Biology is far more complex than quantum physics, the universe, and stars. And in biology, the brain is much the most complex system with the possible exception of single cells and the immune system, as close seconds. 

But for all its 80-100 billion nerve cells and the trillions of connections between those nerve cells, the brain’s code is based on sending and receiving of electrical signals called action potentials — brief several millisecond reversals of the normal transmembrane potential across the membranes of nerve cells and their branches — which are transmitted with speeds, which range from 70 metres per second (250 kilometres an hour) in the largest diameter nerve fibres to as slow as one metre per second (3.6 km/hour) in the smallest diameter nerve fibres.  

All but the latter small-sized nerve fibres in the central and peripheral nervous systems are surrounded by a fatty sheath called myelin, which allows the action potential to skip along the nerve fibre with much greater efficiency and speed than is possible for smaller un-myelinated nerve fibres where conduction of the nerve impulse is continuous, with no skipping. 

At points where nerve fibres contact their target cells lies a thin gap (the synaptic cleft) where the action potential reaching the terminal of the nerve fibre, triggers the release of a chemical (acetylcholine, serotonin, glutamate, dopamine or others) which crosses the gap and generates a sub-threshold potential or even an action potential in the target cell. 

Understanding these processes, the generation of action potentials and how they conduct from one point to another in nerve fibres and trigger a response, excitatory or in some instances inhibitory in the target cell, was highlighted by the award of a Nobel Prize shared by Alan Hodgkin, Andrew Huxley, John Eccles and Bernard Katz.

With such an elegant system for sending and receiving signals — a system which, with some variations, has been conserved through hundreds of millions of years of evolution, usually a sure sign that the system works really well — what could go wrong? 

As it turns out, a lot can go wrong. 

Information is coded in the nervous system not only by what cells are connected to other cells but by the frequency with which action potentials occur.

Unfortunately, diseases such as multiple sclerosis in the brain and acute and chronic demyelinating disorders affecting the peripheral nervous system, often attack the myelin sheath with the result that action potentials are blocked, or their firing rates significantly curtailed. 

The result in the case of motor nerve fibres is weakness, or, for sensory fibres, loss of sensation, whether touch, thermal or pain or, in some instances, spontaneous bursts of action potentials in the most affected regions of the cells or their nerve fibres, which can evoke tingling, burning or electric shock-like pain.

Fortunately, for the three disorders mentioned, conduction may be restored, at least partially, paving the way for more normal function.

Worse than the consequences of partial or complete loss of the myelin sheath is when the cell-body or its peripheral processes begin to die, whether related to age or more often some inflammatory, autoimmune, toxic, nutritional deficiency or other mechanisms — the list is long. 

On the motor side, the loss of motoneurons in the brainstem or spinal cord may go unrecognized because of functional compensation. Motoneurons are connected to a family of muscle fibres which constitute what Sir Charles Sherrington (another Nobel laureate) called the motor unit. 

Loss of up to a third of motoneurons may be masked by surviving motoneurons which establish connections with the orphaned muscle fibers following the death of their parent motor nerve cells.

This means that there may be little or no weakness or atrophy of affected muscles for many months in diseases, such as amyotrophic lateral sclerosis, or ALS, because of surviving nerve cells that pick up the slack.

That’s the good news. The bad news is that should those surviving motoneurons become affected together with their greatly expanded innervation field of muscle fibres, the loss of function will be much greater because they’re carrying more than their natural load of muscle fibres. 

Similar forms of functional compensations probably take place in the brain, when in the case of Parkinson’s disease, up to half or more of the dopaminergic neurons in the substantial nigra – an early target in Parkinson’s –  may be lost before symptoms and/or signs of Parkinson’s become apparent clinically.

Ditto for some of the dementias, such as Alzheimer’s disease, where the disease, and associated deposition of beta-amyloid and tau proteins, has usually been going on for several decades before the disease is recognized clinically.

These illustrations of the impact of losses of the myelin sheath and nerve cells make the point that interfering with signalling in the peripheral and central nervous systems has serious functional consequences, the effects of which may be masked by the capacity of surviving nerve fibres and nerve cells to carry the load — up to a point. 

Beginning March 19, there will be a new series on signalling in the nervous system and what happens when those signals fail in diseases. Contact Debbie Krause at the Niagara-on-the-Lake Library if interested.

Dr. William Brown is a professor of neurology at McMaster University and co-founder of the InfoHealth series at the Niagara-on-the-Lake Public Library.