Functional anatomy of hippocampal seizures

Lothman, Eric W.; Bertram, Edward H.; Stringer, Janet L.

doi:10.1016/0301-0082(91)90011-o

Cited by 333 publications

(204 citation statements)

References 290 publications

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“…These SREDs or "seizure episodes" occurred for the life of the neurons in culture and demonstrated paroxysmal depolarization shifts, a pathophysiological characteristic of epilepsy (Fig. 1B) [9,16]. Two SREDs lasting between 1-1.5 min are observed in this epileptic neuron in a continuous 30-min recording (Fig.…”

Section: Nih Public Accessmentioning

confidence: 78%

“…It is characterized by the occurrence of spontaneous recurrent epileptiform discharges (SREDs) or seizures [9,16]. Status epilepticus (SE) is a major…”

Section: Introductionmentioning

confidence: 99%

“…Seizure initiation and termination are governed by complex synaptic regulation of neuronal excitability [4,9]. However, little is known about the molecular mechanisms that mediate seizure termination and prevent development of SE in populations of epileptic neurons.…”

mentioning

confidence: 99%

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Cannabinoid CB1 receptor antagonists cause status epilepticus-like activity in the hippocampal neuronal culture model of acquired epilepsy

Deshpande

Sombati

Blair

et al. 2007

Neuroscience Letters

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Status epilepticus is a major medical emergency associated with a significant morbidity and mortality. Little is known about the mechanisms that terminate seizure activity and prevent the development of status epilepticus. Cannabinoids possess anticonvulsant properties and the endocannabinoid system has been implicated in regulating seizure duration and frequency. Endocannabinoids regulate synaptic transmission and dampen seizure activity via activation of the presynaptic cannabinoid receptor 1 (CB1). This study was initiated to evaluate the role of CB1 receptor-dependent endocannabinoid synaptic transmission towards preventing the development of status epilepticuslike activity in the well-characterized hippocampal neuronal culture model of acquired epilepsy using patch clamp electrophysiology. Application of the CB1 receptor antagonists SR141716A (1 μM) or AM251 (1 μM) to "epileptic" neurons caused the development of continuous epileptiform activity, resembling electrographic status epilepticus. The induction of status epilepticus-like activity by CB1 receptor antagonists was reversible and could be overcome by maximal concentrations of CB1 agonists. Similar treatment of control neurons with CB1 receptor antagonists did not produce status epilepticus or hyperexcitability. These findings suggest that CB1 receptor-dependent endocannabinoid endogenous tone plays an important role in modulating seizure frequency and duration and preventing the development of status epilepticus-like activity in populations of epileptic neurons. The regulation of seizure activity and prevention of status epilepticus by the endocannabinoid system offers an important insight into understanding the basic mechanisms that control the development of continuous epileptiform discharges. KeywordsCB1 receptor; status epilepticus; cannabinoid; epilepsy; endocannabinoid tone Epilepsy is one of the most common neurological disorders affecting approximately 1-2% of the world population [5]. It is characterized by the occurrence of spontaneous recurrent epileptiform discharges (SREDs) or seizures [9,16]. Status epilepticus (SE) is a majorTo whom correspondence should be addressed: Robert J. DeLorenzo, M.D., Ph.D., M.P.H., Virginia Commonwealth University, School of Medicine, PO Box 980599, Richmond, VA 23298, Phone: 804-828-8969, Fax: 804-828-6432, E-mail: rdeloren@hsc.vcu.edu. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. [2,12,18,19]. The CB1 receptor has been shown to mediate many of the anticonvulsant effects of cannabinoids [20] and to play an important role in regulating synaptic transmissio...

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Section: Nih Public Accessmentioning

confidence: 78%

“…It is characterized by the occurrence of spontaneous recurrent epileptiform discharges (SREDs) or seizures [9,16]. Status epilepticus (SE) is a major…”

Section: Introductionmentioning

confidence: 99%

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Cannabinoid CB1 receptor antagonists cause status epilepticus-like activity in the hippocampal neuronal culture model of acquired epilepsy

Deshpande

Sombati

Blair

et al. 2007

Neuroscience Letters

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“…More inhibition might be detected with different methods, such as use of slices cut on a different axis, blockade of excitatory inputs (Scharfman, 1992a), or whole-cell recording (Soltesz and Mody, 1994). The fact that EPSPs were the predominant synaptic responses is consistent with the fact that granule cells are strongly inhibited under normal conditions (Otis et al, 1991), and that the dentate gyrus is a strongly inhibited structure (Lothman et al, 1991).…”

Section: Types Of Responsesmentioning

confidence: 80%

Electrophysiological diversity of pyramidal‐shaped neurons at the granule cell layer/hilus border of the rat dentate gyrus recorded in vitro

Scharfman

1995

Hippocampus

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In the rat dentate gyrus, pyramidal-shaped cells located on the border of the granule cell layer and the hilus are one of the most common types of γ-aminobutyric acid (GABA)-immunoreactive neurons. This study describes their electrophysiological characteristics. Membrane properties, patterns of discharge, and synaptic responses were recorded intracellularly from these cells in hippocampal slices. Each cell was identified as pyramidal-shaped by injecting the marker Neurobiotin intracellularly (n = 17).In several respects the membrane properties of the sampled cells were similar to "fast-spiking" cells (putative inhibitory interneurons) that have been described in other areas of the hippocampus. For example, input resistance was high (mean 91.3 megohms), the membrane time constant was short (mean 7.7 ms), and there was a large afterhyperpolarization following a single action potential (mean 10.5 mV at resting potential). However, the action potentials of most pyramidalshaped cells were not as brief (mean 1.2 ms total duration) as those of most previously described fast-spiking cells. Many pyramidal-shaped neurons had strong spike frequency adaptation relative to other fast-spiking cells. Although these latter two characteristics were apparent in the majority of the sampled cells, there were exceptional pyramidal-shaped neurons with fast action potentials and weak adaptation, demonstrating the electrophysiological variability of pyramidal-shaped cells.Responses to outer molecular layer stimulation were composed primarily of excitatory postsynaptic potentials (EPSPs) rather than inhibitory postsynaptic potentials (IPSPs), and were usually small (EPSPs evoked at threshold were often less than 2 mV), and brief (less than 30 ms). There was variability, because in a few cells EPSPs evoked at threshold were much larger. However, regardless of EPSP amplitude, suprathreshold stimulation (up to 4 times the threshold stimulus strength) rarely evoked more than one action potential in any cell. The results suggest that stimulation of perforant path axons produces limited excitatory synaptic responses in pyramidal-shaped neurons. This may be one of the reasons why they are relatively resistant to prolonged perforant path stimulation.The pyramidal-shaped neurons located at the base of the granule cell layer have been associated historically with a basket plexus around granule cell somata, and have been called pyramidal "basket" cells. However, basket-like endings were rare and axon collaterals outside the granule cell layer were common. Many axon collaterals were as far from the granule cell layer as the outer molecular layer and the central hilus, and antidromic action potentials could be recorded in some

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“…It is characterized by the occurrence of spontaneous, recurrent unprovoked seizure discharges (Lothman et al, 1991). A seizure is the symptomatic, behavioral manifestation of abnormal, disordered, spontaneous and synchronized, high frequency firing of populations of neurons in the CNS (Delorenzo et al, 2005;Lothman et al, 1991;McNamara, 1999).…”

Section: Introductionmentioning

confidence: 99%

The novel antiepileptic drug carisbamate (RWJ 333369) is effective in inhibiting spontaneous recurrent seizure discharges and blocking sustained repetitive firing in cultured hippocampal neurons

et al. 2008

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SummaryThis study was initiated to investigate effects of the novel neuromodulator carisbamate (RWJ 333369) in the hippocampal neuronal culture model of status epilepticus and spontaneous epileptiform discharges. Whole-cell current clamp techniques were used to determine the effects of carisbamate on spontaneous recurrent epileptiform discharges (SREDs, in vitro epilepsy), depolarization-induced sustained repetitive firing (SRF) and low Mg 2+ -induced continuous high frequency spiking (in vitro status epilepticus). This in vitro model is an important tool to study the effects of anticonvulsant drugs (AEDs) on SREDs that occur for the life of the neurons in culture. Carisbamate dose dependently blocked the expression and reoccurrence of SREDs. The ED 50 value for its antiepileptic effect was 58.75 ± 2.43 μM. Inhibition of SRF is considered a common attribute of many AEDs. Carisbamate (100 μM) significantly decreased SRF in hippocampal neurons. All these effects of carisbamate were reversed during a 5 to 30 min drug washout period. When exposed to low Mg 2+ medium cultured hippocampal neurons exhibit high frequency spiking. This form of in vitro status epilepticus is not effectively blocked by conventional AEDs that are known to be effective in treating status epilepticus in humans. Carisbamate, like phenytoin and phenobarbital, had little or no effect on low Mg 2+ -induced continuous high frequency spiking. These results characterize the effects of carisbamate in the hippocampal neuronal culture model of epileptiform discharges and suggest that the ability of carisbamate to inhibit depolarization-induced SRF may account in part for some of it's anticonvulsant effect.

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Functional anatomy of hippocampal seizures

Cited by 333 publications

References 290 publications

Cannabinoid CB1 receptor antagonists cause status epilepticus-like activity in the hippocampal neuronal culture model of acquired epilepsy

Cannabinoid CB1 receptor antagonists cause status epilepticus-like activity in the hippocampal neuronal culture model of acquired epilepsy

Electrophysiological diversity of pyramidal‐shaped neurons at the granule cell layer/hilus border of the rat dentate gyrus recorded in vitro

The novel antiepileptic drug carisbamate (RWJ 333369) is effective in inhibiting spontaneous recurrent seizure discharges and blocking sustained repetitive firing in cultured hippocampal neurons

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