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greaterthan, originally uploaded by kaleidoscopikr.
GABA-A receptors are found on neurons all over your brain. When other neurons send them some GABA they let chloride ions flow across the cell membrane. This typically has the effect of increasing negative ions inside the cell and quieting things down (in the general case, more positive = more active). GABA-A antagonists injected into most any part of the brain would have remove GABA-mediated inhibition to a large extent. Cells would start firing a lot. These chemicals give us a tool to crank up neural activity for a period, to see what happens downstream. They were initially discovered as convulsants (you can imagine how convulsions could arise from reduced neural inhibition). Whoa, I almost thought that second weakest one was called tuRbocurarine. The TigerLillies have a song called QRV that always makes me think of curare on their Gorey tribute album.
It really does fuel disgust for police officers when they blatantly break the law, and it lends plausibility to all other accusations of misconduct (brutality, discrimination, etc). Jimmy Justice tracks them down and takes them to task. I wonder how he avoids arrest on trumped up charges. That is def the scariest part about confronting the beast.
Filed under: audio, science, visual | Tags: digital clubbing, prostaglandin, tecktonik
From The hippocratic finger points the blame at PGE2 by Coggins Coffman and Koller:
Digital clubbing has been recognized since the time of the ancient Greeks as a sign of systemic disease.
Faculty of 1000 let me know over the weekend that there isn’t enough thujone in vintage absinthe to have any psychotropic effects. Absinthe isn’t any more dangerous than liquor, showing yet again how far U.S. policy on controlled substances is from an empriical basis. From the abstract:
All things considered, nothing besides ethanol was found in the absinthes that was able to explain the syndrome “absinthism.
Fulltext article here.
lots of new types of small RNAs to digest. also, technicolour tracing with the brain bow mouse. and a glutamate receptor review from dr. ehlers who has brought us some really nice vesicle trafficking videos in the past and careful studies of the half-lives of proteins in the post-synaptic density.
too lazy for links
http://www.sciencemag.org/cgi/content/summary/320/5879/1023
http://www.sciencemag.org/cgi/content/full/sci;320/5879/1077
http://www.nature.com/doifinder/10.1038/453430e
http://dx.doi.org/10.1038/nature06908
http://dx.doi.org/10.1038/nature06904
http://dx.doi.org/10.1038/nature06965
http://www.neuron.org/content/article/abstract?uid=PIIS089662730800408X&feed=NEURON
http://www.current-biology.com/content/article/abstract?uid=PIIS0960982208003849&feed=CURBIO
http://www.current-biology.com/content/article/abstract?uid=PIIS0960982208003230&feed=CURBIO
http://www.nature.com/nrg/journal/v9/n6/abs/nrg2341.html
http://www.nature.com/nrn/journal/v9/n6/full/nrn2406.html
http://www.nature.com/doifinder/10.1038/ng.138
http://www.nature.com/nrn/journal/v9/n6/full/nrn2391.html
http://www.plosgenetics.org/article/info%3Adoi%2F10.1371%2Fjournal.pgen.1000068
Here’s a fine piece of work from Miwa et al. comparing the role of NR2B subunits in the lateral amygdala versus the CA1 region. NMDA receptors are glutamate receptors heavily implicated in the initiation of synaptic plasticity underlying learning and memory. They consist of NR1 subunits in complex with any of the subtypes of NR2 units (NR2A-NR2D). The story goes that NR2B subunits are prominent early in development but are replaced with NR2A subunits in adulthood. The “doogie mouse” was created by transgenically increasing the NR2B contribution in adult mice because NR2Bs allow a longer time window in which to initiate plasticity processes. SInce then, a story has emerged that NR2Bs are typically found outside the synapse and are only activated when the signal is so strong that glutamate spills over. Miwa et al take that apart by showing through electrophysiology and immunogold electron microscopy that NR2Bs are present in synapses in the LA and CA1. They then run down a whole list of differences between the two regions.
“The properties of NMDA receptors in the LA were distinct from those in the CA1 region: a greater contribution of the NR2B subunit to synaptic NMDA responses ; a higher NR2B/NR2A ratio and a higher ratio of NMDA to AMPA receptor-mediated synaptic transmission ; smaller synaptic currents in the I–V curve of NMDA receptors; and lower Mg2+ sensitivity.”
Ignoring all caveats for a minute, the amygdala is where fear memories are made and the hippocampus is where memories of space, context, and personal events are made. It’s interesting to consider how the different memory systems will respond to drugs that affect NMDA receptors and perhaps disorders such as epilepsy and schizophrenia that are sometimes associated with NMDA receptor malfunctions.
Functional contributions of synaptically localized NR2B subunits of the NMDA receptor to synaptic transmission and long-term potentiation in the adult mouse CNS
Hideki Miwa, Masahiro Fukaya, Ayako M. Watabe, Masahiko Watanabe and Toshiya Manabe
Filed under: science | Tags: axon guidance, guidepost cells, handshake hypothesis, tissir, transgenics
Transgenic manipulations are starting to feel like an address book. You flox your gene and the look up the promoter in your fave neighborhood. I guess if the brain is the world then Foxg1 corresponds to a continent and Emx1 is a big important nation in that continent. Funny how hard it is to avoid a hemisphere analogy. Zhou et al use the technique on an axon-guiding cell-adhesion molecule to piece apart the necessity of Celsr3 in the dorsal versus ventral telencephalon for connecting major fiber tracts. If Celsr3 is knocked out mainly in layer 5 of the neocortex, the connections between the cortex and the thalamus are generally spared. I don’t quite get what the ‘handshake hypothesis’ is yet. Need more background in axon guidance.
Early Forebrain Wiring: Genetic Dissection Using Conditional Celsr3 Mutant Mice
Libing Zhou, Isabelle Bar, Younès Achouri, Kenneth Campbell, Olivier De Backer, Jean M. Hebert, Kevin Jones, Nicoletta Kessaris, Catherine Lambert de Rouvroit, Dennis O’Leary, William D. Richardson, Andre M. Goffinet, Fadel Tissir
I don’t expect I’ll get too far into these Gamma papers, but it is important to know about this source of artifacts. Looks like scalp recording is susceptible to a trompe l’oeil so to speak. The Fries et al. commentary assures that gamma-band synchronization (30-100 Hz oscillations) still exists, and that MEG and local recordings don’t have the issue. If I scanned correctly, EEG can be salvaged by eschewing event-related potential types of analysis.
Finding Gamma
Pascal Fries, René Scheeringa, and Robert Oostenveld.
Transient Induced Gamma-Band Response in EEG as a Manifestation of Miniature Saccades
Shlomit Yuval-Greenberg, Orr Tomer, Alon S. Keren, Israel Nelken, and Leon Y. Deouell.
Berke et al. have a paper in Hippocampus that reminds me of this Loren Frank paper I saw a couple months ago. There’s an idea floating around that increased temporal coordination might give neurons the cue to link up to create new representations. Certain types of plasticity are best induced with temporally organized stimuli. Maybe other people have a strong idea about which organization produces which plasticity. I’ll have to look into that more. Anyway, the Frank paper has oscillations in the 150-250 Hz range in response to novelty, while Berke et al are in the 23-30 Hz. What is the significance of the frequency???
Transient 23-30 Hz oscillations in mouse hippocampus during exploration of novel environments
Joshua D. Berke, Vaughn Hetrick, Jason Breck, Robert W. Greene
And finally, my boss sent us all an interesting paper from Brain exploring the rhesus brain with a new imaging technique designed for examining connectivity. I don’t have any idea what this is about, but the images are gorgeous. The commentary by Catani warns not to get hypnotized by that aspect, so I spose I’ll have to dig in deeper.
From hodology to function
Marco Catani
Association fibre pathways of the brain: parallel observations from diffusion spectrum imaging and autoradiography
Jeremy D. Schmahmann, Deepak N. Pandya, Ruopeng Wang, Guangping Dai, Helen E. D’Arceuil, Alex J. de Crespigny and Van J. Wedeen
