| Summary: | <p>Structural and functional changes in the hippocampal neuronal network of the brain allow organisms to adapt to the environment. Such plasticity leads to the encoding of newly acquired information and the replacement or updating of stored knowledge by new experience. Information is carried by the output of active pyramidal cell assemblies during transient network oscillations. In the CA1 area, the activity of pyramidal cells is regulated by at least twenty-two distinct types of GABAergic interneuron with different molecular expression profiles and innervating defined pyramidal cell compartments. The <em>in vivo</em> spike-timing of identified types of GABAergic cell in freely moving rodents has been largely unknown until recently. Although thousands of interneurons have been reported from large scale extracellular recordings their cell type identity has remained uncertain.</p> <p>How do different types of GABAergic cell regulate pyramidal cell output during behaviour? In order to test the hypothesis that differences in connectivity and molecular composition amongst cell types reflect the specialisation of their functions, I have recorded single pyramidal cells and GABAergic interneurons extracellularly in the CA1 area of freely moving rats during theta- and sharp wave associated ripple-oscillations (SWRs), and subsequently I have labelled the recorded neurons using the juxtacellular technique (Lapray et al., 2012). My main findings are: <b>1.</b> I have identified PV&plus; basket, axo-axonic, bistratified and O-LM cells, together with an "unconventional interneuron". <b>2.</b> Behaviour and network states differentiate the activities of GABAergic cell types in freely moving rats. <b>3.</b> During sleep, PV&plus; basket and bistratified cells fire at higher rates than axo-axonic and O-LM cells, and unlike axo-axonic and O-LM cells, strongly increase spiking during SWRs. <b>4.</b> Axo-axonic and O-LM cells decrease firing during sleep relative to awake states and are inhibited during all or most SWRs, respectively. <b>5.</b> During movement, axo-axonic and PV&plus; basket cells fire with similarly high frequencies but on complementary segments of the descending slope of theta cycles. <b>6.</b> Bistratified and O-LM cells fire cooperatively during movement at the troughs of theta oscillations but with different frequencies. <b>7.</b> The "unconventional interneuron", in contrast to the other identified cell types, has a low spike rate and becomes activated exclusively during SWRs. <b>8.</b> Behaviour and rhythmic network events differentiate GABA and peptide release to distinct membrane domains of pyramidal cells. <b>9.</b> My results have validated many of the spike-timing characteristics determined under urethane anaesthesia (Klausberger and Somogyi, 2008; Somogyi, 2010), although, in average, firing rates are higher under physiological, drug-free conditions.</p> <p>My results demonstrate specialisations of distinct types of GABAergic interneuron during network operations. Distinct cell types contribute to the rhythmic redistribution of GABAergic action on different pyramidal cell membrane domains, at both slower and faster time scales, from the axon initial segment through the cell body down to the distal apical tuft and back, which is necessary for the rhythmic separation of network function during different stages of mnemonic processing.</p>
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