Our Electric Mind: The Neuron Doctrine

TRANSCRIPT FROM A LECTURE SERIES BY Professor Jeanette Norden, Vanderbilt University

How do neurons communicate with each other? If there is a gap between them, how is communication possible? Understanding this phenomena took a giant step forward with the discovery that axons actually generate electricity.

Image of neurons for the neuron doctrine article

The Neuron Doctrine established that neurons are the individual cellular units of the nervous system, surrounded by a cellular membrane and separate from other structures like the cells in any other organ in the body. Unlike most cells in the body, however, neurons are specifically designed to receive and to transmit information.

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Santiago Ramon y Cajal, the Spanish neuroscientist

This Neuron Doctrine was championed by the most famous neuroanatomist who has ever lived, Santiago Ramon y Cajal. The winner of the 1906 Nobel Prize, Cajal determined that in young animals you could actually follow axons with that specific method to their termination. From these studies he established that neurons were structural and functional units.

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Charles Scott Sherrington, the English neurophysiologist

That neurons are the individual units of the nervous system and separate from other cells was also suggested by Sir Charles Sherrington—who also won a Nobel Prize. Sherrington, on the basis of theoretic considerations alone, believed that neurons had to have a space in between them, a gap in between the various neurons in the nervous system. When he looked at conduction as a physiologist—looked at conduction in nerve trunks—it was much faster than if he looked in gray matter in the brain. On the basis of that alone, he believed that neurons were individual structural units that had to have a space or a gap in between them. This was all the more important since synapses were not actually seen with an electron microscope until the early 1950s.

We believe that synapses are the places in the brain where one neuron interacts with another neuron. A synapse is where the communication takes place between one neuron and the next neuron in the chain. The axon terminal is where the first neuron makes contact with the second. At the terminal, there are synaptic vesicles, which release a chemical that will interact with the postsynaptic membrane—the dendrites or the cell body of that second neuron.

Bridging the Gap between Neurons

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Fig 1. Diagram of a neuron (click to enlarge)

How do neurons communicate with each other? If there is a gap between them, what is responsible for the communication? A great advance forward in understanding this came about with the discovery that axons actually generate electricity.

An electrical signal gets propagated and it begins at the axon hillock. One of the most important things to remember is that the axon is not just an extension of the cell body, it’s a specialized structure and it’s attached to the cell body at the axon hillock. An electrical signal is generated at the axon hillock and it’s propagated down the axon, in an “all-or-none” fashion. That means that the signal does not degrade. The signal will travel down the axon in a particular way. It jumps from node to node, in between the myelin wrappings.

If all action potentials of a given neuron are the same amplitude and they don’t degrade, then how is it that intensity would be encoded in the nervous system or encoded in a neuron like this? And what is responsible for the quality of the stimulation? We need to learn something about what the code is.

The Intensity and Quality of a Stimulus

The intensity of a stimulus is encoded in neurons by changing the frequency of the firing. A more intense stimulus causes neurons to increase their firing rate. The quality of the stimulus, on the other hand, is a little bit different. The quality of a stimulus is the result of the stimulation of different kinds of neurons, transmission along specific pathways, and also “interpretation” by different areas of the brain, especially the cerebral cortex.

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The quality of the stimulus in vision—what we experience ultimately as vision—comes about because an electrical signal is started by cells in the eye that absorb light.

Let’s think about this in terms of vision. The quality of the stimulus in vision—what we experience ultimately as vision—comes about because an electrical signal is started by cells in the eye that absorb light. These cells have to be specialized to absorb light. Then an electrical signal is transmitted to the brain along visual pathways. That’s what it means to say that the brain is made up of these various types of systems. Ultimately, the interpretation—or what mental construct we interpret as seeing—is the result of these pathways eventually reaching the cortex and being interpreted by very specific visual areas of the brain. The neurons themselves are going to communicate always with these potentials that are generated in axons.

What is actually happening when this action potential or this electrical signal is being generated in an axon? To appreciate this and how neurons communicate, we have to understand something about the internal and the external environment of neurons and how the change in the distribution of particular atoms is going to be the signaling mechanism for transmitting information.

Neurons are structural and functional units of the nervous system. They are cells like any other cell of the body.

Neurons are structural and functional units of the nervous system. They are cells like any other cell of the body. They have a membrane surrounding them that makes them a separate unit. This is inside the cell. And neurons, like almost all cells in the body, have organelles inside of them. They have special structures that are involved in making proteins, for example, packaging proteins. They also have within them atoms that are ions, which are basically charged atoms, and that just means atoms that have either gained or lost an electron.

Charging the Neuron

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Fig 2. In the resting state, the inside of a neuronal cell is more negatively charged than the outside. (click to enlarge)

Inside of the cell body, there are organelles and ions and other molecules. Outside of the neuronal cell membrane is extracellular space. In this extracellular space there are also ions. You could find potassium again, sodium, chloride, calcium, other ions. What is important in understanding how signaling takes place in the nervous system is to realize that the distribution of ions in a cell, in a neuron, is different between the inside and the outside of the cell. The ions are distributed unequally across the neuronal membrane, so that in what we refer to as the resting state, the inside of the cell is going to be more negatively charged than the outside. That is a fundamental principle. The resting state means the neuron at a time when it is not firing. In its resting state the ions are distributed unequally across the membrane so that the inside of this cell is more negative than the outside.

This charge differential—because remember, ions are basically atoms that have either gained or lost an electron, so they are charged—is maintained in a number of ways. One of the ways it’s maintained is that in the membrane of neurons are molecules that act as little pumps, and they make sure that the intracellular ion concentration is regulated very carefully. It’s very important that the ionic concentrations be regulated, because any abnormality in this system or control mechanisms can lead to an abnormal electrical discharge. And an abnormal electrical discharge could set up seizures in the brain or could even kill neurons. In the resting state, this charge differential is maintained by molecules that actually exist in the membrane, that act as little pumps that make sure the right charged ions are distributed across the membrane in a very particular way.

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Regulating Ionic Concentration

In the extracellular space, which is outside of a single neuron, the role of regulating ion concentration is the job of astrocytes. Astrocytes—star-shaped glial cells derived from the same progenitor cells that give rise to neurons—play a critical role in regulating the ionic concentration outside of the neuron. They do this because they actually act as little sinks for particular charged atoms. The extracellular ionic environment is regulated down to the atom by astrocytes and the intracellular charge is going to be regulated down to the atom by specific molecules across the membrane.

What happens when a neuron is stimulated? When a neuron is stimulated, the distribution of ions is altered across the membrane. If ions now become distributed when the cell is stimulated, the differential charge results in the inside of the neuron becoming more positive; we call that depolarization. If the inside of the cell becomes even more negative than it was before, then it’s going to become hyperpolarized. In the resting state the charge differential is about -70 mV.

How to Fire a Neuron

When the charge reaches a particular point—when the inside of the cell becomes more positive to about -55 mV—it sets off an action potential at the axon hillock. What we have then is depolarization—making the inside more positive—an excitation in the nervous system. If the inside is more negative, it’s called hyperpolarization—an inhibition in the nervous system. Action potentials are generated at that axon hillock of the neuron and propagated down the axon, jumping from node to node in between the myelin sheaths (see fig 1).  Their very rapid and transient changes in the membrane potential are going to occur at every place where the axon is basically bare. Because the action potential jumps from node to node, it’s called saltatory conduction. That means a “jumping conduction.”

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Speeding up the Signal

The velocity of the propagation down the axon is due to how large those myelin sheaths are around the neuron. The larger the neuron and the greater the myelin, the faster the conduction. If your axon was unmyelinated, the conduction would be very slow, and it’s actually very easy to understand why. If you are going to jump from node to node, then the only place you need to change the differential charge is at the spaces in between each node. If you have an unmyelinated axon, then you have to change the charge at each individual point along the axon. Synaptic transmission in myelinated axons is a lot faster than in unmyelinated, because it just jumps from node to node. That’s why you can have a neuron and motor cortex, and you can think that you want to reach out and touch an object and then do it almost instantaneously. Yet those action potentials had to go from motor neurons in your cortex, down to your spinal cord, synapse in the spinal cord and go out to cause contraction of the muscle. But it seems almost instantaneous to us because these are myelinated axons that are very, very fast.

Our next question is, what happens when the action potential reaches the axon terminal endings? That would seem to be the next place to go. The neuron propagates an action potential to the axon terminals, where they will form synapses with the next cell. What happens here at the synapse?

Calcium, Neurotransmitters, and Receptors

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Fig 3. A synapse with the presynaptic structure on the left and the postsynaptic structure on the right. (click to enlarge)

See Fig 3. The action potential—the electrical charge—causes a particular thing to happen. It causes the presynaptic membrane, the terminal ending, to open up channels that allow an influx of calcium—one of the charged ions in that extracellular space. When calcium comes into the nerve terminal, it sets up a cascade of events that are going to result in the movement of little vesicles to the membrane termination point. These membranes fuse with the presynaptic membrane and dump their contents—neurotransmitters—out into the cleft, the space that separates one neuron from another neuron.

The last question is, what happens now in the postsynaptic structure? The only way the first neuron can communicate with the second neuron is through some kind of signal that it can read. And what happens? The action potential causes the release ultimately of neurotransmitter or chemicals from this presynaptic terminal. Those chemicals diffuse across the synaptic cleft to interact with specific receptors on the postsynaptic cell. Interaction of the neurotransmitter with those postsynaptic receptors is going to do one of two things. It’s either going to directly open channels in that postsynaptic membrane—the channel is just a protein that controls the flow of ions across its membrane. Or, it’s going to bind to another molecule that eventually will also result in different ions being distributed across the postsynaptic membrane. We refer to the changes taking place at a synapse as membrane potentials or postsynaptic membrane potentials.

Grading Postsynaptic Potential

These potentials are different from action potentials in a number of ways. First of all, they are generated in dendrites and spines. Dendrites are just extensions of the cell body and spines are just protuberances of the dendritic surface to increase the surface area. Synaptic potentials can be depolarizing or hyperpolarizing. In other words, they can be excitatory or inhibitory. But unlike action potentials, synaptic potentials are graded and “decremental.”

Neurons have a variety of axonal inputs. These are axons coming from different places, other nuclei in the brain, synapsing upon the cell; either its cell body or its dendrites or spines. Graded and decremental means that the synaptic potentials, which are generated in the dendrites or spines, are graded in that how big they are depends on how much neurotransmitter got released. Decremental means something interesting. Spines and dendrites are not myelinated. These are true extensions of the cell body surface. And this means that a synapse on the edge of a cell has to change the membrane and ion distribution at each point along the way to the cell body and the axon hillock. That means as that signal is transferred, it decrements, so that it becomes smaller.

Now what is the consequence of this? What does it mean? Well, it means that it’s the sum of all the excitatory and inhibitory input to this neuron that will ultimately determine whether an action potential will be fired at the axon hillock. There are thousands of synapses coming in and either exciting the postsynaptic membrane or inhibiting the postsynaptic membrane, and then the addition of all these thousands of synapses and their excitation and their inhibition will determine whether an action potential will be generated at the axon hillock. And once that’s generated, that action potential will then be propagated in an all-or-none fashion to a synapse again, and on and on and on in a chain of neurons.

From the lecture series Understanding the Brain
Taught by Professor Jeanette Norden, Vanderbilt University

3 Comments

    • Yes I am interested in harnessing the energy in the brain in a healing manner. Interested in any findings in the parispirit realm.

  1. I would appreciate news on brain research. I have been a studying neuroscience for many years and used brain compatible learning techniques when I was still teaching (I am retired now after forty years as an educator).

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