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4 Janelia Publications

Showing 1-4 of 4 results
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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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    Ji LabMagee LabBetzig Lab
    02/01/08 | High-speed, low-photodamage nonlinear imaging using passive pulse splitters. (With commentary)
    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.

    Commentary: Na Ji came to me early in her postdoc with an idea to reduce photodamage in nonlinear microscopy by splitting the pulses from an ultrafast laser into multiple subpulses of reduced energy. In six weeks, we constructed a prototype pulse splitter and obtained initial results confirming the validity of her vision. Further experiments with Jeff Magee demonstrated that the splitter could be used to increase imaging speed or reduce photodamage in two photon microscopy by one to two orders of magnitude. This project is a great example of how quickly one can react and exploit new ideas in the Janelia environment.

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