Songbirds need so-called “human language gene” to learn new tunes

Blogging on Peer-Reviewed ResearchThe nasal screech of Chris Tucker sound worlds apart from the song of a nightingale but both human speech and birdsong actually have a lot in common. Both infants and chicks learn their respective tongues by imitating others. They pick up new material most easily during specific periods of time as they grow up, they need practice to improve and they pick up local dialects. And as infants unite words to form sentences, so do songbirds learn to combine separate riffs into a full song. Songbirds need so-called “human language gene” to learn new tunes

Because of these similarities, songbirds make a good model for inquisitive neuroscientists looking to understand the intricacies of human speech. Zebra finches are a particularly enlightening species and they have just shown Sebastian Haesler that the so-called human ‘language gene’ FOXP2 also controls an songbird’s ability to pick up new material.

FOXP2 has a long and sordid history of fascinating science and shoddy science writing. It has been consistently mislabelled as “the language gene” and after the discovery that the human and chimp versions differed by just two small changes, it was also held responsible for the evolution of human language. Even though these claims are far-fetched (for reasons I’ll delve into later), there is no doubt that faults in FOXP2 can spell disaster for a person’s ability to speak.

Mutated versions cause a speech impairment called developmental verbal dyspraxia (DVD), where people are unable to coordinate the positions of their jaws, lips, tongues and faces, even though their minds and relevant muscles are in reasonable working order. They’re like an orchestra that plays a cacophony despite having a decent conductor and tuned instruments.

Brain scans of people with DVD have revealed abnormalities in the basal ganglia, an group of neurons at the heart of the brain with several connections to other areas. Normal people show strong activation of FOXP2 here and fascinatingly, so do songbirds. Haesler reasoned that studying the role of this gene in birds could tell him more about its human counterpart.

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Broken chains and faulty mirrors cause problems for autistic children

Blogging on Peer-Reviewed Research

Autistic children have sever social problemsYour brain has an amazing ability to predict the future. For example, if you see someone reach for a chocolate, you can guess that they’re likely to pick it up, put it in their mouths and eat it. Like most people, you have a talent for understanding the goal of an action while you see it being performed – in this case, you know that reaching for the chocolate is only a step towards eating it.

That may not sound very impressive, but as with many mental skills, it’s only apparent how complicated it is when you see people who can’t do it.

Autistic people, for example, find it incredibly difficult to relate to other people and this may, in part, be because they can’t understand the why of someone else’s actions. While a typical child would understand that a mother holding her hands out is readying for a hug, an autistic child might be baffled by the gesture.

Now, a new study by Luigi Cattaneo, Giacomo Rizzolatti and colleagues suggests that autistic people find it difficult to understand the purpose of an act because they cannot string together different actions into a coherent whole. And underlying this problem is a special group of nerve cells called mirror neurons.

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‘Brainbow’ paints individual neurons with different colours

Brainbow - psychedelic neuroscienceAt Harvard University, a group of creative scientists have turned the brains of mice into beautiful tangles of colour. By mixing together a palette of fluorescent proteins, they have painted individual neurons with up to 90 different colours. Their technique, dubbed ‘Brainbow’, gives them an unprecedented vision of how the brain’s cells are connected to each other.

Black-and-white to colour

The art of looking at neurons had much greyer beginnings. Over a century ago, a Spanish scientist called Santiago Ramón y Cajal, one of the founders of modern neuroscience, became the first person to get a clear look at the neural network that houses our thoughts. He found that neurons stood out among other cells when stained with a silver chromate salt.

These monochrome images told us what neurons were, but made it very difficult to work out how they joined up into a network. It would be like trying to make sense of London’s famous tube map if all the lines were coloured with the same dull grey. Nowadays, neuroscientists can ‘tag’ neurons with fluorescent proteins, but even these are available in only a few shades.

Enter Brainbow, the brain-child of Jean Livet, Jeff Lichtman and colleagues from Harvard. It uses combinations of just four basic fluorescent proteins – which glow in either red, orange, yellow or blue ­– to paint neurons with a vast range of hues. It works like a TV, which combines red, green and blue light to form the entire colour spectrum.

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Fruit flies have a taste for fizzy drinks

Humans can detect five different taste sensations. Now scientists have found the first animal with a sixth type. Fruit flies, it seems, love the taste of the carbon dioxide dissolved in fizzy water.

Drosophila’s tongue can pick up carbon dioxide dissolved in liquids.Fizzy drinks like Perrier and Coca-Cola are targeted at a huge range of social groups, but if fruit flies had any capital to spend, they’d be at the top of the list. Unlike posh diners or hyperactive kids, flies have taste sensors that are specially tuned to the flavour of carbonated water.

Humans can pick up five basic tastes – sweet, salty, sour, bitter and umami (savoury). But other animals, with very different diets, can probably expand on this set.

And what better place to start looking for these unusual senses than the fruit fly Drosophila, a firm favourite of geneticists worldwide, and an animal with very different taste in food to our own.

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Simple sponges provide clues to origin of nervous system

The possible origins of the nervous system have been found in the simple sponge, an animal with no nervous system of its own. Sponges carry the genetic components of synapses, which may have been co-opted by evolution as a starting point for proper nerve cells

Sponges are the most primitive of all animals. They are immobile, and live by filtering detritus from the water. They have no brains or, for that matter, any organs, tissues or nervous system of any sort. If you were looking for the evolutionary origins of animal intelligence, you couldn’t really pick a less likely subject to study.

Over time, evolution co-opted the early PSD of the sponge and used it to craft true nervous systems.So it was with great surprise that Onur Sakarya from the University of California, Santa Barbara found that sponges carry the beginnings of a nervous system.

With no neurons to speak of, these animals still have the genetic components of synapses, one of the most crucial parts of the nervous system. And their versions share startling similarities with those of humans.

Synapses (and proto-synapses)

Synapses are junctions between two nerve cells that are allow the cells to pass on signals to each other. Signals are carried by molecules that cross the synaptic gap called neurotransmitters. When they reach the receiving cell, they come across an elaborate tangle of proteins called the post-synaptic density (PSD; labelled in red below). The PSD processes the neurotransmitters, among many other important roles, and allows the receiving cell to respond appropriately to the nervous signal

Sakarya searched for equivalents of the human PSD proteins in the genomes of other animals. For a start, he found an almost complete set in the starlet sea anemone (Nematostella vectensis). The anemone (like its cousins, the jellyfish) is one of the Cnidarians, a group of animals that have the most rudimentary of nervous systems. Finding PSD genes in them is surprising but reasonable.

The synapse relays signals from one cell to another.But Sakarya was really surprised when he found the vast majority of the PSD assemblage in the sponge Amphimedon queenslandica, an animal that doesn’t even have a nervous system! The sponge’s PSD proteins bore remarkable resemblances to those of humans and other animals, and were built of similar arrangements of domains.

One in particular, the PDZ domain, allows PSD proteins to recognise one another and assemble correctly. When Sakarya compared the structures of the human and sponge PDZ domains, he found that at the atomic level, the parts they used to interact with other proteins were almost 90% identical. So not only does the sponge have the full set of PSD parts, it can assemble them into a fully-functioning whole.


So what is the PSD, part of the nervous system, doing in an animal without one? Sakarya believes that the PSD is an example of exaptation, a process where evolution co-opts an existing structure for another purpose. Bird feathers are a good example of this – they evolved in small dinosaurs to help them regulate their body temperature, and were only later used for flight.

Exaptation can explain how complex, integrated structures like the nervous system can evolve. Rather than building the whole thing from scratch, evolution took ‘off-the-shelf’ components, like the PSD, and put them together in exciting new ways.

Sponges are the simplest of animals but even they have genetic components of synapsesIn the same way, the PSD of sponges is switched on in a type of cell called the ‘flask cell’. Flask cells are only found in sponge larvae, which, unlike the adults, are free-swimming. These cells could help the larvae to sense their environment, and could well have been a starting point for the evolution of neurons.

Sakarya cautions that there could be another explanation. Sponges could be degenerate relics of a more advanced branch of animals, that stripped away their complexity in favour of life in the (very) slow lane. In this scenario, the flask cells are evolutionary remnants of neurons proper.

Nonetheless, under both scenarios, these findings strongly suggest that the common ancestor of all living animals already has an early working version of the PSD. This practically pre-adapted it for the evolution of nervous systems. With minimal additional evolutionary steps, this early scaffold could have been transformed into the functional synapses that drive our thoughts today. The ancestor was pre-adapted to a future with neurons.

It’s worth noting that this discovery was only made possible because the genome of Amphimedon has been fully sequenced. In an age where genome sequencing could start to be taken for granted, this drives home the importance of sequencing a wide variety of living things that represent crucial junctures in evolution.

Reference: Sakarya, Armstrong, Adamska, Adamski, Wang, Tidor, Degnan, Oakley & Kosik. 2007. A post-synaptic scaffold at the origin of the animal kingdom. PLOS One 6, e506: 1-7.

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Of flowers and pollinators – a case study in punctuated evolution
Natural selection does a handbrake turn – quick evolution at work
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Living optic fibres bypass the retina’s back-to-front structure

Related stories about nervous systems:
Maternal hormone shuts down babies’ brain cells during birth
No new brain cells for you – settling the neurogenesis debate
Bats create spatial memories without making new brain cells

Monkeys (and their neurons) are calculating statisticians

Using a simple psychological test, scientists have found that monkeys can use simple statistical calculations to make decisions. They even managed to catch individual neurons in the act of computing.

Say the word ‘statistician’ and most people might think of an intelligent but reclusive person, probably working in a darkened room and almost certainly wearing glasses. But a new study shows that a monkey in front of a monitor can make a reasonably good statistician too.

Rhesus macaques can compute statistics in a simple psychological task.Tianming Yang and Michael Shadlen from the University of Washington found that rhesus macaques can perform simple statistical calculations, and even watched their neurons doing it.

Psychologists often train animals to learn simple tasks, where the right choice earns them a reward and the wrong one leaves them empty-handed or punished. But real life, of course, is not like that.

Mostly, there are risks and probabilities in lieu of guarantees or right answers. Animals must weigh up the available information, often from multiple sources, and decide on the course of action most likely to work out in their favour.

A simple psychological test

Yang and Shadlen tested this decision-making ability in two rhesus macaques using a variation of the well-known weather prediction task used to test human volunteers. In the human version, people are shown a series of cards that represent various probabilities of good or bad weather. After some training, they are shown combinations and asked to predict the likely weather from these.

The monkeys had a slightly simpler task – they had to look at either a green or a red target. If they picked the right one (which changed from trial to trial), they were rewarded with a tasty drink. To help the monkeys choose, Yang and Shadlen showed them a series of shapes that represented the probability that the rewarding target was red or green.

For example, a square strongly indicated that the red target was the rewarding one, while a triangle strongly favoured the green one, and an hourglass only slightly favoured the green. The monkeys were shown four shapes out of a possible ten, and to get the right answer, they had to add up the probabilities indicated by these shapes.

Monkey see, monkey decide

Yang and Shadlen saw individual neurons performing computations.And that is exactly what they did. They learned to base their decisions on the combined probabilities of the four shapes, and chose the appropriate target. It did, however, take them a while to learn (or two months of training with over 130,000 trials to be exact). Any statisticians reading this don’t need to fear about being replaced by monkeys any time soon.

They weighed up the strength of the evidence too. When the shapes strongly suggested one colour, the monkeys almost always went with that colour. When the summed probability lay between the two extremes, they chose either target but still favoured the one indicated by the shapes.

With 715 different combinations of shapes, the experiment’s design makes it highly unlikely that the monkeys simply memorised the ‘answers’ for different mixes. And because the shapes only dealt in probabilities, it was still possible to choose the wrong target, even if the monkey strictly adhered to the shapes’ advice. They were clearly reasoning with probabilities, and in pretty subtle ways.

Calculating neurons

For their next trick, Yang and Shadlen visualised this reasoning directly by looking at 64 neurons in the monkeys’ lateral intraparietal area (LIP). This part of the brain is responsible for several higher functions like mathematical skills. Other studies have found that the LIP collects data from the visual cortex, and helps to process what the monkey sees.

Monkeys can calculate the sums of different probabilities.When the monkeys saw a shape, the activity of their LIP neurons was proportional to the probability indicated by that shape. As the four shapes were shown in sequence, the neurons altered their rate of firing to account for the new information. As the evidence was building up, the monkeys were busy doing sums in their heads. Yang and Shadlen were seeing arithmetic in action.

Of course, monkeys are living things and not fuzzy calculators, and they were not equally good at statistical reasoning. One was clearly better than the other, and Yang and Shadlen put this down to differences in their neurons.

Each neuron varies slightly in its typical firing rate, and summed together, these variations can lead to biases in how the monkeys deal with calculations. This explains why the monkeys sometimes did different things when shown the same combination of shapes.

Their confusion was particularly apparent when the shapes gave no strong inclination to pick one target or another. We can certainly relate to that – after all, it’s certainly harder to make a decision, when neither option seems particularly better than the other.

Yang and Shadlen believe that human brains use similar methods to make decisions. Cues about probabilities are funnelled into the brain’s control centres (like the LIP), which act like calculators powered by the firing of neurons.

Reference: Yang & Shadlen. 2007. Probabilistic reasoning by neurons. Nature (doi:10.1038/nature05852)

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Related posts on neuroscience:
Bats create spatial memories without making new brain cells
Simple sponges provide clues to origin of nervous system
Maternal hormone shuts down babies’ brain cells during birth
No new brain cells for you – settling the neurogenesis debate
Drugs and stimulating environments reverse memory loss in brain-damaged mice

Bats create spatial memories without making new brain cells

Neurogenesis in the hippocampus is not necessarily a source of new spatial memories.In an earlier post, I wrote about a study which used carbon-dating to show that our brains are mostly stuck with the same neurons they are born with. After birth, neurogenesis – the manufacture of new neurons – is completely absent in most of the brain.

There are only two exceptions, where new neurons are made. The first is the olfactory bulb, which governs our sense of smell. The second, the hippocampus, is involved in spatial awareness and memory. Why these regions alone should produce fresh neurons is unclear.

For the hippocampus at least, scientists thought they had an answer – the fresh neurons play a role in spatial learning and memory. They could allow mammals to learn about new places, routes and directions.

But Imgard Amrein and colleagues from the University of Zurich have found evidence that disputes this idea. When he looked at the hippocampuses of some of the most accomplished mammal navigators, the bats, he found a startling lack of neurogenesis.


Bats need superb spatial awareness to effortlessly fly in three dimensions. Those that feed on fruit and nectar need especially good spatial memories, and indeed, their hippocampuses are relatively large compared to other mammals.

Bats are some of the best navigators among the mammals.Their memories allow them to remember where the tastiest or ripest food sources are. And they also remember the locations of plants they have recently visited so that they don’t arrive at restaurants with no stock.

Amrein searched for signs of new neurons in 12 species of bats using special antibodies. Some detected proteins that only appear when new cells are born. Others homed in on proteins used by newborn neurons when they migrate to new places.

As expected, these molecular trackers picked up new neurons in the olfactory bulb. But they found no neurogenesis at all in the hippocampus of 9 species, and only the faintest traces in the other three. Clearly, the bats don’t need new hippocampal neurons to learn where things are or to remember how to find them.

Flexibility vs consistency

While Amrein’s bats were few in number, they were also a diverse bunch. They hailed form different evolutionary groups and had diverse diets, territory sizes and ages. This makes it unlikely that these variations in these factors were secretly responsible the trends that Amrein saw.

Instead, he believes that the dearth of new neurons in bats reflects their relatively long lifespans. Humans, apes and monkeys are similarly long-lived, and we too have low levels of neurogenesis as adults.

In contrast, rats and other rodents have short and brutal lives. In order to avoid becoming food for a predator, their behaviour must be as flexible as possible. When threatened, their stream of new hippocampal neurons could allow them to rapidly plan an escape route or find new hiding places.

Bats, and certainly humans, have far fewer predators, and can afford to take things easier. In our long lives, fixed long-term mental maps are very useful and to produce them, we can sacrifice some flexibility in our spatial memories.

This may explain why people tend to rely on the same routes more and more as they age. Fortunately for us, bats show a similar trend. Their reliance on the same flight paths allows canny researchers to catch them in well-placed nets and study how their brains work.

More about bats: 
Moths mimic each others’ sounds to fool hungry bats
Bats: internal compasses and record-breaking tongues

More about neurogenesis:
No new brain cells for you – settling the neurogenesis debate

More about neurons:
Simple sponges provide clues to origin of nervous systems
Monkeys (and their neurons) are calculating statisticians
Non-coding DNA drove brain evolution by making nerve cells stickier
Maternal hormone shuts down babies’ brain cells during birth


Reference: Amrein, Dechmann, Winter & Lipp. 2007. Absent or Low Rate of Adult Neurogenesis in the Hippocampus of Bats (Chiroptera) PLoS ONE.

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Drugs and stimulating environments reverse memory loss in brain-damaged mice

Scientists have restored lost memories in brain-damaged mice by giving them an experimental group of drugs, or by placing them in a stimulating environment. Their remaining neurons re-wired themselves and retrieved memories that had been misplaced, not lost, providing hope for treating human conditions like dementia and Alzheimer’s disease.

Dementia results in massive neuron loss, but that doesn’t mean memories are destroyed.You swallow the pill. As it works its way through your digestive system, it slowly releases its chemical payload, which travels through your bloodstream to your brain. A biochemical chain reaction begins. Old disused nerve cells spring into action and form new connections with each other. And amazingly, lost memories start to flood back.

The idea of a pill for memory loss sounds like pure science fiction. But scientists from the Massachussetts Institute for Technology have taken a first important step to making it a reality, at least for mice.

Andre Fischer and colleagues managed to restore lost memories of brain-damaged mice by using a group of drugs called HDAC inhibitors, or by simply putting them in interesting surroundings.

They used a special breed of mouse, engineered to duplicate the symptoms of brain diseases that afflict humans, such as Alzheimer’s. The mice go about their lives normally, but if they are given the drug doxycycline, their brains begin to atrophy.

The drug switches on a gene called p25 implicated in various neurodegenerative diseases, which triggers a massive loss of nerve cells. The affected become unable to learn simple tasks and lose long-term memories of tasks they had been trained in some weeks earlier.

A richer environment

Lost memories can be recovered by encouraging surviving neurons to re-wire themselves.Fischer moved some of the brain-damaged mice from their usual Spartan cages, to more interesting accommodation. Their new cages were small adventure playgrounds, replete with climbing frames, tunnels and running wheels, together with plentiful food and water.

In their new stimulating environments, the mice returned to their normal selves. Their ability to learn improved considerably, and amazingly, seemingly lost memories were resurrected.

They didn’t grow any new neurons, and their brains remained the same size. But Fischer found that they did have many more synapses – the connections between nerve cells – than brain-damaged peers. Even though they had lost a substantial number of neurons, their enriched environments triggered the surviving cells to re-wire themselves.

These experiments suggest that lost memories are in fact not lost at all, but misplaced. The dead neurons take important connections with them and the survivors, though incommunicado, still retain latent traces of memory.

When they are jolted into action and form new networks, these trace memories are reinstated. And that provides genuine hope for people affected by dementia, Alzheimer’s and other conditions.

Memory-restoring drugs

Brain damage from Alzheimer’s disease could potentially be reversed by HDAC inhibitors.It would be a touch silly to suggest putting such people in the equivalent of a large playpen. But Fischer also found a group of drugs called HDAC inhibitors that have the same effect – the molecular equivalent of a stimulating environment.

HDACs or histone deacetylases control whether genes are switched on or off by altering other proteins called histones. DNA winds around histones like spools, which serves to package this long and unwieldy molecule into a compact and more manageable form.

HDACs change the histones so that they wrap more tightly around DNA and render its genetic code unreadable. Any genes contained in these stretches of DNA are silenced. Drugs like sodium butyrate (SB) neutralise HDACs, freeing DNA from the repressive grip of histones.

Any silenced genes can now be freely switched on and among these, are genes that allow the brain’s neurons to sprout new synapses. The details still need to be ironed out, but the results are clear – just like mice housed in fun cages, those treated with SB regained lost memories.

The next steps

Naysayers might point out that these results are all very good for mice, but are a long way off benefiting people. But while our brains outclass those of mice, we appear to store memories in very similar ways. New experienced are initially encoded among the neurons of the hippocampus, only to be transferred into deeper and long-term stores about three or four weeks later.

Four years ago, a man who had been barely conscious for almost 20 years began to move and speak again. His nerves, badly damaged by a car crash, had started to re-wire themselves and form new connections, in the same way that Fischer’s rats did. The possibilities are there; it’s just the method that needs refinement.

At the moment, the biggest problem with Fischer’s approach is that it’s akin to shooting at a fly with a shotgun. HDAC inhibitors have far-reaching effects on a multitude of different genes. It’s fortunate that these include genes that lead to brain re-wiring, but such a scattershot approach is prone to collateral damage.

Documenting the full actions of HDAC inhibitors is vital. It will allow scientists to understand what side effects such treatments would have in people, while designing more sophisticated drugs with a narrower range of targets.

Reference: Fischer, Sananbenesi, Wang, Dobbin & Tsai. 2007. Recovery of learning and memory is associated with chromatin remodelling. Nature doi:10.1038/nature05772

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Maternal hormone shuts down baby’s brain cells during birth

During birth, a baby’s still-developing brain is very vulnerable. New research shows that mothers protect their babies’ brain cells during birth by stopping them from firing, using a hormone called oxytocin.

Childbirth can be a difficult experience, not least for a baby's brainIt is the instinct of every mother to protect their children as they grow up, shielding them from the dangers of the outside world. Right from birth, life can be a difficult experience. Within a few hours, the child is sent from a safe, warm, constantly-nourished cocoon into a bright, noisy and threatening world.

This stressful transition poses a serious threat to the newborn’s vulnerable and still-developing mind. But new research has shown that even in these first vital hours, mothers are already inadvertently protecting their children – by shutting down their brain cells.

In foetuses and new-born mammals, brain activity depends on a vital molecule called gamma-aminobutyric acid, known by the friendlier name of GABA. GABA is a neurotransmitter, a chemical that sends messages between nerve cells, and in young mammals, its message almost always says “Fire.”

GABA is one of the most important signalling chemicals in a newborn brain. But Roman Tyzio and colleagues from the Mediterranean University, Marseilles, found that in the brains of baby rats, the message changes just before delivery.

For a brief time window, rather than stimulating brain activity, GABA puts a finger to its lips and silences nerve cells instead. During this time, Tyzio saw that the number of cells affected by GABA plummeted to negligible levels.

His group found that this chemical volte face is triggered by the mother, through an all-important, multi-purpose hormone called oxytocin.

Oxytocin is another neurotransmitter, and one that is almost synonymous with social relationships. It has been linked to sexual arousal, feelings of trust, love and monogamy. During childbirth, massive amounts of oxytocin are released by the mother and can reach the foetus via the placenta.

Artificially adding oxytocin to the brain tissue of foetal rats caused cells to ignore GABA just as they do before delivery. And giving expectant mothers atosiban, an anti-oxytocin chemical, stopped this from happening. It seems that oxytocin’s long list of abilities now includes temporarily shutting down an infant’s nervous system during birth.

Many mothers might dream of doing the same later on in their child’s life but at this crucial juncture, it protects them from the dangers of oxygen deprivation. A lack of oxygen during birth is the number one cause of death or brain damage in newborns. But because oxytocin silences a baby’s brain cells, it greatly reduces their energy needs and their dependency on oxygen.

Tyzio found that the brain cells of baby rats survived without oxygen for an hour if they were delivered naturally. But if mothers were given atosiban, the brain cells of their babies died within 45 minutes.

Other studies in sheep have found that the massive flush of oxytocin during childbirth is crucial if mothers are to form stable emotional ties to their babies. Now, thanks to Tyzio’s team, we know that oxytocin might also be important for the baby’s mental development.

These findings have important implications for human mothers too. The oxytocin spike relies on the baby pressing against the cervix during birth. Those delivered through caesarean sections may miss out on the hormone and all its benefits.

Caesarean sections are becoming increasingly popular, mainly as an elective procedure rather than an emergency one. Studies like this could give women who opt for these operations pause for thought.

Tyzio, Cossart, Khalilov, Minlebaev, Hubner, Represa, Ben-Ari & Khazipov. 2006. Science 314: 1788-1792.

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Non-coding DNA drove human brain evolution by making nerve cells stickier

Most of our genome is made up of the poorly named ‘junk DNA’. New research shows that these sequences may have been vital in the evolution of human brains, by allowing our neurons to make better contacts with each other.

DNA, and little of it is 'junk'.Two months ago, a group of scientists found that the gene that has evolved fastest since our evolutionary split from chimpanzees is found in our so-called ‘junk DNA’. DNA is a code that tells our cells how to build their molecular workforce – proteins.

But the vast majority of our DNA sequence is never translated into proteins. While some considered this ‘junk’ DNA to be meaningless, recent research has shown that it makes important contributions to our most human of organs – our brains.

Now, Shyam Prabhakar and James Noonan at the Lawrence Berkeley National Laboratory have found further proof of the link between non-coding DNA and our mental evolution.

They studied over 110,000 stretches of DNA called ‘conserved non-coding sequences’ (CNSs), that are largely similar in a wide variety of animals. Of these sequences, 992 showed large numbers of changes that were specific to humans.

This number is much higher than would be expected if these DNA regions were drifting aimlessly in the evolutionary river. Their frequency is the mark of natural selection – these sequences must have changed for a reason.

To discover what this reason might have been, Prabhakar and Noonan looked at which genes these CNSs were in, and what they do in the body. They found that a large proportion of the genes in question were involved in the adhesion of neurons (nerve cells).

These genes are vital for the growth and development of our brains and allow neurons to make connections with each other, and with their surrounding framework of supportive cells.

The duo found a similar number of CNSs with chimpanzee-specific changes and many of these were also involved in nerve cell adhesion. But there was hardly any overlap between the chimp-specific and human-specific sequences.

Both lineages have developed nerve cells that make better contacts with each other, but have done so in separate ways using different genes.

It is possible that human and chimp brains have evolved different mental abilities to satisfy different evolutionary pressures. Identifying the precise role of the human-specific CNSs will help to test this possibility and it is the next big challenge facing Prabhakar and Noonan.

In the meantime, this research once again shows that non-coding DNA, far from being useless junk, was vitally important for the evolution of the human brain and its many unique abilities. Subtle changes in these sequences separate us from even our closest animal relatives.

Prabhakar, Noonan, Paabo & Rubin. 2006. Science 314: 786.
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No new brain cells for you – settling the neurogenesis debate

The human neocortex – the brain’s control centre – is fantastically versatile and constantly processes a vast amount of information. Amazingly, it does this using the same set of neurons (nerve cells) that it retains from birth, never adding new cells to the mix.

You are not the person you used to be. Two weeks ago, the surface of your skin was covered with a completely different set of cells, which have since died and flaked off. Four month ago, you had a wholly different set of red blood cells. Since birth, your body has grown tremendously in size and much of it is constantly regenerating, replacing old cells with new ones.

But your brain is different. At birth, the part of your brain that controls your most human abilities – the neocortex – came fully equipped with 100 billion nerve cells, or neurons. These same neurons have lasted throughout the years and still power your thoughts today.

The big questionThe neocortex is the outer layer of the large bit.

The neocortex makes up most of the brain. Its relatively large size is unique to humans, and with good reason.

In addition to controlling our bodies, its collection of neurons house our most characteristic qualities – our experiences, and our powers of language, reasoning and creativity. For this reason, the development of these neurons has fascinated scientists for decades.

Throughout our lives, the neocortex needs to change at an incredible pace as we accrue new memories and skills. One of the most hotly contested questions in neuroscience is how it copes – does it constantly grow new neurons (a process called neurogenesis), or do we have the same set from birth?

Until now, the question has had no hard answers because of inaccurate and easily misinterpreted research techniques. A reported sighting of newly-made neurons in primate brains fanned the flames of debate but could not be confirmed. Clearly, a new breakthrough was needed. It came from the most unlikely of techniques.

Carbon-dating neurons

Carbon dating measures the levels of 14C, a radioactive form of carbon found in small background levels in the atmosphere. It is a useful technique for working out the age of ancient artefacts, but it’s only accurate to about 30 years and has limited use for studying living cells.

But Ratan Bhardwaj and colleagues at the Karolinska Institute, Stockholm, found a way to do this. They exploited the fact that during the Cold War, the world’s superpowers busied themselves by testing their new nuclear arsenals. In doing so, they unleashed large amounts of 14C into the atmosphere and from 1955, global levels doubled in eight years.

The Test Ban Treaty of 1963 put an end to both nuclear testing and the rising 14C levels, which fell exponentially in the following decades. Meanwhile, the high atmospheric levels of 14C were converted into carbon dioxide and taken in by plants. In this way, 14C worked its way up the food chain, and some of it made it into the bodies and neurons of people alive at the time.

Nuclear testing sent 14C levels skyrocketing. So, the levels of 14C in any neuron acts as a time stamp, directly reflecting the amount of 14C in the air at the time it was created. Because the atmospheric levels changed so much from year to year, the team could accurately work out the birthday of each cell.

Bhardwaj and his colleagues looked at the levels of 14C in the neurons of 7 people born between 1933 and 1973.

The results were unequivocal. For each person, the levels of 14C in their neurons matched the levels in the air when they were born – high in those born after nuclear testing, and low in those born before it. The team studied millions of neurons, across the four distinct parts of the neocortex. Not a single one was younger than the brain that carried it.

The final blow

Bhardwaj did another study to confirm his sensational result. He looked at the brains of cancer patients who were injected with a chemical called BrdU before they died. BrdU is a variant of one of the four bases that make up DNA and once injected, it gets incorporated into newly-created DNA. In this way, the presence of BrdU acts as a marker for newborn cells.

Again, the experiment left no room for doubt – in these patients, many different types of cell were labelled with BrdU, but not a single one of them was a neuron.

While Bhardwaj admits that the techniques have their limits, they are incredibly sensitive. Any new neurons missed by the two methods would account for under 1% of the neocortex’s collection, and would be very short-lived.

At most, the neocortex adds one new neuron every year for every 7000 existing ones. Their impact on the existing million-strong network would be insignificant.

At last, a clear answer

Bhardwaj’s elegant experiments finally bring the debate crashing down in favour of one side. It is clear that all 100 million neurons in our neocortex are produced during a strict developmental window while we are still inside the womb. We are then stuck with these cells for our entire lives.How does a static neural population cope with new information?

How can a static population of neurons be reconciled with a dynamic adaptable brain that is anything but static?

Without new neurons, the neocortex’s vaunted flexibility must come from changing connections between existing neurons, constantly rewiring our mental circuits in the face of new experiences and sensations.

When it comes to neurons, it’s not how many you have, it’s how you use them that counts.

Evolving stability

Fish, reptiles and birds renew their neurons throughout their lives, but further along the evolutionary tree, the situation looks more human. In primates and rodents, new neurons only appear in two parts of the brain – the olfactory bulb, which controls the sense of smell, and the hippocampus, a region associated with building short-term memories.

There is good evidence that new neurons are created in these same regions in humans. But in the neocortex, stability is the order of the day. Bhardwaj believes that mammals have evolved a stable neural network so that we can retain important information throughout our lives, such as our language skills.

Our mental network was forged through experience, but new neurons are naïve. Adding them into the mix would change the flow of currents through the existing system existing network, causing potential problems. Anyone who watched the England football team recently can appreciate the chaos that ensues when new players are unexpectedly thrust into a stable formation.

Preventing the development of new neurons may even have been a critical step in the evolution of human intelligence. It is deliciously ironic that rigidly fixing the number of neurons in our brain may have allowed us to become more mentally dynamic than any animal could ever hope to be.

More about neurogenesis:
Bats create spatial memories without making new brain cells

And more about neurons: 
Simple sponges provide clues to origin of nervous systems
Monkeys (and their neurons) are calculating statisticians
Non-coding DNA drove brain evolution by making nerve cells stickier
Maternal hormone shuts down babies’ brain cells during birth

Reference:  Bhardwaj, Curtis, Spalding, Buchholz, Fink, Bjork-Eriksson, Nordborg, Gage, Druid, Eriksson & Frisen. 2006. PNAS 103: 12564-12568.

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Hidden ‘junk’ gene separates human brains from chimpanzees

Scientists used to believe that 98.5% of our DNA is junk and serves no useful purpose. But new discoveries are showing that this assumption is wrong. We now know that one of the most important genes that separates humans from chimpanzees lies among this supposed junk.


We’ve all found gems hidden among junk before – the great album you own but never listened to, the book on your shelf that you never read, or the boot sale item that’s worth a fortune. Geneticists are no different. Last month, Katherine Pollard and Sofie Salama discovered that one of the most important genes in human evolution has been lying in plain sight, hidden within a pile of genetic junk.

Humans and chimps share over 98.5% of our DNA.

Humans and our closest cousins, chimpanzees, evolved from a common ancestor, and we famously share anywhere from 96-99% of our DNA. This similarity suggests an obvious question: what are the key genetic differences that separate us from chimps? The search for these differences is now possible because the entire human and chimp genomes have been sequenced. The genomes represent each species’ entire DNA repertoire and by comparing them, Pollard and Salama sought to hunt down the genetic innovations that shaped our very humanity.

The duo and their colleagues at the University of California, Santa Cruz, clocked the rate of evolution in different parts of the human genome. They specifically looked for bits that had remained relatively stable for eons, but had exploded into evolutionary action since we and chimps diverged form our common ancestor.

They found 47 such areas which they appropriately named ‘human accelerated regions’ or HARs. And among these, a clear winner emerged – HAR1, a stretch of DNA that had changed 18 times faster than expected since the human and chimp dynasties split. HAR1 is part of a gene called HAR1F, and when the duo homed in on its location, they were in for a shock.

Hidden gems

98.5% of our DNA is apparently junk

HAR1F is part of our so-called ‘junk DNA’. DNA is a code that becomes useful when it is deciphered into messages written in a related molecule called RNA. RNA messages then act as recipes for building the molecular workforce of our bodies, proteins. But 98.5% of our genes do not code for proteins.

This poorly-named ‘junk DNA’ produces RNA messages that are never translated. For a time, they were largely thought to be ignored by evolutionary forces, and while some research hinted at an active function, actual details about their roles have remained elusive.

Over the last decade or so, geneticists have come to appreciate that certain stretches of ‘junk DNA’ may actually be vitally important. The discovery of HAR1F provides massive evidence that this line of thought is correct. In fact, 47 out of the 49 HARs were found among junk DNA and many of these lie next to genes that code for proteins involved in brain development.

Pollard and Salama believe that HAR1F and its colleagues control when, where and how these brain development genes are switched on, effectively redeploying our protein arsenal in interesting ways. When they looked at the brains of embryos, they found that HAR1F showed up between the second and fifth months of development. It is found in special brain cells called Cajal-Retzius cells, which control the migration of neurons from their birthplace to other parts of the brain.

It is unsurprising that one of the fastest evolving genes in our collection affects the brain or that many of the other HARs also control brain development. After all, our large brains (three times larger than a chimp’s) are arguably our most defining attribute. But this study suggests that evolution fashioned our brains not by substituting in new proteins but by creatively changing the formation and tactics of the existing squad.

The evidence has never been stronger that the previously over-looked 98.5% of our genome is far from junk. Instead, this is an area littered with hidden gems that are essential to being human.

Reference: Pollard, Salama, Lambert, Lambot, Coppens, Pedersen, Katzman, King, Onodera, Siepel, Kern, Dehay, Igel, Ares, Vanderhaeghen & Haussler. 2006. Nature. Epub ahead of print.

Related posts on DNA and chimp/human evolution:
Non-coding DNA drove brain evolution by making nerve cells stickier
Chimps have more adaptive genetic changes than humans
Opinion: Not so unique – the chimpanzee Stone Age, and our place among intelligent animals
Chimps show that actions spoke louder than words in language evolution
Orang-utan study suggests that upright walking may have started in the trees