Altered Inhibition in Lateral Amygdala Networks in a Rat Model of Temporal Lobe Epilepsy

2006 ◽  
Vol 95 (4) ◽  
pp. 2143-2154 ◽  
Author(s):  
Ruba Benini ◽  
Massimo Avoli
Keyword(s):  
Temporal Lobe Epilepsy ◽  
Temporal Lobe ◽  
Brain Slices ◽  
Reversal Potential ◽  
Neuronal Firing ◽  
Network Activity ◽  
Limbic Seizures ◽  
Inhibitory Mechanisms ◽  
Field Activity ◽  
Lateral Nucleus

Clinical and experimental evidence indicates that the amygdala is involved in limbic seizures observed in patients with temporal lobe epilepsy. Here, we used simultaneous field and intracellular recordings from horizontal brain slices obtained from pilocarpine-treated rats and age-matched nonepileptic controls (NECs) to shed light on the electrophysiological changes that occur within the lateral nucleus (LA) of the amygdala. No significant differences in LA neuronal intrinsic properties were observed between pilocarpine-treated and NEC tissue. However, spontaneous field activity could be recorded in the LA of 21% of pilocarpine-treated slices but never from NECs. At the intracellular level, this network activity was characterized by robust neuronal firing and was abolished by glutamatergic antagonists. In addition, we could identify in all pilocarpine-treated LA neurons: 1) large amplitude depolarizing postsynaptic potentials (PSPs) and 2) a lower incidence of spontaneous hyperpolarizing PSPs as compared with NECs. Single-shock stimulation of LA networks in the presence of glutamatergic antagonists revealed a biphasic inhibitory PSP (IPSP) in both NECs and pilocarpine-treated tissue. The reversal potential of the early GABAA receptor–mediated component, but not of the late GABAB receptor–mediated component, was significantly more depolarized in pilocarpine-treated slices. Furthermore, the peak conductance of both fast and late IPSP components had significantly lower values in pilocarpine-treated LA cells. Finally, paired-pulse stimulation protocols in the presence of glutamatergic antagonists revealed a less pronounced depression of the second IPSP in pilocarpine-treated slices compared with NECs. Altogether, these findings suggest that alterations in both pre- and postsynaptic inhibitory mechanisms contribute to synaptic hyperexcitability of LA networks in epileptic rats.

scholarly journals Chronobiology of limbic seizures: Potential mechanisms and prospects of chronotherapy for mesial temporal lobe epilepsy

2019 ◽  
Vol 98 ◽  
pp. 122-134 ◽  
Author(s):  
Daniel Leite Góes Gitai ◽  
Tiago Gomes de Andrade ◽  
Ygor Daniel Ramos dos Santos ◽  
Sahithi Attaluri ◽  
Ashok K. Shetty
Keyword(s):  
Temporal Lobe Epilepsy ◽  
Temporal Lobe ◽  
Mesial Temporal Lobe Epilepsy ◽  
Limbic Seizures ◽  
Mesial Temporal Lobe

Changes in Granule Cell Firing Rates Precede Locally Recorded Spontaneous Seizures by Minutes in an Animal Model of Temporal Lobe Epilepsy

2008 ◽  
Vol 99 (5) ◽  
pp. 2431-2442 ◽  
Author(s):  
Mark R. Bower ◽  
Paul S. Buckmaster
Keyword(s):  
Temporal Lobe Epilepsy ◽  
Dentate Gyrus ◽  
Firing Rate ◽  
Temporal Lobe ◽  
Granule Cells ◽  
Neuronal Firing ◽  
Seizure Onset ◽  
Electrographic Seizure ◽  
Firing Rates ◽  
Spontaneous Seizures

Although much is known about persistent molecular, cellular, and circuit changes associated with temporal lobe epilepsy, mechanisms of seizure onset remain unclear. The dentate gyrus displays many persistent epilepsy-related abnormalities and is in the mesial temporal lobe where seizures initiate in patients. However, little is known about seizure-related activity of individual neurons in the dentate gyrus. We used tetrodes to record action potentials of multiple, single granule cells before and during spontaneous seizures in epileptic pilocarpine-treated rats. Subsets of granule cells displayed four distinct activity patterns: increased firing before seizure onset, decreased firing before seizure onset, increased firing only after seizure onset, and unchanged firing rates despite electrographic seizure activity in the immediate vicinity. No cells decreased firing rate immediately after seizure onset. During baseline periods between seizures, action potential waveforms and firing rates were similar among the four subsets of granule cells in epileptic rats and in granule cells of control rats. The mean normalized firing rate of granule cells whose firing rates increased before seizure onset deviated from baseline earliest, beginning 4 min before dentate gyrus electrographic seizure onset, and increased progressively, more than doubling by seizure onset. It is generally assumed that neuronal firing rates increase abruptly and synchronously only when electrographic seizures begin. However, these findings show heterogeneous and gradually building changes in activity of individual granule cells minutes before spontaneous seizures.

Limbic Network Interactions Leading to Hyperexcitability in a Model of Temporal Lobe Epilepsy

2002 ◽  
Vol 87 (1) ◽  
pp. 634-639 ◽  
Author(s):  
Margherita D'Antuono ◽  
Ruba Benini ◽  
Giuseppe Biagini ◽  
Giovanna D'Arcangelo ◽  
Michaela Barbarosie ◽  
...  
Keyword(s):  
Temporal Lobe Epilepsy ◽  
Temporal Lobe ◽  
Neuronal Damage ◽  
Cell Damage ◽  
Brain Slices ◽  
Hippocampal Damage ◽  
Functional Changes ◽  
Interictal Discharges

In mouse brain slices that contain reciprocally connected hippocampus and entorhinal cortex (EC) networks, CA3 outputs control the EC propensity to generate experimentally induced ictal-like discharges resembling electrographic seizures. Neuronal damage in limbic areas, such as CA3 and dentate hilus, occurs in patients with temporal lobe epilepsy and in animal models (e.g., pilocarpine- or kainate-treated rodents) mimicking this epileptic disorder. Hence, hippocampal damage in epileptic mice may lead to decreased CA3 output function that in turn would allow EC networks to generate ictal-like events. Here we tested this hypothesis and found that CA3-driven interictal discharges induced by 4-aminopyridine (4AP, 50 μM) in hippocampus-EC slices from mice injected with pilocarpine 13–22 days earlier have a lower frequency than in age-matched control slices. Moreover, EC-driven ictal-like discharges in pilocarpine-treated slices occur throughout the experiment (≤6 h) and spread to the CA1/subicular area via the temporoammonic path; in contrast, they disappear in control slices within 2 h of 4AP application and propagate via the trisynaptic hippocampal circuit. Thus, different network interactions within the hippocampus-EC loop characterize control and pilocarpine-treated slices maintained in vitro. We propose that these functional changes, which are presumably caused by seizure-induced cell damage, lead to seizures in vivo. This process is facilitated by a decreased control of EC excitability by hippocampal outputs and possibly sustained by the reverberant activity between EC and CA1/subiculum networks that are excited via the temporoammonic path.

scholarly journals Hippocampal adult-born granule cells drive network activity in a mouse model of chronic temporal lobe epilepsy

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
F. T. Sparks ◽  
Z. Liao ◽  
W. Li ◽  
A. Grosmark ◽  
I. Soltesz ◽  
...  
Keyword(s):  
Temporal Lobe Epilepsy ◽  
Temporal Lobe ◽  
Granule Cells ◽  
Topic Model ◽  
Network Activity ◽  
Relative Contribution ◽  
Epileptiform Discharges ◽  
Interictal Epileptiform Discharges ◽  
Cell Type Specific ◽  
Specific Contribution

AbstractTemporal lobe epilepsy (TLE) is characterized by recurrent seizures driven by synchronous neuronal activity. The reorganization of the dentate gyrus (DG) in TLE may create pathological conduction pathways for synchronous discharges in the temporal lobe, though critical microcircuit-level detail is missing from this pathophysiological intuition. In particular, the relative contribution of adult-born (abGC) and mature (mGC) granule cells to epileptiform network events remains unknown. We assess dynamics of abGCs and mGCs during interictal epileptiform discharges (IEDs) in mice with TLE as well as sharp-wave ripples (SPW-Rs) in healthy mice, and find that abGCs and mGCs are desynchronized and differentially recruited by IEDs compared to SPW-Rs. We introduce a neural topic model to explain these observations, and find that epileptic DG networks organize into disjoint, cell-type specific pathological ensembles in which abGCs play an outsized role. Our results characterize identified GC subpopulation dynamics in TLE, and reveal a specific contribution of abGCs to IEDs.

scholarly journals Unitary synaptic connections among substantia nigra pars reticulata neurons

2016 ◽  
Vol 115 (6) ◽  
pp. 2814-2829 ◽  
Author(s):  
Matthew H. Higgs ◽  
Charles J. Wilson
Keyword(s):  
Substantia Nigra ◽  
Firing Rate ◽  
Success Probability ◽  
Brain Slices ◽  
Reversal Potential ◽  
Network Activity ◽  
Substantia Nigra Pars Reticulata ◽  
Direct Measurements ◽  
Inhibitory Coupling ◽  
Kinetics Of

Neurons in substantia nigra pars reticulata (SNr) are synaptically coupled by local axon collaterals, providing a potential mechanism for local signal processing. Because SNr neurons fire spontaneously, these synapses are constantly active. To investigate their properties, we recorded spontaneous inhibitory postsynaptic currents (sIPSCs) from SNr neurons in brain slices, in which afferents from upstream nuclei are severed, and the cells fire rhythmically. The sIPSC trains contained a mixture of periodic and aperiodic events. Autocorrelation analysis of sIPSC trains showed that a majority of cells had one to four active unitary inputs. The properties of the unitary IPSCs (uIPSCs) were analyzed for cells with one unitary input, using a model of periodic presynaptic firing and stochastic synaptic transmission. The inferred presynaptic firing rates and coefficient of variation of interspike intervals (ISIs) corresponded well with direct measurements of spiking in SNr neurons. Methods were developed to estimate the success probability, amplitude distributions, and kinetics of the uIPSCs, while removing the contribution from aperiodic sIPSCs. The sIPSC amplitudes were not increased upon release from halorhodopsin silencing, suggesting that most synapses were not depressed at the spontaneous firing rate. Gramicidin perforated-patch recordings indicated that the average reversal potential of spontaneous inhibitory postsynaptic potentials was −64 mV. Because of the change in driving force across the ISI, the unitary inputs are predicted to have a larger postsynaptic impact when they arrive late in the ISI. Simulations of network activity suggest that this very sparse inhibitory coupling may act to desynchronize the activity of SNr neurons while having only a small effect on firing rate.

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.

scholarly journals Are Absence and Limbic Seizures Mutually Exclusive?: An Experimental Approach to Enigmatic Clinical Concept

2021 ◽  
Vol 10 (02) ◽  
pp. 045-050
Author(s):  
Filiz Yılmaz Onat ◽  
Esat Eşkazan
Keyword(s):  
Temporal Lobe Epilepsy ◽  
Temporal Lobe ◽  
Experimental Approach ◽  
Mesial Temporal Lobe Epilepsy ◽  
Theoretical Understanding ◽  
Limbic Seizures ◽  
Mesial Temporal Lobe ◽  
Clinical Questions ◽  
Underlying Mechanisms ◽  
Clinical Concept

AbstractThe impressive advances in the several disciplines including neurophysiology, molecular biology, neuroimmunology, neurogenetics, neuroimaging, and neuropharmacology of epilepsies have been stimulating a mutual interaction among basic scientists, clinicians, and professionals from other disciplines, leading to the identification of clinical questions and then the design of basic science paradigms to test enigmatic clinical issues. Based on a clinical observation that the coexistence of genetic (idiopathic) generalized typical absence and mesial temporal lobe epilepsy in the same patient is extremely rare and debatable, we addressed the rare coexistence in the same individual, designed an experimental approach to test the validity of this clinical concept and to study the underlying mechanisms involved. Here we presented evidence of a mutual cross-interaction in the circuits involved in typical absence and temporal lobe epilepsy. This article delineates a phenomenological picture and comprehends a theoretical understanding of a mutual cross-interaction in typical absence as a representative of genetic generalized epilepsies and limbic epilepsy in which seizures often start from the mesial temporal lobe.

scholarly journals Deficits in Behavioral and Neuronal Pattern Separation in Temporal Lobe Epilepsy

2020 ◽  
Author(s):  
A.D. Madar ◽  
J.A. Pfammatter ◽  
J. Bordenave ◽  
E.I. Plumley ◽  
S. Ravi ◽  
...  
Keyword(s):  
Temporal Lobe Epilepsy ◽  
Dentate Gyrus ◽  
Temporal Lobe ◽  
Granule Cells ◽  
Brain Slices ◽  
Neural Computation ◽  
Pattern Separation ◽  
Behavioral Deficits ◽  
Cortical Input ◽  
Eeg Abnormalities

AbstractIn temporal lobe epilepsy, the ability of the dentate gyrus to limit excitatory cortical input to the hippocampus breaks down, leading to seizures. The dentate gyrus is also thought to help discriminate between similar memories by performing pattern separation, but whether epilepsy leads to a breakdown in this neural computation, and thus to mnemonic discrimination impairments, remains unknown. Here we show that temporal lobe epilepsy is characterized by behavioral deficits in mnemonic discrimination tasks, in both humans and mice. Using a recently developed assay in brain slices of the same epileptic mice, we reveal a decreased ability of the dentate gyrus to perform certain forms of pattern separation. This is due to a subset of granule cells with abnormal bursting that can develop independently of early EEG abnormalities. Overall, our results linking physiology, computation and cognition in the same mice, advance our understanding of episodic memory mechanisms and their dysfunction in epilepsy.

Prolonged GABA responses in dentate granule cells in slices isolated from patients with temporal lobe sclerosis

1995 ◽  
Vol 74 (1) ◽  
pp. 378-387 ◽  
Author(s):  
A. Williamson ◽  
A. E. Telfeian ◽  
D. D. Spencer
Keyword(s):  
Temporal Lobe Epilepsy ◽  
Temporal Lobe ◽  
Medial Temporal Lobe ◽  
Granule Cells ◽  
Hippocampal Slices ◽  
Reversal Potential ◽  
Pathological Finding ◽  
Cell Loss ◽  
Synaptic Reorganization ◽  
Dentate Granule Cells

1. Medial temporal lobe sclerosis is a common pathological finding in patients with medically intractable temporal lobe epilepsy. This disease is characterized by extensive cell loss in the hilus and the hippocampal CA1 and CA3 cell fields in addition to synaptic reorganization throughout the dentate gyrus. 2. The dentate granule cells from hippocampal slices of patients diagnosed with medial temporal lobe sclerosis exhibit reduced synaptic inhibition with concommitant hyperexcitability. These physiological changes were studied relative to the hippocampi of patients with temporal lobe tumors in which the cell loss and synaptic reorganization are not seen. 3. We attempted to determine if this disinhibition was because of changes in the postsynaptic sensitivity to the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) by studying the responses to exogenously applied transmitter. As in rodents, the GABA responses in human dentate granule cells studied at the resting membrane potential were depolarizing and were mediated primarily by GABAA receptors. In many cases, these depolarizing GABA responses could trigger action potentials. Thus in some situations, GABA could act as an excitatory neurotransmitter. 4. We found that GABAA receptor-mediated responses in the sclerotic hippocampi were approximately 80% longer than in the comparison population. This difference was not because of changes in either the GABA reversal potential or the GABA-induced conductance change. The data support the hypothesis that the GABA transport system is impaired in sclerotic tissue: application of the GABA uptake inhibitor NNC711 (a tiagibine derivative) greatly prolonged the GABA responses in the tumor-related temporal lobe epilepsy tissue, but had little effect on the sclerotic tissue.

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