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5 Publications

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    01/22/10 | Impact of spikelets on hippocampal CA1 pyramidal cell activity during spatial exploration.
    Epsztein J, Lee AK, Chorev E, Brecht M
    Science. 2010 Jan 22;327(5964):474-7. doi: 10.1126/science.1182773

    In vivo intracellular recordings of hippocampal neurons reveal the occurrence of fast events of small amplitude called spikelets or fast prepotentials. Because intracellular recordings have been restricted to anesthetized or head-fixed animals, it is not known how spikelet activity contributes to hippocampal spatial representations. We addressed this question in CA1 pyramidal cells by using in vivo whole-cell recording in freely moving rats. We observed a high incidence of spikelets that occurred either in isolation or in bursts and could drive spiking as fast prepotentials of action potentials. Spikelets strongly contributed to spiking activity, driving approximately 30% of all action potentials. CA1 pyramidal cell firing and spikelet activity were comodulated as a function of the animal’s location in the environment. We conclude that spikelets have a major impact on hippocampal activity during spatial exploration.

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    01/01/09 | Head-anchored whole-cell recordings in freely moving rats.
    Lee AK, Epsztein J, Brecht M
    Nature Protocols. 2009;4(3):385-92. doi: 10.1038/nprot.2009.5

    Intracellular recordings are routinely used to study the synaptic and intrinsic properties of neurons in vitro. A key requirement for these recordings is a mechanically very stable preparation; thus their use in vivo had been limited previously to head-restrained animals. We have recently demonstrated that anchoring the electrode rigidly in place with respect to the skull provides sufficient stabilization for long-lasting, high-quality whole-cell recordings in awake, freely moving rats. This protocol describes our procedure in detail, adds specific instructions for targeting hippocampal CA1 pyramidal neurons and updates it with changes that facilitate patching and improve the success rate. The changes involve combining a standard, nonhead-mounted micromanipulator with a gripper to firmly hold the recording pipette during the anchoring process then gently release it afterwards. The procedure from the beginning of surgery to the end of a recording takes approximately 5 h. This technique allows new studies of the mechanisms underlying neuronal integration and cellular/synaptic plasticity in identified cells during natural behaviors.

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    08/17/06 | Whole-cell recordings in freely moving rats.
    Lee AK, Manns ID, Sakmann B, Brecht M
    Neuron. 2006 Aug 17;51:399-407. doi: 10.1016/j.neuron.2006.07.004

    Intracellular recording, which allows direct measurement of the membrane potential and currents of individual neurons, requires a very mechanically stable preparation and has thus been limited to in vitro and head-immobilized in vivo experiments. This restriction constitutes a major obstacle for linking cellular and synaptic physiology with animal behavior. To overcome this limitation we have developed a method for performing whole-cell recordings in freely moving rats. We constructed a miniature head-mountable recording device, with mechanical stabilization achieved by anchoring the recording pipette rigidly in place after the whole-cell configuration is established. We obtain long-duration recordings (mean of approximately 20 min, maximum 60 min) in freely moving animals that are remarkably insensitive to mechanical disturbances, then reconstruct the anatomy of the recorded cells. This head-anchored whole-cell recording technique will enable a wide range of new studies involving detailed measurement and manipulation of the physiological properties of identified cells during natural behaviors.

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    10/01/04 | A combinatorial method for analyzing sequential firing patterns involving an arbitrary number of neurons based on relative time order.
    Lee AK, Wilson MA
    Journal of Neurophysiology. 2004 Oct;92(4):2555-73. doi: 10.1152/jn.01030.2003

    Information processing in the brain is believed to require coordinated activity across many neurons. With the recent development of techniques for simultaneously recording the spiking activity of large numbers of individual neurons, the search for complex multicell firing patterns that could help reveal this neural code has become possible. Here we develop a new approach for analyzing sequential firing patterns involving an arbitrary number of neurons based on relative firing order. Specifically, we develop a combinatorial method for quantifying the degree of matching between a "reference sequence" of N distinct "letters" (representing a particular target order of firing by N cells) and an arbitrarily long "word" composed of any subset of those letters including repeats (representing the relative time order of spikes in an arbitrary firing pattern). The method involves computing the probability that a random permutation of the word’s letters would by chance alone match the reference sequence as well as or better than the actual word does, assuming all permutations were equally likely. Lower probabilities thus indicate better matching. The overall degree and statistical significance of sequence matching across a heterogeneous set of words (such as those produced during the course of an experiment) can be computed from the corresponding set of probabilities. This approach can reduce the sample size problem associated with analyzing complex firing patterns. The approach is general and thus applicable to other types of neural data beyond multiple spike trains, such as EEG events or imaging signals from multiple locations. We have recently applied this method to quantify memory traces of sequential experience in the rodent hippocampus during slow wave sleep.

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    12/19/02 | Memory of sequential experience in the hippocampus during slow wave sleep.
    Lee AK, Wilson MA
    Neuron. 2002 Dec 19;36(6):1183-94

    Rats repeatedly ran through a sequence of spatial receptive fields of hippocampal CA1 place cells in a fixed temporal order. A novel combinatorial decoding method reveals that these neurons repeatedly fired in precisely this order in long sequences involving four or more cells during slow wave sleep (SWS) immediately following, but not preceding, the experience. The SWS sequences occurred intermittently in brief ( approximately 100 ms) bursts, each compressing the behavioral sequence in time by approximately 20-fold. This rapid encoding of sequential experience is consistent with evidence that the hippocampus is crucial for spatial learning in rodents and the formation of long-term memories of events in time in humans.

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