Differential responses between CA1 pyramidal cells and dentate gyrus granule cells to ischemia-like conditions in rat hippocampal slices

1. In this report we compare changes in inhibitory neurotransmission within the CA1 region and the dentate gyrus (DG) in a model of chronic temporal lobe epilepsy (TLE). Extracellular and intracellular recordings were obtained in combined hippocampal-parahippocampal slices > or = 1 mo after a period of self-sustaining limbic status epilepticus (SSLSE) induced by continuous hippocampal stimulation. 2. Polysynaptic inhibitory postsynaptic potentials (IPSPs) were induced by positioning electrodes to activate specific afferent pathways and evoking responses in the absence of glutamate receptor antagonists [D(-)-2-amino-5-phosphonovaleric acid (APV) and 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX)]. Polysynaptic IPSPs were evoked in CA1 pyramidal cells from electrodes positioned in stratum radiatum and in stratum lacunosum/moleculare. Polysynaptic IPSPs were evoked in DG granule cells from electrodes positioned over the perforant path located in the subiculum. Monosynaptic IPSPs were induced by positioning electrodes within 200 microns of the intracellular recording electrode (near site stimulation) and stimulating in the presence of APV and CNQX to block ionotropic glutamate receptors. Monosynaptic IPSPs were evoked in CA1 pyramidal cells with electrodes positioned in the stratum lacunosum/moleculare and stratum pyramidale. Monosynaptic IPSPs were evoked in DG granule cells with electrodes positioned in the stratum moleculare. 3. Population spike (PS) amplitudes were employed to assure that a full range of stimulus strengths, from subthreshold for action potentials to an intensity giving maximal-amplitude PSs, was used to elicit polysynaptic IPSPs in CA1 pyramidal cells in both post-SSLSE and control slices. In control tissue, polysynaptic IPSPs were biphasic, composed of early and late events. In post-SSLSE tissue, polysynaptic IPSPs were markedly diminished. The diminution of polysynaptic IPSPs was detected at all levels of stimulus intensity. Both early IPSPs [mediated by gamma-aminobutyric acid-A (GABAA) receptors] and late IPSPs (mediated by GABAB receptors) were diminished. Polysynaptic IPSPs were diminished with both stratum radiatum and with stratum lacunosum/moleculare stimulation. 4. Reversal potentials for either polysynaptic early or polysynaptic late IPSPs evoked in CA1 pyramidal cells by stratum radiatum stimulation were not different in slices from post-SSLSE animals as compared with control animals. Likewise, reversal potentials for either polysynaptic early or polysynaptic late IPSPs evoked by stratum lacunosum/moleculare stimulation did not differ in the two groups. These findings excluded changes in driving force as an explanation for the diminished amplitude of IPSPs in CA1 pyramidal cells in the post-SSLSE model.(ABSTRACT TRUNCATED AT 400 WORDS)

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Changes in excitatory neurotransmission in the CA1 region and dentate gyrus in a chronic model of temporal lobe epilepsy

Journal of Neurophysiology ◽

10.1152/jn.1995.74.2.841 ◽

1995 ◽

Vol 74 (2) ◽

pp. 841-848 ◽

Cited By ~ 39

Author(s):

E. W. Lothman ◽

D. A. Rempe ◽

P. S. Mangan

Keyword(s):

Temporal Lobe Epilepsy ◽

Dentate Gyrus ◽

Temporal Lobe ◽

Granule Cells ◽

Pyramidal Cells ◽

Postsynaptic Potentials ◽

Ca1 Pyramidal Cells ◽

Control Tissue ◽

Ca1 Region ◽

Excitatory Neurotransmission

1. In this report we compare changes of excitatory neurotransmission within the CA1 region and the dentate gyrus (DG) in a model of chronic temporal lobe epilepsy (TLE). Extracellular and intracellular recordings were obtained from in vitro hippocampal-parahippocampal slices > or = 1 mo after a period of self-sustaining limbic status epilepticus (SSLSE) induced by continuous hippocampal stimulation. Pyramidal cells in CA1 were activated by electrodes in the stratum lacunosum/moleculare or stratum radiatum. Granule cells in DG were similarly activated by electrodes positioned in the perforant path. 2. Monosynaptic excitatory postsynaptic potentials (EPSPs) evoked in CA1 pyramidal cells in post-SSLSE tissue were always longer than those evoked in control tissue, irrespective of whether hyperresponsiveness was present or not. EPSPs elicited by stimulus subthreshold for action potentials (APs) in post-SSLSE and in control slices and matched in amplitude had a statistically greater duration in the post-SSLSE slices. Durations of monosynaptic EPSPs elicited by stimuli subthreshold for APs in DG granule cells in post-SSLSE slices were not longer than EPSPs of equal amplitude elicited in control slices. 3. Higher-intensity stimuli produced EPSPs with associated APs and, in certain cases in the post-SSLSE tissue, hyperresponsive events with multiple (> or = 3) APs. Durations of depolarizing profiles with stimuli producing APs were overall longer in both CA1 pyramidal cells and DG granule cells and correlated with the degree of hyperresponsiveness. 4. Neither the amplitudes nor the durations of monosynaptic EPSPs evoked in CA1 pyramidal cells in slices from control animals were affected by the addition of D(-)-2-amino-5-phosphonovaleric acid (APV), a blocker of the N-methyl-D-aspartate (NMDA) receptor, to the artificial cerebrospinal fluid (ACSF) bathing the slices. In contrast to the situation in control tissue, in post-SSLSE tissue APV shortened EPSPs evoked in CA1 pyramidal cells while not changing their amplitudes. After APV, inhibitory postsynaptic potentials (IPSPs) remained greatly diminished or absent in CA1 pyramidal cells. APV did not statistically decrease amplitudes of monosynaptic EPSPs evoked in DG granule cells in either control slices or post-SSLSE slices. APV decreased EPSP durations in both types of slices, more so in the post-SSLSE tissue. 5. In control slices, APV did not change the amplitudes or durations of depolarizing profiles of responses evoked by stimuli producing APs in CA1. Similarly, APV did not change the amplitudes of such responses in DG. However, APV did reduce the durations of such responses in DG in control slices.(ABSTRACT TRUNCATED AT 400 WORDS)

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Strychnine-Sensitive Glycine Receptors Depress Hyperexcitability in Rat Dentate Gyrus

Journal of Neurophysiology ◽

10.1152/jn.00908.2002 ◽

2003 ◽

Vol 89 (3) ◽

pp. 1339-1342 ◽

Cited By ~ 47

Author(s):

Siriporn C. Chattipakorn ◽

Lori L. McMahon

Keyword(s):

Dentate Gyrus ◽

Chloride Channels ◽

Granule Cells ◽

Hippocampal Slices ◽

Physiological Role ◽

Pyramidal Cells ◽

Epileptic Activity ◽

Action Potential Firing ◽

Neuronal Inhibition ◽

Novel Target

Previously we have shown that strychnine-sensitive glycine-gated chloride channels (GlyRs) are functionally expressed by CA1 pyramidal cells and GABAergic interneurons in mature rat hippocampal slices. We now report that glycine application to dentate granule cells and hilar interneurons recorded in acute slices from adolescent rats elicits a strychnine-sensitive current similar to glycine-mediated currents recorded in area CA1, indicating that GlyRs are also present on neurons in the dentate gyrus. This finding suggests that GlyRs have a widespread distribution in the hippocampal region. The physiological role of GlyRs in forebrain is unclear, but it is possible that these receptors mediate neuronal inhibition, similar to γ-aminobutyric acid-A (GABAA) receptors and thus could be a novel target for antiepileptic therapy. Therefore we tested the hypothesis that activation of inhibitory GlyRs could suppress neuronal hyperexcitability in dentate, a brain region vulnerable to epileptic activity. In whole-cell current-clamp recordings of granule cells, we observed a membrane potential hyperpolarization followed by cessation of the action potential firing pattern in hyperexcitable slices induced by elevated extracellular K+ or by blocking GABAA receptors with bicuculline. The GlyR antagonist, strychnine, prevented the antiepileptic effect of glycine. These results demonstrate that glycine, acting at GlyRs, elicits neuronal inhibition in dentate. Further, our findings suggest the possibility that these receptors could be a therapeutic target for the treatment of epilepsy.

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