Wiring the Brain

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51 posts · 88,841 views

This blog will highlight and comment on current research and hypotheses relating to how the brain wires itself up during development, how the end result can vary in different people and what happens when it goes wrong. It will include discussions of the genetic and neurodevelopmental bases of traits such as intelligence and personality characteristics, as well as of conditions such as schizophrenia, autism, dyslexia, epilepsy, synaesthesia and others.

Kevin Mitchell
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  • February 27, 2012
  • 04:56 AM

Nerves of a feather, wire together

by Kevin Mitchell in Wiring the Brain

Finding your soulmate, for a neuron, is a daunting task. With so many opportunities for casual hook-ups, how do you know when you find “the one”? In the early 1960’s Roger Sperry proposed his famous “chemoaffinity theory” to explain how neural connectivity arises. This was based on observations of remarkable specificity in the projections of nerves regenerating from the eye of frogs to their targets in the brain. His first version of this theory proposed that each neuron found its t........ Read more »

Osterhout, J., Josten, N., Yamada, J., Pan, F., Wu, S., Nguyen, P., Panagiotakos, G., Inoue, Y., Egusa, S., Volgyi, B.... (2011) Cadherin-6 Mediates Axon-Target Matching in a Non-Image-Forming Visual Circuit. Neuron, 71(4), 632-639. DOI: 10.1016/j.neuron.2011.07.006  

Williams, M., Wilke, S., Daggett, A., Davis, E., Otto, S., Ravi, D., Ripley, B., Bushong, E., Ellisman, M., Klein, G.... (2011) Cadherin-9 Regulates Synapse-Specific Differentiation in the Developing Hippocampus. Neuron, 71(4), 640-655. DOI: 10.1016/j.neuron.2011.06.019  

  • February 7, 2012
  • 11:33 AM

I’ve got your missing heritability right here…

by Kevin Mitchell in Wiring the Brain

A debate is raging in human genetics these days as to why the massive genome-wide association studies (GWAS) that have been carried out for every trait and disorder imaginable over the last several years have not explained more of the underlying heritability. This is especially true for many of the so-called complex disorders that have been investigated, where results have been far less than hoped for. A good deal of effort has gone into quantifying exactly how much of the genetic variance ha........ Read more »

Manolio, T., Collins, F., Cox, N., Goldstein, D., Hindorff, L., Hunter, D., McCarthy, M., Ramos, E., Cardon, L., Chakravarti, A.... (2009) Finding the missing heritability of complex diseases. Nature, 461(7265), 747-753. DOI: 10.1038/nature08494  

Zuk, O., Hechter, E., Sunyaev, S., & Lander, E. (2012) The mystery of missing heritability: Genetic interactions create phantom heritability. Proceedings of the National Academy of Sciences, 109(4), 1193-1198. DOI: 10.1073/pnas.1119675109  

  • January 25, 2012
  • 04:45 PM

From miswired brain to psychopathology – modelling neurodevelopmental disorders in mice

by Kevin Mitchell in Wiring the Brain

Normal.dotm 0 0 1 1677 9561 Trinity College Dublin 79 19 11741 12.0 0 false 18 pt 18 pt 0 0 false false false /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-parent:""; mso-padding-alt:0in 5.4pt 0in 5.4pt; mso-para-margin:0in; mso-para-margin-bottom:.0001pt; mso-pagination:wido........ Read more »

  • January 8, 2012
  • 11:51 AM

Jump-starting regeneration of injured nerves

by Kevin Mitchell in Wiring the Brain

Normal.dotm 0 0 1 1072 6113 Trinity College Dublin 50 12 7507 12.0 0 false 18 pt 18 pt 0 0 false false false /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-parent:""; mso-padding-alt:0in 5.4pt 0in 5.4pt; mso-para-margin:0in; mso-para-margin-bottom:.0001pt; mso-pagination:widow........ Read more »

Sun F, Park KK, Belin S, Wang D, Lu T, Chen G, Zhang K, Yeung C, Feng G, Yankner BA.... (2011) Sustained axon regeneration induced by co-deletion of PTEN and SOCS3. Nature, 480(7377), 372-5. PMID: 22056987  

  • November 7, 2011
  • 06:35 AM

What is a gene "for"?

by Kevin Mitchell in Wiring the Brain

“Scientists discover gene for autism” (or ovarian cancer, or depression, cocaine addiction, obesity, happiness, height, schizophrenia… and whatever you’re having yourself). These are typical newspaper headlines (all from the last year) and all use the popular shorthand of “a gene for” something. In my view, this phrase is both lazy and deeply misleading and has caused widespread confusion about what genes are and do and about their influences on human traits and disease.The problem........ Read more »

Jamain S, Quach H, Betancur C, Råstam M, Colineaux C, Gillberg IC, Soderstrom H, Giros B, Leboyer M, Gillberg C.... (2003) Mutations of the X-linked genes encoding neuroligins NLGN3 and NLGN4 are associated with autism. Nature genetics, 34(1), 27-9. PMID: 12669065  

  • October 1, 2011
  • 12:59 PM

Does brain plasticity trump innateness?

by Kevin Mitchell in Wiring the Brain

The fact that the adult brain is very plastic is often held up as evidence against the idea that many psychological, cognitive or behavioural traits are innately determined. At first glance, there does indeed appear to be a paradox. On the one hand, behavioural genetic studies show that many human psychological traits are strongly heritable and thus likely determined, at least in part, by innate biological differences. On the other, it is very clear that even the adult brain is highly plastic........ Read more »

  • August 11, 2011
  • 05:06 AM

Split brains, autism and schizophrenia

by Kevin Mitchell in Wiring the Brain

A new study suggests that a gene known to be causally linked to schizophrenia and other psychiatric disorders is involved in the formation of connections between the two hemispheres of the brain. DISC1 is probably the most famous gene in psychiatric genetics, and rightly so. It was discovered in a large Scottish pedigree, where 18 members were affected by psychiatric disease.
The diagnoses ranged from schizophrenia and bipolar disorder to depression and a range of “minor” psychiatric con........ Read more »

Osbun N, Li J, O'Driscoll MC, Strominger Z, Wakahiro M, Rider E, Bukshpun P, Boland E, Spurrell CH, Schackwitz W.... (2011) Genetic and functional analyses identify DISC1 as a novel callosal agenesis candidate gene. American journal of medical genetics. Part A, 155(8), 1865-76. PMID: 21739582  

  • August 3, 2011
  • 06:14 AM

Welcome to your genome

by Kevin Mitchell in Wiring the Brain

There is a common view that the human genome has two different parts – a “constant” part and a “variable” part. According to this view, the bases of DNA in the constant part are the same across all individuals. They are said to be “fixed” in the population. They are what make us all human – they differentiate us from other species. The variable part, in contrast, is made of positions in the DNA sequence that are “polymorphic” – they come in two or more different versio........ Read more »

Gravel S, Henn BM, Gutenkunst RN, Indap AR, Marth GT, Clark AG, Yu F, Gibbs RA, The 1000 Genomes Project, & Bustamante CD. (2011) Demographic history and rare allele sharing among human populations. Proceedings of the National Academy of Sciences of the United States of America, 108(29), 11983-11988. PMID: 21730125  

McClellan, J., & King, M. (2010) Genetic Heterogeneity in Human Disease. Cell, 141(2), 210-217. DOI: 10.1016/j.cell.2010.03.032  

  • July 25, 2011
  • 04:06 PM

Hallucinating neural networks

by Kevin Mitchell in Wiring the Brain

Hearing voices is a hallmark of schizophrenia and other psychotic disorders, occurring in 60-80% of cases. These voices are typically identified as belonging to other people and may be voicing the person’s thoughts, commenting on their actions or ideas, arguing with each other or telling the person to do something. Importantly, these auditory hallucinations are as subjectively real as any external voices. They may in many cases be critical or abusive and are often highly distressing to the........ Read more »

  • July 8, 2011
  • 09:56 AM

Environmental influences on autism - splashy headlines from dodgy data

by Kevin Mitchell in Wiring the Brain

A couple of recent papers have been making headlines in relation to autism, one claiming that it is caused less by genetics than previously believed and more by the environment and the other specifically claiming that antidepressant use by expectant mothers increases the risk of autism in the child. But are these conclusions really supported by the data? Are they strongly enough supported to warrant being splashed across newspapers worldwide, where most readers will remember only the headlin........ Read more »

Hallmayer J, Cleveland S, Torres A, Phillips J, Cohen B, Torigoe T, Miller J, Fedele A, Collins J, Smith K.... (2011) Genetic Heritability and Shared Environmental Factors Among Twin Pairs With Autism. Archives of general psychiatry. PMID: 21727249  

Lichtenstein P, Carlström E, Råstam M, Gillberg C, & Anckarsäter H. (2010) The genetics of autism spectrum disorders and related neuropsychiatric disorders in childhood. The American journal of psychiatry, 167(11), 1357-63. PMID: 20686188  

Rosenberg, R., Law, J., Yenokyan, G., McGready, J., Kaufmann, W., & Law, P. (2009) Characteristics and Concordance of Autism Spectrum Disorders Among 277 Twin Pairs. Archives of Pediatrics and Adolescent Medicine, 163(10), 907-914. DOI: 10.1001/archpediatrics.2009.98  

Croen LA, Grether JK, Yoshida CK, Odouli R, & Hendrick V. (2011) Antidepressant Use During Pregnancy and Childhood Autism Spectrum Disorders. Archives of general psychiatry. PMID: 21727247  

  • June 28, 2011
  • 05:15 AM

Complex interactions among epilepsy genes

by Kevin Mitchell in Wiring the Brain

A debate has been raging over the last few years over the nature of the genetic architecture of so-called “complex” disorders. These are disorders - such as schizophrenia, epilepsy, type II diabetes and many others - which are clearly heritable across the population, but which do not show simple patterns of inheritance. A new study looking at the profile of mutations in hundreds of genes in patients with epilepsy dramatically illustrates this complexity. The possible implications are far........ Read more »

Klassen T, Davis C, Goldman A, Burgess D, Chen T, Wheeler D, McPherson J, Bourquin T, Lewis L, Villasana D.... (2011) Exome sequencing of ion channel genes reveals complex profiles confounding personal risk assessment in epilepsy. Cell, 145(7), 1036-48. PMID: 21703448  

Kasperaviciute, D., Catarino, C., Heinzen, E., Depondt, C., Cavalleri, G., Caboclo, L., Tate, S., Jamnadas-Khoda, J., Chinthapalli, K., Clayton, L.... (2010) Common genetic variation and susceptibility to partial epilepsies: a genome-wide association study. Brain, 133(7), 2136-2147. DOI: 10.1093/brain/awq130  

Mitchell KJ. (2011) The genetics of neurodevelopmental disease. Current opinion in neurobiology, 21(1), 197-203. PMID: 20832285  

  • June 21, 2011
  • 09:10 AM

Synaesthesia and savantism

by Kevin Mitchell in Wiring the Brain

“We only use 10% of our brain”. I don’t know where that idea originated but it certainly took off as a popular meme – taxi drivers seem particularly taken with it. It’s rubbish of course – you use more than that just to see. But it captures an idea that we humans have untapped intellectual potential – that in each of us individually, or at least in humans in general lies the potential for genius. Part of what has fed into that idea is the existence of so-called “savants” ........ Read more »

  • May 25, 2011
  • 10:43 AM

Somatic mutations make twins’ brains less identical

by Kevin Mitchell in Wiring the Brain

There is a paradox at the heart of behavioural and psychiatric genetics. On the one hand, it is very clear that practically any psychological trait one cares to study is partly heritable - i.e., the differences in the trait between people are partly caused by differences in their genes. Similarly, psychiatric disorders are also highly heritable and, by now, mutations in hundreds of different genes have been identified that cause them. However, these studies also highlight the limits of geneti........ Read more »

  • May 14, 2011
  • 08:42 AM

The miswired brain; making connections from neurodevelopment to psychopathology

by Kevin Mitchell in Wiring the Brain

Recent evidence indicates that psychiatric disorders can arise from differences, literally, in how the brain is wired during development. Psychiatric genetic approaches are finding new mutations associated with mental illness at an amazing rate, thanks to new genomic array and sequencing technologies. These mutations include so-called copy number variants (deletions or duplications of sections of a chromosome) or point mutations (a change in the code at one position of the DNA sequence). At t........ Read more »

  • January 12, 2011
  • 05:14 AM

Hotheads by nature

by Kevin Mitchell in Wiring the Brain

If some guy spilt your beer by accident, would you punch him in the face? If he was unapologetic, you might at least consider it – you might in fact feel a pretty strong urge to do it. What stops you? Or, if you’re the type who acts on those urges, what doesn’t stop you? New research has found a mutation in one gene that may contribute to these differences in temperament. Self-control is the ability to inhibit an immediate course of action in the pursuit of a longer-term goal or to c........ Read more »

Verweij KJ, Zietsch BP, Medland SE, Gordon SD, Benyamin B, Nyholt DR, McEvoy BP, Sullivan PF, Heath AC, Madden PA.... (2010) A genome-wide association study of Cloninger's temperament scales: implications for the evolutionary genetics of personality. Biological psychology, 85(2), 306-17. PMID: 20691247  

Bevilacqua L, Doly S, Kaprio J, Yuan Q, Tikkanen R, Paunio T, Zhou Z, Wedenoja J, Maroteaux L, Diaz S.... (2010) A population-specific HTR2B stop codon predisposes to severe impulsivity. Nature, 468(7327), 1061-6. PMID: 21179162  

  • December 21, 2010
  • 05:13 AM

Self-organising principles in the nervous system

by Kevin Mitchell in Wiring the Brain

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 bet........ Read more »

Kaschube M, Schnabel M, Löwel S, Coppola DM, White LE, & Wolf F. (2010) Universality in the evolution of orientation columns in the visual cortex. Science (New York, N.Y.), 330(6007), 1113-6. PMID: 21051599  

  • November 29, 2010
  • 06:51 AM

New insights into Rett syndrome

by Kevin Mitchell in Wiring the Brain

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........ Read more »

Muotri AR, Marchetto MC, Coufal NG, Oefner R, Yeo G, Nakashima K, & Gage FH. (2010) L1 retrotransposition in neurons is modulated by MeCP2. Nature, 468(7322), 443-6. PMID: 21085180  

  • November 22, 2010
  • 04:17 PM

A synaesthetic mouse?

by Kevin Mitchell in Wiring the Brain

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 powe........ Read more »

Beauchamp MS, & Ro T. (2008) Neural substrates of sound-touch synesthesia after a thalamic lesion. The Journal of neuroscience : the official journal of the Society for Neuroscience, 28(50), 13696-702. PMID: 19074042  

  • October 24, 2010
  • 01:51 PM

Searching for a needle in a needle-stack

by Kevin Mitchell in Wiring the Brain

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........ Read more »

Mitchell KJ. (2010) The genetics of neurodevelopmental disease. Current opinion in neurobiology. PMID: 20832285  

  • October 18, 2010
  • 10:21 AM

Colour my world

by Kevin Mitchell in Wiring the Brain

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 illustrat........ Read more »

Field GD, Gauthier JL, Sher A, Greschner M, Machado TA, Jepson LH, Shlens J, Gunning DE, Mathieson K, Dabrowski W.... (2010) Functional connectivity in the retina at the resolution of photoreceptors. Nature, 467(7316), 673-7. PMID: 20930838  

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