Science
Neural Pathways and Action Potentials
Neural pathways
The simplest type of neural pathway is a monosynaptic (single connection) reflex pathway, like in the knee-jerk reflex. When the doctor taps a certain spot on your knee with a rubber hammer, receptors send a signal into the spinal cord through a sensory neuron. The sensory neuron passes the message to a motor neuron that controls your leg muscles. Nerve impulses travel down the motor neuron and stimulate the appropriate leg muscle to contract. Nerve impulses also travel to the opposing leg muscle to inhibit contraction so that it relaxes (this pathway involves interneurons). The response is a quick muscular jerk that does not involve your brain. Humans have lots of hardwired reflexes like this, but as tasks become more complex, the pathway “circuitry” gets more complicated and the brain gets involved.
nerve cross section
Action potentials
We have talked about nerve signals and mentioned that they are electrochemical in nature, but what does that mean?
To understand how neurons transmit signals, we must first look at the structure of the cell membrane. The cell membrane is made of fats or lipids called phospholipids. Each phospholipid has an electrically charged head that sticks near water and two polar tails that avoid water. The phospholipids arrange themselves in a two-layer lipid sandwich with the polar heads sticking into water and the polar tails sticking near each other. In this configuration, they form a barrier that separates the inside of the cell from the outside and that does not permit water-soluble or charged particles (like ions) from moving through it.
So how do charged particles get into cells? We’ll find out on the next page.
Concentration gradients and active transport
When you cut an onion at one end of a room, you will eventually smell it at the other end. This is because the onion juice molecules move through the air. Although their motion is random, they generally tend to move from an area of high concentration (the onion) to an area of low concentration (the other end of the room). You also see this behavior when you add a drop of food dye to water — eventually, the dye spreads out through the water. This phenomenon is called diffusion. The driving force for diffusion is a difference in concentration, or concentration gradient. Now, for ions and molecules to move across a membrane, two conditions must be met:
* There must be a concentration gradient across the membrane.
* The membrane must be permeable to that particular molecule or ion.
The ion or molecule will move “down” its concentration gradient (from high concentration to low concentration). It is possible to get an ion or molecule to move against its concentration gradient (”uphill”), but this requires energy and is called active transport. The energy for this active transport can come from ATP (the cell’s energy currency) or by coupling the “uphill” transport of this ion or molecule to the “downhill” transport of another ion or molecule on the same carrier (counter-transport or exchange).
Ion Channels
Because ions are charged and water-soluble, they must move through small tunnels or channels (specialized proteins) that span the cell membrane’s lipid bilayer. Each channel is specific for only one type of ion. There are specific channels for sodium ions, potassium ions, calcium ions and chloride ions. These channels make the cell membrane selectively permeable to various ions and other substances (like glucose). The selective permeability of the cell membrane allows the inside to have a different composition than the outside.
For the purposes of nerve signals, we are interested in the following characteristics:
* The outside fluid is rich in sodium, a concentration about 10 times higher than the inside fluid
* The inside fluid is rich in potassium, a concentration about 20 times higher inside the cell than outside.
* There are large negatively charged proteins inside the cell that are too big to move across the membrane. They give the inside of the cell a negative electrical charge compared to the outside. The charge is about 70 to 80 millivolts (mV) — 1 mV is 1/1000th of a volt. For comparison, the charge in your house is about 120 V, about 1.2 million times more.
* The cell membrane is slightly “leaky” to sodium and potassium ions, so a sodium-potassium pump is located in the membrane. This pump uses energy (ATP) to pump sodium ions from the inside to the outside and potassium ions from the outside to the inside.
* Because sodium and potassium ions are positively charged, they carry tiny electrical currents when they move across the membrane. If sufficient numbers move across the membrane, you can measure the electrical currents.
Nerve Growth and Regeneration
When nerves grow, they secrete a substance called nerve growth factor (NGF). NGF attracts other nerves nearby to grow and establish connections. When peripheral nerves become severed, surgeons can place the severed ends near each other and hold them in place. The injured nerve ends will stimulate the growth of axons within the nerves and establish appropriate connections. Scientists don’t entirely understand this process.
For unknown reasons, nerve regeneration appears most often in the peripheral and autonomic nervous systems but seems limited within the central nervous system. However, some regeneration must be able to occur in the central nervous system because some spinal cord and head trauma injuries show some degree of recovery.
Nerve Signals
The nerve signal, or action potential, is a coordinated movement of sodium and potassium ions across the nerve cell membrane. Here’s how it works:
1. As we discussed, the inside of the cell is slightly negatively charged (resting membrane potential of -70 to -80 mV).
2. A disturbance (mechanical, electrical, or sometimes chemical) causes a few sodium channels in a small portion of the membrane to open.
3. Sodium ions enter the cell through the open sodium channels. The positive charge that they carry makes the inside of the cell slightly less negative (depolarizes the cell).
4. When the depolarization reaches a certain threshold value, many more sodium channels in that area open. More sodium flows in and triggers an action potential. The inflow of sodium ions reverses the membrane potential in that area (making it positive inside and negative outside — the electrical potential goes to about +40 mV inside)
5. When the electrical potential reaches +40 mV inside (about 1 millisecond later), the sodium channels shut down and let no more sodium ions inside (sodium inactivation).
6. The developing positive membrane potential causes potassium channels to open.
7. Potassium ions leave the cell through the open potassium channels. The outward movement of positive potassium ions makes the inside of the membrane more negative and returns the membrane toward the resting membrane potential (repolarizes the cell).
8. When the membrane potential returns to the resting value, the potassium channels shut down and potassium ions can no longer leave the cell.
9. The membrane potential slightly overshoots the resting potential, which is corrected by the sodium-potassium pump, which restores the normal ion balance across the membrane and returns the membrane potential to its resting level.
10. Now, this sequence of events occurs in a local area of the membrane. But these changes get passed on to the next area of membrane, then to the next area, and so on down the entire length of the axon. Thus, the action potential (nerve impulse or nerve signal) gets transmitted (propagated) down the nerve cell.
action potential graphs
There are a few things to note about the propagation of the action potential.
When an area has been depolarized and repolarized and the action potential has moved on to the next area, there is a short period of time before that first area can be depolarized again (refractory period). This refractory period prevents the action potential from moving backward and keeps everything moving in one direction.
# The action potential is an “all-or-none” response. Once the membrane reaches a threshold, it will depolarize to +40 mV. In other words, once the ionic events are set in motion, they will continue until the end.
# These ionic events occur in many excitable cells besides neurons (like muscle cells).
# Action potentials are propagated rapidly. Typical neurons conduct at 10 to 100 meters per second. Conduction speed varies with the diameter of the axon (larger = faster) and the presence of myelin (myelinated = faster). The rapid nerve conductions throughout the neural circuitry enable you to respond to stimuli in fractions of a second.
# The channels can be poisoned and prevented from opening. Various toxins (puffer fish toxin, snake venom, scorpion venom) can prevent specific channels from opening and distort the action potential or prevent it from happening altogether. Similarly, many local anesthetics (e.g. lidocaine, novocaine, benzocaine) can prevent action potentials from being propagated in the nerve cells in an area and temporarily prevent you from feeling pain.
# The propagation of the action potential is also sensitive to temperature in experimental settings. Colder temperatures slow down the action potential, but this usually doesn’t happen in an individual. However, you can use cold-block techniques to temporarily anesthetize an area (like putting ice on an injured finger).
So, if the size of the action potential does not vary, how does an action potential code information? Information is encoded by the frequency of action potentials, much like FM radio. A small stimulus will initiate a low frequency train of a few action potentials. As the intensity of the stimulus increases, so does the frequency of action potentials.
Synaptic TransmissionLike wires in your home’s electrical system, nerve cells make connections with one another in circuits called neural pathways. Unlike wires in your home, nerve cells do not touch, but come close together at synapses. At the synapse, the two nerve cells are separated by a tiny gap, or synaptic cleft. The sending neuron is called the presynaptic cell, while the receiving one is called the postsynaptic cell. Nerve cells send chemical messages with neurotransmitters in a one-way direction across the synapse from presynaptic cell to postsynaptic cell. serotonin reuptake
Let’s look at this process in a neuron that uses the neurotransmitter serotonin:
1. The presynaptic cell (sending cell) makes serotonin (5-hydroxytryptamine, 5HT) from the amino acid tryptophan and packages it in vesicles in its end terminals.
2. An action potential passes down the presynaptic cell into its end terminals.
3. The action potential stimulates the vesicles containing serotonin to fuse with the cell membrane and dump serotonin into the synaptic cleft.
4. Serotonin passes across the synaptic cleft, binds with special proteins called receptors on the membrane of the postsynaptic cell (receiving cell) and sets up a depolarization in the postsynaptic cell. If the depolarizations reach a threshold level, a new action potential will be propagated in that cell. Some neurotransmitters cause the postsynaptic cell to hyperpolarize (the membrane potential becomes more negative, which would inhibit the formation of action potentials in the postsynaptic cell). Serotonin fits with its receptor like a lock and key.
5. The remaining serotonin molecules in the cleft and those released by the receptors after use get destroyed by enzymes in the cleft (monoamine oxidase (MAO), catechol-o-methyl transferase (COMT)). Some get taken up by specific transporters on the presynaptic cell (reuptake). In the presynaptic cell, MAO and COMT destroy the absorbed serotonin molecules. This enables the nerve signal to be turned “off” and readies the synapse to receive another action potential.
6. There are several types of neurotransmitters besides serotonin, including acetylcholine, norepinephrine, dopamine and gamma-amino butyric acid (GABA). Any given neuron produces only one type of neurotransmitter. Any one nerve cell may have synapses on it from excitatory presynaptic neurons and from inhibitory presynaptic neurons. In this way, the nervous system can turn various cells (and subsequent neural pathways) “on” and “off.” Finally, nerve cells synapse on effector cells (muscles, glands, etc.) to evoke or inhibit responses.
XXanya Sofra Weiss
