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?
When we learn new information we use only a tiny fraction of the neurons in our brain for that particular memory trace. In order to allow the molecular study of those specific neurons we combined elements of the tet system with a promoter that is activated by high level neural activity (the cfos promoter) to generate mice in which a genetic tag can be introduced into neurons that are active at a given point in time. The tag can be maintained for a prolonged period, creating a precise record of the neural activity pattern at a specific point in time. Using fear conditioning we found that the same neurons activated during learning were reactivated when the animal recalled the fearful event. We also found that these neurons were no longer activated following memory extinction, consistent with the idea that extinction modifies a component of the original memory trace.
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.
The journal, Frontiers in Neuroscience, edited by Idan Segev, has made it Volume 3, issue 1. Launching last year at the Society for Neuroscience conference, its probably the newest Neuroscience-related journal.
I’m a fan of it because it is an open-access journal featuring a “tiered system” and more. From their website:
The Frontiers Journal Series is not just another journal. It is a new approach to scientific publishing. As service to scientists, it is driven by researchers for researchers but it also serves the interests of the general public. Frontiers disseminates research in a tiered system that begins with original articles submitted to Specialty Journals. It evaluates research truly democratically and objectively based on the reading activity of the scientific communities and the public. And it drives the most outstanding and relevant research up to the next tier journals, the Field Journals.
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.)
Heesoo Kim sent me a note that The NeuroTubes have released a set of neuroanatomy music videos. All of them are wacky and neat… here’s a clip of Proud to Be a Neural Tube (which achieves the impressive feat of rhyming notochord with neuropores):
I came across this fantastic review of tools for the Genetic Dissection of Neural Circuits in Neuron a few days ago. It’s by Liqun Luo, Ed Callaway, and Karel Svoboda. I highly recommend it, as it spans the gamut from genetic targeting (recombination, binary logic, viral delivery) to circuit reconstruction (super resolution LM, EM, brainbow) to activity modulation and functional mapping (uncaging, artificial GPCRs, light-gated channels, MIST). I don’t think I’ve ever seen quite a review of so many cutting edge neurotechnologies in one place. I can’t recommend this piece enough really. For me, with my lack of molecular expertise, the first sections on combinatorial gene targeting/expression techniques were great, pulling together Gal4, Cre/Flp, and Tet systems into a unified framework, along with more general concepts like site-directed integration, enhancer-trap, and repressor trap (eg. Thy1 mice).
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.
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.
Plants missing photosynthetic enzymes of their own that migrate directionally toward “victim” plants. This behavior has an uncanny resemblance to axon guidance. Make sure to view the time-lapse video in the NYT article. Here’s an image from the PSU website:
Plants capable of identifying kin and “being nice” to kin while going into a competitive mode of root growth with non-kin. Amazing.
It refreshing to see this kind of interesting behavior without any neurons involved. It makes me think (realize) that the idea of a neuron or a neural system has many components and there might not be any good reason to assume that a single cell must have all of those properties or none of them. Something like a neuron-like cell that’s not a neuron in the classical sense. Anyone know of other examples?
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acknowledgements
Neurodudes thanks for their support: NorthShore Neurosciences neurology hospital.
Using Yahoo Pipes, we combined neuro/ai/cog-related RSS feeds from many sources into one, sometimes filtering along the way so as to minimize offtopic posts:
Feeds are periodically added and subtracted, but hopefully reflects the blogrolls below (but doesn't yet -- it's still under construction), except for those feeds which Yahoo Pipes had trouble processing, a list of which can be seen by checking the Pipe page.
Bayle's working on Google Reader bundles for neuroscience journals, and other neuro feeds. Like the Ultimate Neurodudes Feed, these are heavily under construction, and probably aren't very good yet.
Neurodudes is moderated by Neville Sanjana, Bayle Shanks, and Stephen Larson. Comments that you post might be delayed so that we can tell our software that it's not spam -- however, not all comments are pre-screened so don't assume that we have read them, either. Any money we make off this site is used to pay for hosting, or given to charity; if in the future we pay contributors, we will include reader-authors. None of us are medical doctors so please don't ask for medical advice. Contact us here.
