PhDs in Press

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While scouring Pubmed for published articles featuring Stanford Neuro-student authors for a recent post, I had two thoughts. 1) Students in the Stanford Neuro program were on a hell of a lot of papers

2) There was definitely a better way to highlight those papers than a retrospective every 6-months that took forever to type up and even longer to actually read (see thought 1).

Thus was born a new semi-regular feature for the neuroblog: PhDs in Press - of which this post is the first example.

Part shameless publicity, part proud bragging, part intra-program PSA, this feature will highlight recently published articles featuring an author (or authors) who is a current member of the Stanford Neuroscience Ph.D program.

[Note regarding the mechanics of this feature: This is purely through the magic of an ongoing My NCBI search for the names of Neuro PhD students. I wouldn't be surprised if there were some false negatives in the data set. Neuro students - let me know if I've missed your paper, and I'll gladly add it.]

[Additional Note: Links in the list below access anchor links within the main body of the post (which contains full titles, abstracts, and additional links to the article themselves). To allow link functionality, please continue reading this post below the fold.]

Without further ado, and with many congratulations to the authors, the papers:

First Author papers:
Second through n-th Author papers:

[Continue reading below the fold to allow link functionality above]

First Author Papers

Adelson et al 2012. Neuroprotection from Stroke in the Absence of MHCI or PirB. Neuron. 2012 Mar 22;73(6):1100-7. Epub 2012 Mar 21.

Abstract: Recovery from stroke engages mechanisms of neural plasticity. Here we examine a role for MHC class I (MHCI) H2-Kb and H2-Db, as well as PirB receptor. These molecules restrict synaptic plasticity and motor learning in the healthy brain. Stroke elevates neuronal expression not only of H2-Kb and H2-Db, but also of PirB and downstream signaling. KbDb knockout (KO) or PirB KO mice have smaller infarcts and enhanced motor recovery. KO hippocampal organotypic slices, which lack an intact peripheral immune response, have less cell death after in vitro ischemia. In PirB KO mice, corticospinal projections from the motor cortex are enhanced, and the reactive astrocytic response is dampened after MCAO. Thus, molecules that function in the immune system act not only to limit synaptic plasticity in healthy neurons, but also to exacerbate brain injury after ischemia. These results suggest therapies for stroke by targeting MHCI and PirB.

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Maheswaranathan et al 2012. Emergent bursting and synchrony in computer simulations of neuronal cultures. Front. Comput. Neurosci. 6:15. doi: 10.3389/fncom.2012.00015

Abstract: Experimental studies of neuronal cultures have revealed a wide variety of spiking network activity ranging from sparse, asynchronous firing to distinct, network-wide synchronous bursting. However, the functional mechanisms driving these observed firing patterns are not well understood. In this work, we develop an in silico network of cortical neurons based on known features of similar in vitro networks. The activity from these simulations is found to closely mimic experimental data. Furthermore, the strength or degree of network bursting is found to depend on a few parameters: the density of the culture, the type of synaptic connections, and the ratio of excitatory to inhibitory connections. Network bursting gradually becomes more prominent as either the density, the fraction of long range connections, or the fraction of excitatory neurons is increased. Interestingly, biologically prevalent values of parameters result in networks that are at the transition between strong bursting and sparse firing. Using principal components analysis, we show that a large fraction of the variance in firing rates is captured by the first component for bursting networks. These results have implications for understanding how information is encoded at the population level as well as for why certain network parameters are ubiquitous in cortical tissue.

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Wang et al 2012. Axon degeneration: molecular mechanisms of a self-destruction pathway. J Cell Biol. 2012 Jan 9;196(1):7-18. Review.

Abstract: Axon degeneration is a characteristic event in many neurodegenerative conditions including stroke, glaucoma, and motor neuropathies. However, the molecular pathways that regulate this process remain unclear. Axon loss in chronic neurodegenerative diseases share many morphological features with those in acute injuries, and expression of the Wallerian degeneration slow (WldS) transgene delays nerve degeneration in both events, indicating a common mechanism of axonal self-destruction in traumatic injuries and degenerative diseases. A proposed model of axon degeneration is that nerve insults lead to impaired delivery or expression of a local axonal survival factor, which results in increased intra-axonal calcium levels and calcium-dependent cytoskeletal breakdown.

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Second through Nth-Author Papers

Byers et al 2012. SNCA triplication Parkinson's patient's iPSC-derived DA neurons accumulate α-synuclein and are susceptible to oxidative stress. PLoS One. 2011;6(11):e26159. Epub 2011 Nov 16.

Abstract: Parkinson's disease (PD) is an incurable age-related neurodegenerative disorder affecting both the central and peripheral nervous systems. Although common, the etiology of PD remains poorly understood. Genetic studies infer that the disease results from a complex interaction between genetics and environment and there is growing evidence that PD may represent a constellation of diseases with overlapping yet distinct underlying mechanisms. Novel clinical approaches will require a better understanding of the mechanisms at work within an individual as well as methods to identify the specific array of mechanisms that have contributed to the disease. Induced pluripotent stem cell (iPSC) strategies provide an opportunity to directly study the affected neuronal subtypes in a given patient. Here we report the generation of iPSC-derived midbrain dopaminergic neurons from a patient with a triplication in the α-synuclein gene (SNCA). We observed that the iPSCs readily differentiated into functional neurons. Importantly, the PD-affected line exhibited disease-related phenotypes in culture: accumulation of α-synuclein, inherent overexpression of markers of oxidative stress, and sensitivity to peroxide induced oxidative stress. These findings show that the dominantly-acting PD mutation is intrinsically capable of perturbing normal cell function in culture and confirm that these features reflect, at least in part, a cell autonomous disease process that is independent of exposure to the entire complexity of the diseased brain.

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Akam et al 2012. Oscillatory dynamics in the hippocampus support dentate gyrus-CA3 coupling. Nat Neurosci. 2012 Apr 1. doi: 10.1038/nn.3081.

Abstract: Gamma oscillations in the dentate gyrus and hippocampal CA3 show variable coherence in vivo, but the mechanisms and relevance for information flow are unknown. We found that carbachol-induced oscillations in rat CA3 have biphasic phase-response curves, consistent with the ability to couple with oscillations in afferent projections. Differences in response to stimulation of either the intrinsic feedback circuit or the dentate gyrus were well described by varying an impulse vector in a two-dimensional dynamical system, representing the relative input to excitatory and inhibitory neurons. Responses to sinusoidally modulated optogenetic stimulation confirmed that the CA3 network oscillation can entrain to periodic inputs, with a steep dependence of entrainment phase on input frequency. CA3 oscillations are therefore suited to coupling with oscillations in the dentate gyrus over a broad range of frequencies.

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Tasic et al 2012. Extensions of MADM (Mosaic Analysis with Double Markers) in Mice. PLoS One. 2012;7(3):e33332. Epub 2012 Mar 27.

Abstract: Mosaic Analysis with Double Markers (MADM) is a method for generating genetically mosaic mice, in which sibling mutant and wild-type cells are labeled with different fluorescent markers. It is a powerful tool that enables analysis of gene function at the single cell level in vivo. It requires transgenic cassettes to be located between the centromere and the mutation in the gene of interest on the same chromosome. Here we compare procedures for introduction of MADM cassettes into new loci in the mouse genome, and describe new approaches for expanding the utility of MADM. We show that: 1) Targeted homologous recombination outperforms random transgenesis in generation of reliably expressed MADM cassettes, 2) MADM cassettes in new genomic loci need to be validated for biallelic and ubiquitous expression, 3) Recombination between MADM cassettes on different chromosomes can be used to study reciprocal chromosomal deletions/duplications, and 4) MADM can be modified to permit transgene expression by combining it with a binary expression system. The advances described in this study expand current, and enable new and more versatile applications of MADM

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