should reflect the relative contribution of inhibitory potentials to the PSP on the basis of the assumption that a robust inhibitory component will sharpen the PSP resulting in a small half-width, whereas a weak inhibitory component will allow a broader PSP resulting in a large half-width (Peng and Frank, 1989;Turner, 1990;Turner and Wheal, 1991). Indeed, we find a significant difference ( p Ͻ 0.01, t test) in the mean half-width in our control (7.2 Ϯ 0.5 msec; n ϭ 22) and DNDS-Cs (9.2 Ϯ 0.5 msec; n ϭ 25) groups.…”

Hippocampal AMPA and NMDA mRNA levels correlate with aberrant fascia dentata mossy fiber sprouting in the pilocarpine model of spontaneous limbic epilepsy

“…There are similar time-dependent changes in excitatory postsynaptic potentials (EPSP) in the same animal models. Following status epilepticus and/or kindling, fascia dentata granule cells, CA1 pyramids, and cells within the entorhinal cortex and basolateral amygdala show epileptiform activity that is locally generated, enhanced after GABAergic blockade, and partly or completely blocked by NMDA and AMPA receptor pharmacologic antagonists (Tauck and Nadler, 1985;Wheal, 1986, 1987;Mody and Heinemann, 1987;Turner and Wheal, 1991;Cronin et al, 1992;Meier et al, 1992;Köhr et al, 1993;Bernard and Wheal, 1995;Bear et al, 1996;Smith and Dudek, 1997;Patrylo and Dudek, 1998). Similar electrophysiologic findings, especially involving NMDA receptors, have been found in human granule cells of hippocampal sclerosis patients with intractable limbic epilepsy (Masukawa et al, 1989(Masukawa et al, , 1992Urban et al, 1990;Isokawa and Levesque, 1991;Franck et al, 1995).…”