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1381 Janelia Publications

Showing 11-20 of 1381 results
06/20/18 | A transgenic mouse for imaging activity-dependent dynamics of endogenous Arc mRNA in live neurons.
Das S, Moon HC, Singer RH, Park HY
Science Advances. 2018 Jun;4(6):eaar3448. doi: 10.1126/sciadv.aar3448

Localized translation plays a crucial role in synaptic plasticity and memory consolidation. However, it has not been possible to follow the dynamics of memory-associated mRNAs in living neurons in response to neuronal activity in real time. We have generated a novel mouse model where the endogenous Arc/Arg3.1 gene is tagged in its 3' untranslated region with stem-loops that bind a bacteriophage PP7 coat protein (PCP), allowing visualization of individual mRNAs in real time. The physiological response of the tagged gene to neuronal activity is identical to endogenous Arc and reports the true dynamics of Arc mRNA from transcription to degradation. The transcription dynamics of Arc in cultured hippocampal neurons revealed two novel results: (i) A robust transcriptional burst with prolonged ON state occurs after stimulation, and (ii) transcription cycles continue even after initial stimulation is removed. The correlation of stimulation with Arc transcription and mRNA transport in individual neurons revealed that stimulus-induced Ca activity was necessary but not sufficient for triggering Arc transcription and that blocking neuronal activity did not affect the dendritic transport of newly synthesized Arc mRNAs. This mouse will provide an important reagent to investigate how individual neurons transduce activity into spatiotemporal regulation of gene expression at the synapse.

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06/19/18 | Lamellar projections in the endolymphatic sac act as a relief valve to regulate inner ear pressure.
Swinburne IA, Mosaliganti KR, Upadhyayula S, Liu T, Hildebrand DG, Tsai TY, Chen A, Al-Obeidi E, Fass AK, Malhotra S, Engert F, Lichtman JW, Kirchausen T, Betzig E, Megason SG
eLife. 2018 Jun 19;7:. doi: 10.7554/eLife.37131

The inner ear is a fluid-filled closed-epithelial structure whose function requires maintenance of an internal hydrostatic pressure and fluid composition. The endolymphatic sac (ES) is a dead-end epithelial tube connected to the inner ear whose function is unclear. ES defects can cause distended ear tissue, a pathology often seen in hearing and balance disorders. Using live imaging of zebrafish larvae, we reveal that the ES undergoes cycles of slow pressure-driven inflation followed by rapid deflation. Absence of these cycles in mutants leads to distended ear tissue. Using serial-section electron microscopy and adaptive optics lattice light-sheet microscopy, we find a pressure relief valve in the ES comprised of partially separated apical junctions and dynamic overlapping basal lamellae that separate under pressure to release fluid. We propose that this lmx1-dependent pressure relief valve is required to maintain fluid homeostasis in the inner ear and other fluid-filled cavities.

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06/18/18 | A novel pyramidal cell type promotes sharp-wave synchronization in the hippocampus.
Hunt DL, Linaro D, Si B, Romani S, Spruston N
Nature Neuroscience. 2018 Jun 18:. doi: 10.1038/s41593-018-0172-7

To support cognitive function, the CA3 region of the hippocampus performs computations involving attractor dynamics. Understanding how cellular and ensemble activities of CA3 neurons enable computation is critical for elucidating the neural correlates of cognition. Here we show that CA3 comprises not only classically described pyramid cells with thorny excrescences, but also includes previously unidentified 'athorny' pyramid cells that lack mossy-fiber input. Moreover, the two neuron types have distinct morphological and physiological phenotypes and are differentially modulated by acetylcholine. To understand the contribution of these athorny pyramid neurons to circuit function, we measured cell-type-specific firing patterns during sharp-wave synchronization events in vivo and recapitulated these dynamics with an attractor network model comprising two principal cell types. Our data and simulations reveal a key role for athorny cell bursting in the initiation of sharp waves: transient network attractor states that signify the execution of pattern completion computations vital to cognitive function.

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Murphy Lab
06/13/18 | Distinct cell types in the superficial superior colliculus project to the dorsal lateral geniculate and lateral posterior thalamic nuclei.
Gale SD, Murphy GJ
Journal of Neurophysiology. 2018 Jun 13:. doi: 10.1152/jn.00248.2018

The superficial layers of the superior colliculus (sSC) receive retinal input and project to thalamic regions - the dorsal lateral geniculate (dLGN) and lateral posterior (LP; or pulvinar) nuclei -that convey visual information to cortex. A critical step towards understanding the functional impact of sSC neurons on these parallel thalamo-cortical pathways is determining whether different classes of sSC neurons, which are known to respond to different features of visual stimuli, innervate overlapping or distinct thalamic targets. Here, we identified a transgenic mouse line that labels sSC neurons that project to dLGN but not LP. We utilized selective expression of fluorophores and channelrhodopsin in this and previously characterized mouse lines to demonstrate that distinct cell types give rise to sSC projections to dLGN and LP. We further show that the glutamatergic sSC cell type that projects to dLGN also provides input to the sSC cell type that projects to LP. These results clarify the cellular origin of parallel sSC-thalamo-cortical pathways and reveal an interaction between these pathways via local connections within the sSC.

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06/12/18 | A connectome based hexagonal lattice convolutional network model of the Drosophila visual system.
Tschopp FD, Reiser MB, Turaga SC
arXiv. 2018 Jun 12:1806.04793

What can we learn from a connectome? We constructed a simplified model of the first two stages of the fly visual system, the lamina and medulla. The resulting hexagonal lattice convolutional network was trained using backpropagation through time to perform object tracking in natural scene videos. Networks initialized with weights from connectome reconstructions automatically discovered well-known orientation and direction selectivity properties in T4 neurons and their inputs, while networks initialized at random did not. Our work is the first demonstration, that knowledge of the connectome can enable in silico predictions of the functional properties of individual neurons in a circuit, leading to an understanding of circuit function from structure alone.

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05/28/18 | Discrete flow posteriors for variational inference in discrete dynamical systems.
Aitchison L, Adam V, Turaga SC
arXiv. 2018 May 28:1805.10958

Each training step for a variational autoencoder (VAE) requires us to sample from the approximate posterior, so we usually choose simple (e.g. factorised) approximate posteriors in which sampling is an efficient computation that fully exploits GPU parallelism. However, such simple approximate posteriors are often insufficient, as they eliminate statistical dependencies in the posterior. While it is possible to use normalizing flow approximate posteriors for continuous latents, some problems have discrete latents and strong statistical dependencies. The most natural approach to model these dependencies is an autoregressive distribution, but sampling from such distributions is inherently sequential and thus slow. We develop a fast, parallel sampling procedure for autoregressive distributions based on fixed-point iterations which enables efficient and accurate variational inference in discrete state-space latent variable dynamical systems. To optimize the variational bound, we considered two ways to evaluate probabilities: inserting the relaxed samples directly into the pmf for the discrete distribution, or converting to continuous logistic latent variables and interpreting the K-step fixed-point iterations as a normalizing flow. We found that converting to continuous latent variables gave considerable additional scope for mismatch between the true and approximate posteriors, which resulted in biased inferences, we thus used the former approach. Using our fast sampling procedure, we were able to realize the benefits of correlated posteriors, including accurate uncertainty estimates for one cell, and accurate connectivity estimates for multiple cells, in an order of magnitude less time.

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06/07/18 | Science holds the key to unlocking economic success.
Phillips J, Phillips M
The Telegraph. 2018 Jun 07:

The 2008 crisis should have led us to reshape how our economy works. But a decade on, what has really changed? The public knows that the same attitude that got us into the previous economic crisis will not bring us long-term prosperity, yet there is little vision from our leaders of what the future should look like. Our politicians are sleeping, yet have no dreams. To solve this, we must change emphasis from creating “growth” to creating the future: the former is an inevitable product of the latter.

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06/05/18 | Persistent sodium current mediates the steep voltage dependence of spatial coding in hippocampal pyramidal neurons.
Hsu C, Zhao X, Milstein AD, Spruston N
Neuron. 2018 Jun 05:. doi: 10.1016/j.neuron.2018.05.025

The mammalian hippocampus forms a cognitive map using neurons that fire according to an animal's position ("place cells") and many other behavioral and cognitive variables. The responses of these neurons are shaped by their presynaptic inputs and the nature of their postsynaptic integration. In CA1 pyramidal neurons, spatial responses in vivo exhibit a strikingly supralinear dependence on baseline membrane potential. The biophysical mechanisms underlying this nonlinear cellular computation are unknown. Here, through a combination of in vitro, in vivo, and in silico approaches, we show that persistent sodium current mediates the strong membrane potential dependence of place cell activity. This current operates at membrane potentials below the action potential threshold and over seconds-long timescales, mediating a powerful and rapidly reversible amplification of synaptic responses, which drives place cell firing. Thus, we identify a biophysical mechanism that shapes the coding properties of neurons composing the hippocampal cognitive map.

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06/04/18 | Motor control: three-dimensional metric of head movements in the mouse brain.
Finkelstein A
Current Biology : CB. 2018 Jun 04;28(11):R660-R662. doi: 10.1016/j.cub.2018.04.079

Many forms of human and animal behavior involve head movements. A new study reveals the neural code for three-dimensional head movements in the midbrain of freely moving mice.

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06/01/18 | Adaptive optical microscopy for neurobiology.
Rodriguez C, Ji N
Current Opinion in Neurobiology. 2018 Jun;50:83-91. doi: 10.1016/j.conb.2018.01.011

Highlights:

  • Biological specimens introduce wavefront aberrations and deteriorate the image quality of optical microscopy.
  • Adaptive optics is used in optical microscopy to recover ideal imaging performance.
  • Adaptive optical imaging improves structural imaging of neurons, allowing for synaptic-level resolution at depth.
  • Adaptive optical imaging leads to a more accurate characterization of the functional properties of neurons.

With the ability to correct for the aberrations introduced by biological specimens, adaptive optics—a method originally developed for astronomical telescopes—has been applied to optical microscopy to recover diffraction-limited imaging performance deep within living tissue. In particular, this technology has been used to improve image quality and provide a more accurate characterization of both structure and function of neurons in a variety of living organisms. Among its many highlights, adaptive optical microscopy has made it possible to image large volumes with diffraction-limited resolution in zebrafish larval brains, to resolve dendritic spines over 600μm deep in the mouse brain, and to more accurately characterize the orientation tuning properties of thalamic boutons in the primary visual cortex of awake mice.

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