Dataset Information

Sub region-specific modulation of synchronous neuronal burst firing after a kainic acid insult in organotypic hippocampal cultures.

ABSTRACT:

Background

Excitotoxicity occurs in a number of pathogenic states including stroke and epilepsy. The adaptations of neuronal circuits in response to such insults may be expected to play an underlying role in pathogenesis. Synchronous neuronal firing can be induced in isolated hippocampal slices and involves all regions of this structure, thereby providing a measure of circuit activity. The effect of an excitotoxic insult (kainic acid, KA) on Mg2+-free-induced synchronized neuronal firing was tested in organotypic hippocampal culture by measuring extracellular field activity in CA1 and CA3.

Results

Within 24 hrs of the insult regional specific changes in neuronal firing patterns were evident as: (i) a dramatic reduction in the ability of CA3 to generate firing; and (ii) a contrasting increase in the frequency and duration of synchronized neuronal firing events in CA1. Two distinct processes underlie the increased propensity of CA1 to generate synchronized burst firing; a lack of ability of the CA3 region to 'pace' CA1 resulting in an increased frequency of synchronized events; and a change in the 'intrinsic' properties limited to the CA1 region, which is responsible for increased event duration. Neuronal quantification using NeuN immunoflurescent staining and stereological confocal microscopy revealed no significant cell loss in hippocampal sub regions, suggesting that changes in the properties of neurons within this region were responsible for the KA-mediated excitability changes.

Conclusion

These results provide novel insight into adaptation of hippocampal circuits following excitotoxic injury. KA-mediated disruption of the interplay between CA3 and CA1 clearly increases the propensity to synchronized firing in CA1.

SUBMITTER: Reid CA

PROVIDER: S-EPMC2474631 | biostudies-literature | 2008 Jul

REPOSITORIES: biostudies-literature

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Publications

Sub region-specific modulation of synchronous neuronal burst firing after a kainic acid insult in organotypic hippocampal cultures.

Reid Christopher A CA Adams Brendan E L BE Myers Damian D O'Brien Terence J TJ Williams David A DA

BMC neuroscience 20080702

<h4>Background</h4>Excitotoxicity occurs in a number of pathogenic states including stroke and epilepsy. The adaptations of neuronal circuits in response to such insults may be expected to play an underlying role in pathogenesis. Synchronous neuronal firing can be induced in isolated hippocampal slices and involves all regions of this structure, thereby providing a measure of circuit activity. The effect of an excitotoxic insult (kainic acid, KA) on Mg2+-free-induced synchronized neuronal firing ...[more]

PMID: 18593482

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Project description:Neurogenesis in the adult hippocampus has become an intensively investigated research topic, as it is essential for proper hippocampal function and considered to bear therapeutic potential for the replacement of pathologically lost neurons. On the other hand, neurogenesis itself is frequently affected by CNS insults. To identify processes leading to the disturbance of neurogenesis, we made use of organotypic hippocampal slice cultures (OHSC), which, for unknown reasons, lose their neurogenic potential during cultivation. In the present study, we show by BrdU/Prox1 double-immunostaining that the generation of new granule cells drops by 90% during the first week of cultivation. Monitoring neurogenesis dynamically in OHSC from POMC-eGFP mice, in which immature granule cells are endogenously labeled, revealed a gradual decay of the eGFP signal, reaching 10% of initial values within 7 days of cultivation. Accordingly, reverse transcription quantitative polymerase chain reaction analysis showed the downregulation of the neurogenesis-related genes doublecortin and Hes5, a crucial target of the stem cell-maintaining Notch signaling pathway. In parallel, we demonstrate a strong and long-lasting activation of astrocytes and microglial cells, both, morphologically and on the level of gene expression. Enhancement of astroglial activation by treating OHSC with ciliary neurotrophic factor accelerated the loss of neurogenesis, whereas treatment with indomethacin or an antagonist of the purinergic P2Y12 receptor exhibited potent protective effects on the neurogenic outcome. Therefore, we conclude that OHSC rapidly lose their neurogenic capacity due to persistent inflammatory processes taking place after the slice preparation. As inflammation is also considered to affect neurogenesis in many CNS pathologies, OHSC appear as a useful tool to study this interplay and its molecular basis. Furthermore, we propose that modification of glial activation might bear the therapeutic potential of enabling neurogenesis under neuropathological conditions.

Dataset Information

Sub region-specific modulation of synchronous neuronal burst firing after a kainic acid insult in organotypic hippocampal cultures.

Background

Results

Conclusion

Publications

Sub region-specific modulation of synchronous neuronal burst firing after a kainic acid insult in organotypic hippocampal cultures.

Similar Datasets

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