Chapters 1 & 2

 The Cells of the Nervous System

There are only two kinds of cells that make up the nervous system. Neurons are the ones we hear the most about, as they’re the ones that actually receive and transmit information. Glia perform many functions to support the nervous system’s work.

Neurons

There are a lot of neurons in our brains -- the average adult has 86 billion, plus another billion in the spinal cord. However, it varies from person to person. In addition to the organelles most cells have, like a nucleus, mitochondria, and ribosomes, neurons have unique structures. The main parts of a neuron are the:

• Soma: the main cell body, containing typical cell organelles
• Dendrites: branching fibers lined with synaptic receptors to receive information from other neurons
• Axon: a thin fiber which conveys an impulse. The impulse can be headed to other neurons, an organ, or a muscle. Axons can be very long -- we have axons that stretch from our spinal cords to our feet.
• The end of an axon has one or more presynaptic terminals, which they use to release chemicals to another cell.

    Neurons can differ from each other in the organization, number (except for the soma and axon), and relative size of these different parts. Some neurons even lack axons, and some lack defined dendrites. 

    Something I didn’t know until this week is that developing axons travel. I always thought they stayed in place and some were used more than others, like roads. But the growth cone at the end of a developing axon travels, using the filopodia and lamellipodia “fingers” off the growth cone. Filopodia move out in response to. They can adhere to cells and axons, and chemicals from guidepost cells encourage them to move toward that cell or away from it. The guidepost cells made me think of someone saying “You’re getting hotter” or “You’re getting colder” when giving someone hints about a hidden object.

Glia

Also known as neuroglia, there are about as many glia as neurons in the brain. In the cerebral cortex, glia outnumber neurons. Some types of glia:

• Oligodendrocytes: produce myelin sheaths to insulate axons in the central nervous system
• Schwann cells: produce myelin sheaths to insulate axons in the peripheral nervous system
• Astrocytes: pass chemicals between a neuron and blood or between neurons. They also synchronize the signaling of related axons
• Microglia: Remove toxic materials, repairing brain damage, and also "prune" weak synapses, leading to learning
• Radial glia: guide the migration of neurons during an embryo’s development

Blood-Brain Barrier

The blood doesn’t have easy access to the brain. This is to protect the brain from viruses, bacteria, and harmful chemicals, as neurons are rarely replaceable.

Viruses that do cross the blood-brain barrier, like in rabies and syphilis, often are fatal. Microglia can fight viruses without killing the neurons the viruses have overtaken, but they sometimes can only contain the virus rather than eliminating it. This is why chicken pox/shingles and genital herpes can produce periodic issues after being long dormant if they manage to infect the nervous system. Alzheimer’s occurs when the cells of the barrier shrink, enabling harmful chemicals to enter the brain. 

The walls of capillaries are made of endothelial cells. In the brain, these cells are joined together much tighter than anywhere else in the body, forming a more of a barrier than a permeable wall. 

 Some substances can still pass through easily, like oxygen and carbon dioxide (because they’re small and not charged), and some fat-soluble molecules like vitamin A and D, and drugs from antidepressants to heroin. Water uses a special protein channel. Glucose, amino acids, and other minerals have to rely on active transport systems, which use energy. It’s not known how hormones like insulin cross.

One downside of the barrier is that conditions like brain cancers are hard to treat, because most chemotherapy drugs cannot pass it.

Unlike most cells, vertebrate neurons rely almost totally on glucose, rather than using other carbohydrates and fat as well. It’s the only nutrient that can cross the blood-brain barrier in large quantities. The brain uses 25% of the body’s glucose, and 20% of the body’s oxygen to metabolize it.

The Nerve Impulse

Electric impulses lose strength over distance, particularly if the material used to conduct the impulse is not as conductive as, say, a copper wire. This could pose a problem for conducting impulses from places far from the brain, like the feet. Axons regenerate impulses at each neuron to keep the strength of the impulse consistent. 

Impulses from farther parts of the body do take a bit longer. But the brain can account for this, and does so with amazing accuracy, particularly with input from different spots on the retina in our eyes.

Resting Potential

The resting potential of a neuron is the difference in electrical charge between the inside and outside of the cell. Neurons maintain an electrical potential slightly negative compared to outside, due to negatively charged proteins in the cell. The level can be measured with microelectrodes, and tends to be around -70 millivolts (mV).

Like the blood-brain barrier, the membrane of a neuron itself is selectively permeable. Sodium and potassium can pass into and out of the neurons, but only through protein channel “gates,” which are closed by default.

Neurons have a sodium-potassium pump, which transports three sodium ions (Na+) into the cell for every two potassium ions (K+) that enter. K+ can leak out of the cell (due to concentration gradient), but Na+ cannot enter. The pump and leakage create an electrical gradient across the membrane, for a negative resting potential. Other negatively charged proteins also maintain the resting potential.

Action Potential

The resting potential is important because it allows neurons to respond rapidly to impulses. Slight impulses don’t have as much of an effect, but if a depolarization reaches a threshold of excitation, the sodium channels open and sodium ions flow into the cell, driven by an imbalance of concentration and charge. This spikes the level of depolarization. This is called an action potential. 

Action potentials are all fairly equal in amplitude and velocity for a given neuron. As long as the threshold is reached, the same result is produced. Thus, signals occur as a binary: action potential or no action potential. They do vary from neuron to neuron, though, based on the axon. Thicker axons can convey action potentials faster and can convey more of them per second. 

To convey a strong signal, a “bigger” action potential can’t be sent. But number, rapidity, and pattern can change. The same taste axon sends different rhythms for bitter and sweet.

Once an action potential reaches its peak, the sodium channels close again. The positive charge and the concentration imbalance lead potassium ions to flow out of the cell through open potassium channels. This returns net charge in the neuron to negative, and actually leads to a slight hyperpolarization. After returning to negative charge, the neuron maintains resting potential by using its sodium-potassium pump, and moving sodium out in exchange for potassium again.

This process actually doesn’t occur all at once on an axon, in a "domino effect" where an action potential at each point on the axon depolarizes the next part of the axon, triggering an action potential there. The first depolarization at the top of an axon also “back-propagates” into the cell and dendrites. This back-propagation makes the dendrite more susceptible to structural changes, and these changes are how learning happens.

Myelin sheaths increase the speed of an action potential’s travel down an axon. Action potentials are generated at each node of Ranvier, but not at the parts in between because they are sheathed by myelin and don’t have sodium channels. This causes the action potential to “jump” down the axon. This is faster and leads to fewer channels needing to be opened as well, conserving energy.

    After the sodium channels are shut again, neurons experience a brief refractory period, when the channels can't open again, or require a much stronger stimulus than usual in order to open.

Local Neurons

Local neurons are small neurons with no axon. They can exchange information with its immediate neighbors, though.

Unlike neurons with an axon, local neurons have a graded potential, meaning its potential varies in relation to the intensity of the stimulus.

Less is known about local neurons, because they are small and hard to stick an electrode in. Scientists used to think they were immature or backup neurons, but this was an assumption not based in any factual knowledge about the role local neurons play. At the moment, local neurons are more of a mystery to us.

The Concept of the Synapse

Charles Scott Sherrington studied reflexes in dogs, which led him to proposing a theory of a synapse between nerve cells. He noticed that:

1. Reflexes are slower than conduction on an axon. He decided this must be because the process for impulses to travel between a neuron must be different than traveling within one. He called the gap a synapse.
2. Several weak stimuli at either nearby places (spatial summation) or over a short space of time (temporal summation) produce a stronger reflex than one weak stimulus. Multiple small excitations, either in succession from the same presynaptic neuron or from different presynaptic neurons, can combine to reach the threshold in the postsynaptic neuron.
3. When one set of muscles flexes, another set relaxes. When the flexor muscles of one leg contract, its extensor muscles relax. At the same time, the extensor muscles of other legs contract so the dog can maintain balance. This is coordinated by an interneuron in the spinal cord, which excites some motor neurons and inhibits others.

Inhibitory postsynaptic potentials are actually the result of a hyperpolarization of a neuron. This makes the threshold further from the neuron’s current potential, which means it is harder to reach the threshold. It can occur either when potassium gates open (K+ leaves the cell) or chloride gates open (Cl- enters the cell). Sherrington’s proposal of inhibition was controversial at the time, but it’s turned out to be an important concept, eventually proven, for neuroscience and psychology.

Other interesting facts:

1. Local anesthetics like Novocain attach to sodium channels and prevent sodium ions from opening. Thus, receptors detect pain but can’t pass along the message.
2. Back-propagation makes dendrites more susceptible to structural change, which leads to learning.
3. Multiple sclerosis occurs when the immune system attacks myelin sheaths. Because axons that are supposed to have myelin sheaths only have sodium channels at nodes of Ranvier, axons have difficulty propagating action potentials. This leads to a lot of impairments.
4. Sodium-powered action potentials can either operate through AND and OR functions. But a new discovery (2021) or calcium-powered action potentials in the cerebral cortex can also use XOR. So far, rats don’t seem to have the same calcium-powered signals.