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5 Janelia Publications

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    Magee LabSpruston Lab
    09/23/15 | Inhibitory gating of input comparison in the CA1 microcircuit.
    Milstein AD, Bloss EB, Apostolides PF, Vaidya SP, Dilly GA, Zemelman BV, Magee JC
    Neuron. 2015 Sep 23;87(6):1274-89. doi: 10.1016/j.neuron.2015.08.025

    Spatial and temporal features of synaptic inputs engage integration mechanisms on multiple scales, including presynaptic release sites, postsynaptic dendrites, and networks of inhibitory interneurons. Here we investigate how these mechanisms cooperate to filter synaptic input in hippocampal area CA1. Dendritic recordings from CA1 pyramidal neurons reveal that proximal inputs from CA3 as well as distal inputs from entorhinal cortex layer III (ECIII) sum sublinearly or linearly at low firing rates due to feedforward inhibition, but sum supralinearly at high firing rates due to synaptic facilitation, producing a high-pass filter. However, during ECIII and CA3 input comparison, supralinear dendritic integration is dynamically balanced by feedforward and feedback inhibition, resulting in suppression of dendritic complex spiking. We find that a particular subpopulation of CA1 interneurons expressing neuropeptide Y (NPY) contributes prominently to this dynamic filter by integrating both ECIII and CA3 input pathways and potently inhibiting CA1 pyramidal neuron dendrites.

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    Magee LabHarris Lab
    07/13/15 | Conjunctive input processing drives feature selectivity in hippocampal CA1 neurons.
    Bittner KC, Grienberger C, Vaidya SP, Milstein AD, Macklin JJ, Suh J, Tonegawa S, Magee JC
    Nature Neuroscience. 2015 Jul 13:. doi: 10.1038/nn.4062

    Feature-selective firing allows networks to produce representations of the external and internal environments. Despite its importance, the mechanisms generating neuronal feature selectivity are incompletely understood. In many cortical microcircuits the integration of two functionally distinct inputs occurs nonlinearly through generation of active dendritic signals that drive burst firing and robust plasticity. To examine the role of this processing in feature selectivity, we recorded CA1 pyramidal neuron membrane potential and local field potential in mice running on a linear treadmill. We found that dendritic plateau potentials were produced by an interaction between properly timed input from entorhinal cortex and hippocampal CA3. These conjunctive signals positively modulated the firing of previously established place fields and rapidly induced new place field formation to produce feature selectivity in CA1 that is a function of both entorhinal cortex and CA3 input. Such selectivity could allow mixed network level representations that support context-dependent spatial maps.

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    07/13/15 | Continuous volumetric imaging via an optical phase-locked ultrasound lens.
    Kong L, Tang J, Little JP, Yu Y, Lämmermann T, Lin CP, Germain RN, Cui M
    Nature Methods. 2015-Jul 13;12(8):759-62. doi: 10.1038/nmeth.3476

    In vivo imaging at high spatiotemporal resolution is key to the understanding of complex biological systems. We integrated an optical phase-locked ultrasound lens into a two-photon fluorescence microscope and achieved microsecond-scale axial scanning, thus enabling volumetric imaging at tens of hertz. We applied this system to multicolor volumetric imaging of processes sensitive to motion artifacts, including calcium dynamics in behaving mouse brain and transient morphology changes and trafficking of immune cells.

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    Magee Lab
    02/06/15 | Dendritic function in vivo.
    Grienberger C, Chen X, Konnerth A
    Trends in Neuroscience. 2015 Jan;38(1):45-54. doi: 10.1016/j.tins.2014.11.002

    Dendrites are the predominant entry site for excitatory synaptic potentials in most types of central neurons. There is increasing evidence that dendrites are not just passive transmitting devices but play active roles in synaptic integration through linear and non-linear mechanisms. Frequently, excitatory synapses are formed on dendritic spines. In addition to relaying incoming electrical signals, spines can play important roles in modifying these signals through complex biochemical processes and, thereby, determine learning and memory formation. Here, we review recent advances in our understanding of the function of spines and dendrites in central mammalian neurons in vivo by focusing particularly on insights obtained from Ca(2+) imaging studies.

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    Magee Lab
    01/21/15 | Distribution and function of HCN channels in the apical dendritic tuft of neocortical pyramidal neurons.
    Harnett MT, Magee JC, Williams SR
    Journal of Neuroscience. 2015 Jan 21;35(3):1024-37. doi: 10.1523/JNEUROSCI.2813-14.2015

    The apical tuft is the most remote area of the dendritic tree of neocortical pyramidal neurons. Despite its distal location, the apical dendritic tuft of layer 5 pyramidal neurons receives substantial excitatory synaptic drive and actively processes corticocortical input during behavior. The properties of the voltage-activated ion channels that regulate synaptic integration in tuft dendrites have, however, not been thoroughly investigated. Here, we use electrophysiological and optical approaches to examine the subcellular distribution and function of hyperpolarization-activated cyclic nucleotide-gated nonselective cation (HCN) channels in rat layer 5B pyramidal neurons. Outside-out patch recordings demonstrated that the amplitude and properties of ensemble HCN channel activity were uniform in patches excised from distal apical dendritic trunk and tuft sites. Simultaneous apical dendritic tuft and trunk whole-cell current-clamp recordings revealed that the pharmacological blockade of HCN channels decreased voltage compartmentalization and enhanced the generation and spread of apical dendritic tuft and trunk regenerative activity. Furthermore, multisite two-photon glutamate uncaging demonstrated that HCN channels control the amplitude and duration of synaptically evoked regenerative activity in the distal apical dendritic tuft. In contrast, at proximal apical dendritic trunk and somatic recording sites, the blockade of HCN channels decreased excitability. Dynamic-clamp experiments revealed that these compartment-specific actions of HCN channels were heavily influenced by the local and distributed impact of the high density of HCN channels in the distal apical dendritic arbor. The properties and subcellular distribution pattern of HCN channels are therefore tuned to regulate the interaction between integration compartments in layer 5B pyramidal neurons.

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