scholarly journals Synaptic Reorganization of the Perisomatic Inhibitory Network in Hippocampi of Temporal Lobe Epileptic Patients

2017 ◽  
Vol 2017 ◽  
pp. 1-13 ◽  
Author(s):  
Lucia Wittner ◽  
Zsófia Maglóczky

GABAergic inhibition and particularly perisomatic inhibition play a crucial role in controlling the firing properties of large principal cell populations. Furthermore, GABAergic network is a key element in the therapy attempting to reduce epileptic activity. Here, we present a review showing the synaptic changes of perisomatic inhibitory neuronal subtypes in the hippocampus of temporal lobe epileptic patients, including parvalbumin- (PV-) containing and cannabinoid Type 1 (CB1) receptor-expressing (and mainly cholecystokinin-positive) perisomatic inhibitory cells, known to control hippocampal synchronies. We have examined the synaptic input of principal cells in the dentate gyrus and Cornu Ammonis region in human control and epileptic hippocampi. Perisomatic inhibitory terminals establishing symmetric synapses were found to be sprouted in the dentate gyrus. Preservation of perisomatic input was found in the Cornu Ammonis 1 and Cornu Ammonis 2 regions, as long as pyramidal cells are present. Higher density of CB1-immunostained terminals was found in the epileptic hippocampus of sclerotic patients, especially in the dentate gyrus. We concluded that both types of (PV- and GABAergic CB1-containing) perisomatic inhibitory cells are mainly preserved or showed sprouting in epileptic samples. The enhanced perisomatic inhibitory signaling may increase principal cell synchronization and contribute to generation of epileptic seizures and interictal spikes.

2006 ◽  
Vol 12 (4) ◽  
pp. 191-199 ◽  
Author(s):  
Adhemar Pettri Filho ◽  
Arthur Cukiert ◽  
Luis Diambra

RATIONALE: The development of closed-loop devices suitable for use in the treatment of epileptic patients would very likely rely on the adequate development of paradigms able to forecast the occurrence of seizures. In this paper, we studied the usefulness of approximate enthropy, of a non-linear paradigm, in this patient population. METHODS: We applied approximate entropy (ApEn) analysis to study the variability in the complexity of the peri-ictal electrocorticogram (ECoG) of patients with refractory epileptic seizures of the temporal lobe origin. Three patients were implanted with chronic subdural grids. The ApEn algorithm measured the complexity of interictal, peri-ictal and ictal phases. We selected one representative channel disclosing interictal activity for each patient and two channels per patient with ictal recordings. RESULTS: In all patients, we found one channel where the interictal activity registered in the ECoG was associated with high complexity and where ApEn was higher than 0.59. But in the other two channels, for each patient that presented interictal/ictal transitions, clinical manifestations of epileptic seizures occurred around 3.5 seconds after the entropy drop, when entropy was below 0.5. In contrast, when entropy was higher than 0.5, clinical manifestation occurred 9.5 seconds after the entropy drop. The 3.5 seconds shorter delay possibly indicates focal activity in the channel analyzed. CONCLUSIONS: Our results suggest that ApEn may be a useful instrument for early detection of epileptic activity. Its application may be indicated for prevention and diagnosis of epileptic seizures.


2015 ◽  
Vol 113 (5) ◽  
pp. 1616-1630 ◽  
Author(s):  
Latefa Yekhlef ◽  
Gian Luca Breschi ◽  
Laura Lagostena ◽  
Giovanni Russo ◽  
Stefano Taverna

GABAergic interneurons are thought to play a critical role in eliciting interictal spikes (IICs) and triggering ictal discharges in temporal lobe epilepsy, yet the contribution of different interneuronal subtypes to seizure initiation is still largely unknown. Here we took advantage of optogenetic techniques combined with patch-clamp and field recordings to selectively stimulate parvalbumin (PV)- or somatostatin (SOM)-positive interneurons expressing channelrhodopsin-2 (CHR-2) in layers II–III of adult mouse medial entorhinal cortical slices during extracellular perfusion with the proconvulsive compound 4-aminopyridine (4-AP, 100–200 μM). In control conditions, blue laser photostimulation selectively activated action potential firing in either PV or SOM interneurons and, in both cases, caused a robust GABAA-receptor-mediated inhibition in pyramidal cells (PCs). During perfusion with 4-AP, brief photostimuli (300 ms) activating either PV or SOM interneurons induced patterns of epileptiform activity that closely replicated spontaneously occurring IICs and tonic-clonic ictal discharges. Laser-induced synchronous firing in both interneuronal types elicited large compound GABAergic inhibitory postsynaptic currents (IPSCs) correlating with IICs and preictal spikes. In addition, spontaneous and laser-induced epileptic events were similarly initiated in concurrence with a large increase in extracellular potassium concentration. Finally, interneuron activation was unable to stop or significantly shorten the progression of seizurelike episodes. These results suggest that entorhinal PV and SOM interneurons are nearly equally effective in triggering interictal and ictal discharges that closely resemble human temporal lobe epileptic activity.


Author(s):  
Rady Yousif ◽  
M. Ossama Abdulghani ◽  
A. Gaber ◽  
Naglaa El Khayat ◽  
Y. A. Abo Elnaga ◽  
...  

Abstract Background Available data from witnessed and monitored sudden unexpected death in epilepsy (SUDEP) cases postulate that ictal central apnea (ICA) and ictal arrhythmias are the main causes of SUDEP. ICA is a frequent semiological feature of focal epilepsy and occasionally the only clinical manifestation of focal seizures. The aim of this study was to assess the frequency of ICA and cardiac arrhythmias in epileptic patients and to study the risk factors and predictors of their occurrence. Methods Fifty patients diagnosed with epilepsy were recruited in this study. All participants underwent prolonged surface video electroencephalography (VEEG) study using the 10-20 international electrode system with concomitant polysomnography including electrocardiography (ECG), heart rate monitoring, and peripheral capillary oxygen saturation (SpO2) using pulse oximetry. Also inductance plethysmography was used to record chest and abdominal excursions. Results Complete datasets were available in 50 patients and 112 seizures were recorded. ICA occurred exclusively in focal epilepsy (P <0.001). Temporal lobe epilepsy was associated with higher occurrence of ICA in comparison to extratemporal epilepsy (P <0.001). In addition, seizures lateralized to the left hemisphere were associated with higher occurrence of ICA (P <0.001). On the other side, tachycardia was found to be more associated with temporal lobe epilepsy and left hemispheric seizure onset (P <0.001). Conclusion ICA occurred exclusively in focal seizures and tachycardia magnitude was more with focal seizures, and both had higher percentage in temporal lobe epilepsy in comparison to other types and in seizures with left hemispheric onset.


2013 ◽  
Vol 7 (3) ◽  
pp. 77-84
Author(s):  
Chiara Pizzanelli ◽  
Lorenzo Caciagli ◽  
Veronica Bartolami ◽  
Filippo Sean Giorgi ◽  
Ilaria Pesaresi ◽  
...  

The question regarding  the existence of abnormalities in the neuroimaging exams immediately after status epilecticus or epileptic seizures, but showing complete reversibility after a proper antiepileptic therapy, has long been debated. The first reports attempting to demonstrate their existence date back to the 1980s, and relied upon computed tomography as the imaging method of choice. After the introduction of MRI, a more appropriate characterization of these abnormalities was obtained along with the description of their most frequent features: (a) T2 signal hyperintensity in the white matter and, occasionally, (b) reduced apparent diffusion coefficient (ADC) and increased signal in DWI sequences.The MRI abnormalities induced by epileptic activity pose a broad differential diagnosis including infections, inflammatory autoimmune encephalopathies, neoplasms. It remains a diagnosis of exclusion and requires proper diagnostic iter in order to reduce the risk of misdiagnosis and unnecessary intervention.In this case report, a thorough presentation will be outlined about MRI alterations in the left mesial temporal lobe, which resulted completely reversible after a proper antiepileptic therapy.


2021 ◽  
Author(s):  
Kaoutsar Nasrallah ◽  
Maria Agustina Frechou ◽  
Young J Yoon ◽  
Subrina Persaud ◽  
Tiago Goncalves ◽  
...  

Epilepsy is a devastating brain disorder whose cellular mechanisms remain poorly understood. Excitatory mossy cells (MCs) in the dentate gyrus of the hippocampus are implicated in temporal lobe epilepsy, the most common form of focal epilepsy in adults. However, the role of MCs during initial seizures, before MC loss occurs, is unclear. Here, we show that initial seizures induced with kainic acid (KA) intraperitoneal injection in adult mice, a well-established model of experimental epilepsy, not only increased MC and granule cell (GC) activity in vivo, but also triggered a BDNF-dependent long-term potentiation at MC-GC synapses (MC-GC LTP). In vivo induction of MC-GC LTP worsened KA-induced seizures, whereas selective MC silencing and Bdnf genetic removal from GCs, which abolishes LTP, were both anti-epileptic. Thus, initial seizures strengthen MC-GC synaptic transmission, thereby promoting epileptic activity. Our findings reveal a potential mechanism of epileptogenesis that may help develop therapeutic strategies for early intervention.


Hippocampus ◽  
1994 ◽  
Vol 4 (5) ◽  
pp. 583-593 ◽  
Author(s):  
Katsuhisa Uruno ◽  
Michael J. O'Connor ◽  
Leona M. Masukawa

1995 ◽  
Vol 74 (2) ◽  
pp. 829-840 ◽  
Author(s):  
P. S. Mangan ◽  
D. A. Rempe ◽  
E. W. Lothman

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)


1992 ◽  
Vol 579 (1) ◽  
pp. 119-127 ◽  
Author(s):  
Leona M. Masukawa ◽  
Katsuhisa Uruno ◽  
Michael Sperling ◽  
Michael J. O'Connor ◽  
Linda J. Burdette

1995 ◽  
Vol 74 (2) ◽  
pp. 841-848 ◽  
Author(s):  
E. W. Lothman ◽  
D. A. Rempe ◽  
P. S. Mangan

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)


2020 ◽  
Vol 43 (1) ◽  
pp. 55-72 ◽  
Author(s):  
Steven J. Middleton ◽  
Thomas J. McHugh

Although Lorente de No’ recognized the anatomical distinction of the hippocampal Cornu Ammonis (CA) 2 region, it had, until recently, been assigned no unique function. Its location between the key players of the circuit, CA3 and CA1, which along with the entorhinal cortex and dentate gyrus compose the classic trisynaptic circuit, further distracted research interest. However, the connectivity of CA2 pyramidal cells, together with unique patterns of gene expression, hints at a much larger contribution to hippocampal information processing than has been ascribed. Here we review recent advances that have identified new roles for CA2 in hippocampal centric processing, together with specialized functions in social memory and, potentially, as a broadcaster of novelty. These new data, together with CA2's role in disease, justify a closer look at how this small region exerts its influence and how it might best be exploited to understand and treat disease-related circuit dysfunctions.


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