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OYM 29: Learning the Milky Way

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Schematic of the Experimental Design from  Parylak, Deng & Gage 2013 commentary (c) NPG

Schematic of the Experimental Design from Parylak, Deng & Gage 2013 commentary (c) NPG

  Last week, OYM made its conference debut at a local interdisciplinary graduate research symposium and, although it meant we all had to switch up our approach to conferences, it was a great experience.  Welcome to all the new listeners we talked to over the two days, it’s nice to have you with us!

On top of conference prep, this week’s been loaded with out-of-lab responsibilities for the gang.  Kat and Liam spent some time inspiring the next generation of neuroscientists through their involvement in BrainReach, a local initiative that brings neuroscience to high school students around Montreal.  They used a cockroach to show how neurons produce and respond to electrical current, and a healthy dose of failure to demonstrate that experiments don’t always pan out in science.  But it could be worse, at least we don’t have to sting ourselves with bees in the name of science, like Michael Smith, a grad student at Cornell.

Liam’s got politics on his mind, after he was mistakenly caught up in, yet another, student protest, and Adel’s been exploring the idea of diminishing returns on investments in science.  After a stimulating conversation about how scientific productivity should be measured, we’re onto this week’s review of an article published in Nature Neuroscienceearlier this year.

Tumor necrosis factor alpha (TNF) is a pro-inflammatory peptide that’s known to regulate a number of pathways in the immune system and is necessary to the development of a number of immune organs.  TNF is also expressed, at low levels, in the brain and some reports of TNF knockout mice show altered behavior in the absence of the TNF gene.  What’s particularly interesting is that there is conflicting evidence of altered behavior, depending on whether TNF knockout animals were compared to their wildtype (WT) littermates or pups from an entirely different litter.  The authors of this paper took this to suggest that there might be an interaction between parental and offspring genotype and that TNF might be involved in early brain development.

In order to differentiate between the effect of parental genotype and TNF impairment in the offspring, the authors, rather elegantly, generated 4 groups of mice: those who were WT for the TNF gene and came from WT parents (WT(WT)), WT pups from a cross between two heterozygous parents (WT(H)), and TNF deficient mice from  either heterozygous (KO(H)) or knockout parents (KO(KO)).  They trained adult mice from all groups in the Morris Water Maze, which measures spatial learning ability, and showed that mice from TNF deficient parents, performed better, regardless of their own TNF genotype.  Similarly, KO(KO) mice learned to associate a specific context, but not a specific cue, with a fearful stimuli faster than WT(WT) mice.  Together, their results suggest that hippocampal functioning is enhanced in offspring of parents with hematopoietic TNF deficiency.

Next, they labelled proliferating cells in the hippocampus and found that there was a transient increase of neural precursor cells in these animals at postnatal day 14 but that these differences normalize in adult mice.  Genes associated with acetylcholine neurotransmission are upregulated and  inhibitory neuropeptide genes are downregulated in the adult hippocampus of animals with TNF deficient parents so the authors theorize that the spike in cell proliferation at P14, leads to an increase in hippocampal excitation that lasts through adulthood.

Although we’d like to have seen some electrophysiology to support this theory, the authors do show that these animals have longer dendrites, and therefore more dendritic spines, in the cells of the granule layer.

Last, but not least, the authors use cross fostering experiments to demonstrate that the effect of parental genotype is postnatal, and protein analysis to show that the level of a number of cytokines are decreased in the milk of TNF deficient mothers.  Interestingly, supplementing the milk with the deficient cytokines reverses the behavioral and histological phenotype in these offspring.

At the end of this paper, we’re given a potential evolutionary explanation for these results.  While we’re left unsure of how this relates to human hippocampal development or neurological disease, we’re convinced that this paper adds support to the importance of breastfeeding and the interaction between brain development and peripheral systems.

Paper!

Liu B, Zupan B, Laird E, Klein S, Gleason G, Bozinoski M, Gal Toth J, & Toth M (2014). Maternal hematopoietic TNF, via milk chemokines, programs hippocampal development and memory. Nature neuroscience, 17 (1), 97-105 PMID: 24292233

Sneaky Pdf

Links!!

Backyard Brains DIY Neuroscience

Carl Zimmer’s science tattoo emporium

Bee Sting Pain Index:   and its blog coverage at National Geographic: and, if you’re still not satisfied, descriptive pain levels of various insect stings (seriously read this)

Diminishing returns in science

NSF Report on scientific publishing practices in the US

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The post OYM 29: Learning the Milky Way appeared first on On Your Mind Podcast.


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