2-Minute Neuroscience: Membrane potential and action potential

In these two videos, I discuss membrane potential and the action potential. Membrane potential refers to the difference in charge between the inside and outside of a neuron, which is created due to the unequal distribution of ions on both sides of the cell. The term action potential refers to the electrical signaling that occurs within neurons. This electrical signaling leads the release of neurotransmitters, and therefore is important to the chemical communication that occurs between neurons. Thus, understanding the action potential is important to understanding how neurons communicate.

Know your brain: Meninges

Where are they?

Close-up view of the meninges surrounding the brain.

Close-up view of the meninges surrounding the brain.

The term meninges comes from the Greek for "membrane" and refers to the three membranes that surround the brain and spinal cord. The membrane layers (discussed in detail below) from the outside in are the: dura mater, arachnoid mater, and pia mater. Their positioning around the brain can be seen in the image to the right.

What are they and what do they do?

The brain is soft and mushy, and without structural support it would not be able to maintain its normal shape. In fact, a brain taken out of the head and not properly suspended (e.g. in saline solution) can tear simply due to the effects of gravity. While the bone of the skull and spine provide most of the safeguarding and structural support for the central nervous system (CNS), alone it isn't quite enough to fully protect the CNS. The meninges help to anchor the CNS in place to keep, for example, the brain from moving around within the skull. They also contain cerebrospinal fluid (CSF), which acts as a cushion for the brain and provides a solution in which the brain is suspended, allowing it to preserve its shape.

The outermost layer of the meninges is the dura mater, which literally means "hard mother." The dura is thick and tough; one side of it attaches to the skull and the other adheres to the next meningeal layer, the arachnoid mater. The dura provides the brain and spinal cord with an extra protective layer, helps to keep the CNS from being jostled around by fastening it to the skull or vertebral column, and supplies a complex system of veinous drainage through which blood can leave the brain.

The arachnoid gets its name because it has the consistency and appearance of a spider web. It is much less substantial than the dura, and stretches like a cobweb between the dura and pia mater. By connecting the pia to the dura, the arachnoid helps to keep the brain in place in the skull. Between the arachnoid and the pia there is also an area known as the subarachnoid space, which is filled with CSF. The arachnoid serves as an additional barrier to isolate the CNS from the rest of the body, acting in a manner similar to the blood-brain barrier by keeping fluids, toxins, etc. out of the brain.

The pia mater is another thin layer, but unlike the arachnoid it closely follows all of the contours (i.g. gyri and sulci) of the brain. Thus, instead of a cobweb, it forms a tight membrane around the brain and spinal cord. The pia acts as a barrier and also aids in the production of CSF.

These three layers are similar in structure and function around both the spinal cord and brain, but there are a few differences. While there is not normally a space between the dura and skull, there is one between the dura of the spinal cord and the bone of the vertebral column. It is known as epidural space, and analgesics and anasthesia are sometimes injected here. Also, the dura of the spinal cord and its accompanying arachnoid layer extend several vertebrae below the end of the cord. This creates a CSF-filled area called the lumbar cistern where there is no spinal cord present. The lack of the presence of the cord makes the lumbar cistern a good place to sample CSF when necessary because one doesn't have to worry about damaging the spinal cord with a needle puncture. Thus, the lumbar cistern is the site where CSF is aspirated in a lumbar puncture, also known as a spinal tap.

There are a number of things that can go wrong with the meninges. Due to the large numbers of blood vessels that travel through these membranes, many problems are vascular in nature. For example, blood (e.g. due to damage caused by trauma) can collect in spaces between the layers of the meninges, creating a hematoma that can put pressure on the brain as it expands. Also, the meninges are susceptible to infection, most commonly due to viruses or bacteria. Such an infection can cause meningitis, which is characterized by an inflammation of the meninges. Because of the importance of the meninges in protecting the brain and maintaining normal brain function, meningitis can pose a serious threat to the brain and potentially be life-threatening.

Patel, N., & Kirmi, O. (2009). Anatomy and Imaging of the Normal Meninges Seminars in Ultrasound, CT and MRI, 30 (6), 559-564 DOI: 10.1053/j.sult.2009.08.006

Know your brain: Thalamus

Where is it?

Thalamus (in red).

Thalamus (in red).

The thalamus is a large, symmetrical (meaning there is one in each hemisphere) structure that makes up most of the mass of the diencephalon. A large number of pathways travel through the thalamus, including all of the sensory pathways other than those devoted to olfaction (smell).

What is it and what does it do?

The thalamus is often described as a relay station. This is because almost all sensory information (with the exception of smell) that proceeds to the cortex first stops in the thalamus before being sent on to its destination. The thalamus is subdivided into a number of nuclei that possess functional specializations for dealing with particular types of information. Sensory information thus travels to the thalamus and is routed to a nucleus tailored to dealing with that type of sensory data. Then, the information is sent from that nucleus to the appropriate area in the cortex where it is further processed.

For example, visual information from your retina travels to the lateral geniculate nucleus of the thalamus, which is specialized to handle visual information, before being sent on to the primary visual cortex (the main area for visual processing in the brain). A similar pathway through the thalamus can be delineated for all sensory information except smell. In fact, the majority of all of the signals (not just sensory) that pass to the cortex first pass through the thalamus.

Thus, the thalamus has a major role as a gatekeeper for information on its way to the cortex, making sure that the information gets sent to the right place. However, to consider the thalamus as just a gatekeeper or relay station is selling this structure a bit short. A significant portion of the incoming fibers to the thalamus come not from sensory systems, but from the cortex itself. There are many connections to the thalamus that are involved in taking information from the cortex, modulating it, and then sending it back to the cortex. This means that the thalamus is an important part of cortical processing in general, and more than just a brief stop for signals on their way to the cortex.

With this in mind, it shouldn't be that surprising that the thalamus is involved in complex brain processes like sleep and wakefulness. It even is thought to play a crucial role in maintaining consciousness. So, far from just a relay station, the thalamus is an integral area involved in higher-order brain processing of various types.

Sherman, S., & Guillery, R. (2002). The role of the thalamus in the flow of information to the cortex Philosophical Transactions of the Royal Society B: Biological Sciences, 357 (1428), 1695-1708 DOI: 10.1098/rstb.2002.1161

History of neuroscience: Hodgkin and Huxley

Hodgkin and Huxley used the large axons of the giant squid to measure voltage changes during an action potential.

Hodgkin and Huxley used the large axons of the giant squid to measure voltage changes during an action potential.

By the late 1930s, researchers had come to understand several important things about the conduction of signals within neurons. For example, they knew that signaling within neurons is electrical in nature (as opposed to signaling between neurons, which is usually chemical), and that it occurs in bursts of activity called action potentials. And they knew that action potentials are stimulated by the movement of sodium ions across the neuronal membrane through proteins called ion channels. But the full details of what is going on during an action potential were not made completely clear until Alan Hodgkin and Andrew Huxley started collaborating on the issue in 1939.

What is an action potential?

To understand Hodgkin and Huxley's findings, it helps to have some background on what happens during an action potential. When a neuron is at rest, there are a variety of charged particles called ions that are unevenly distributed inside and outside of the cell. Ions are simply atoms that have either gained or lost an electron; this gain or loss of electrons gives the atoms a negative or positive overall charge, respectively. When a neuron isn't excited, positively-charged sodium ions accumulate outside of the neuron, while positively-charged potassium ions accumulate inside. There are also negatively-charged chloride ions that accumulate outside and organic ions that accumulate inside the cell. A number of mechanisms, including both passive (e.g. diffusion) and active (e.g. the Na-K pump) processes, work to maintain a unequal balance of positively- and negatively-charged particles between the inside and outside of the neuron. This difference in charge is known as the resting membrane potential; typically in neurons it is around -65 to -70 mV, which means that the inside of the neuron is negatively-charged with respect to the outside.

During an action potential, the membrane potential rapidly changes. By Hodgkin and Huxley's time it was already suspected that this rapid change was produced by the movement of positively-charged sodium ions from the outside to the inside of a neuron through ion channels. The influx of positively-charged particles was thought to be the basis for the burst of electrical energy that then proceeded to travel down the neuron as an action potential. However, the extent of the change in membrane potential wasn't known, and the exact role of the different types of ions found in the intracellular and extracellular fluid of neurons had yet to be elucidated.

Voltage clamps and giant squid axons

One of the difficulties in understanding action potentials before Hodgkin and Huxley's work was that neurons are incredibly small. (At their largest they are about 100 micrometers, but they can be under 10 micrometers. By comparison, a human hair is about 80 micrometers.) Scientists found that the size of the axons in most species made it difficult or impossible to insert a recording device to measure voltage changes during an action potential.

Hodgkin and Huxley got around this problem by studying action potentials in the relatively enormous axons (up to 1 mm in diameter) of the giant squid. They inserted a fine capillary electrode into the giant squid axon and were able to measure electrical changes within the axon during an action potential. They found that the membrane potential of the neuron actually reversed during an action potential, causing the neuron to momentarily have a positive membrane potential. This rapid reversal of membrane potential was the impetus for the generation of the electrical signal underlying the action potential.

Hodgkin and Huxley also utilized an innovative tool that allowed them to determine the contribution of different ions to the change in membrane potential seen during an action potential. The device, called a voltage clamp, uses electrical stimulation and feedback to set the membrane potential of a neuron at a particular voltage and keep it there. Previous attempts to gauge the exact contribution of different ions to the action potential were stymied by the voltage-dependency of the ion channels involved. Voltage-dependent ion channels open and close when the membrane potential reaches a particular voltage. Thus, because the action potential involves rapid changes in membrane potential, it also involves rapid fluctuations in the opening and closing of ion channels. This happens so quickly that researchers before Hodgkin and Huxley were unable to slow it down enough to get an understanding of what was going on. By using a voltage clamp, Hodgkin and Huxley essentially were able to "freeze" the neuron at particular voltages, which allowed them to gather details on what was happening in the neuron at each stage in the action potential.

Hodgkin and Huxley used the voltage clamp while also manipulating the levels of different ions in the extracellular fluid. In this way they were able to determine the exact contribution of sodium and potassium (and chloride and organic) ions to the action potential. They determined that an influx of sodium ions through voltage-gated sodium ion channels causes a rapid shift in membrane potential, which causes the initiation of the electrical signal that is known as the action potential. Immediately after this change in membrane potential, however, ion channels open that allow potassium ions to flow out of the neuron. This helps the membrane potential to return to its normal level.

Hodgkin and Huxley's work for the first time allowed researchers a step-by-step view of the processes involved in an action potential. Their findings caused interest in electrophysiology to skyrocket, eventually inspiring the development of a more precise form of the voltage clamp known as the patch clamp, which allows for the measurement of current across single ion channels. Perhaps most importantly, however, Hodgkin and Huxley's successful efforts at precisely modeling the action potential would lay the groundwork for a more quantitative approach to biology in the twentieth century.

Schwiening, C. (2012). A brief historical perspective: Hodgkin and Huxley The Journal of Physiology, 590 (11), 2571-2575 DOI: 10.1113/jphysiol.2012.230458