Why you can't see the colour of the car that hit you

The visual system is one of the best understood in all neuroscience (not that there aren't plenty of mysteries about it!), and its most salient features is its economy. The brain is an expensive organ, evolutionarily - pound for pound, it consumes 22 times more energy than muscle (which is itself rather expensive), and all this has to be repaid by eating more in reply. Therefore, any bit of it that doesn't absolutely have to be around won't make the cut as the aeons roll by.

One way you could have designed the retina would be to cover it densely with both cones (for high acuity colour vision) and rods (for high sensitivity night vision). In this way, no matter where the photons landed, you would get the best image possible.

But the eye chooses a more elegant system. It concentrates almost all its cones in and around the fovea centralis, a region near the centre of the eye. To some extent, it has put almost all its eggs in one basket, since any images that are attempting to form themselves elsewhere on the retina are left to the low quality rods to fumble with. The visual system makes up for this by constantly rotating the eyeball so that the centre of our visual field falls on it; in this way, whatever we are 'looking at' can be rendered in the highest possible quality.

Furthermore, our brain hides this flaw from us by rapidly darting the eye around a particular scene, and patching the numerous, small high quality images together. It may surprise you to find out just how bad your peripheral vision actually is. The only way to do this is to keep your eyes absolutely still and then try to make out the details of something in the periphery of your vision.

Reading is a good example. Place something with large letters in near to you. (Take care not to peek at what the text says, or the brain will cheat, as I've mentioned. One way of minimising this likelihood is to ask a friend to write something down instead.) If you are stringent about keeping your eyes staring straight ahead, it won't be possible to make out any letters even a few degrees from centre.

Furthermore, since cones are used for both high-acuity vision and colour vision, you won't be able to make out the colour of an object seen only with your peripheral vision. If anything, this fact is even more surprising, but if you're as strict with your eyeball as before, you can easily confirm this.

Note also how clever the brain is at filling in the details. After you have seen an object with your central (cone-dominated) visual apparatus, the brain will give the illusion of still seeing that object in colour long after it has moved to your peripheral vision, where this is no longer possible! Its amazing how good the virtual reality generator is...

One thing the peripheral vision really is good at, though, is detecting movement. (It isn't hard to see how this might be beneficial.) The slightest movement, and the eyeballs rotate to lock the powerful central vision on to the object.

Upper motor neuron vs lower motor neuron weakness

Weakness of one or more of our limbs is most often neurological. Classically, there are two distinct patterns of neurological weakness, and identifying the one you're dealing with is rather useful. I'm referring to upper motor neuron vs lower motor neuron weakness, of course.

The ‘lower motor neuron’ is simply the last neuron to touch the relevant muscle. It always starts in the spinal cord and ends in a muscle. Damage to any of the neurons in the motor pathway before this point (e.g. spinal cord, brainstem, or cerebrum) will give you an ‘upper motor neuron’ pattern of weakness.

Although both syndromes present with muscle weakness, they thereafter part company in the following ways:

	Upper Motor Neuron	Lower Motor Neuron
Tone	Increased, with ‘clasp knife’ quality	Decreased
Clonus	Present	Absent
Fasciculations	Absent	Present
Muscle Wasting	Absent, but disuse atrophy eventually results	Present (within 2-3 weeks)
Tendon Reflexes	Increased. Extensor plantar reflexes.	Decreased or absent. Flexor plantar reflexes.
Distribution	Whole limbs, with more weakness in the upper limb extensors and lower limb flexors	Specific muscle groups affected (e.g. in the distribution of a spinal segment, or just the proximal muscles, etc.)

Of course, there are a few caveats and qualifications to be made to this handy list.

• Although the deep tendon reflexes follow the above protocol, there are also superficial tendon reflexes (such as the abdominal or cremasteric) that obey the opposite pattern. It is rare to test for these reflexes, though.
• The pattern with cranial nerves is a little more complicated, since most of the muscles supplied by them receive bilateral innervation. For instance, the tongue is supplied by the XII cranial nerve from both the left and the right side, and so damage to only one side won’t produce any discernible weakness. The one large exception to this rule is the lower 2/3 of the facial nerve’s supply, which follows convention and is unilateral. Therefore it is not uncommon to see a stroke patient with a drooping face – but with a forehead that is mysteriously spared.

Lastly, the lopsided distribution of weakness found with upper motor neuron lesions produces a particular 'spastic posture'. Since the weakness is greatest in the upper limb extensors, the limb tends to become flexed. The reverse is true for the lower limb, which is consequently extended. (Frustratingly, I can't seem to find a nice picture of this important clinical sign...)

Why astronomers use red light to read by

You may recall that our retinas are packed with two types of photon-detectors: rods and cones. Under conditions of sufficient light, we almost only use our cones. Since these come in three flavours, each responding maximally to a different range of light frequencies, we get to see in colour during the day. Furthermore, since they are densely packed right where the images focus (at the fovea), and since they are cleverly wired up, the visual acuity that we get with our cones is really good. This type of vision - under well-lit conditions - is known as photopic vision.

When light levels drop, however, we have to switch to low light, scotopic vision, which uses our rods. There's only one 'flavour' of these cells, and so our vision at night is monochromatic. Also, because these cells are 1000 times more sensitive to light than the cone cells are, they permit us to see in the dark. However, they are distributed largely at the peripheries of the retina, and so the image they collect is rather distorted. Furthermore, many rods all club together to send a message to the brain (via the bipolar cells, if you remember your retinal anatomy) and although this increases the chance of a bipolar cell responding to dim light, it also means that localisation is less precise. Together, these two facts conspire to ensure that our visual acuity at night is rather poor.

Enter the astronomer. She comes with an unreasonable demand: she needs scoptopic vision to make out faint stars by night (her cones wouldn't detect anything at these low levels), but she also occasionally needs her high acuity photopic vision to consult her star charts, or to write notes. For this she needs to add enough light to her page for her cones to kick in.

This may sound like a nice plan, but unfortunately to get her rods to see optimally in the dark requires about 30 minutes. Consider walking off the street at noon into a dark theatre: you are functionally blind for a good few seconds, and your retina only gradually adapts to the dark thereafter. Clearly switching frequently between enough-light-to-read-by and dark-enough-to-see-stars is impractical unless one has many hours to kill. So what to do?

Fortunately, there is a partial solution. Shine most shades of light at levels bright enough to excite your cones and you will knock out your rods for several minutes (e.g. walking into the theatre from a bright street). However, your rods are fortunately rather insensitive to pure red light when they are dark-adapted. In fact, they are 50 to 100-fold less sensitive than the flavour of cones that happens to detect red light. What this means is that if you use red light that isn't too bright, you can excite your cones enough to read by, without blowing your rods. In other words, you can then switch quickly between scotopic and photopic vision without having to wait for your eyes to adjust to the change in light levels.

Why do you do a MRI of the mediastinum in patients with myasthenia gravis?

Myasthenia gravis is a neurological condition that manifests with muscle weakness and - importantly - fatigability. It particularly involves the muscles of the head and neck (although it can involve the limbs too), and its presenting symptoms are therefore usually diplopia, ptosis, dysarthria and nasal speech.

Mediastinal MRIs are indicated in all patients who are diagnosed with myasthenia gravis, and this is because 10% of myasthenia patients have thymomas (tumours of the thymus). These are mostly benign, but even in this state they can cause problems due to compression of adjacent structures:

• superior vena cava → superior vena cava syndrome
• oesophagus → dysphagia
• trachea → dyspnoea, cough

Some, however, are malignant.

Even in the absence of a thymoma, 85% of patients clinically improve after thymectomy (the reason for this isn't clear), and so many authorities recommend routinely removing it in all patients with generalised myasthenia gravis if you're anywhere between a teenager and 55 years old.

Why do the cysts in neurocystcercosis end up in the brain? Accident or design?

Life cycles can be complicated things.  One of my pathology lecturers used to reassure us that he wouldn't test us on the life cycle of some of the parasitic worms, because every time he tried to work them out, he ended up with carnivorous sheep!

I think some of the difficulty stems from not being able to distinguish the woods from the trees. Fundamentaly, Taenia solium, like certain other parasitic worms (helminths), needs an intermediate host before it can settle down in a definitive host.  

A definitive host is where the worm goes to retire in its old age.  Therefore, it is in the definitive host that it exists in its adult form.  It must also replicate (like all evolutionary organisms), and so it must be producing eggs.  It makes sense that T. solium therefore sits in the human intestine, shedding eggs for as long as it can. 

The intermediate host is a temporary vehicle that the helminth needs in order to prepare for its glorious days in the definitive host.  It therefore exists in this vehicle in something other than adult form.  It must also stand a reasonable chance of getting to the definitive host.  In this case, T. solium tries to burrow its way into the nice juicy meat of the intermediate host, hoping to be eaten by the definitive host.  If that occurs, the infectious cysts in the skeletal muscle of the poor dead intermediate host get awoken, and try to find their way into the intestine, ultimately to stay there as mature adults. Thus, the cycle is completed.  Got it?

In the case of T. solium, the definitive host is one of us humans, while the intermediate host is a pig.  That's what is supposed to happen, at least.  This all goes a bit haywire on occasion, if we happen to ingest one of the infectious eggs (made from an adult tapeworm sitting in our, or somebody else's, intestine).  Put another way, things go belly up if we accidentally act as the intermediate host, instead of as the definitive one.  

Under the belief that they have been successfully ingested by a pig (which is false, or at least only metaphorically true), the eggs go into cyst-making mode.  They thus wait expectantly to be eaten by the definitive host, a day that will never come.  They can wait for years on end, and are so successful at hiding from the immune system that they almost never evoke a response until they die of old age.

Oh, and why do they go to the brain (or eye) in  humans, and not the skeletal muscle like they are programmed to?  Simple: they are programmed to go to the skeletal muscle of a pig, and being in the wrong host messes up their plans.  Making cysts in the brain or eye is a mistake (not many of us are cannibals).  It is a mistake they make because they think they are in the correct intermediate host (i.e. a pig), rather than in a human.

In the brain they most commonly cause seizures and headaches.  Here's a MRI of a brain infected with neurocysticercosis.  The think to look for is the ring-shaped lesion towards the bottom, which is causing all the problems.

 

What are the commonest types of brain tumours?

On the whole, brain tumours occur in around 6 per 100 000 people. 

In adults, the commonest tumours are gliomas, metastases and meningiomas.  The commonest site is in the supratentorial compartment (i.e. above the tentorium cerebelli). 

In children, the commonest tumours are medulloblastomas and cerebellar astrocytomas, and the intratentorial compartment is the most probable site.

And what is a glioma?  The term has varying amounts of support, but is fundamentally an umbrella term for tumour of the glial cells.  The glial cells are the ‘support’ cells of the brain substance, and thus exclude neurones.  Specifically therefore, gliomas are meant to include astrocytomas (which are the most likely to be implicated), oligodendrogliomas, ependymomas and gliobastoma multiforme.  (The latter is now best thought of as a poorly differentiated astrocytic tumour, though.)

Whew!  Enough terminology?

Source:  Neurology and Neuroscience Illustrated (4^th edn.), Lindsay and Bone.

What does alcohol do to the cerebellum?

Alcoholism has the potential to cause quite a diverse range of neurological sequelae, but it is often unclear how much of this is due to (i) a direct toxic effect from alcohol versus (ii) a coexisting thiamine deficiency, which is common is alcoholism.

Nonetheless, one of the regions the alcoholism seems to target is the cerebellum, where it is probably the commonest cause of an acquired cerebellar ataxia. As you'd expect from its cause, males are predominantly affected, and the condition requires years of heavy drinking - it isn't an acute intoxication state.

Although all the cells in the cerebellum take a hit, the worst affected are the Purkinje cells in the vermis. Knowing this, and having read the previous post, you can pretty much work out what the symptoms are. And you'd be right! According to the (terse) textbook^* in front of me, "ataxia of gait with lower limb inco-ordination predominates. The upper limbs are spared. Nystagmus is rarely present. Cerebellar dysarthria is usually mild."

What's the prognosis? It's hard to say. Sometimes one makes a full recovery (if alcohol is stopped and nutrition improved), sometimes the conditions stabilises, and sometimes it is progressive. (Yes, I know that pretty much covers all the options, but still.)

^* "Neurology and Neurosurgery Illustrated", 4th edn., Lindsay and Bone

What's a good approach to cerebellar diseases?

I can obviously only answer this in a personal manner (what makes sense to me may not do so for you), but here goes:

Firstly, you need to know the signs of cerebellar dysfunction. The whole battery is almost never present (see below), so you have to actually seek out most of them.

Ataxia is poorly coordinated movement. Not all ataxia is caused by cerebellar disorders, of course. Gait ataxia refers to a jerky, unsure gait, where the steps vary in size and the feet are usually widely separated. (In subtle cases, only heel-to-toe walking may be impaired: the patient duly falls to one side on cue.) Truncal ataxia is manifested by the patient having difficulty keeping his/her trunk upright, whether sitting or standing. It is usually most marked when the feet are close together. Limb ataxia is shown by limbs that are clumsy, discoordinated, and that have difficulty with rapidly alternating movements (a phenomenon unhelpfully known as dysdiadochokinesis).

An intention tremor is one of the classic hallmarks of cerebellar disease. The person's tremor only occurs when he/she is wanting to touch a stationary object, and subsides once it has been reached.

Dysarthria has many causes, but if it caused by cerebellar disease, it is slow and monotonous with syllables abnormally separated. It sounds strikingly like limb ataxia looks.

Nystagmus - refers, as always, to an abnormal 'to and fro' movement of the eyes.

Tone - Tone should technically be slightly reduced on the affected side, but this is usually pretty difficult to detect. The patient's reflexes are said to be 'pendular' (i.e. they muscle swings like a pendulum).

Once you've looked for these things (there are even more in textbooks, but this should be sufficient), I've always found it helpful to sort the signs into one of two broad syndromes:

• Lateral Cerebellar Syndrome - Caused by lesions of one of the cerebral hemispheres, these patients with limb ataxia, and a tendency to fall to the affected side. Common causes include tumours, abscesses, strokes, trauma and multiple sclerosis.

• Central Cerebellar Syndrome, and Pan-cerebellar Syndrome- Vermal lesions affect equilibrium and result in gait ataxia with little or no limb ataxia. Flocculonodular lobe lesions present in the same way, but additional symptoms include nystagmus and vertigo. Alternatively, pretty much all the cerebellar signs may be present; we can call this 'pan-cerebellar syndrome'. Whether 'central' or 'pan-cerebellar', the common causes are drugs (phenytoin, alcohol, others), infections (including post-infectious syndromes), paraneoplastic syndromes, hypothyroidism, familial ataxias (e.g. Friedreic's ataxia) and developmental abnormalities of the brain.

I know it's still a lot, but at least we've been able to narrow the huge list of possible cerebellar insults down to five or six common ones, depending on our clinical findings. It works for me, most of the time, but perhaps you have other ideas?

What's the difference between "tardive dyskinesia" and "drug-induced parkinsonism", clinically?

Both the above conditions are potential side-effects of antipsychotic (and other) medications.

Drug-induced parkinsonism shares the clinical characteristics with parkinson's disease, except that it is caused by ... drugs! Therefore the four chief aspects are a resting tremor, bradykinesia, postural instability, and mild rigidity. I've covered these in more detail here. Unlike parkinson's disease, however, drug-induced parkinsonism is reversible if you stop taking the drug, although this may take months to accomplish.

Tardive dyskinesia, on the other hand, is a manifested by repetitative, pointless, involuntary movements. The commonest parts of the body to be affected are the tongue and mouth, producing symptoms such as grimacing, lip smacking, tongue protrusions. However, other parts of the body may be involved instead, or in addition, such as the hands or even the trunk.

Thus, the clinical features are actually remarkably different. I suppose the tremor of parkinsonism might be confused with a dyskinesia of the hands, but the bradykinesia of parkinsonism is usually quite striking in the rest of these patients. By contrast, tardive dyskinesia patients should give the impression of being 'fidgety', and will complain of not being able to keep still.

In tardive dyskinesia, removing the offending agent has a slower, less satisfactoy response, and may even persist forever. Sadly, the best strategy is prevention.

What causes Alzheimer's diasese?

According to the New England Journal of Medicine review article in front of me, Alzheimer's disease is a progressive neurodegenerative disorder manifested by cognitive and memory deterioration, progressive impairment of activities of daily living, and a variety of neuropsychiatric and behavioural disturbances. It sounds nasty, and it is. It is by far the largest single cause of dementia.

When you look at the brains of Alzheimer's patients under the microscope, the major abnormalities are extracellular senile plaques, intraneuronal neurofibrillary tangles and amyloid angiopathy.

'Senile' plaques are composed of a central core of amyloid material that is su
rrounded by dystrophic neurites (axons and dendrites). The spherical things you can see on the right are plaques as seen by a light microscope.

Neurofibrillary tangles are intracellular bundles of filaments that displace or encircle the nucleus of neurones. They are composed of paired helical filaments largely composed of a hyperphosphorylated form of the microtubule-associated protein tau.

Amyloid angiopathy refers to the deposition of amyloid material within the blood vessel walls. It predisposes to haemorrhagic strokes.

Although there is controversy about the exact pathogenesis, the leading hypothesis at present centres around the role of amyloid formation in the brain. The specific type of amyloid found in patients with Alzheimer's disease is formed from β-amyloid peptide. This peptide is derived from a much larger transmembrane protein found in neurones, called amyloid precursor protein (APP) which, despite its name, has important normal roles to play in neurone growth and repair.



It is not entirely clear what causes β-amyloid to accumulate in Alzheimer's disease, but it involves aberrant intracellular processing of APP. Whatever the cause, the resultant β-amyloid peptides aggregate and form the amyloid that is found in the brains of people with Alzheimer's disease.

β-amyloid is toxic to neurones by a variety of methods, including altering glucose metabolism and mitochrondrial function and altering calcium homeostasis. The resulting damage induces apoptosis of the neurones, and this cell death is believed to cause the symptoms of Alzheimer's disease.

Sources:
1. Robbins Pathologic Basis of Disease (6th Edn.) - Cotran, Kumar, Collins
2. Pathophysiology of Disease (4th End.) - McPhee, Lingappa, Ganong
3. Wikipedia Commons for the pictures

After losing one eye, what percentage of the visual field is lost?

This question obviously refers to the combined visual field, since it is self-evident that loss of one eye causes a total loss of that eye's visual field!

Together, the eyes have about a 180 degrees of vision, but there is overlap for most of this. Therefore, the loss of one eye doesn't actually cause the loss of anywhere near half of this field, as you might otherwise expect. Only about 40 degrees aren't covered by both eyes, meaning that the loss of one eye leaves you with a visual field of roughly 140 degrees.

In other words, you lose somewhere between a fifth and a quarter of your visual field if you lose an eye.  Obviously, there are other problems with this - the loss of binocular vision means that your 3D perception isn't as good for close objects, and your overall visual acuity is also decreased.

What is the difference between parkinsonism and Parkinson's disease?

Parkinsonism is a syndrome diagnosed on the presence of:

• A resting tremor - usually in one limb (esp. one hand), and it disappears with voluntary movement.
  
• Rigidity - a term that is too non-specific for my liking, but which here refers to a resistance to passive movement of the joints
• Bradykinesia - slowness and paucity of movement
• Postural instability - an unsteadiness on their feet, whether standing or walking

Not all these features need to be present; postural instability, for instance, generally only occurs late in the disease course (and is non-specific anyway).

There are numerous causes, such as certain medications, encephalitis and toxins.  However, the commonest cause is:

Parkinson's disease, which is a specific entity caused by a loss of dopamine-secreting neurones in the basal ganglia, specifically in a part of the brain called the substantia nigra, and which is deemed to be primary, or idiopathic.  In other words, no specific cause of the loss of dopaminergic neurones can be established in Parkinson's disease (although theories abound).  This latter stipulation is important, since many of the other causes of parkinsonism also cause a loss of dopamine-secreting neurones in the substantia nigra.

Can one neuron release more than one neurotransmitter?

Go here to find out!

One question for pondering: why does the brain use so many different neurotransmitters? If their purpose is simply to transmit information (in a sort of analogue way, as opposed to the more digital action potentials), why can't you just have one, or at best two (one excitatory, one inhibitory) type of neurotransmitter to do all the work? Hmm...

Wake up and smell the cheese!

In medical school, you are sometimes given the impression than our sense of smell is fairly useless; a rather lame and impotent hangover from our evolutionary past with little function today other than in helping to identify various food flavours.

But that's simply not the case - more and more research is showing that our sense of smell is very much an integral part of much of our lives. The reason that we tend not to notice the powerful deductions that are made from smell is that this data is kept at a subconscious level most of the time. Much of the newly discovered powers of olfaction relate to our social environment. People can distinguish HLA genotype, friends vs strangers, male vs female and even gay vs straight - just from a person's odour.

It truly is amazing, and for a nice summary of the above and more, go to this excellent article I came across online at the Scientific American website.

Having read the article, there are a few questions that popped into mind:

• What are the effects of using body deodorants on all this?
• Why is so much of this information kept subconscious by the brain?

Any thoughts?

What is referred pain?

The axons of each nociceptor neurone* (pain-sensing neurone) travel until they reach the dorsal horn of the spinal cord, where they synapse with a secondary neurone. In fact, each primary nociceptor neurone synapses with multiple secondary neurones, and each secondary neurone receives multiple inputs.


One odd thing about this system is that the nociceptor neurones innervating the visceral organs (like the heart, diaphragm or gallbladder) always terminate in a secondary neurone that they share with nociceptor neurones innervating a patch of skin. This is illustrated schematically in the following diagram:




The problem with this arrangement is that the secondary neurone, and thus the brain, will therefore have no way of telling whether it was activated by trouble in the skin or by trouble in the visceral organ. All it knows is that it has been activated, but it can't say from which of the two sources this signal came.

So what does the brain do? As it turns out, it resolves this dilemma by choosing to represent this pain as coming from the skin. Perhaps it takes this option because the skin is much more likely to actually be the source. (However, I'm pretty sure an electrician could do better than this odd system!)

Therefore, if a visceral organ is damaged or inflamed, we will feel this pain as if it comes from a particular part of our skin. Exactly where on the skin we feel it depends on which of the secondary neurones they share. For instance, the innervation of the diaphragm comes from the cervical spinal neurones in the C3-5 area. The part of the skin that these nerves also innervate is situated around the shoulder. Thus, if the diaphragm is inflamed, the patient will complain of pain around the shoulder! Similarly, pain in the heart (e.g. during an angina attack) is referred to the centre-left chest, left shoulder and/or left arm (and sometimes even the left jaw). And so on.

* 'Neurone' is the usual spelling of the word, but Americans and Candadians spell the word 'neuron' instead. Take your pick - I don't care!

What is the commonest neurological complication of HIV?

Peripheral neuropathy.

Specifically, the neuropathy tends to be painful, and is most commonly felt distally, usually in the legs. It is a polyneuropathy, inclining to be bilateral and symmetrical.

The pathology is well characterised, and includes distal degeneration of the long axons and prominent local macrophage activation. Just why these things occur is still a matter of debate, however. Options include immune dysregulation, a leaky blood-nerve barrier, neurotoxic byproducts of HIV replication, treatment toxicitities and even opportunistic infections.

Is there anything you can do to treat it? Yes, although the results vary.

The most obvious starting point would be analgesics, but not all of them have been shown to work better than placebos. The most well-established analgesics are the opioids, used both systemically or locally, but they have their own associated problems (like addiction). Other options are lamotrigine (an anticonvulsant), lidocaine cream (a local anaesthetic) and local capsaicin patches. A summary of a recent study with high-dose capsaicin patches can be found here.

Do you always have a preceding episode of diarrhoea in Guillain-Barré syndrome?

Edit: I've reworked this post a little. It was done late at night, and was, like me at the time, confused! ;)

Guillain-Barré syndrome consists of four subtypes of acute peripheral neuropathies. It most commonly presents as a peripheral motor and sensory neuropathy, but can spread to involve more critical muscles, like those for respiration.

Guillain-Barré is believed to be predominantly an auto-immune disorder. Both antibody and cell-mediated reactions to peripheral nerve myelin are involved. As the condition progresses, segmental demyelination results. Eventually, if the process is ongoing and severe, there is axonal damage and nerve cell death; at this point, regeneration cannot occur.

Why does the body start attacking peripheral nerve myelin? It is believed to be a case of mistaken identity - certain antigens that the body is exposed to are sufficiently similar to antigens on the peripheral myelin to incite an attack by the immune system in susceptible patients. But what is this cross-reactive antigen?

It is clear that, at least in many cases, the responsible agent is infectious. In particular, Campalobacter jejuni, Mycoplasma and viral infections (e.g. varicella-zoster, mumps, cytomegalovirus) have been implicated, although the long list includes immunisations, antitoxins, surgery, trauma and malignancy.

So, no, you don't always have a preceding episode of diarrhoea. If you are already suspicious that you are dealing with Guillian-Barré and this does come up in the history, it does contribute somewhat to the likelihood that you are right in your suspicions.

Just when you thought you knew neuroscience basics...

Alas, just when I thought I knew my neuroscience basics, along comes someone who actually works in the field, and so has his finger on the pulse. If you'd like to surprise and annoy your lecturers or colleagues, go and have a look at this list of 6 iconoclastic discoveries about the brain. Keeps you ahead of the pack, if nothing else ;)

What is the point of our pupils constricting when bright light is shone on them?

As you probably know, the pupil is just a space - a narrow window though which light must pass before it hits the retina. The size of the pupil is regulated by the iris (the bit that people refer to if they say you have 'blue' eyes). Depending on which of its muscles contract, the iris can dilate or constrict, allowing more or less light in respectively.
Why why have a pupil at all? Surely it would always be helpful to let as much light in as possible? After all, we know if we don't have enough light, we can't see - this is what happens in the dark.

No, not really. The trick is to consider the sensitivity of the light-reactive retinal cells (the well-named photoreceptors). For any receptor there is an intensity of the stimulus that it will respond best to, and the photoreceptors are no exception. If less light than this is shone, the image will be too dark. And if the light shone is less than the lower limit of its sensitivity, it won't register it at all - for all intents and purposes it would be as if there were no light.

What if we move to the other extreme and shine light of such an intensity that it exceeds the optimal level for our photoreceptors? Again, we lose image clarity - too many photoreceptors are excited, and the image starts to resemble a 'whiteout'. You can get a glimpse of this when looking at a photo that has been 'overexposed'. Here the effect is similar.

In summary: we need a fairly constant level of light intensity to best form useful images with our eyes. And this is the main function of the pupillary light reflex that the question refers to. Too little light (for our photoreceptors), and the pupil dilates, letting more light in. Too much light and the pupil constricts, diminishing the quantity of photons hitting the retina.

(Postscript: there at least one more vital function, and it has to do with image sharpness. Can anyone guess?)

How do nerves (and muscles) establish a resting membrane potential?

In our quest to understand how neurones work, we've so far covered the functional anatomy of these cells. We've hinted at input and output areas, and whispered about transistors. Now it's time to be more forthright: neurones communicate by 'firing', and this 'firing' is in the form of a sudden change in the electrical potentials across their membranes.

If this makes no sense, worry not; we'll take it slowly. In this post, we'll just discuss the amazing phenomenon of how a cell comes to have an electrical potential difference across its membrane in the first place - the resting membrane potential.

Firstly, what is meant by "electrical potential across the membrane"? This is actually not difficult at all. All it refers to is that the inside of the cell has a different charge relative to the outside of the cell. In the case of many neurones, the inside of the cell might by 90mV less than the outside of the cell. Therefore there is an electrical difference between the two. Normally any electrical difference causes a current to flow, from the more positive side to the more negative side (by convention). But in our cells the electrical difference is usually only a potential difference, since there is a barrier to the charge flowing: the cell membrane. Putting it back together again, 'electrical potential across the membrane" actually can make sense now!

This might seem a strange fact to you. After all, electricity seems to be a distinctly 'unnatural' phenomenon, but here it is, the rock on which our brains and muscles are foundered. Neurones have a resting membrane potential (the electrical potential when the cell is not firing). When the cell does decide to fire, the electrical potentials change extremely rapidly, causing a chain of events that culminates in the neurone having some effect. Often this is simply signalling some information to other neurones, but it need not be. It may be to contract a muscle, for instance. In the next post, we'll discuss this 'firing'. For now, we'll just concentrate on how the resting membrane potential is created, for without a resting membrane potential, no firing would be possible.

The key to creating a resting membrane potential (RMP) is having a semi-permeable membrane. In other words, have a membrane that acts as a barrier to some substances, but not to others. Once you have this in place, interesting things start happening.

Take potassium (K+) for example, and say that the membrane is permeable to potassium, but not to other substances. Now, potassium is normally 25-40 times more abundant inside the cell than outside. Therefore, if the membrane is permeable to the ion, it will tend to diffuse outwards: But not forever. Since it is positively charged, and since no negatively charged ions can move out with it, there will very soon be a large positive charge on the outside of the neurone. After a short while, this positive charge is large enough to prevent further potassium from diffusing outwards (since 'like' charges repel each other). You could say that the chemical gradient is opposed by an electrical gradient. The end result? The outside of the cell has become more positive and the inside more negative (since the moved potassium is positively charged). In other words, there is an electrical potential on either side of the cell membrane. There is an equation, the Nernst equation, which can actually tell us how big the potential difference will be: -94mV. (The minus sign, by convention, means that the inside of the cell is more negative than the outside of the cell).

And this is basically how the cell establishes a RMP. Postassium is the main determinant of the RMP but the other ion to consider is sodium (Na+) . Its concentration is much higher outside the cell than in, so it tends to diffuse inwards. Like potassium, it is also positvely charged, but since its concentration gradient is in the opposite direction, it tends to make the inside of the cell more positive than before (counteracting potassium to some degree). However, it does not have nearly as strong an effect as potassium, only dragging the membrane potential from the -94 mV that potassium 'wants' to -86 mV.

The cell is permeable to potassium and sodium by means of potassium-sodium "leak" channels, through which the ions can, well, leak down their concentration gradiants. The leak channels are normally about a hundred times more permeable to potassium than to sodium, accounting for potassium's dominant status in determining the RMP. A small additional contribution to the RMP is made by the sodium-potassium pump, which is present on all cell membranes. It actively pumps 3 Na+ from the inside of the cell to the outside, and takes 2 K+ ions from the outside to the inside. Since it is taking more positively charged ions outside than it is bringing inside, it tends to make the RMP more negative (by an additional 4 mV; total: -90mV). Below is a diagram of the pump and the abovementioned 'leak' channel. (The 'ATP' refers to the body's currency of energy, and is to remind you that the pump obviously requires energy to work, since it is working against a concentration gradient.)To summarise nerves (and muscle cells) have a resting membrane potential. Rapid changes of this RMP occur for the nerve to fire (or the muscle to contract). And that'll be the topic of this section's next post.