neurodudes

I’ve been thumbing through pubmed, online resources, and lab members’ collective consciences looking for a complete list of pharmacological agents acting on receptors (i.e. metabotropic glutamate receptors), phenomena (i.e. AMPA receptor desensitization), and any other players that can affect neurotransmission at the synapse. No such list seems to exist.

So, if you have some knowledge to contribute, please add to this list of agents and effects on a new wiki page. Warning: the current format is really simple (any improvements would be welcome), but it’s a first pass at a much needed electrophysiology resource.

— davematthews

Henry Markram, the director of the IBM-sponsored Blue Brain Project has written an article in the latest issue of Nature Reviews: Neuroscience that provides the most technical details about the project to date.

From the article:

“The three-dimensional neurons are then imported into BlueBuilder, a circuit builder that loads neurons into their layers according to a ‘recipe’ of neuron numbers and proportions. A collision detection algorithm is run to determine the structural positioning of all axo-dendritic touches, and neurons are jittered and spun until the structural touches match experimentally derived statistics. [...] Probabilities of connectivity between different types of neuron are used to determine which neurons are connected, and all axo-dendritic touches are converted into synaptic connections. The manner in which the axons map onto the dendrites between specific anatomical classes and the distribution of synapses received by a class of neurons are used to verify and fine-tune the biological accuracy of the synaptic mapping between neurons. It is therefore possible to place 10–50 million synapses in accurate three-dimensional space, distributed on the detailed three-dimensional morphology of each neuron.”

–Stephen

We’ve heard in the past about neurogenesis in adults, but as far as we understand, this only happens in limited locations throughout the brain. However, what if those new neurons migrate to different places?

New evidence in mice suggests that after being born, new neurons can travel along the flow of spinal fluid to end up in the olfactory bulb.

If there is migration to other locations in the brain, the ramifications for computational models of brain systems are significant.

–Stephen

In this nice open-access (ie. free!) essay in October’s PLoS Biology, David Kleinfeld and Oliver Griesbeck describe the revolution in neural recording that is taking electrophysiology from the realm of dark-arts (lots of training) to simpler genetically-encoded, imaging-based techniques. A lot of ground is covered in the article, including the creation of many new colors of fluorescent proteins (XFPs) that can be genetically targeted and the tagging of the XFPs with Ca, voltage, and pH sensors. A nice summary table is included comparing the techniques too:

As you have likely noticed, Bayle and I post heavily about these new recording techniques because of our strong belief that a lot of neuroscience will be enabled by improving our ability to stimulate and record from entire networks of neurons with high resolution. Yesterday, I was listening to one of the many recent neuroscience talks here at MIT in which philosopher Pat Churchland suggested, as many others also have, that the problem of consciousness might be more of an artifact of primitive science than an actual scientific problem. She made a very nice analogy with a problem from centuries ago when scientists were unsure about the existence of life forces and what precisely made an animal alive. Of course, with modern cell biology, we now have a cellular theory of life, disease, and death. (To be fair, Churchland went on to say that people like Christof, Crick et al. are misguided in attempting to study neural correlates of consciousness. I completely disagree with that; at the very least, those scientists are helping to extend our understanding of the visual system and the difference between perception that we are aware of [conscious] and perception that has a neural correlate but that we are not aware of [unconscious]. Honestly, who cares if they say they’re studying consciousness or not — make a judgement based on the science.)

Timid Mice Made Daring by Removing One Gene - New York Times

Original article in Cell.

This project was announced several months ago, but I didn’t see a post here so I thought I would add it.

The project, dubbed “Blue Brain“, represents a team up between Henry Markram, (who co-authored the chapter on the neocortex in the acclaimed reference The Synaptic Organization of the Brain), and IBM’s Blue Gene super computer.

From the New Scientist article: For over a decade Markram and his colleagues have been building a database of the neural architecture of the neocortex, the largest and most complex part of mammalian brains.

Very thin slices of mouse brain were kept alive under a microscope and probed electrically before being stained to reveal the synaptic, or nerve, connections. “We have the largest database in the world of single neurons that have been recorded and stained,” says Markram.

–Stephen

In the August PLoS Biology, there is an article showing the production of pure neural stem cells from human embryonic stem cells.

The procedure is quite simple: Add growth factors FGF-2 and EGF to the ES cells and you get pure NS cells, which overcomes several of the limitations of previous neurosphere-based assays [Nature Methods].

Neuron has a nice review article about the role of miRNAs, one of the new hot areas in molecular bio, in neuroscience. A little technical but a great look at a really neat emerging area.

Human neural stem cells differentiate and promote locomotor recovery in spinal cord-injured mice — PNAS

This article has some very promising results. I haven’t read the paper in detail, but here’s the executive summary. Human neural stem cells (hNSCs) were injected into mice that received a precision contusion (laminectomy) injury at spinal level T9. Control groups had vehicle and human fibroblast cell injections after receiving the same injury.

The group receiving hNSCs showed a significant functional recovery from the vehicle group. The fibroblast group did not. Then, to prove that the functional recovery was due to the new neurons and glia from the hNSC, the investigators injected the recovered mice with diptheria toxin, which affects human neurons while essentially leaving mouse neurons alone. After the toxin injection, the recovered mice with hNSC regressed back to the same behavioral performance as the vehicle group. That is, the functional recovery reversed after selective de-activation of the hNSC-derived neurons.

Additionally, the hNSCs produced both neurons and oligodendrocytes (myelin producers) in the mice. Through EM, it was verified the hNSC-derived neurons formed synapses with endogenous mouse neurons.

Amazing. Work like this shows how genetically similar mouse and human neurons (well, at least spinal cord neurons) must be. And, with regard to the race to understand and control stem cell development, this provides further evidence of how strongly the local environment can influence differentiation.

Some recent work in Neuron (full article; easy to read summary) shows how hippocampal neurons can cause neural progenitor cells to produce new neurons in the hippocampus. I find this fascinating since the network literally is replacing itself through its own dynamics.

The mechanism seems to be that GABAergic cells synapse onto progenitor cells and cause calcium entry due to the depolarization. (GABAergic synapses are often excitatory in young cells which have elevated intracellular chloride levels.) The increased calcium entry leads then to activation of genes coding for neuronal differentiation-related proteins.

Also, here’s some earlier work from Malenka’s lab along the same lines.