Network dynamics of encoding and retrieval of behavioural spike sequences during theta and ripples in a CA1 model of the hippocampus

BMC Neuroscience (Impact Factor: 2.85). 07/2010; 11(Suppl 1). DOI: 10.1186/1471-2202-11-S1-P55
Source: DOAJ
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    ABSTRACT: Calcium has been proposed as a postsynaptic signal underlying synaptic spike-timing-dependent plasticity (STDP). We examine this hypothesis with computational modeling based on experimental results from hippocampal cultures, some of which are presented here, in which pairs and triplets of pre- and postsynaptic spikes induce potentiation and depression in a temporally asymmetric way. Specifically, we present a set of model biochemical detectors, based on plausible molecular pathways, which make direct use of the time course of the calcium signal to reproduce these experimental STDP results. Our model features a modular structure, in which long-term potentiation (LTP) and depression (LTD) components compete to determine final plasticity outcomes; one aspect of this competition is a veto through which appropriate calcium time courses suppress LTD. Simulations of our model are also shown to be consistent with classical LTP and LTD induced by several presynaptic stimulation paradigms. Overall, our results provide computational evidence that, while the postsynaptic calcium time course contains sufficient information to distinguish various experimental long-term plasticity paradigms, small changes in the properties of back-propagation of action potentials or in synaptic dynamics can alter the calcium time course in ways that will significantly affect STDP induction by any detector based exclusively on postsynaptic calcium. This may account for the variability of STDP outcomes seen within hippocampal cultures, under repeated application of a single experimental protocol, as well as for that seen in multiple spike experiments across different systems.
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    ABSTRACT: The hippocampus is one of the most widely studied brain region. One of its functional roles is the storage and recall of declarative memories. Recent hippocampus research has yielded a wealth of data on network architecture, cell types, the anatomy and membrane properties of pyramidal cells and interneurons, and synaptic plasticity. Understanding the functional roles of different families of hippocampal neurons in information processing, synaptic plasticity and network oscillations poses a great challenge but also promises deep insight into one of the major brain systems. Computational and mathematical models play an instrumental role in exploring such functions. In this paper, we provide an overview of abstract and biophysical models of associative memory with particular emphasis on the operations performed by the diverse (inter)neurons in encoding and retrieval of memories in the hippocampus.
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    ABSTRACT: It has been proposed that the hippocampal theta rhythm (4-7 Hz) can contribute to memory formation by separating encoding (storage) and retrieval of memories into different functional half-cycles (Hasselmo et al. (2002) Neural Comput 14:793-817). We investigate, via computer simulations, the biophysical mechanisms by which storage and recall of spatio-temporal input patterns are achieved by the CA1 microcircuitry. A model of the CA1 microcircuit is presented that uses biophysical representations of the major cell types, including pyramidal (P) cells and four types of inhibitory interneurons: basket (B) cells, axo-axonic (AA) cells, bistratified (BS) cells and oriens lacunosum-moleculare (OLM) cells. Inputs to the network come from the entorhinal cortex (EC), the CA3 Schaffer collaterals and medial septum. The EC input provides the sensory information, whereas all other inputs provide context and timing information. Septal input provides timing information for phasing storage and recall. Storage is accomplished via a local STDP mediated hetero-association of the EC input pattern and the incoming CA3 input pattern on the CA1 pyramidal cell target synapses. The model simulates the timing of firing of different hippocampal cell types relative to the theta rhythm in anesthetized animals and proposes experimentally confirmed functional roles for the different classes of inhibitory interneurons in the storage and recall cycles (Klausberger et al., (2003, 2004) Nature 421:844-848, Nat Neurosci 7:41-47). Measures of recall performance of new and previously stored input patterns in the presence or absence of various inhibitory interneurons are employed to quantitatively test the performance of our model. Finally, the mean recall quality of the CA1 microcircuit is tested as the number of stored patterns is increased.
    Hippocampus 01/2009; 20(3):423-46. DOI:10.1002/hipo.20661 · 4.30 Impact Factor

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