Dysfunction of hippocampal interneurons in epilepsy

Liu, Yuqiang; Yu, Fangfang; Liu, Wanhong; He, Xiaohua; Peng, Biwen

doi:10.1007/s12264-014-1478-4

Cited by 50 publications

(34 citation statements)

References 95 publications

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“…Parvalbumin (PV) is expressed by subset of GABAergic interneurons, including basket, axo-axonic, bistratified, and oriens-lacunosum moleculare cells in the hippocampus (Schwaller et al, 2004; Liu et al, 2014). Quantification of PV immunostaining of inhibitory interneuron soma in the CA1 revealed a significantly decreased staining in 12 wk CPZ mice compared to normal (Figure 4D, H *p≤0.05, η 2 =0.4372).…”

Section: Resultsmentioning

confidence: 99%

“…The hippocampal formation frequently exhibits profound changes in MS (Geurts et al, 2007) and MTLE, and has been implicated as a focus of seizure initiation (de Lanerolle et al, 2012) and maintenance (Ellender et al, 2014; Toyoda et al, 2015). These changes include loss of inhibitory interneuron populations, degeneration of CA1 principle neurons, and derangement of dentate gyrus projections into CA regions (de Lanerolle et al, 2012; Liu et al, 2014). For these reasons, we probed CA1 neuronal pathology, including parvalbumin (PV) + inhibitory interneurons due to this population's vulnerability in demyelination and seizure models (Schwaller et al, 2004; Rossi et al, 2012; Liu et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

“…These changes include loss of inhibitory interneuron populations, degeneration of CA1 principle neurons, and derangement of dentate gyrus projections into CA regions (de Lanerolle et al, 2012; Liu et al, 2014). For these reasons, we probed CA1 neuronal pathology, including parvalbumin (PV) + inhibitory interneurons due to this population's vulnerability in demyelination and seizure models (Schwaller et al, 2004; Rossi et al, 2012; Liu et al, 2014). …”

Section: Introductionmentioning

confidence: 99%

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Chronic demyelination-induced seizures

et al. 2017

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Multiple sclerosis (MS) patients are three to six times more likely to develop epilepsy compared to the rest of the population. Seizures are more common in patients with early onset or progressive forms of the disease and prognosticate rapid progression to disability and death. Grey matter atrophy, hippocampal lesions, interneuron loss, and elevated juxtacortical lesion burden have been identified in MS patients with seizures; however, translational studies aimed at elucidating the pathophysiological processes underlying MS epileptogenesis are limited. Here, we report that cuprizone-mediated chronically demyelinated (9-12 weeks) mice exhibit marked changes in electroencephalography (EEG) and evidence of overt seizure activity in mice. Subsequently, histopathological correlates were probed by immunohistochemistry, revealing extensive demyelination, loss of parvalbumin inhibitory interneurons in the hippocampus CA1 subregion, widespread gliosis and changes to astrocytic aquaporin-4 expression. Our results suggest that chronically demyelinated mice are a valuable model with which we may begin to understand the mechanisms underlying demyelination-induced seizures.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Chronic demyelination-induced seizures

et al. 2017

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“…The classification of interneurons rests on axonal innervation patterns of the subcellular domains of postsynaptic cells (eg, basket cells innervate the perisomatic region), as well as on other properties such as location, protein or neuropeptide expression, intrinsic physiology, distribution of axonal arborization, and others (Freund and Buzsáki, 1996; Klausberger et al, 2003; Somogyi and Klausberger, 2005). The loss and alteration of function of hippocampal interneurons in epilepsy has been reviewed elsewhere (Liu et al, 2014). However, as we are focusing here on anatomical changes to the microcircuit, we have summarized the work on interneuronal cell loss, by subtype, in various models of TLE and present it in Table 1.…”

Section: Organization and Reorganization Of Microcircuits: Anatomicmentioning

confidence: 99%

Organization and control of epileptic circuits in temporal lobe epilepsy

Alexander¹,

Maroso²,

Soltész³

2016

Progress in Brain Research

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When studying the pathological mechanisms of epilepsy, there are a seemingly endless number of approaches from the ultrastructural level—receptor expression by EM—to the behavioral level—comorbid depression in behaving animals. Epilepsy is characterized as a disorder of recurrent seizures, which are defined as “a transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain” (Fisher et al., 2005). Such abnormal activity typically does not occur in a single isolated neuron; rather, it results from pathological activity in large groups—or circuits—of neurons. Here we choose to focus on two aspects of aberrant circuits in temporal lobe epilepsy: their organization and potential mechanisms to control these pathological circuits. We also look at two scales: microcircuits, ie, the relationship between individual neurons or small groups of similar neurons, and macrocircuits, ie, the organization of large-scale brain regions. We begin by summarizing the large body of literature that describes the stereotypical anatomical changes in the temporal lobe—ie, the anatomical basis of alterations in microcircuitry. We then offer a brief introduction to graph theory and describe how this type of mathematical analysis, in combination with computational neuroscience techniques and using parameters obtained from experimental data, can be used to postulate how microcircuit alterations may lead to seizures. We then zoom out and look at the changes which are seen over large whole-brain networks in patients and animal models, and finally we look to the future.

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“…The balancing of cellular events is performed by excitatory pyramidal cells and specialized inhibitory http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1067 neurons that comprise approximately 10–15% of cortical neurons (Ascoli et al, 2008), and it is generally accepted that the spread of epileptiform discharges involves a primary dysfunction of interneurons (Buhl et al, 1996; Prince et al, 1997; DeFelipe, 1999; Bausch, 2005). The fate of interneurons depends upon the subtype, and the diverse roles that interneurons play in epilepsy are becoming more evident; for example, seizure susceptibility is apparent in patients with reduced inhibitory circuitry (Wittner et al, 2005; Liu et al, 2014). …”

Section: Introductionmentioning

confidence: 99%

Cannabidiol exerts antiepileptic effects by restoring hippocampal interneuron functions in a temporal lobe epilepsy model

Khan

Shekh‐Ahmad²,

Khalil³

et al. 2018

British J Pharmacology

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Background and PurposeA non‐psychoactive phytocannabinoid, cannabidiol (CBD), shows promising results as an effective potential antiepileptic drug in some forms of refractory epilepsy. To elucidate the mechanisms by which CBD exerts its anti‐seizure effects, we investigated its effects at synaptic connections and on the intrinsic membrane properties of hippocampal CA1 pyramidal cells and two major inhibitory interneurons: fast spiking, parvalbumin (PV)‐expressing and adapting, cholecystokinin (CCK)‐expressing interneurons. We also investigated whether in vivo treatment with CBD altered the fate of CCK and PV interneurons using immunohistochemistry.Experimental ApproachElectrophysiological intracellular whole‐cell recordings combined with neuroanatomy were performed in acute brain slices of rat temporal lobe epilepsy in in vivo (induced by kainic acid) and in vitro (induced by Mg2+‐free solution) epileptic seizure models. For immunohistochemistry experiments, CBD was administered in vivo (100 mg·kg−1) at zero time and 90 min post status epilepticus, induced with kainic acid.Key ResultsBath application of CBD (10 μM) dampened excitability at unitary synapses between pyramidal cells but enhanced inhibitory synaptic potentials elicited by fast spiking and adapting interneurons at postsynaptic pyramidal cells. Furthermore, CBD restored impaired membrane excitability of PV, CCK and pyramidal cells in a cell type‐specific manner. These neuroprotective effects of CBD were corroborated by immunohistochemistry experiments that revealed a significant reduction in atrophy and death of PV‐ and CCK‐expressing interneurons after CBD treatment.Conclusions and ImplicationsOur data suggest that CBD restores excitability and morphological impairments in epileptic models to pre‐epilepsy control levels through multiple mechanisms to reinstate normal network function.

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Dysfunction of hippocampal interneurons in epilepsy

Cited by 50 publications

References 95 publications

Chronic demyelination-induced seizures

Chronic demyelination-induced seizures

Organization and control of epileptic circuits in temporal lobe epilepsy

Cannabidiol exerts antiepileptic effects by restoring hippocampal interneuron functions in a temporal lobe epilepsy model

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