Imaging of 4-AP-induced, GABAA-dependent spontaneous synchronized activity mediated by the hippocampal interneuron network

Saurabh R. Sinha, Peter Saggau

    Research output: Contribution to journalArticlepeer-review


    Under conditions of increased excitability, such as application of the K+ channel blocker 4-aminopyridine (4-AP, 100 μM), interneurons in the hippocampal slice show an additional form of synchronized activity that is distinct from the ictal and interictal epileptiform activity induced by these manipulations. In principal neurons, i.e., pyramidal and granule cells, this synchronized interneuron activity (SIA) generates large, multi-component synaptic potentials, which have been termed long-lasting depolarizations (LLDs). These LLDs are dependent on GABAA receptor-mediated synaptic transmission but not on excitatory amino acid (EAA) receptors. Intracellular recordings from hilar interneurons have shown that depolarizing GABAA receptor-mediated synaptic potentials are also largely responsible for the synchronization of interneurons. The spatiotemporal characteristics of this interneuron activity have not been investigated previously. Using a voltage-sensitive dye and optical techniques that are capable of recording spontaneous synchronized activity, we have characterized the spatiotemporal pattern of SIA (in the presence of 4-AP + EAA receptor antagonists) and compared it with interictal epileptiform activity (in 4-AP only). Like interictal activity, SIA could be observed throughout the hippocampal slice. Unlike interictal activity, which originated in area CA2/CA3 and spread from there, SIA was most prominent in area CA1 and originated either there or in the subiculum. In CA1, interictal activity was largest in and near stratum pyramidale, while SIA was mainly located in s. lacunosum moleculare. Furthermore SIA was equally likely to propagate in either direction, and multiple patterns of propagation could be observed within a single brain slice. These studies suggest that hippocampal area CA1 has the highest propensity for SIA, that multiple locations can serve as the site of origin, and that interneurons located in s. lacunosum moleculare or interneurons that specifically project to this region may be particularly important for synchronized interneuron activity.

    Original languageEnglish (US)
    Pages (from-to)381-391
    Number of pages11
    JournalJournal of neurophysiology
    Issue number1
    StatePublished - 2001

    ASJC Scopus subject areas

    • Neuroscience(all)
    • Physiology

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