Saturday, 10 August 2013

A new way of thinking about how the brain works | Mo Costandi

Modern neuroscience is based on the discovery of the neuron, but this is only half the story

My book, 50 Human Brain Ideas You Really Need to Know, is out now, and is available at a discount price from Amazon and the Guardian bookshop. (And here's a lovely review by Vaughan Bell, who calls it "a concise, solid grounding in neuroscience? remarkably lucid? balanced and entertaining".) When I first announced its publication, I said that I had come to the conclusion that one idea has been more important than any other in shaping how we think about the brain, and asked people to suggest what that idea might be.

Several neuroscientists responded on Twitter: Vincent Walsh of UCL suggested otopy, referring to the spatial arrangement of certain brain areas, such as the primary somatosensory cortex, in which adjacent neurons receive inputs from adjacent parts of the body, and Sarah-Jayne Blakemore (also at UCL) suggested neural plasticity, an umbrella term for the different ways in which the brain can change in response to experience. Otopy is an important organizational principle in neuroscience, and plasticity an important functional one, and although the book includes chapters on both, neither is the idea I had in mind?

In my opinion, the single most important idea in neuroscience is the Neuron Doctrine, which simply states that the nervous system consists of discrete units called cells. In retrospect, this may sound trivial, but the discovery of the neuron came only after decades of laborious research by some of the world's best scientists, not to mention a long and furious debate among them.

This debate began in the mid-nineteenth century, and revolved around the fine structure of the nervous system. At the time, microscopes weren't powerful enough to see nervous tissue in any great detail. Some researchers argued that the nervous system must, like all other living things, consist of cells; others, failing to see nerve cells or synapses properly, argued that it was comprised of a single, continuous network. The Neuron Doctrine emerged in the 1890s, following improvements in microscopy and techniques for staining the tissue to highlight individual cells.

The biggest proponent of the Neuron Doctrine was the Spanish neuroanatomist Santiago Ram�n y Cajal, who devoted his entire career to the close examination nervous tissue from both humans and a wide variety of animals. As formulated by him, the Neuron Doctrine states that: (1) the neuron is the fundamental structural and functional unit of the nervous system; (2) neurons are discrete cells which are not continuous with other cells; (3) the neuron is composed of 3 parts ? the dendrites, axon and cell body; and (4) information flows along the neuron in one direction (from the dendrites to the axon, via the cell body).

The reason I believe this to be most important idea in neuroscience is because neurons are invariably mentioned in explanations of virtually every aspect of brain function. On one level, for example, changes in the strength of connections within neuronal networks are widely thought to be critical for learning and memory. On another, distant brain regions are now thought to communicate with each other using brain wave oscillations of different frequencies, which are produced by the synchronous firing of large numbers of neurons in each area.

Strictly speaking, though, the Neuron Doctrine no longer holds true, and needs to be revised in light of new findings. The second and third of its points can still be taken as they are ? neurons are indeed discrete cells, which consist of a cell body, axon and dendrites, and function by producing electrical signals and transmitting them to one another. But the fourth point ? which Cajal named the Law of dynamic polarization ? cannot. We now know that electrical signals can be generated in parts of the neuron, and that these signals can also travel from the axon to the cell body and beyond to the dendrites. Most neuroscientists still think of this as the "wrong direction," but the latest research suggests that this backward signalling, or 'antidromic' firing, probably contributes to the brain's information processing capabilities.

More importantly, the first point needs to be completely re-thought. Neurons are fundamental structural and functional units in the nervous system, but not the fundamental units. It turns out that neurons are only half the picture ? they are one of several different discrete units, all of which are fundamental to proper brain function.

The others are several different types of non-neuronal cells, which are collectively known as glia. The brain contains three types of glial cells ? astrocytes, microglia, and oligodendrocytes ? which were discovered at around the same time as neurons. At first, however, researchers couldn't distinguish between them, and quickly dismissed as supporting cells that do little more than provide neurons with nourishment and the pack the spaces between them. This purported function is reflected in their name ? glia means "glue".

Glial cells do indeed perform the functions first ascribed to them. Oligodendrocytes, for example, produce a fatty tissue called myelin, which wraps itself around axons in the brain, insulating them and helping them to conduct impulses. But there is much more to glial cell function than just support and nutrition, and research published in the past decade or so has revealed that astrocytes and microglia in particular play far more crucial for proper brain function than previously thought. This new research leaves little doubt that astrocytes and microglia contribute to the brain's information processing capabilities ? something which is still widely thought of as the sole preserve of neurons ? and are probably just as important neurons for these capabilities.

Astrocytes are star-shaped cells that come in various different forms. Like neurons, they form networks and send signals to each other. Although they apparently do not produce electrical signals themselves, astrocytes can send signals to neurons, and also regulate the signals that pass between neurons. In some parts of the rodent brain, a single astrocyte can come into contact with, and presumably regulate the function of, hundreds of thousands of synapses. They also control the flow of blood through capillaries in the brain Human astrocytes are larger and even more elaborate. They boost memory function when transplanted into the brains of mice, suggesting that they perform additional functions that we still don't know about, and were probably vital for evolution of the human brain.

Similarly, microglia perform important roles that were unheard of just 10 years ago. They are the brain's resident immune cells, migrating to the site of injury or infection to mop up dead cells or microbes. Until recently, they were thought to rest at other times, but a landmark 2005 paper showed that they were anything but inactive, but instead constantly patrol their immediate surroundings by extending and retracting their finger-like projections. Subsequent research showed that they literally eat unwanted synapses in the developing brain, and likely perform the same function in the adult brain, which makes new synapses, and breaks old ones, all the time (during memory formation, consolidation and storage, for example).

It is, therefore, time to revise the Neuron Doctrine to take all of this into account. Most neuroscientists are still extremely "neuron-centric," thinking almost exclusively in terms of neuronal activity when explaining brain function, while ignoring glia. But it now seems very clear that we cannot reach a proper understanding of how the brain works without factoring glial cells into the equation.

Alexei Verkhratsky, a neurophysiologist at the University of Manchester, puts it like this: "It's very obvious that we have to redefine our approach to the brain, and to stop dividing it into neurons and glia. We need a new theory, which looks at the brain as a tissue containing different cell types, which have distinct functions but work together in the process of communication."


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Source: http://www.theguardian.com/science/neurophilosophy/2013/aug/09/a-new-way-of-thinking-about-how-the-brain-works

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