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49 Publications

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    Magee Lab
    12/22/11 | Observations on clustered synaptic plasticity and highly structured input patterns.
    Magee JC
    Neuron. 2011 Dec 22;72(6):887-8. doi: 10.1016/j.neuron.2011.12.009

    In this issue of Neuron, Makino and Malinow and Kleindienst et al. present evidence of a behaviorally induced form of synaptic plasticity that would encourage the development of fine-scale structured input patterns and the binding of features within single neurons.

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    Magee Lab
    08/01/10 | Network mechanisms of theta related neuronal activity in hippocampal CA1 pyramidal neurons.
    Losonczy A, Zemelman BV, Vaziri A, Magee JC
    Nature Neuroscience. 2010 Aug;13(8):967-72. doi: 10.1038/nn.2597

    Although hippocampal theta oscillations represent a prime example of temporal coding in the mammalian brain, little is known about the specific biophysical mechanisms. Intracellular recordings support a particular abstract oscillatory interference model of hippocampal theta activity, the soma-dendrite interference model. To gain insight into the cellular and circuit level mechanisms of theta activity, we implemented a similar form of interference using the actual hippocampal network in mice in vitro. We found that pairing increasing levels of phasic dendritic excitation with phasic stimulation of perisomatic projecting inhibitory interneurons induced a somatic polarization and action potential timing profile that reproduced most common features. Alterations in the temporal profile of inhibition were required to fully capture all features. These data suggest that theta-related place cell activity is generated through an interaction between a phasic dendritic excitation and a phasic perisomatic shunting inhibition delivered by interneurons, a subset of which undergo activity-dependent presynaptic modulation.

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    Magee Lab
    06/29/10 | Two-photon single-cell optogenetic control of neuronal activity by sculpted light.
    Andrasfalvy BK, Zemelman BV, Tang J, Vaziri A
    Proceedings of the National Academy of Sciences of the United States of America. 2010 Jun 29;107(26):11981-6. doi: 10.1073/pnas.1006620107

    Recent advances in optogenetic techniques have generated new tools for controlling neuronal activity, with a wide range of neuroscience applications. The most commonly used approach has been the optical activation of the light-gated ion channel channelrhodopsin-2 (ChR2). However, targeted single-cell-level optogenetic activation with temporal precessions comparable to the spike timing remained challenging. Here we report fast (< or = 1 ms), selective, and targeted control of neuronal activity with single-cell resolution in hippocampal slices. Using temporally focused laser pulses (TEFO) for which the axial beam profile can be controlled independently of its lateral distribution, large numbers of channels on individual neurons can be excited simultaneously, leading to strong (up to 15 mV) and fast (< or = 1 ms) depolarizations. Furthermore, we demonstrated selective activation of cellular compartments, such as dendrites and large presynaptic terminals, at depths up to 150 microm. The demonstrated spatiotemporal resolution and the selectivity provided by TEFO allow manipulation of neuronal activity, with a large number of applications in studies of neuronal microcircuit function in vitro and in vivo.

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    Magee LabHarris Lab
    06/01/10 | Multi-array silicon probes with integrated optical fibers: light-assisted perturbation and recording of local neural circuits in the behaving animal.
    Royer S, Zemelman BV, Barbic M, Losonczy A, Buzsáki G, Magee JC
    The European Journal of Neuroscience. 2010 Jun;31:2279-91. doi: 10.1002/cbic.201000254

    Recordings of large neuronal ensembles and neural stimulation of high spatial and temporal precision are important requisites for studying the real-time dynamics of neural networks. Multiple-shank silicon probes enable large-scale monitoring of individual neurons. Optical stimulation of genetically targeted neurons expressing light-sensitive channels or other fast (milliseconds) actuators offers the means for controlled perturbation of local circuits. Here we describe a method to equip the shanks of silicon probes with micron-scale light guides for allowing the simultaneous use of the two approaches. We then show illustrative examples of how these compact hybrid electrodes can be used in probing local circuits in behaving rats and mice. A key advantage of these devices is the enhanced spatial precision of stimulation that is achieved by delivering light close to the recording sites of the probe. When paired with the expression of light-sensitive actuators within genetically specified neuronal populations, these devices allow the relatively straightforward and interpretable manipulation of network activity.

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    Magee LabChklovskii Lab
    12/01/09 | Experience-dependent compartmentalized dendritic plasticity in rat hippocampal CA1 pyramidal neurons.
    Makara JK, Losonczy A, Wen Q, Magee JC
    Nature Neuroscience. 2009 Dec;12(12):1485-7. doi: 10.1038/nn.2428

    The excitability of individual dendritic branches is a plastic property of neurons. We found that experience in an enriched environment increased propagation of dendritic Na(+) spikes in a subset of individual dendritic branches in rat hippocampal CA1 pyramidal neurons and that this effect was mainly mediated by localized downregulation of A-type K(+) channel function. Thus, dendritic plasticity might be used to store recent experience in individual branches of the dendritic arbor.

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    Magee Lab
    10/16/09 | Fast synaptic subcortical control of hippocampal circuits.
    Varga V, Losonczy A, Zemelman BV, Borhegyi Z, Nyiri G, Domonkos A, Hangya B, Holderith N, Magee JC, Freund TF
    Science. 2009 Oct 16;326(5951):449-53. doi: 10.1126/science.1178307

    Cortical information processing is under state-dependent control of subcortical neuromodulatory systems. Although this modulatory effect is thought to be mediated mainly by slow nonsynaptic metabotropic receptors, other mechanisms, such as direct synaptic transmission, are possible. Yet, it is currently unknown if any such form of subcortical control exists. Here, we present direct evidence of a strong, spatiotemporally precise excitatory input from an ascending neuromodulatory center. Selective stimulation of serotonergic median raphe neurons produced a rapid activation of hippocampal interneurons. At the network level, this subcortical drive was manifested as a pattern of effective disynaptic GABAergic inhibition that spread throughout the circuit. This form of subcortical network regulation should be incorporated into current concepts of normal and pathological cortical function.

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    Magee Lab
    04/16/09 | Pathway interactions and synaptic plasticity in the dendritic tuft regions of CA1 pyramidal neurons.
    Takahashi H, Magee JC
    Neuron. 2009 Apr 16;62(1):102-11. doi: 10.1016/j.neuron.2009.03.007

    Input comparison is thought to occur in many neuronal circuits, including the hippocampus, where functionally important interactions between the Schaffer collateral and perforant pathways have been hypothesized. We investigated this idea using multisite, whole-cell recordings and Ca2+ imaging and found that properly timed, repetitive stimulation of both pathways results in the generation of large plateau potentials in distal dendrites of CA1 pyramidal neurons. These dendritic plateau potentials produce widespread Ca2+ influx, large after-depolarizations, burst firing output, and long-term potentiation of perforant path synapses. Plateau duration is directly related to the strength and temporal overlap of pathway activation and involves back-propagating action potentials and both NMDA receptors and voltage-gated Ca2+ channels. Thus, the occurrence of highly correlated SC and PP input to CA1 is signaled by a dramatic change in output mode and an increase in input efficacy, all induced by a large plateau potential in the distal dendrites of CA1 pyramidal neurons.

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    Magee Lab
    08/15/08 | Altered synaptic and non-synaptic properties of CA1 pyramidal neurons in Kv4.2 knockout mice.
    Andrásfalvy BK, Makara JK, Johnston D, J.C. Magee
    The Journal of Physiology. 2008 Aug 15;586(16):3881-92. doi: 10.1113/jphysiol.2008.154336

    Back-propagating action potentials (bAPs) travelling from the soma to the dendrites of neurons are involved in various aspects of synaptic plasticity. The distance-dependent increase in Kv4.2-mediated A-type K(+) current along the apical dendrites of CA1 pyramidal cells (CA1 PCs) is responsible for the attenuation of bAP amplitude with distance from the soma. Genetic deletion of Kv4.2 reduced dendritic A-type K(+) current and increased the bAP amplitude in distal dendrites. Our previous studies revealed that the amplitude of unitary Schaffer collateral inputs increases with distance from the soma along the apical dendrites of CA1 PCs. We tested the hypothesis that the weight of distal synapses is dependent on dendritic Kv4.2 channels. We compared the amplitude and kinetics of mEPSCs at different locations on the main apical trunk of CA1 PCs from wild-type (WT) and Kv4.2 knockout (KO) mice. While wild-type mice showed normal distance-dependent scaling, it was missing in the Kv4.2 KO mice. We also tested whether there was an increase in inhibition in the Kv4.2 knockout, induced in an attempt to compensate for a non-specific increase in neuronal excitability (after-polarization duration and burst firing probability were increased in KO). Indeed, we found that the magnitude of the tonic GABA current increased in Kv4.2 KO mice by 53% and the amplitude of mIPSCs increased by 25%, as recorded at the soma. Our results suggest important roles for the dendritic K(+) channels in distance-dependent adjustment of synaptic strength as well as a primary role for tonic inhibition in the regulation of global synaptic strength and membrane excitability.

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    Magee Lab
    03/27/08 | Compartmentalized dendritic plasticity and input feature storage in neurons.
    Losonczy A, Makara JK, Magee JC
    Nature. 2008 Mar 27;452(7186):436-41. doi: 10.1038/nature06725

    Although information storage in the central nervous system is thought to be primarily mediated by various forms of synaptic plasticity, other mechanisms, such as modifications in membrane excitability, are available. Local dendritic spikes are nonlinear voltage events that are initiated within dendritic branches by spatially clustered and temporally synchronous synaptic input. That local spikes selectively respond only to appropriately correlated input allows them to function as input feature detectors and potentially as powerful information storage mechanisms. However, it is currently unknown whether any effective form of local dendritic spike plasticity exists. Here we show that the coupling between local dendritic spikes and the soma of rat hippocampal CA1 pyramidal neurons can be modified in a branch-specific manner through an N-methyl-d-aspartate receptor (NMDAR)-dependent regulation of dendritic Kv4.2 potassium channels. These data suggest that compartmentalized changes in branch excitability could store multiple complex features of synaptic input, such as their spatio-temporal correlation. We propose that this ’branch strength potentiation’ represents a previously unknown form of information storage that is distinct from that produced by changes in synaptic efficacy both at the mechanistic level and in the type of information stored.

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    Ji LabMagee LabBetzig Lab
    02/01/08 | High-speed, low-photodamage nonlinear imaging using passive pulse splitters.
    Ji N, Magee JC, Betzig E
    Nature Methods. 2008 Feb;5(2):197-202. doi: 10.1038/nmeth.1175

    Pulsed lasers are key elements in nonlinear bioimaging techniques such as two-photon fluorescence excitation (TPE) microscopy. Typically, however, only a percent or less of the laser power available can be delivered to the sample before photoinduced damage becomes excessive. Here we describe a passive pulse splitter that converts each laser pulse into a fixed number of sub-pulses of equal energy. We applied the splitter to TPE imaging of fixed mouse brain slices labeled with GFP and show that, in different power regimes, the splitter can be used either to increase the signal rate more than 100-fold or to reduce the rate of photobleaching by over fourfold. In living specimens, the gains were even greater: a ninefold reduction in photobleaching during in vivo imaging of Caenorhabditis elegans larvae, and a six- to 20-fold decrease in the rate of photodamage during calcium imaging of rat hippocampal brain slices.

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