readings> a role for spindle cells?

It's a strange fact that humans suffer from many brain diseases that appear unique. Alzheimer's, multiple sclerosis, schizophrenia, autism - some of our most common illnesses don't seem to occur in chimps, gorillas or other apes despite the great similarity in our genes. A new field of comparative neurology has sprung up to find out why.

Of course, it's possible that we just haven't looked hard enough. For example, the latest research has suggested that chimps can have psychopathic personalities like humans. But equally, evidence suggesting the human brain has suffered the stress of "too rapid evolution" has been spilling out comparative studies like the Great Ape Ageing Project.

There are four general ways that Homo sapiens has pushed the neurodevelopmental envelope. Our brains are much larger (four times the size); more lateralised (though apes show some lateralisation); and far slower maturing (our critical periods stretch into early adulthood). More recently a fourth has been added to the list. The human brain has been found to have greater "top-downness". The weight of inhibitory and constraining neural traffic is far in excess of that found in the apes.

Particular attention is being paid to special long-range neurons found in the frontal cortex, especially in the anterior cingulate and frontoinsula cortex. One of these is the spindle cell, an exceptionally large neuron found in cortex layer Vb, so-named because it has only a single dendrite at either end. Associated with these spindle cells are an unusual class of pyramidal cells - unusual in being GABAergic and so most probably a long-range inhibitory projection.

What has grabbed the headlines is that these neurons are not found in monkeys or other animals. And while they are present in both humans and apes, there is a marked evolutionary trend in that orang-utans have hardly any, gorillas and chimps have a few, and humans have many.

The hunt is now on for more such fine-scale neural changes. Another big finding has been the discovery of a unique migration of GABAergic neurons from the frontal cortex to the dorsal association areas of the thalamus in the developing human embryo, but not in monkeys or mice. Neurodevelopmentalists were stunned to find cells from the telencephalon mixing with those of the diencephalon in this way. However it all adds up to a neat picture of rapidly increasing top-downness in the brain hierarchy.

A key trend in human brain evolution has been a growing ability to take attentional control over our habitual and emotional responses. This top-downness shows in many ways. Tool-making and language use both depend on being able to form a complex conscious intent - to have a plan in mind - and then supervise its execution by more rapid and automatic processes, our quick tongues and nimble fingers.

Frontal lobe oversight is also basic to our more social lifestyles. We need to be able to control our facial expressions, our vocal tone, our outward emotions, so that we can manoeuvre and manipulate in a social setting - what primatologists call the rise of Machiavellian intelligence in the great apes.

The finding of spindle cells and other novel long-range projections in the frontal cortex fits this hypothesis perfectly. They look exactly like a beefed-up machinery for monitoring and exerting top-down control over the lower brain.

So we have at least four neurodevelopmental shifts that were probably present when the hominid line branched from the rest of the apes, but have clearly been cranked up to an extreme with modern Homo sapiens. Speculation is now about how exactly this relates to common human neurological conditions.

For instance, researchers have found that in humans, spindle cells are among the hardest hit in Alzheimer's, yet the same cells appear to show no deterioration even in very old chimps and gorillas. So has there been some recent extra change in the characteristics of these neurons?

Schizophrenia and autism are further likely suspects in any story about an over-developed brain. The need to make tricky top-down connections across a now grossly swollen organ with a complex maturational schedule and using only recently evolved molecular signalling machinery - well it's all too easy to understand how things might go wrong.

It remains to be seen how much mileage there is in this evolutionary approach. But it should be remembered that other medical disciplines are well-used to blaming our ancestors for many of our ills. Just think of all the hospital time spent on bad backs and knees, appendixes and narrow birth canals. Now we want to ask just how many of our most common neurological complaints are also due largely to the evolutionary rush to get to where we are?<

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