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

What are the basal ganglia?

Where are they?

Nuclei of the basal ganglia.

Nuclei of the basal ganglia.

The basal ganglia are a cluster of nuclei found deep within the cerebral hemispheres. The nuclei generally included in the basal ganglia are the caudate, putamen, globus pallidus, and nucleus accumbens in the cerebrum, the substantia nigra in the midbrain, and the subthalamic nucleus in the diencephalon. Despite the name, the basal ganglia are not actually ganglia.

What are they and what do they do?

The separate nuclei of the basal ganglia all have extensive roles of their own in the brain, but when referring to them as one network the function most frequently associated with the basal ganglia involves movement.

The basal ganglia receive information from the cortex, much of which is sent first to the caudate and putamen (which together are often referred to as the striatum). After the information is processed by the basal ganglia, it is sent back to the cortex by way of the thalamus. Thus, the pathway from the cortex to the basal ganglia and then back to the cortex via the thalamus forms a loop.

In simplistic terms, the functions of the basal ganglia in motor control are to facilitate movement and inhibit competing movements. For example, when someone tries to make an intentional movement like reaching for a pencil, the basal ganglia help to facilitate the movement by allowing motor plans associated with that movement (reaching and grasping in this case) to be activated. At the same time, the basal ganglia cause motor plans that might counteract the movement (perhaps flexing in this case) to be inhibited. The result is a smooth and fluid movement.

Although exactly how the basal ganglia achieve this fluidity of movement is not completely understood, we can see the importance of the basal ganglia to smooth movement when we look at cases where the basal ganglia are damaged. In Parkinson's disease, for example, dopaminergic neurons of the substantia nigra degenerate. When this happens, the ability of the basal ganglia to inhibit contradictory movements is affected. This causes individuals with Parkinson's disease to have difficulty initiating movements, and results in some of the symptoms associated with Parkinson's disease like rigidity and slow movement.

On the other hand, in a disorder like Huntington's disease, neurons that project to the globus pallidus degenerate, causing the globus pallidus to become unusually active. This leads to excessive activation of movement-related circuits and results in the jerky and writhing involuntary movements seen in Huntington's disease.

A balance between the ability to inhibit and facilitate movement is critical to making normal, smooth movements, and the proper functioning of the basal ganglia is essential to maintaining that balance. The basal ganglia, however, are also thought to have roles in habitual behavior, emotion, and cognition. Thus, in addition to movement disorders, the basal ganglia are now being investigated in attempts to understand disorders like Tourette's syndrome, schizophrenia, and obsessive-compulsive disorder.

Know your brain: Cerebellum

Where is it?

Cerebellum (in red).

Cerebellum (in red).

The cerebellum is hard to miss when you're looking at a brain. Cerebellum is Latin for "little brain", and indeed the cerebellum looks a bit like a smaller version of our brain. It protrudes from the back and bottom of the cerebral cortex. You can see it when looking at a side view of a brain as the most posterior and inferior portion of the brain (see picture to the right).

What is it and what does it do?

Although the cerebellum is involved in a number of brain functions, it is best known for its part in the modulation of movement. When we make a voluntary movement, the signal to initiate that movement originates in the motor cortices. Before the signal is sent to our muscles, however, it is sent to the cerebellum.

In addition to receiving information about the planned movement from the cortex, the cerebellum also gets information about the position of the body from the spinal cord. It uses this information to coordinate the movement and allow us to make it in a smooth manner, while maintaining our balance and equilibrium.

For example, imagine you are standing up and there is a piece of cake on the table in front of you. A plan to reach for the cake originates in the motor cortex. But, in order for that plan to result in a fluid movement, a number of things have to happen. For example, the movement must be executed with the current position of the body in mind. If you are standing stably on two feet, the action would require a different motor plan than if you were trying to balance on one foot. Also, muscles that oppose the movement must be inhibited; otherwise your attempt to extend your arm might be negated by the muscles whose role is to flex your arm. When the cerebellum receives information about the motor plan from the motor cortex, it incorporates what it knows about the position of the body and muscles; then it sends the plan back to the cortex to put it into action.

As you reach for the cake, however, there will also be a number of small corrections that must be made along the way. Although to us our movements seem like they are made up of large components (e.g. reaching, grasping), in the brain they are actually made of up very small increments. The plan for each increment is developed based on the results of the previous one. In other words, when you reach for the cake your brain is constantly getting data about the position of your hand and arm in real-time and using that data to make minor adjustments to the movement as it occurs.

Thus, the movement of our arm is made up of a number of smaller movements that involve slight deviations and then a return to the originally designated course. It is similar to the approach an airplane uses to get from, for example, New York to San Francisco. Although the course between the two cities seems to be straightforward, due to variables like wind and weather the route will never be exactly the same. When any particular trip is examined closely, one will see that the plane frequently deviated and then returned to its path. Similarly, your brain must get information about where your arm is in space and, if it is not on the mark in reaching for the cake, the path must be corrected.

These corrections are happening on the order of milliseconds, and so we are not aware of them, but the cerebellum is essential to making them happen. When the cerebellum detects any potential deviations from the route originally planned, it uses that information to send a modified plan back to the motor cortex. This corrected plan is what is used to generate the next increment of movement in reaching for the cake.

In this way, the cerebellum provides an error detection and correction mechanism. This allows our movements to appear smooth, precise, and coordinated. The importance of the cerebellum in facilitating smooth movement can especially be seen in someone who has experienced cerebellar damage. They may develop cerebellar ataxia, which involves problems not in the initiation, but in the execution, of movement. Their movements may be abnormally timed, jerky, and riddled with tremors. See the video to the right for an example.

The cerebellum also seems to be important to the learning of motor movements. When we repeat a motor movement over and over again, we gradually learn to execute it more smoothly and precisely. This learning process is based in part on the strengthening of synapses in the cerebellum.

Someone who experiences cerebellar damage (e.g. through a stroke) may also display cognitive and emotional disturbances or deficits. Thus, there appears to be more to the cerebellum than just its role in movement. However, due to the distinctive movement disorders that appear when someone experiences cerebellar damage, its capacity to promote smooth and coordinated movement is what the cerebellum is best known for.