scholarly journals Disruption of Inhibition in Area CA1 of the Hippocampus in a Rat Model of Temporal Lobe Epilepsy

2001 ◽  
Vol 86 (5) ◽  
pp. 2231-2245 ◽  
Author(s):  
Maria J. Denslow ◽  
Tore Eid ◽  
Fu Du ◽  
Robert Schwarcz ◽  
Eric W. Lothman ◽  
...  
Keyword(s):  
Temporal Lobe Epilepsy ◽  
Dentate Gyrus ◽  
Temporal Lobe ◽  
Rat Model ◽  
Inhibitory Interneurons ◽  
Paired Pulse ◽  
Inhibitory Function ◽  
Electrolytic Lesions ◽  
Pulse Stimulation ◽  
Stimulation Of

Previous studies have revealed a loss of neurons in layer III of the entorhinal cortex (EC) in patients with temporal lobe epilepsy. These neurons project to the hippocampus and may activate inhibitory interneurons, so that their loss could disrupt inhibitory function in the hippocampus. The present study evaluates this hypothesis in a rat model in which layer III neurons were selectively destroyed by focal injections of the indirect excitotoxin, aminooxyacetic acid (AOAA). Inhibitory function in the hippocampus was assessed by evaluating the discharge of CA1 neurons in response to stimulation of afferent pathways in vivo. In control animals, stimulation of the temporo-ammonic pathway leads to heterosynaptic inhibition of population spikes generated by subsequent stimulation of the commissural projection to CA1. This heterosynaptic inhibition was substantially reduced in animals that had received AOAA injections 1 mo previously. Stimulation of the commissural projection also elicited multiple population spikes in CA1 in AOAA-injected animals, and homosynaptic inhibition in response to paired-pulse stimulation of the commissural projection was dramatically diminished. These results suggest a disruption of inhibitory function in CA1 in AOAA-injected animals. To determine whether the disruption of inhibition occurred selectively in CA1, we assessed paired-pulse inhibition in the dentate gyrus. Both homosynaptic inhibition generated by paired-pulse stimulation of the perforant path, and heterosynaptic inhibition produced by activation of the commissural projection to the dentate gyrus appeared largely comparable in AOAA-injected and control animals; thus abnormalities in inhibitory function following AOAA injections occurred relatively selectively in CA1. Electrolytic lesions of the EC did not cause the same loss of inhibition as seen in animals with AOAA injections, indicating that the loss of inhibition in CA1 is not due to the loss of excitatory driving of inhibitory interneurons. Also, electrolytic lesions of the EC in animals that had been injected previously with AOAA had little effect on the abnormal physiological responses in CA1, suggesting that most alterations in inhibition in CA1 are not due to circuit abnormalities within the EC. Comparisons of control and AOAA-injected animals in a hippocampal kindling paradigm revealed that the duration of afterdischarges elicited by high-frequency stimulation of CA3, and the number of stimulations required to elicit kindled seizures were comparable. Taken together, our results reveal that the selective loss of layer III neurons induced by AOAA disrupts inhibitory function in CA1, but this does not create a circuit that is more prone to at least one form of kindling.

Responses of Deep Entorhinal Cortex are Epileptiform in an Electrogenic Rat Model of Chronic Temporal Lobe Epilepsy

1998 ◽  
Vol 80 (1) ◽  
pp. 230-240 ◽  
Author(s):  
Nathan B. Fountain ◽  
Jonathan Bear ◽  
Edward H. Bertram ◽  
Eric W. Lothman
Keyword(s):  
Temporal Lobe Epilepsy ◽  
Entorhinal Cortex ◽  
Temporal Lobe ◽  
Rat Model ◽  
Action Potentials ◽  
Nmda Antagonist ◽  
Target Cells ◽  
Excitatory Postsynaptic Potential ◽  
Inhibitory Interneurons ◽  
And Control

Fountain, Nathan B., Jonathan Bear, Edward H. Bertram III, and Eric W. Lothman. Responses of deep entorhinal cortex are epileptiform in an electrogenic rat model of chronic temporal lobe epilepsy. J. Neurophysiol. 80: 230–240, 1998. We investigated whether entorhinal cortex (EC) layer IV neurons are hyperexcitable in the post-selfsustaining limbic status epilepticus (post-SSLSE) animal model of temporal lobe epilepsy. We studied naive rats ( n = 44), epileptic rats that had experienced SSLSE resulting in spontaneous seizures ( n = 45), and electrode controls ( n = 7). There were no differences between electrode control and naive groups, which were pooled into a single control group. Intracellular and extracellular recordings were made from deep layers of EC, targeting layer IV, which was activated by stimulation of the superficial layers of EC or the angular bundle. There were no differences between epileptic and control neurons in basic cellular characteristics, and all neurons were quiescent under resting conditions. In control tissue, 77% of evoked intracellular responses consisted of a short-duration [8.6 ± 1.3 (SE) ms] excitatory postsynaptic potential and a single action potential followed by γ-aminobutyric acid-A (GABAA) and GABAB inhibitory post synaptic potentials (IPSPs). Ten percent of controls did not contain IPSPs. In chronically epileptic tissue, evoked intracellular responses demonstrated prolonged depolarizing potentials (256 ± 39 ms), multiple action potentials (13 ± 4), and no IPSPs. Ten percent of epileptic responses were followed by rhythmic “clonic” depolarizations. Epileptic responses exhibited an all-or-none response to progressive increases in stimulus intensity and required less stimulation to elicit action potentials. In both epileptic and control animals, intracellular responses correlated precisely in morphology and duration with extracellular field potentials. Severing the hippocampus from the EC did not alter the responses. Duration of intracellular epileptic responses was reduced 22% by the N-methyl-d-aspartate (NMDA) antagonist d(−)-2-amino-5-phosphonovaleric acid (APV), but they did not return to normal and IPSPs were not restored. Epileptic and control responses were abolished by the non-NMDA antagonist 6,7-dinitroquinoxaline-2-3-dione (DNQX). A monosynaptic IPSP protocol was used to test connectivity of inhibitory interneurons to primary cells by direct activation of interneurons with a stimulating electrode placed near the recording electrode in the presence of APV and DNQX. Using this protocol, IPSPs similar to control ( P > 0.05) were seen in epileptic cells. The findings demonstrate that deep layer EC cells are hyperexcitable or “epileptiform” in this model. Hyperexcitability is not due to interactions with the hippocampus. It is due partially to augmented NMDA-mediated excitation. The lack of IPSPs in epileptic neurons may suggest inhibition is impaired, but we found evidence that inhibitory interneurons are connected to their target cells and are capable of inducing IPSPs.

Circadian dentate gyrus excitability in a rat model of temporal lobe epilepsy

2012 ◽  
Vol 234 (1) ◽  
pp. 105-111 ◽  
Author(s):  
Julia Matzen ◽  
Katharina Buchheim ◽  
Martin Holtkamp
Keyword(s):  
Temporal Lobe Epilepsy ◽  
Dentate Gyrus ◽  
Temporal Lobe ◽  
Rat Model

scholarly journals Low frequency stimulation of ventral hippocampal commissures reduces seizures in a rat model of chronic temporal lobe epilepsy

Epilepsia ◽  
2011 ◽  
Vol 53 (1) ◽  
pp. 147-156 ◽  
Author(s):  
Saifur Rashid ◽  
Gerald Pho ◽  
Michael Czigler ◽  
Mary A. Werz ◽  
Dominique M. Durand
Keyword(s):  
Temporal Lobe Epilepsy ◽  
Temporal Lobe ◽  
Rat Model ◽  
Low Frequency ◽  
Low Frequency Stimulation ◽  
Frequency Stimulation ◽  
Stimulation Of

scholarly journals Pharmacological plasticity of GABAAreceptors at dentate gyrus synapses in a rat model of temporal lobe epilepsy

2004 ◽  
Vol 557 (2) ◽  
pp. 473-487 ◽  
Author(s):  
Claire Leroy ◽  
Pierrick Poisbeau ◽  
A. Florence Keller ◽  
Astrid Nehlig
Keyword(s):  
Temporal Lobe Epilepsy ◽  
Dentate Gyrus ◽  
Temporal Lobe ◽  
Rat Model

Survival of mossy cells of the hippocampal dentate gyrus in humans with mesial temporal lobe epilepsy

2009 ◽  
Vol 111 (6) ◽  
pp. 1237-1247 ◽  
Author(s):  
László Seress ◽  
Hajnalka Ábrahám ◽  
Zsolt Horváth ◽  
Tamás Dóczi ◽  
József Janszky ◽  
...  
Keyword(s):  
Temporal Lobe Epilepsy ◽  
Dentate Gyrus ◽  
Temporal Lobe ◽  
Pyramidal Neurons ◽  
Hippocampal Sclerosis ◽  
Mesial Temporal Lobe Epilepsy ◽  
Drug Resistant ◽  
Hippocampal Dentate Gyrus ◽  
Mossy Cells ◽  
Mesial Temporal Lobe

Object Hippocampal sclerosis can be identified in most patients with mesial temporal lobe epilepsy (TLE). Surgical removal of the sclerotic hippocampus is widely performed to treat patients with drug-resistant mesial TLE. In general, both epilepsy-prone and epilepsy-resistant neurons are believed to be in the hippocampal formation. The hilar mossy cells of the hippocampal dentate gyrus are usually considered one of the most vulnerable types of neurons. The aim of this study was to clarify the fate of mossy cells in the hippocampus in epileptic humans. Methods Of the 19 patients included in this study, 15 underwent temporal lobe resection because of drug-resistant TLE. Four patients were used as controls because they harbored tumors that had not invaded the hippocampus and they had experienced no seizures. Histological evaluation of resected hippocampal tissues was performed using immunohistochemistry. Results Mossy cells were identified in the control as well as the epileptic hippocampi by using cocaine- and amphetamine-regulated transcript peptide immunohistochemistry. In most cases the number of mossy cells was reduced and thorny excrescences were smaller in the epileptic hippocampi than in controls; however, there was a significant loss of pyramidal cells and a partial loss of granule cells in the same epileptic hippocampi in which mossy cell loss was apparent. The loss of mossy cells could be correlated with the extent of hippocampal sclerosis, patient age at seizure onset, duration of epilepsy, and frequency of seizures. Conclusions In many cases large numbers of mossy cells were present in the hilus of the dentate gyrus when most pyramidal neurons of the CA1 and CA3 areas of the Ammon's horn were lost, suggesting that mossy cells may not be more vulnerable to epileptic seizures than the hippocampal pyramidal neurons.

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