neurodudes

Jia, H., Rochefort, N., Chen, X., & Konnerth, A. (2010). Dendritic organization of sensory input to cortical neurons in vivo Nature, 464 (7293), 1307-1312 DOI: 10.1038/nature08947

Consider a a cortical neuron in V1, layer 2/3, whose output shows sharp orientation tuning. What are the orientation tunings of the most important inputs to that neuron? What is the spatial distribution of these inputs in the neuron’s dendritic tree?

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A very cool article on a new open source, online system to crowd source the assemblage of data in neuroscience from the Voice of San Diego.  From the article:

Traditionally, the study of the brain was organized somewhat like an archipelago. Neuroscientists would inhabit their own island or peninsula of the brain, and see little reason to venture elsewhere.

Molecular neuroscientists, who study how DNA and RNA function in the brain, didn’t share their work with cognitive specialists who study how psychological and cognitive functions are produced by the brain, for example.

But there has been an awakening to the idea that brains of humans and mammals should be studied like the complex, and interrelated systems that they are. Neuroscientists realized that they had to start collaborating across disciplines and sharing their data if they wanted to make advances in their own field.

[...]

Ellisman and his UCSD colleagues have devised a solution: crowdsource a brain. And this week they unveiled their years-long project — the Whole Brain Catalog — at the annual convention of the Society for Neuroscience, the largest gathering of brain experts in the world.

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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.

Two approaches

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.)

As has become a hallmark of the Svoboda lab, this new paper in Nature (advance online publication) combines several cutting edge technologies (rAAV-delivered ChR2, most prominently, and 2-photon 1-photon laser stimulation) to do some interesting synaptic physiology.

The subcellular organization of neocortical excitatory connections : Article : Nature.

They used ChR2 (with TTX and 4-AP to block action potentials) to find where on the dendritic tree particular inputs synapsed onto L3 and L5 cells and to measure the strength of those inputs. ChR2 depolarizes the input axon locally (60um spot diameter) at points of (potential) axodendritic contact. If you’ve heard the term “potential synapse” before, then think of this technique as a way of checking potential synapses and seeing if there really is an actual synapse there.

The technique allowed them to map on a L3 barrel cortex pyramidal cell where different thalamic inputs (VPm, POm) and cortical inputs (M1, barrel L2/3, barrel L4):

sCRACM stands for subcellular ChR2-assisted circuit mapping.

This new technique from Cori Bargmann’s lab is one of the neatest that I’ve seen in a while. The authors split GFP into two pieces, expressing one piece presynaptically and the other postsynaptically. This creates functional (ie. fluorescing) GFP only at sites of synaptic contact where the protein can reconstitute. They call the technique GFP Reconstitution Across Synaptic Partners (GRASP). Check out an example labeling here:

The neurons are expressing mCherry in the cytoplasm but GFP is expressed only at the site of synaptic contacts where the split GFP peptides can be reconstituted into a complete GFP fluorophore.

Postdoctoral/research scientist positions are available in the inter-disciplinary group of Dmitri Chklovskii at the new Janelia Farm Research Campus of the Howard Hughes Medical Institute located in the suburbs of Washington, D.C. Candidates are expected to have a PhD in neuroscience, physics, computer science or electrical engineering. Most of the work is theoretical or computational and is done in collaboration with several experimental laboratories. Successful applicants will work on projects centered on neuronal circuits such as high-throughput reconstruction of wiring diagrams as well as combining structural and physiological data to infer circuit function. Salary will be commensurate with qualifications. For more information about research directions in the group please see: http://www.hhmi.org/research/groupleaders/chklovskii.html
Interested applicants should send their CV and a statement of research interests to mitya (at) janelia.hhmi.org, and arrange for three recommendation letters to be emailed to me.

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.

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.
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