Showing posts from 2010

Self-organising principles in the nervous system

The circuitry of the brain is too complex to be completely specified by genetic information – at least not down to the level of each connection. There are hundreds of billions of neurons in your brain, each making an average of 1,000 connections to other cells. There are simply not enough genes in the genome to specify all of these connections.

What the genetic program can achieve is a very good wiring diagram of initial projections between neurons in different brain areas (or layers or between particular cell types). This circuitry is then refined and elaborated at the cellular level by processes of activity-dependent development, under the principle that “cells that fire together, wire together”. The circuitry of the brain is thus a self-organising system, which assembles under the influence of local interactions, mediated first by molecular interactions and second by patterns of electrical activity.

A new study highlights an important additional factor that allows global pat…

New insights into Rett syndrome

A pair of papers from the lab of Fred Gage has provided new insights into the molecular and cellular processes affected in Rett syndrome. This syndrome is associated with arrested development and autistic features. It affects mainly girls, who typically show normal development until around age two, followed by a sudden and dramatic deterioration of function, regression of language skills and the emergence of autistic symptoms. It is caused mainly by mutations in the gene encoding MeCP2, which resides on the X chromosome. Complete removal of the function of this gene is effectively lethal, explaining why Rett syndrome is not observed in boys – males who inherit that mutation are not viable. Females, who have a back-up copy of the X chromosome survive but subsequently show the symptoms of the disease.

The function of the MeCP2 protein seems very far removed from the kinds of symptoms observed when it is deleted. The job of MeCP2 is to bind to DNA that carries a specific chemical …

A synaesthetic mouse?

An amazing study just published in Cell starts out with fruit flies insensitive to pain and ends up with what looks very like a synaesthetic mouse. Penninger and colleagues were interested in the mechanisms of pain sensation and have been using the fruit fly as a model to investigate the underlying biological processes. Like any good geneticist faced with profound ignorance of how a process works, they began by screening for mutant flies that are insensitive to pain. Making use of a very powerful genetic resource developed in Vienna (a bank of fly lines expressing RNA interference constructs for every gene in the genome) they screened through all these genes to see which ones were required in neurons for flies to respond to pain. (In particular, pain caused by excessive heat).

Why should anyone care how a fly feels pain? Well, like practically everything else you can think of, the basic physiology and molecular biology of pain sensation is very highly conserved from flies to mamma…

Announcing the Wiring the Brain conference 2011

I am pleased to announce the Wiring the Brain conference, which will be held over the 12th-15th April 2011, in Ireland. This is an international scientific conference which aims to explore how the brain is wired and what happens when that wiring is faulty.

It will bring together world-leaders in developmental neurobiology, psychiatric genetics, molecular and cellular neuroscience, systems and computational neuroscience, cognitive science and psychology. A major goal is to break down traditional boundaries between these disciplines to enable links to be made between differing levels of observation and explanation.

We will explore, for example, how mutations in genes controlling the formation of synaptic connections between neurons can alter local circuitry, changing the interactions between brain regions, thus altering the functions of large-scale neuronal networks, leading to specific cognitive dysfunction, which may ultimately manifest as the symptoms of schizophrenia or autism. …

Searching for a needle in a needle-stack

Whole-genome sequencing is a game-changer for human genetics. It is now possible to deduce every base of an individual’s genome (all 6 billion of them – two copies of 3 billion each) for a couple of thousand euros, and dropping. (Yes, euros). Even Ozzy Osbourne just got his genome sequenced! For researchers searching for the causes of genetic disease (or resistance to vast quantities of drugs and alcohol), this means they no longer have to infer where a mutation is by tracking a sampling of “markers” spaced across the genome – they can directly see all of the genetic information.

The problem is, they directly see all of the genetic information. If each of us carries thousands of mutations – changes that are very rare or may even have never been seen before in any other person – then telling which one of those changes is actually causing the condition is a tough task. Researchers in psychiatric genetics are currently grappling with how to handle this glut of information.

The pr…

Colour my world

Colour does not exist. Not out in the world at any rate. All that exists in the world is a smooth continuum of light of different wavelengths. Colour is a construction of our brains. A lot is known about how the brain does this, beginning with complicated circuits in the retina itself. Thanks to a new paper from Greg Field and colleagues we now have an even more detailed picture of how retinal circuits are wired to enable light to be categorized into different colours. This study illustrates a dramatic and fundamental principle of brain wiring – namely that cells that fire together, wire together.

Colour discrimination begins with the absorption of light of different wavelengths. This is accomplished by photopigment proteins, called opsins, which are expressed in cone photoreceptor cells in the retina. Humans have three opsin genes, which encode proteins that preferentially absorb light of different wavelengths: short (S, in what we perceive as the blue part of the spectrum),…

Mice with fully functioning human brains

I wouldn’t usually discuss politics in a blog like this, but a recent story caught my eye, as it provides an example of the depressing and sometimes bizarre level of scientific illiteracy among elected officials or some people who hope to be elected. The example is from the United States, which is an easy target in this regard, but we have had a similar episode in Ireland recently so I don’t think we (or indeed any other non-Americans) can feel particularly smug about it. This one is especially funny, though.

Christine O’Donnell has recently won the Republican nomination in Delaware for the upcoming election to the Senate. I just love her – for comic entertainment this woman is very good value. She makes Sarah Palin look like the most reasonable, well-informed, level-headed person around. Among many clangers that she has dropped in the past, the one that really got my attention was the following assertion, made during a debate on stem cells on The O’Reilly Factor show on Fox News …

Ancient origins of the cerebral cortex

Just how special is the human brain? Compared to other mammals, the thing that stands out most is the size of the cerebral cortex – the thick sheet of cells on the outside of the brain, which is so expanded in humans that it has to be folded in on itself in order to fit inside the skull. The cortex is the seat of higher brain functions, the bit of the brain we see with, hear with, think with. In particular, one of its main functions is association – bringing sensory information together with information on internal states and motivation to enable flexible and context-dependent decisions to be taken, rather than simple reflexive actions in response to isolated stimuli. While undoubtedly vastly more developed in humans, a new study suggests the cerebral cortex may have much more ancient origins than previously suspected.

All mammals have a cortex and it generally increases in size over evolution. Mice and rats have a smooth cortex, while that of cats is somewhat expanded and fold…

Wild-type humans

Wild-type is the term geneticists use to refer to non-mutants. It literally means organisms that are the same, genetically, as those in the wild, compared to ones that have been grown under coddled conditions in the lab for generations, going soft in the absence of natural selection, or that are specifically mutant at some gene or other. There are no wild-type humans.

Well, maybe there are a few, somewhere, but even they are not really non-mutants. We all carry millions of mutations in our genome – positions where the sequence in our genome differs from the typical sequence. Where everyone else has a “T”, you might have an “A”, for example. Most of these mutations have no consequence – they are simply neutral variation in DNA that has no discernible function. It turns out that most of the genome is not made of genes – the bits of DNA that code for proteins actually comprise only about 2-3% of the total sequence. Mutations that change the code for proteins are by far the most l…

Coloured hearing in Williams syndrome

The idea that our genes can affect many of the traits that define us as individuals, including our personality, intelligence, talents and interests is one that some people find hard to accept. That this is the case is very clearly and dramatically demonstrated, however, by a number of genetic conditions, which have characteristic profiles of psychological traits. Genetic effects include influences on perception, sometimes quite profound, and other times remarkably selective. A recent study suggests that differences in perception in two conditions, synaesthesia and Williams syndrome, may share some unexpected similarities.

Williams syndrome is a genomic disorder caused by deletion of a specific segment of chromosome 7. Due to the presence of a number of repeated sequences, this region is prone to errors during replication that can result in deletion of the intervening stretch of the chromosome, which contains approximately 28 genes. The disorder is characterised by typical facia…

When to blame your parents, and for what

Studies linking some aspect of parental behaviour with some trait in their offspring are depressingly common in the sociological literature. Though these studies typically only report a correlation between parental behaviour and whatever the trait is in the offspring, the implication, and often the explicit conclusion, is that one causes the other. These kinds of stories get huge play in the popular press (and in the blogosphere), where the conclusion of a causative relationship is rarely challenged. For example, the finding that children who grow up with more books in the house are more successful academically is taken as evidence that simply having books around makes kids smarter.

This kind of thinking illustrates a common and fundamental flaw in interpreting sociological or epidemiological findings – correlation does not imply causation. Red hair and freckles are highly correlated but one does not cause the other. Both are caused by something else (a mutation in a gene contro…