scholarly journals Aberrant hippocampal mossy fibers in temporal lobe epilepsy target excitatory and inhibitory neurons

Epilepsia ◽  
2021 ◽  
Author(s):  
Barbara Puhahn‐Schmeiser ◽  
Kathrin Leicht ◽  
Florian Gessler ◽  
Thomas M. Freiman
Keyword(s):  
Temporal Lobe Epilepsy ◽  
Temporal Lobe ◽  
Mossy Fibers ◽  
Inhibitory Neurons

Developing cell transplantation for temporal lobe epilepsy

2008 ◽  
Vol 24 (3-4) ◽  
pp. E17 ◽  
Author(s):  
R. Mark Richardson ◽  
Nicholas M. Barbaro ◽  
Arturo Alvarez-Buylla ◽  
Scott C. Baraban
Keyword(s):  
Temporal Lobe Epilepsy ◽  
Cell Transplantation ◽  
Temporal Lobe ◽  
Neuronal Loss ◽  
Mesial Temporal Lobe Epilepsy ◽  
Careful Consideration ◽  
Inhibitory Neurons ◽  
Local Inhibition ◽  
Neuronal Precursors ◽  
Exact Etiology

✓ Mesial temporal lobe epilepsy (MTLE) is presumed to develop progressively as a consequence of synaptic reorganization and neuronal loss, although the exact etiology of seizure development is unknown. Nearly 30% of patients with MTLE have disabling seizures despite pharmacological treatment, and the majority of these patients are recommended for resection. The authors review cell transplantation as an alternative approach to the treatment of epilepsy. Recent work in animal models shows that grafted neuronal precursors that differentiate into inhibitory interneurons can increase the level of local inhibition. Grafts of these inhibitory neurons could help restore equilibrium in MTLE. Developing a sound transplantation strategy involves careful consideration of the etiology of MTLE and the expected functional role of transplanted cells. These issues are reviewed, with a focus on those factors most likely to influence clinically applicable results.

scholarly journals Glutamate decarboxylase67 is expressed in hippocampal mossy fibers of temporal lobe epilepsy patients

Hippocampus ◽  
2011 ◽  
Vol 22 (3) ◽  
pp. 590-603 ◽  
Author(s):  
Günther Sperk ◽  
Anna Wieselthaler-Hölzl ◽  
Susanne Pirker ◽  
Ramon Tasan ◽  
Sarah S. Strasser ◽  
...  
Keyword(s):  
Temporal Lobe Epilepsy ◽  
Temporal Lobe ◽  
Mossy Fibers

scholarly journals Excitatory Input Onto Hilar Somatostatin Interneurons Is Increased in a Chronic Model of Epilepsy

2010 ◽  
Vol 104 (4) ◽  
pp. 2214-2223 ◽  
Author(s):  
Brian Halabisky ◽  
Isabel Parada ◽  
Paul S. Buckmaster ◽  
David A. Prince
Keyword(s):  
Temporal Lobe Epilepsy ◽  
Temporal Lobe ◽  
Fluorescent Protein ◽  
Hippocampal Slices ◽  
Inhibitory Neurons ◽  
Membrane Properties ◽  
Resting Membrane Potential ◽  
Whole Cell ◽  
Functional Changes

The density of somatostatin (SOM)-containing GABAergic interneurons in the hilus of the dentate gyrus is significantly decreased in both human and experimental temporal lobe epilepsy. We used the pilocarpine model of status epilepticus and temporal lobe epilepsy in mice to study anatomical and electrophysiological properties of surviving somatostatin interneurons and determine whether compensatory functional changes occur that might offset loss of other inhibitory neurons. Using standard patch-clamp techniques and pipettes containing biocytin, whole cell recordings were obtained in hippocampal slices maintained in vitro. Hilar SOM cells containing enhanced green fluorescent protein (EGFP) were identified with fluorescent and infrared differential interference contrast video microscopy in epileptic and control GIN (E GFP-expressing Inhibitory Neurons) mice. Results showed that SOM cells from epileptic mice had 1) significant increases in somatic area and dendritic length; 2) changes in membrane properties, including a small but significant decrease in resting membrane potential, and increases in time constant and whole cell capacitance; 3) increased frequency of slowly rising spontaneous excitatory postsynaptic currents (sEPSCs) due primarily to increased mEPSC frequency, without changes in the probability of release; 4) increased evoked EPSC amplitude; and 5) increased spontaneous action potential generation in cell-attached recordings. Results suggest an increase in excitatory innervation, perhaps on distal dendrites, considering the slower rising EPSCs and increased output of hilar SOM cells in this model of epilepsy. In sum, these changes would be expected to increase the inhibitory output of surviving SOM interneurons and in part compensate for interneuronal loss in the epileptogenic hippocampus.

scholarly journals Early detonation by sprouted mossy fibers enables aberrant dentate network activity

2018 ◽  
Author(s):  
William D. Hendricks ◽  
Gary L. Westbrook ◽  
Eric Schnell
Keyword(s):  
Temporal Lobe Epilepsy ◽  
Temporal Lobe ◽  
High Probability ◽  
Granule Cells ◽  
Mossy Fiber ◽  
Glutamate Release ◽  
Mossy Fibers ◽  
Network Activity ◽  
Short Term ◽  
Dentate Granule Cells

AbstractIn temporal lobe epilepsy, sprouting of hippocampal mossy fiber axons onto dentate granule cell dendrites creates a recurrent excitatory network. However, unlike mossy fibers projecting to CA3, sprouted mossy fiber synapses depress upon repetitive activation. Thus, despite their proximal location, large presynaptic terminals, and ability to excite target neurons, the impact of sprouted mossy fiber synapses on hippocampal hyperexcitability is unclear. We find that despite their short-term depression, single episodes of sprouted mossy fiber activation in hippocampal slices initiated bursts of recurrent polysynaptic excitation. Consistent with a contribution to network hyperexcitability, optogenetic activation of sprouted mossy fibers reliably triggered action potential firing in postsynaptic dentate granule cells after single light pulses. This pattern resulted in a shift in network recruitment dynamics to an “early detonation” mode and an increased probability of release compared to mossy fiber synapses in CA3. A lack of tonic adenosine-mediated inhibition contributed to the higher probability of glutamate release thus facilitating reverberant circuit activity.Significance StatementSprouted mossy fibers are one of the hallmark histopathological findings in temporal lobe epilepsy. These fibers form recurrent excitatory synapses onto other dentate granule cells that display profound short-term depression. Here, however, we show that although these sprouted mossy fibers weaken substantially during repetitive activation, their initial high probability of glutamate release can activate reverberant network activity. Furthermore, we find that a lack of tonic adenosine inhibition enables this high probability of release and, consequently, recurrent network activity.

Regular-spiking cells in the presubiculum are hyperexcitable in a rat model of temporal lobe epilepsy

2014 ◽  
Vol 112 (11) ◽  
pp. 2888-2900 ◽  
Author(s):  
Saad Abbasi ◽  
Sanjay S. Kumar
Keyword(s):  
Temporal Lobe Epilepsy ◽  
Temporal Lobe ◽  
Cell Types ◽  
Inhibitory Neurons ◽  
Temporal Lobes ◽  
Axonal Projections ◽  
Physiological Properties ◽  
Predominant Cell Type ◽  
Altered Cell ◽  
Reduced Activity

Temporal lobe epilepsy (TLE) is the most common form of adult epilepsy, characterized by recurrent seizures originating in the temporal lobes. Here, we examine TLE-related changes in the presubiculum (PrS), a less-studied parahippocampal structure that both receives inputs from and projects to regions affected by TLE. We assessed the state of PrS neurons in TLE electrophysiologically to determine which of the previously identified cell types were rendered hyperexcitable in epileptic rats and whether their intrinsic and/or synaptic properties were altered. Cell types were characterized based on action potential discharge profiles followed by unsupervised hierarchical clustering. PrS neurons in epileptic animals could be divided into three major groups comprising of regular-spiking (RS), irregular-spiking (IR), and fast-adapting (FA) cells. RS cells, the predominant cell type encountered in PrS, were the only cells that were hyperexcitable in TLE. These neurons were previously identified as sending long-range axonal projections to neighboring structures including medial entorhinal area (MEA), and alterations in intrinsic properties increased their propensity for sustained firing of action potentials. Frequency and amplitude of both spontaneous excitatory and inhibitory synaptic events were reduced. Further analysis of nonaction potential-dependent miniature currents (in tetrodotoxin) indicated that reduction in excitatory drive to these neurons was mediated by decreased activity of excitatory neurons that synapse with RS cells concomitant with reduced activity of inhibitory neurons. Alterations in physiological properties of PrS neurons and their ensuing hyperexcitability could entrain parahippocampal structures downstream of PrS, including the MEA, contributing to temporal lobe epileptogenesis.

Neuropeptide Y biosynthesis is markedly induced in mossy fibers during temporal lobe epilepsy of the rat

1990 ◽  
Vol 112 (2-3) ◽  
pp. 143-148 ◽  
Author(s):  
Josef Marksteiner ◽  
Martin Ortler ◽  
Romuald Bellmann ◽  
Günther Sperk
Keyword(s):  
Temporal Lobe Epilepsy ◽  
Neuropeptide Y ◽  
Temporal Lobe ◽  
Mossy Fibers

scholarly journals A Portion of Inhibitory Neurons in Human Temporal Lobe Epilepsy are Functionally Upregulated: An Endogenous Mechanism for Seizure Termination

2014 ◽  
Vol 21 (2) ◽  
pp. 204-214 ◽  
Author(s):  
Bo Wen ◽  
Hao Qian ◽  
Jing Feng ◽  
Rong-Jing Ge ◽  
Xin Xu ◽  
...  
Keyword(s):  
Temporal Lobe Epilepsy ◽  
Temporal Lobe ◽  
Inhibitory Neurons ◽  
Seizure Termination ◽  
Human Temporal Lobe

Theory of mind and social competence in children and adolescents with temporal lobe epilepsy.

2019 ◽  
Vol 33 (7) ◽  
pp. 986-995 ◽  
Author(s):  
Elizabeth Stewart ◽  
Cathy Catroppa ◽  
Linda Gonzalez ◽  
Deepak Gill ◽  
Richard Webster ◽  
...  
Keyword(s):  
Theory Of Mind ◽  
Social Competence ◽  
Temporal Lobe Epilepsy ◽  
Children And Adolescents ◽  
Temporal Lobe

Decreased Dopamine D2/D3-Receptor Binding in the Temporal Lobe and the Bilateral Basal Ganglia in patients with Temporal Lobe Epilepsy

2012 ◽  
Vol 43 (01) ◽  
Author(s):  
VE Bernedo Paredes ◽  
H Schwartz ◽  
M Gartenschläger ◽  
M Gartenschläger ◽  
HG Buchholz ◽  
...  
Keyword(s):  
Basal Ganglia ◽  
Temporal Lobe Epilepsy ◽  
Temporal Lobe ◽  
Receptor Binding ◽  
D3 Receptor ◽  
Dopamine D2
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