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fountains 4: what’s a glial cell?

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Here’s the transcript for the next podcast, which I won’t be putting online for another week or so, when I can afford to buy space to host podcasts directly from this site. Then I’ll be able to stick all the fountains podcasts in one place, with the new logo created by a friend of mine, Stuart Rose:

FoGS logo

What’s a glial cell?

Today, I’m going to make my first, but hopefully not last, foray into neurobiology. And since neurobiology is about the most complicated subject imaginable, I’ve decided to enter it sideways, so to speak, by looking at glial cells, or neuroglia, as they’re sometimes called. Not that this will make it any easier.

Glial cells – ‘glia’ means glue in Greek – perform a whole range of tasks apart from holding neurons together. They also come in many different varieties, and there’s still a lot we don’t know about them. They make up about half the mass of the brain, and they outnumber neurons many times over, making up between 85% and 90% of brain cells.

Considering the great varieties of roles glial cells play in the central nervous system (CNS), the peripheral nervous system (PNS) and in neurogenesis or the development of the brain, it’s hard to start with a summary or overview. They’re generally a lot smaller than neurons, and the glia/neuron ratio varies greatly between species, with the human brain near the top end. Elephants, though, are much higher with 97% glial cells.

Glial cells emerge from the multipotent precursor cells of the neural crest and neural tube. Radial glial cells act as progenitors and also as scaffolding for the growth and migration of neurons in the brain. They play a role in the development and maintenance of synaptic plasticity in the cerebellum. This function of supporting neurons is typical of all glial cells, with some of them having their own quasi-neuronal tasks. In the vertebrate retina, for example, Muller cells or Muller glia have been found, quite recently, to play a role in the formation of synapses. They’ve also been shown, when the retina is damaged, to re differentiate into progenitor cells which can then become photoreceptor cells.

But I’m galloping forward a bit here. The three main types of glial cells in the CNS are the astrocytes, the oligodendrocytes and the microglia, and some of their functions have long been known, though the detail, as well as a growing number of other roles and functions, are only now being focused on, in what some are describing as a revolution in neurobiology. Dr. Douglas Fields, chief of the Nervous System Development & Plasticity Section of the National Institutes of Health in the USA, argues that our understanding of the brain has been overly influenced by what he calls ‘the neuron doctrine’, that’s to say, a relentless focus on the electrical activity of the brain in the form of action potentials between neurons. The fact that glial cells don’t communicate electrically has meant that their role in brain activity has been largely overlooked for the best part of a century, according to Dr Fields. My layman’s perspective suggests to me that, not being electrical, glial cells just aren’t as flashy or sexy as neurons. ‘I sing the body electric’, Walt Whitman memorably wrote, and maybe he wasn’t thinking about neurons, but he definitely wasn’t thinking about glial cells.

So let’s have a look at some of those glial cell types. Astrocytes – so-called because of their star-like shape and projections – perform lots of functions within the CNS, including providing physical support to neurons through the formation of a matrix, cleaning up chemical debris within the brain, and replenishing chemicals within neurons and so keeping them healthy and well-nourished. This clearly requires communication between neurons and glia. Astrocytes also monitor the fluid surrounding neurons and keep it chemically well maintained. They get rid of the flotsam and jetsam through a process called phagocytosis, which involves engulfing the unwanted particles and essentially digesting them, a process performed by dedicated cells throughout the body.

looks like an astrocyte

looks like an astrocyte

Astrocytes nourish the neurons by first obtaining glucose from capillaries, then breaking it down into lactate, the first product of glucose metabolism. The lactate is then released into the fluid surrounding the neurons. The neurons take up this lactate and transport it, as an energy source, to their mitochondria. Astrocytes also maintain a store of glycogen from this process, which may be used in times of high neuronal metabolism.

One of the essential functions of oligodendrocytes is myelination. Now I’m sorry for the polysyllabification there, but I’m talking about the production of myelin sheath, the insulating material that protects the axons of the CNS as well as substantially improving their electrical activity. Myelin is white in colour, and accounts for the white colour of the brain. It’s made up of 80% lipid and 20% protein and it increases, many times over, the strength and efficiency of electrical conduction down the axon. The axon is generally the only part of the neuron sheathed in myelin. The oligodendrocytes are able to sheath as many as 40 axons at once in myelin.

Microglia, the smallest of the glial cells, also engage in phagocytosis to clean up debris, but their most important role is immunological. The brain’s main protection against pathogens is the blood-brain barrier, a layer of endothelial cells similar to the types of cells that line blood vessels and internal organs. When somehow pathogens cross the blood-brain barrier or are introduced into the brain directly, microglia, which are ultra-sensitive to chemical imbalances in the brain, and particularly to extra-cellular potassium levels, move swiftly into action. Microglia perform a similar role in the CNS to that of macrophages in the blood system, but are not as easily replaceable as macrophages, due to the blood-brain barrier. However microglia are extremely plastic which allows them to perform a variety of immunological functions at short notice while also maintaining homeostasis in the brain.

Another type of glia, the Schwann cells, provide support to the nerve cells of the peripheral nervous system (PNS). They wrap themselves around axons, as with oligodendrocytes in the CNS, and in so doing produce myelin, though the process of myelin production is substantially different in the PNS, with one cell producing only one segment of myelin. Schwann cells also clean up debris and play a major role in the regrowth of PNS axons. They arrange themselves into cylinders which guide the tendrils of regenerating axons. When a functioning tendril comes into contact with one of these cylinders it will grow inside it a rate of up to 4mm a day.

There are other types of glia, and the glial cells already mentioned have their subsets and their developmental phases, which all play their part in the development and maintenance of the brain and the nervous systems, yet for a long time neurophysiologists considered the ‘white matter’ of the brain – the glia, predominantly – as passive, with the grey neuronal matter being the active component.

With the renewed interest in glia however, experiments are being conducted that show that when you remove or ablate relevant glial cells, it has a profound effect on an animal’s ability to sense its surroundings. This has been shown in worms and other creatures, and it raises many questions as to how glial cells communicate with neurons in facilitating an effective sense of our environment, without which, we wouldn’t last long.

We now know that the activation of calcium ions provides the principal means of chemical communication between neuroglia and neurons. An increase in calcium ions signals the release of what are now being called gliotransmitters, molecules that travel between cells in a manner similar to neurotransmitters. All this communication has a variety of purposes but it’s the immunological role of neuroglia that has researchers really excited. The neuroglia are able to pick up signals between neurons and respond by controlling neuronal activity, inhibiting or stimulating or refining the action potentials between nerve cells. All of this was completely unsuspected until recently. Their role in such diseases as Parkinson’s, Alzheimer’s, Lou Gehrig’s disease, cancer and AIDS, and even such disorders as OCD (Obsessive-Compulsive Disorder) are now being uncovered through a lot of experimental work. Communication between astrocytes and microglia and neurons are substantially altered in specific ways in each of these diseases. So important have glia become in contemporary neuro-research that there’s talk of ‘the other brain’ or ‘the glial brain’ as opposed to the neural brain. They of course work in tandem, but the point is that we have a lot of catching up to do in researching glia.

It’s worth noting that, though neurons in invertebrate animals are not substantially different from those in vertebrates, glial cells are far less numerous, in proportion to neurons, in invertebrates, where they don’t have the same myelin-producing role. Investigating the increasingly vital and diverse roles played by glia and how they came to evolve in more complex animals will no doubt be a focus of future research.

Written by stewart henderson

January 19, 2013 at 10:06 am

fountains 2: dolphins and their brains

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comp_brain_size

dolphins and their brains

Here’s the transcript of my second ‘fountains of good stuff’ podcast, ‘dolphins and their brains’, (linked to above) minus some bits at the beginning and end.

Dolphins have long been considered our cute, smart underwater friends. In fact you might be surprised at how far back such observations go, and at how interested the ancients were in dolphinkind. Aristotle recognised that dolphins weren’t fish, that they couldn’t breathe underwater, that they had lungs and had to return to the surface to breathe just like us. The ancient poet Oppius of Corycus had this to say about them:

Diviner than the dolphin is nothing yet created; for indeed they were aforetime men and lived in cities along with mortals, but by the devising of Dionysus they exchanged the land for the sea and put on the form of fishes.

In these remarks we find the mixing of genuine observation and fascination with mythologising which still persists today. Some modern claims are that dolphins are idyllically happy and playful creatures, that they have a special bond with humans, that they’re at least equivalent in intelligence to us, bearing in mind the vastly different medium they inhabit, and that they have a highly developed language and a social and cultural complexity that we’ve barely begun to tap into.

So how much truth is there to these claims? Well I think we should first look at the grandest of the claims, about dolphin language and culture.

Many of the more hyperbolic claims for a rich dolphin language and culture, as yet beyond the ken of mere humans, were made by John Lilly, a pioneering researcher of the fifties and sixties. Lilly worked with bottle-nosed dolphins, and that is the species I’m referring to, though of course, all thirty or so species of dolphins and porpoises, as well as the forty or more species of whales, tend to be lumped in together as highly communicative and cultured.

Lilly’s attempts to back up his claims about dolphin language didn’t work out so well, however, and his writings on dolphins became increasingly drug-influenced and fantastical. Another researcher in the mid-sixties, Duane Batteau, tried to translate Hawaiian phonemes into the whistle-sounds frequently used by dolphins, using them to convey simple instructions. However, Batteau could only use the sounds as holophrases, that’s to say, instructions with complex elements, such as ‘jump through the hoop I’m holding’. The dolphins couldn’t be taught to recognise individual semantic elements within the complex instruction, such as ‘hoop’, ‘leap’ or ‘five feet high’, which are essential to building up a whole language, at least one that humans would recognise, and using it in a flexible and creative way. The dolphins took some years to learn about a dozen holophrastic sounds, which indicated none of the complexity or nuance of human language.

Since these early researches, little headway has been gained in trying to teach dolphins, or any other species, to understand human language, which is hardly surprising, as they’ve evolved to communicate very differently. Dolphins are very vocal animals, forever sounding off with whistles and clicks that are incomprehensible to most of us, and many of which we’re not even equipped to hear. But is this dolphin language?

Well, early research on dolphin whistles didn’t come up with anything too promising. Individual dolphins produce their own unique whistles, described as ‘signature whistles’, doubtless for the purpose of identifying themselves to others. Interestingly, female dolphins develop signature whistles that are quite different from their mothers’, while male dolphins don’t. This is explained by the fact that male dolphins, after weaning, hang around together in ‘adolescent gangs’ just as male humans do [and quite a few other species too, such as elephants]. Females tend to stick to their mothers, becoming young mothers themselves. They need to be able to differentiate between mothers and children, which is unnecessary for the males.

Dolphins do sometimes mimic the whistles of other dolphins too, particularly those of their closest relatives, but signature whistles as a form of recognition and differentiation, are a long way from anything like language. After all, many species can recognise their own mates or kin from the distinctive sounds they make, or from their specific odour, or from visual cues. However, a clever experiment carried out more recently, which synthesised these whistles through a computer, so that the whistle pattern was divorced from its distinctive sound, found that the dolphins responded to these patterns even when produced via a different sound. It seemed that they were recognising names. It’s undoubtedly intriguing, but clearly a lot more research is required.

Most attempts to elicit information about dolphin language, and dolphin intelligence generally, suffer from a difficulty in imagining a language system completely alien to our own, so that we always try to translate communication into something that might make sense to us. It’s a kind of anthropomorphism problem, which we can probably only overcome by a greater insight into the social life of these creatures and what they might use language for. It will no doubt be a long and painstaking process.

One of the reasons given for the supreme intelligence of the dolphin is its very large brain, and on first thought, it seems a very sound reason. The human brain is considerably larger, both in absolute terms and in terms of brain body ratio, than that of other primates.

In fact the human brain has become so large that we have trouble pushing our babies’ heads through the birth canal, and their skulls at birth are still soft and collapsible in places to facilitate the birth process. In the few months after birth, the baby’s head has to be supported until it becomes used to carrying that great bony weight on its shoulders all by itself. The average dolphin brain is slightly larger than ours, but so is its body, so its brain body ratio averages out at about the same, or a little less than ours.

The real key to human intelligence, however, is the growth of a specific part of the brain, the neocortex. In most mammals, the neocortex takes up between 10 and 30% of the total brain mass. In primates in general, it takes up 50%. For humans, though it has climbed to a very impressive 80%. So big is our neocortex that is has to be folded in on itself to fit inside our heads.

So what about the dolphin neocortex? Well, it was John Lilly, the sixties researcher, who first discovered that it was even bigger than our own, a fact that led him to to the quite understandable conviction that dolphins were, at the very least, our equals, intelligence-wise.

However, size isn’t everything, especially when we compare land mammals with their underwater cousins. Mammals on land all have about the same nerve cell density, that is, the same number of neurons per square centimetre. Aquatic mammals have far less densely packed neurons in their brains. In fact, their brains are only a quarter as densely packed with neurons as land mammals, and that’s a big difference. It seems that, because dolphins have evolved in water and don’t have to contend with gravity the way we do, their brains have been able to spread out over a larger area, without necessarily increasing complexity. Which isn’t to say that the dolphin brain isn’t extremely complex. We’re only at the beginning of understanding a small fraction of it.

Some of this research has highlighted that the neocortex in dolphins, which naturally reflects more recent evolutionary development, is used for very different purposes, such as breathing, which is regulated by more primitive brain processes in land mammals. Hearing in dolphins requires a far larger proportion of grey matter than in humans, and it’s likely that their complex sonar system is regulated by the neocortex.

In recent years it’s been discovered that spindle neurons, previously only found in higher primates, exist in large numbers in many whale and dolphin species. These neurons are associated with the processing of emotions and social interaction. They’re relatively large and allow for high-speed communication and response across the large brains of hominids, so the fact that many cetaceans [the order that whales, dolphins and porpoises belong to] have some three times the number that humans do, is certainly food for thought.

“The discovery of spindle neurons in cetaceans is a stunning example of neuro-anatomical convergence between cetaceans and primates,”

says Lori Marino of Emory University in Atlanta, Georgia.

“The common ancestor of cetaceans and primates lived over 95 million years ago, and such a highly specific morphological similarity as the finding of spindle cells is clearly due to evolutionary convergence, not shared ancestry,”

she says. The term ‘convergence’ refers to a similarity in adaptive structures and behaviours in unrelated or only distantly related species.

Exactly how these spindle cells function in cetaceans is still unclear, but it’s believed that they’ve been present in these mammals for some thirty million years, compared to 15 to 20 million years in our primate ancestors.

The term ‘intelligence’ is really quite fuzzy, even when we’re applying it only to humans, let alone comparing humans to such vastly different creatures as dolphins, but years of studying the social interactions of cetaceans in general are gradually revealing a world much worth exploring. However, it isn’t necessarily the playful world we associate with the bounding, squealing, apparently perpetually laughing and eagerly performing creatures formerly associated with marinelands the world over.

Some years ago, beginning in 1997, a growing mystery developed when dead porpoises and juvenile dolphins were found washed up on beaches in Scotland and on the other side of the world in Virginia. The animals had suffered massive internal damage, as it turned out, from dolphin attacks. They had literally been beaten to death. A well-known documentary, ‘the Dolphin Murders’, relates the story. Researchers are still unclear as to the motive for these murderous attacks, but they remind us that evolutionary pressures and brutality are just as much a part of life in the oceans as on land, and that even dolphins, who’ve often been reported as saving human lives at sea, can turn themselves into killers.

Dolphin-hugging, metaphorically speaking, has been all the rage in recent decades, but for all its positivity, it risks obscuring what dolphins really are. They’re not always playful and cute, but they’re certainly among the most fascinating creatures on our planet, and the best compliment we can pay them is to try to get to know them a whole lot better.

Written by stewart henderson

December 27, 2012 at 12:22 pm