Beck joins the 2PP club.

Fooled you?! Not the singer. Cool though Beck is, I am not sure he is that cool.
I am referring to a report by Heinz Beck and co-workers in 26 March 2009 edition of Neuron.
Following on from the pioneering work of Jeff Magee's lab, Beck's lab use multi-site uncaging of glutamate to uncover more sublties in branch strength plasticity. Triggering a supralinear local dendritic spike causes a transient depression of the response of that segment to the next bout of uncaging. Triggering a global back-propagating action potential cuases cell-wide depression.

Activity-dependent control of neuronal output by local and global dendritic spike attenuation.
Neuron (2009) 61:906-916.

Today's quiz.

Which leading journal no longer shows the submitted or date received when it publishes an article? I was shocked to see this lack of scholarship. Of course we all know why they want to do this: so that they do not have to make public the turn around time for publishing. It is already common for articles that appear earlier in print to be referred to as appearing "first" when compared to competing work, even if the submission dates overlap. Now at least one journal has taken the next "logical step"!

JAMA jam!

I don't normally quote verbatim, but from 27 March 2009 Science, page 1653:

(OVER)DUE DILIGENCE. The Journal of the American Medical Association (JAMA) this month admitted to having overlooked an author's conflict of interest days after a tense exchange between a journal editor and two academics who had publicized the matter.The paper in question, by psychiatrist Robert Robinson of the University of Iowa and his colleagues, reported that the antidepressant Lexapro could prevent depression in stroke patients if given soon after a stroke. The paper was published in May 2008, and last fall Jonathan Leo of Lincoln Memorial University in Harrogate, Tennessee, and Jeffrey Lacasse of Arizona State University, West, say they "just stumbled on a disclosure" in a previous paper in which Robinson reported that he had been a paid speaker for Forest Pharmaceuticals, which makes the drug. Leo notified JAMA in October, and editors told him they "would look into it." On 5 March, after no further word from JAMA, Leo and Lacasse criticized the paper--and the nondisclosure--in a letter in the British Medical Journal.
Publicizing the case ticked off JAMA's top brass. As first reported in the Wall Street Journal's Health blog, Leo says JAMA Executive Deputy Editor Phil Fontanarosa called him and said, "You are banned from JAMA for life." JAMA Editor-in-Chief Catherine DeAngelis acknowledges that Fontanarosa called Leo to say that "what he was doing was quite unprofessional." But DeAngelis says Fontanarosa actually told Leo that "we certainly don't expect to receive anything from you to be published." On 11 March, JAMA published a letter from Robinson and his co-authors acknowledging the conflict. (Emphasis mine)

UNBELIEVABLE.

Karl is taking over!

Karl Deisseroth and co-workers have two papers online that develop and apply the channelrhodopsin technology for which he has become so famous. In Nature they develop two new light controlled genetic probes to upregulate adenylate cyclase or phospholapise C. The former gives more cAMP, the latter more IP3. They insert these probes into the Nucleus accumbens and use light to modulate neuronal firing rates. Finally, they used their probes to control the behaviour of mice.

In Science they show work using ChR2 to analyze circuits in a mouse model of Parkinson's disease. This is a harder paper to follow (frankly), as it assumes knowledge of this area I do not have. I get the impression that their findings were a surprise. They make a bunch of new mice with ChR2 (or variants) in different areas of the brain, and none of these have any really effect on their model. Then, they turn (ironically?) to a Feng mouse (JAX stock number: 007615, strain: B6.Cg-Tg(Thy1-COP4/EYFP)9Gfng/J) and find that high frequency stimulation of cortical neurons helps locomotion behaviour in their mouse model.

Does Jay Leno know about this work yet?

Temporally precise in vivo control of intracellular signalling. Nature 10.1038/nature07926.

Optical deconstruction of Parkinsonian neural circuitry. Science 10.1126/science.1167093.

CaMK-2 activation is synapse specific during LTP.

Ryohei Yasuda and co-workers paper combing 2-photon uncaging of MNI-glu and FRET-FLIP imaging of CaMK-2 is finally out in Nature this week (those who read Ryohei's Japanese weblog know this paper was accepted a while ago). I had briefly mentioned this technical tour-de-force recently in discussing Sabatini latest Neuron paper using the "PiSing technique" originally developed by Matsuzaki and Kasai. Yasuda's group showed some of their data at SfN in DC last November. Like Kasai, Sabatini and Svoboda, they report synapse-specific induction of LTP using 2P uncaging of MNI-glu induces large and permanent volume changes of targeted spine heads, whilst the near by spines are essentially unaffected. This is due to the exquisite resolution of 2PP (less than 2 microns). In this Nature article Yasuda's lab use FRET-FLIM imaging to reveal that the kinase is only active for a brief period, even though it effects are long lasting. Given Kasai's work, this does not seem too surprising to me. But what do I know?

Seok-Jin R. Lee, Yasmin Escobedo-Lozoya, Erzsebet M. Szatmari & Ryohei Yasuda.
Activation of CaMKII in single dendritic spines during long-term potentiation. Nature (2009) 458:299-304.

A small gripe: the supplemental movies do not play on an Apple computer! This is not unique, would it kill journals to check this before they publish them? About 25% of academics use a Macintosh.

Matsuzaki, M., Honkura, N., Ellis-Davies, G. C. & Kasai, H. Structural basis of long-term potentiation in single dendritic spines. Nature (2004) 429:761-6.

Calcium on the brain.

Brian Bacskai has a lovely paper on how Alzheimer's disease changes astrocytic calcium signaling. (Synchronous hyperactivity and intercellular calcium waves in astrocytes in Alzheimer mice. Science 27 February 2009, Vol. 323. no. 5918, pp. 1211 - 1215. DOI:10.1126/science.1169096)
They find that in a mouse model of AD that amyloid-beta plaques are foci for the initiation of calcium waves in the astrocyte network. Further, diseased mice have higher resting calcium than normal mice. They use a well established mouse model of AD (APPswe:PSdeltaE9, this has APP Swedish mutations Lys670Asn & Met671Leu, and PS1 Pro264Leu, and is available from Jackson Labs). The advantage of this model is that plaques occur early in life (4.5 months) so it makes research a bit cheaper to do (lower cage costs). It should be stressed that this model along with most other mouse models of AD do not show neuronal loss. Neuronal death from AD is, of course, the fundamental human problem. Karen Ashe has suggested that such mice are models only of the early stages of AD in humans. So she has recently developed a very cool new mouse model in which plauqes and tangles (hyperphosphorylated tau) are inducible (tet-off system). The Ashe mouse shows neuronal loss. As far as I know this is unique mouse model. Back to Bacskai. He finds that calcium transients in astrocytes occur more frequently in AD than WT mice. These signals are somewhat larger than normal and are synchronous. Finally they are not dependent upon neuronal activity. These results suggest that plaques change the calcium buffering of astrocytes in a significant way. (As a side-note, I talked with the first author, Kishore, at SfN in DC in 2008, who told me no one in his lab though looking at astrocytes was worth while. Not a bad result for such an unpromising start!) Similar results have been reported by Haydon and Nedergaard for epilepsy, linking calcium waves to another disease (note most glia biologists now think that in vitro calcium waves are artifactual). It will be interesting to see what the mechanistic explanation is for these transients, and if more advanced mouse models show similar trends.

Amyloid Plaque and Neurofibrillary Tangle Pathology in a Regulatable Mouse Model of Alzheimer’s Disease. Am. J. Path. (2008) 173:762-772.

Enhanced astrocytic Ca signals contribute to neuronal excitotoxicity after status epilepticus. J. Neurosci. (2007) 27:10674-10684.

An astrocytic basis of epilepsy. Nature Med. (2005) 11:973-981.

Animal models of Alzheimer's disease and frontotemporal dementia. Nature Rev. Neurosci. (2008) 9:532-544.

Happy birthday Charles!

Charles Darwin was born 200 years ago today.
The BBC has a nice webpage for this event
http://www.bbc.co.uk/darwin/
Unfortunately the iPlayer only works in the UK.
Check out the incomparable David Attenborough:
http://www.wellcometreeoflife.org/
In the USA, the PBS is doing its best to contradict religious prejudice:
http://www.pbs.org/wgbh/evolution/

When I interview prospective PhD students for our department I often ask them who is the greatest (or most important) scientist of all time? Obviously there is no right answer, but many possible wrong answers (Thomas Edison was one choice).

Galileo (my choice), Newton, Einstein and Darwin are surely on everyone's list?