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3 Publications

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    Magee Lab
    12/18/13 | Variable dendritic integration in hippocampal CA3 pyramidal neurons.
    Makara JK, Magee JC
    Neuron. 2013 Dec 18;80(6):1438-50. doi: 10.1016/j.neuron.2013.10.033

    The hippocampal CA3 region is essential for pattern completion and generation of sharp-wave ripples. During these operations, coordinated activation of ensembles of CA3 pyramidal neurons produces spatiotemporally structured input patterns arriving onto dendrites of recurrently connected CA3 neurons. To understand how such input patterns are translated into specific output patterns, we characterized dendritic integration in CA3 pyramidal cells using two-photon imaging and glutamate uncaging. We found that thin dendrites of CA3 pyramidal neurons integrate synchronous synaptic input in a highly supralinear fashion. The amplification was primarily mediated by NMDA receptor activation and was present over a relatively broad range of spatiotemporal input patterns. The decay of voltage responses, temporal summation, and action potential output was regulated in a compartmentalized fashion mainly by a G-protein-activated inwardly rectifying K(+) current. Our results suggest that plastic dendritic integrative mechanisms may support ensemble behavior in pyramidal neurons of the hippocampal circuitry.

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    Magee Lab
    11/06/13 | Imaging neuronal populations in behaving rodents: paradigms for studying neural circuits underlying behavior in the mammalian cortex.
    Chen JL, Andermann ML, Keck T, Xu N, Ziv Y
    The Journal of Neuroscience : the Official Journal of the Society for Neuroscience. 2013 Nov 6;33(45):17631-40. doi: 10.1523/JNEUROSCI.3255-13.2013

    Understanding the neural correlates of behavior in the mammalian cortex requires measurements of activity in awake, behaving animals. Rodents have emerged as a powerful model for dissecting the cortical circuits underlying behavior attributable to the convergence of several methods. Genetically encoded calcium indicators combined with viral-mediated or transgenic tools enable chronic monitoring of calcium signals in neuronal populations and subcellular structures of identified cell types. Stable one- and two-photon imaging of neuronal activity in awake, behaving animals is now possible using new behavioral paradigms in head-fixed animals, or using novel miniature head-mounted microscopes in freely moving animals. This mini-symposium will highlight recent applications of these methods for studying sensorimotor integration, decision making, learning, and memory in cortical and subcortical brain areas. We will outline future prospects and challenges for identifying the neural underpinnings of task-dependent behavior using cellular imaging in rodents.

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    Magee Lab
    08/07/13 | Potassium channels control the interaction between active dendritic integration compartments in layer 5 cortical pyramidal neurons.
    Harnett MT, Xu N, Magee JC, Williams SR
    Neuron. 2013 Aug 7;79:516-29. doi: 10.1016/j.neuron.2013.06.005

    Active dendritic synaptic integration enhances the computational power of neurons. Such nonlinear processing generates an object-localization signal in the apical dendritic tuft of layer 5B cortical pyramidal neurons during sensory-motor behavior. Here, we employ electrophysiological and optical approaches in brain slices and behaving animals to investigate how excitatory synaptic input to this distal dendritic compartment influences neuronal output. We find that active dendritic integration throughout the apical dendritic tuft is highly compartmentalized by voltage-gated potassium (KV) channels. A high density of both transient and sustained KV channels was observed in all apical dendritic compartments. These channels potently regulated the interaction between apical dendritic tuft, trunk, and axosomatic integration zones to control neuronal output in vitro as well as the engagement of dendritic nonlinear processing in vivo during sensory-motor behavior. Thus, KV channels dynamically tune the interaction between active dendritic integration compartments in layer 5B pyramidal neurons to shape behaviorally relevant neuronal computations.

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