Episode 24: Fetch me a GABA switch 3

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Figure 2This week on the On Your Mind Neuroscince Podcast:

We can’t believe he’s growing up so fast!  Our very own Adel is trying to cut the academic umbilical cord and is en route to a med school interview in Toronto.  But he won’t let career prospects get in the way of his weekly science talk with the rest of the gang.  He’s managed to call in and give his input on this week’s episode, including a recent experiment by computer scientists publishing gibberish papers!  We’re talking about programs like SCIgen that create computer science manuscripts using random word generators.  Leave it to computer scientists to troll computer science.

On a more positive note, Kat’s come across a website that acts as a hub for scientific discussion.  Pitched as an online journal club, PubPeer is a database linking any paper published with a DOI with its news and blog coverage.  It’s also a forum for interested science to anonymously ask questions, provide comments or add insight to relevant works.  It, and other online forums like it, are often used in times of controversy – the recent stem cell acid bath debate, for example.

Speaking of controversy, Liam has discovered a story that suggest social scientists have been measuring oxytocin levels incorrectly for years.  In what seems to be a scientific version of the Telephone Game, a missing extraction step may be drastically changing measured yields.  Although it looks at the activity of the oxytocin receptor, our paper this week doesn’t measure oxytocin levels directly, so it avoids this issue.

Our discussion this week, focuses on the changing behaviour of GABA receptors, the role of oxytocin at birth and their potential impacts on Autism Spectrum Disorders. The paper “Oxytocin-Mediated GABA InhibitionDuring Delivery Attenuates AutismPathogenesis in Rodent Offspring” by Tyzio, Nardou, Ferrari et al., in Science (Free PDF) used models of autism in two species to measure the electrophysiological behaviour of the hippocampus during the GABA switch.  GABA is best know as the main inhibitory neurotransmitter in the adult brain, but, due to varied intracellular chloride concentrations during development, it’s exclusively excitatory before birth.  Prenatally, when developing neurons have high intracellular chloride concentrations, the driving force of GABA receptors is above zero.  That is to say, when GABA receptors are activated, they allow chloride ions to leave the cell and cause the cell to depolarize.  After birth, when GABA receptors are activated, chloride enters and hyperpolarizes the neuron.  In both the rat and mouse models of autism studied here, these receptors fail to switch from excitatory to inhibitory.  This seems to have a pronounced effect on the general activity level of the hippocampus and might be reversibly with prenatal inhibition of the chloride importer.  In fact, a clinical trial has already been published using a chloride importer antagonist as a treatment for children with ASD.

The authors suggest a role for oxytocin in mediating this switch.  When they administer an oxytocin receptor antagonist in wild type rodents, they observed electrophysiological phenotypes similar to the autism models.  They show the effect of prenatal chloride importer antagonism on the frequency and quality of vocalizations in their models, but, the relationship between these measures and ASD in humans is still up for debate.

At least we can all agree on the importance of unifying redundancy…

Have you read the paper? let us know what you think:

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SCIgen – an automatic paper generator

ArXiv vs SnarXiv: Guess the real Physics paper:  (Liam also sits around 60%)

PubPeer– an online journal club (we still like OYM better)

The Trouble with Oxytocin, Part II: Extracting the Truth from Oxytocin Research By Michael McCullough

This weeks Paper: Tyzio, R., Nardou, R., Ferrari, D., Tsintsadze, T., Shahrokhi, A., Eftekhari, S., Khalilov, I., Tsintsadze, V., Brouchoud, C., Chazal, G., Lemonnier, E., Lozovaya, N., Burnashev, N., & Ben-Ari, Y. (2014). Oxytocin-Mediated GABA Inhibition During Delivery Attenuates Autism Pathogenesis in Rodent Offspring Science, 343 (6171), 675-679 DOI: 10.1126/science.1247190 (or take this Free PDF)