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

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.

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.

Bacterial speech bubbles : Nature

Bacteria secrete signals to other bacteria of the same species through vesicle packets.

Mashburn and Whiteley describe the unexpected convergence of two seemingly unrelated areas of microbiological research: how bacteria talk to their friends, and how they attack their enemies. The authors studied the bacterial pathogen Pseudomonas aeruginosa, which releases a hydrophobic molecule called the ‘pseudomonas quinolone signal’ (PQS) to send messages to other bacteria of the same species. The surprise is that, rather than being secreted as single molecules, PQS is released in bubble-like ‘vesicles’ that also contain antibacterial agents and probably toxins aimed at host tissue cells as well.

I wonder if this is evolutionarily connected to synaptic vesicles or if this is a case of something like convergent evolution…

Microcephalin, a Gene Regulating Brain Size, Continues to Evolve Adaptively in Humans — Evans et al. 309 (5741): 1717 — Science

Although the finding itself isn’t terribly shocking, the analysis is interesting and raises some even more interesting ethical questions. Methodology: The researchers tracked the occurence of a particular haplotype, which “increased in frequency too rapidly to be compatible with neutral drift [and] this indicates that it has spread under strong positive selection.” Strikingly this gene is not very old (37,000 years) and it has been changing rapidly… the real message: make no mistake, we’re still evolving!

Another interesting issue involves this figure from the paper:

Fig. 3. Global frequencies of Microcephalin haplogroup D chromosomes (defined as having the derived C allele at the G37995C diagnostic SNP) in a panel of 1184 individuals. For each population, the country of origin, number of individuals sampled, and frequency of haplogroup D chromosomes are given (in parentheses) as follows: 1, Southeastern and Southwestern Bantu (South Africa, 8, 31.3%); 2, San (Namibia, 7, 7.1%); 3, Mbuti Pygmy (Democratic Republic of Congo, 15, 3.3%); 4, Masai (Tanzania, 27, 29.6%); 5, Sandawe (Tanzania, 32, 39.1%); 6, Burunge (Tanzania, 28, 30.4%); 7, Turu (Tanzania, 23, 15.2%); 8, Northeastern Bantu (Kenya, 12, 25%); 9, Biaka Pygmy (Central African Republic, 32, 26.6%); 10, Zime (Cameroon, 23, 8.7%); 11, Bakola Pygmy (Cameroon, 24, 10.4%); 12, Bamoun (Cameroon, 28, 17.9%); 13, Yoruba (Nigeria, 25, 24%); 14, Mandenka (Senegal, 24, 16.7%); 15, Mozabite [Algeria (Mzab region), 29, 53.5%]; 16, Druze [Israel (Carmel region), 44, 60.2%]; 17, Palestinian [Israel (Central), 40, 63.8%]; 18, Bedouin [Israel (Negev region), 44, 54.6%]; 19, Hazara (Pakistan, 20, 85%); 20, Balochi (Pakistan, 23, 78.3%); 21, Pathan (Pakistan, 23, 76.1%); 22, Burusho (Pakistan, 25, 66%); 23, Makrani (Pakistan, 24, 62.5%); 24, Brahui (Pakistan, 25, 78%); 25, Kalash (Pakistan, 24, 62.5%); 26, Sindhi (Pakistan, 25, 78%); 27, Hezhen (China, 9, 77.8%); 28, Mongola (China, 10, 100%); 29, Daur (China, 10, 85%); 30, Orogen (China, 10, 100%); 31, Miaozu (China, 9, 77.8%); 32, Yizu (China, 10, 85%); 33, Tujia (China, 10, 75%); 34, Han (China, 41, 82.9%); 35, Xibo (China, 9, 83.3%); 36, Uygur (China, 10, 90%); 37, Dai (China, 9, 55.6%); 38, Lahu (China, 10, 85%); 39, She (China, 9, 88.9%); 40, Naxi (China, 10, 95%); 41, Tu (China, 10, 75%); 42, Cambodian (Cambodia, 11, 72.7%); 43, Japanese (Japan, 27, 77.8%); 44, Yakut [Russia (Siberia region), 25, 98%]; 45, Papuan (New Guinea, 17, 91.2%); 46, NAN Melanesian (Bougainville, 18, 72.2%); 47, French Basque (France, 24, 83.3%); 48, French (France, 28, 78.6%); 49, Sardinian (Italy, 26, 90.4%); 50, North Italian [Italy (Bergamo region), 13, 76.9%]; 51, Tuscan (Italy, 8, 87.5%); 52, Orcadian (Orkney Islands, 16, 81.3%); 53, Russian (Russia, 24, 79.2%); 54, Adygei [Russia (Caucasus region), 15, 63.3%]; 55, Karitiana (Brazil, 21, 100%); 56, Surui (Brazil, 20, 100%); 57, Colombian (Colombia, 11, 100%); 58, Pima (Mexico, 25, 92%); 59, Maya (Mexico, 25, 92%).

Haplogroup D describes a set of mutations in the gene encephalin that, according to the study, have been selected for. The figure/caption above shows that this haplotype occurs at a much lower rate in sub-Saharan populations and highest in East Asian, European, and Latin American populations. Let me be clear: The paper is intended to demonstrate the selective pressure for this haplogroup. Although the authors suggest it, this does not necessarily give us the causal connection that encephalin was selected for because the gene results in a bigger brain.

It is known that encephalin definitely plays a role in determing brain size, but, as this well done NYT article (highly recommended for those unable to access the original Science article) points out, there could be another function of the gene product (perhaps even some non-neural role) that explains the selection.

I do feel strongly that this kind of science is interesting and needs to be done, both for improving our understanding of the world and for public health benefits, but it will be only more controversial as we find more genes and evolutionary scenarios like this. One very nice side-effect I think is that these new levels of individual genotyping precision will really challenge what we think of as race. Once we discover everyone is a genetic mutt, can anyone really be said to belong to one race? .