You’ve probably read by now about the announcement by IBM’s Cognitive Computing group that they had created a “computer system that simulates and emulates the brain’s abilities for sensation, perception, action, interaction and cognition” at the “scale of a cat cortex”. For their work, the IBM team led by Dharmendra Modha was awarded the ACM Gordon Bell prize, which recognizes “outstanding achievement in high-performance computing”.
A few days later, Henry Markram, leader of the Blue Brain Project at EPFL, sent off an e-mail to IBM CTO Bernard Meyerson harshly criticizing the IBM press release, and cc’ed several reporters. This brought a spate of shock media into the usually placid arena of computational neuroscience reporting, with headlines such as “IBM’s cat-brain sim a ‘scam,’ says Swiss boffin: Neuroscientist hairs on end”, and “Meow! IBM cat brain simulation dissed as ‘hoax’ by rival scientist”. One reporter chose to highlight the rivalry as cat versus rat, using the different animal model choice of the two researchers as a theme. Since then, additional criticisms from Markram have appeared online.
Find out more after the jump.
We had read that Dr. Henry Markram of the Blue Brain project had given a talk at TED (technology, entertainment, design), but the video wasn’t released until this month. This talk is geared towards a general audience, rather than getting into the specific details of the Blue Brain project, as he has before. It is engaging and includes many suggestions towards the future of neuroscience and AI.
Watch it online at the TED website.
A set of two articles recently came out in Science that directly visualize two different (and likely complementary) approaches to synapse specific delivery of gene products. Plasticity at specific synapses (input specificity — we’re restricting the discussion to the dendrites of the post-synaptic neuron) requires proteins (eg. new AMPA receptors) to get to those post-synaptic compartments and membranes. But the intructions for these new proteins are contained in the nucleus with the rest of the genome. Clearly, new proteins synthesized in the soma can’t just be sent everywhere, since only specific inputs (eg. particular dendritic spines) need these new proteins. How does this happen? Hence, the postulated synaptic tag.
Broadly, there are two approaches to synaptic tagging: 1) mRNA is distributed widely and translated locally at tagged locations; 2) protein products are distributed widely in the bodies of dendrites but only contact/off-load at tagged synaptic specializations. This News & Views gives a nice overview of the two papers, which find approach 1) in Aplysia cultures with sensorin mRNA and approach 2) in rat hippocampal neurons with Vesl-1S/Homer-1a protein. It amazes me that both were found pretty much simultaneously, but that might have more to do with the use of the photoconvertible Dendra2 protein than anything else.
With both approaches, we still don’t know why mRNA/protein is directed to a certain location. That is, we can visualize synaptic tagging but we don’t know what is the tag, its ontogeny, or the mechanism of tagging. But that might not be so important to understanding more about neural function. These new tools might allow us to image plasticity at many synapses at once, perhaps even in vivo. But before that, more work is needed… does the optical signal (from the Dendra fusion protein) correlate with degree of potentiation? Can we detect plasticity in the opposite direction, ie. synaptic depression, through another tag? (As a sidenote to approach 1), the use of 5′ and 3′ UTRs as a sort of molecular zipcode is also intriguing.)
Although it’s a few months old, Larry Abbott has an excellent article in Neuron on the recent (last 20 years) contributions of theoretical neuroscience. (He came by MIT last week to give a talk and that’s when I found out about the article.) It’s a review that is not too long and provides a good overview with both sufficient (though not overwhelming) detail and original perspective. It’s rare to find a short piece that is so informative. (And for a more experimentally-oriented review with an eye toward the future, see Rafael Yuste’s take on the grand challenges.)
Click on for some of my favorite passages from the Abbott piece. Continue reading
This week’s Nature has quite a few additional halorhodopsin articles for photochannel fans.
Halorhodopsin article from Deisseroth’s lab:
Multimodal fast optical interrogation of neural circuitry [News & Views]
Also, there is an intriguing article on both the general excitement in the neuroscience community with this new technology and a possible intellectual property dispute over it.
It seems Markram is again back to getting some interesting results. Recently a new discovery from the Brain Mind Institute of the EPFL shows that the brain adapts to new experience by unleashing a burst of new neuronal connections, and only the fittest survive. The research further shows that this process of creation, testing, and reconfiguring of brain circuits takes place on a scale of just hours, suggesting that the brain is evolving considerably even during the course of a single day.
The paper can be found Here.
Modulation of intracortical synaptic potentials by presynaptic somatic membrane potential : Nature
Very interesting work. Modulation of the somatic potential seems to influence the EPSP, as measured by paired patch recordings of two layer 5 cells in cortical slice. Somatic depolarization from resting potential to near threshold results in an increase in evoked EPSPs.
In synaptic physiology, we often make a point of distinguishing intrinsic changes (eg. membrane potential) from synaptic conductance changes. Now it looks like the line between those might be a bit blurry!
Here’s a N&V by Eve Marder too.
Cell : Astrocytes Put down the Broom and Pick up the Baton [N&V summary]
Some beautiful work [original article] by Oliet’s lab in a recent issue of Cell demonstrates the importance of glia in synaptic plasticity. The show a system where D-serine and not glycine controls the NMDA receptor in a coagonist role (or perhaps glutamate is really the coagonist…) and show how similar pairing protocols can have opposite effects (LTD vs. LTP) depending on D-serine modulation by astrocytes. Yet more hidden factors in plasticity are being revealed!
Here’s the key figure:
More details from the News & Views summary after the jump. Continue reading
Synaptic tuning : Nature Reviews Neuroscience
For those interested in neuromodulators:
Treatment of striatal neurons with a D1 receptor agonist led to an increase in the dendritic staining intensity of NMDA receptor NR2B subunits. There was also an increase in the association of NR2B subunits with PSD-95 — a scaffold protein required for the assembly of NMDA receptors — and in the surface localization of NR2B-containing receptors.
Original article in J. Neurosci. from Dunah and colleagues. An excerpt from the original aricle of a neat application of FRET continues after the jump.
Two Coincidence Detectors for Spike Timing-Dependent Plasticity in Somatosensory Cortex — Bender et al. 26 (16): 4166 — Journal of Neuroscience
Dan Feldman’s group at UCSD has found that different “sides” of STDP (ie. LTP vs. LTD) at cortical synapses might be mediated through distinct signalling pathways. The major finding was that LTD was induced independent of NMDA receptors. Rather, LTD required mGluRs and VGCCs.
There are many questions here. The most interesting to think about is, Are we going to find different STDP rules all over the brain? And, if so, what will be the commond ground between them?
Here’s the abstract:
Many cortical synapses exhibit spike timing-dependent plasticity (STDP) in which the precise timing of presynaptic and postsynaptic spikes induces synaptic strengthening [long-term potentiation (LTP)] or weakening [long-term depression (LTD)]. Standard models posit a single, postsynaptic, NMDA receptor-based coincidence detector for LTP and LTD components of STDP. We show instead that STDP at layer 4 to layer 2/3 synapses in somatosensory (S1) cortex involves separate calcium sources and coincidence detection mechanisms for LTP and LTD. LTP showed classical NMDA receptor dependence. LTD was independent of postsynaptic NMDA receptors and instead required group I metabotropic glutamate receptors and calcium from voltage-sensitive channels and IP3 receptor-gated stores. Downstream of postsynaptic calcium, LTD required retrograde endocannabinoid signaling, leading to presynaptic LTD expression, and also required activation of apparently presynaptic NMDA receptors. These LTP and LTD mechanisms detected firing coincidence on ~25 and ~125 ms time scales, respectively, and combined to implement the overall STDP rule. These findings indicate that STDP is not a unitary process and suggest that endocannabinoid-dependent LTD may be relevant to cortical map plasticity.