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Neuroanatomy Primer

Anatomy of CNS

Anatomical Regions of the Brain

The science of how the brain works is interesting. We think we know quite a bit about it—and you are going to be exposed to some of what is known—but it is likely that the way the brain works is far more complex and mysterious than we actually know now. So just keep in mind that there is probably a lot more to learn in the future, but what you will learn here will be an interesting journey. One thing to keep in mind is that we will use much of the language that is part of the neuroscientists’ lexicon. This is important because when you are speaking to healthcare professionals that work in the neuroscience field, this is how they talk—so use this opportunity to learn a little bit of a new language.

The nervous system is the network of interlinked nerve cells that coordinates all the sensory and motor activities of the body. It is responsible for controlling our speech and behavior and for regulating the activity of all internal organs and body systems. Anatomically, the nervous system is often considered as two parts: the central nervous system—CNS—and the peripheral nervous system. The brain is part of the CNS.

Select the image of the brain to learn more.

Lobes of the Brain

If we could gently pull the brain out of its protected surroundings, called the skull, we would see an organ that is pretty much three colors, a combination of brown, white and gray. Those colors don’t help differentiate the parts of the brain, so we are going to take the liberty of adding our own color. This will help us see where one lobe ends and another lobe begins. Take a look!

Each cerebral hemisphere is divided into lobes. Although some sources list two additional—small—lobes, the four that are most important are shown on this screen.

Select the image of the brain to learn more.

The Cerebrum

The word cerebrum is used in everyday language to refer to the part of the brain that is used to think. Well, it’s not really that simple, but the cerebrum is one of the important parts of the brain that is involved in cognition—the brain experts’ term for thinking. The cerebrum plays several different roles in our daily lives—and these roles are often employed together to accomplish what we want to do.

Although the two hemispheres seem to be mirror images of each other, they are different. For instance, the ability to form words seems to lie primarily in the left hemisphere, while the right hemisphere seems to control many abstract reasoning skills. Nearly all of the signals from the brain to the body, and vice versa, cross over on their way to and from the brain.

Select the brain to show a magnified view of the cerebrum.

Internal Structures of the Brain

If we go down just a little deeper into the brain, we could see four different structures that work with the cerebrum to accomplish both conscious and subconscious tasks during the day and night. One of these, the corpus callosum, has an interesting job of connecting the left side of the brain with the right side. Can you imagine what it would be like if the two hemispheres were not connected? A lot of things would be nearly impossible to do.

Select the image of the brain to learn more about each component.

Basal Ganglia

Now we are getting in to the parts of the brain that have names that are a little more difficult to remember. These were given Latin names way back when scientists were discovering the parts of the brain and the names haven’t changed since then. But try not to let this get in the way! Maybe you can think of a common way to remember them based on what they sound like.

The basal ganglia consist of several nuclei of gray matter found buried within the white matter of the cerebral hemispheres. There are four principal nuclei: subthalamic nucleus, substantia nigra, striatum, and globus pallidus. The basal ganglia help initiate and terminate movements of the body. They also suppress unwanted movements and regulate muscle tone. In addition, the basal ganglia influence many aspects of cortical function, including sensory, limbic, cognitive, and linguistic functions.

Select the brain to show a magnified view of the basal ganglia.

The Limbic System

Now the limbic system is connected to many other parts of the brain and it is almost always busy. It helps in sensation, hearing, and many other functions that require transmitting messages through circuits to other parts of the brain. Think of it as a branch of the government: each part has its own role, but it works best when all parts communicate!

The limbic system is a functional network rather than an anatomical structure. Nerve fibers are contributed to it from several parts of the brain. The circuitry of the limbic system includes parts of the prefrontal cortex, basal ganglia, the thalamus, and a structure called the amygdala. This set of structures, together with the hippocampus and cingulate cortex, is generally referred to as the limbic system.

Select the brain to show a magnified view of the limbic system.

Microstructures of the Brain

Of course, every part of the brain we have already talked about is made up of tissues and cells. Although we are not going to cover every single type of cell in the brain, there are a few cell types that are almost ubiquitous and that you should know about.

The cerebral cortex contains neurons and supporting cells called neuroglial cells. There are several different types of neurons, and we will focus on these in the next screen. Neuroglial cells—sometimes just called glial cells—are non-neuronal cells in the brain, and they perform a variety of functions. The different types of glial cells include oligodendrocytes, microglia, and astrocytes.

Select the image to show a magnified view of microstructures of the brain.

Neurons

Like cerebrum, neuron is a term that is often used in everyday language to refer to the essential component of a larger structure. It basically means nerve cell and it almost never rests, even when we are sleeping. Let’s take a look at what the neuroscientists say about neurons.

A neuron is a nerve cell that is the basic building block of the nervous system. Neurons are similar to other cells in the human body in a number of ways, but there is one key difference between neurons and other cells: neurons are specialized to transmit information throughout the body.

These highly specialized nerve cells are responsible for communicating information as both chemical and electrical stimuli. There are also several different types of neurons responsible for different tasks in the human body. Sensory neurons carry information from the sensory receptor cells throughout the body to the brain. Motor neurons transmit information from the brain to the muscles of the body. Interneurons are responsible for communicating information between different neurons in the body.

Select the neuron image to show a magnified view.

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Neurotransmitters and Neuropharmacology

What Is a Neurotransmitter?

A neurotransmitter is a chemical messenger that carries, boosts, and modulates signals between neurons and other cells in the body. Neurotransmitters released from synaptic vesicles located in presynaptic axon terminals act on a large variety of receptor molecules to elicit fast excitation or inhibition as well as slower modulatory effects on neuronal excitability and responsiveness to other neurotransmitters. In addition to electrophysiologic effects, chemical transmission triggers long-term effects on function, protein expression, and structure of the target cell. These effects are critical for dynamic, use-dependent, long-term changes in the efficacy of synaptic transmission.

You may have seen those old-fashioned mail tubes that were used to send messages from one office to another—in the same building. The sender would put some papers inside a capsule, screw on the top, pop it into the tube and send it on its way to the recipient. Somehow the vacuum inside that mail tube could control the direction of the capsule so it would end up in the right place. Well, that is kind of what a neurotransmitter does. It is a special kind of messenger that one nerve cell uses to communicate with another—and there are several different types, each with its own function.

Three Neurotransmitters

Select the arrows to toggle the three neurotransmitters.

Select the arrows to toggle the three neurotransmitters.

Select the arrows to toggle the three neurotransmitters.

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The Synapse

There are two major types of neurotransmission: (1) chemical neurotransmission; and (2) electrochemical neurotransmission. In chemical neurotransmission, the first neuron secretes at its nerve-ending synapse a chemical substance called a neurotransmitter (or often called simply a transmitter substance). The neurotransmitter binds to the receptor proteins in the membrane, either activating, inhibiting, or modulating the activity of the receptors.

The synapse is like a gap or space between the sender and the receiver in the nervous system. If all of the nerves were physically connected, it is possible that the messages to and from the brain would be sent too fast for a proper response. What the synapse does is provide a little buffer space so that the neurotransmitter (the messenger) has to take the time to travel across before the receiver gets the message. Now this isn’t very long in reality, but it allows for some pacing of messages that works better for timing purposes.

Select neuron to learn more.

Chemical Transmission

Chemical neurotransmission is a process by which a presynaptic cell, on excitation, releases a specific chemical agent—a neurotransmitter—to cross a synapse to activate, inhibit, or modify receptors in the postsynaptic cell.

Select any of the four labels to learn about the role of each in chemical transmission.

Neurotransmitters

The neurotransmitters cross the synaptic cleft and bind to specific receptors on the postsynaptic neuron.

There are two main classes of chemical substances that serve as neurotransmitters and neuromodulators: small-molecule transmitters and large-molecule transmitters. Small-molecule transmitters include amino acids, such as glutamate, GABA, and glycine; acetylcholine; monoamines, such as norepinephrine, epinephrine, dopamine, and serotonin; and adenosine triphosphate or ATP. Large molecule transmitters include a group of substances called neuropeptides, which will not be covered in this module.

Presynaptic neuron

A potential electrical signal reaches the axon terminal of the presynaptic neuron.

Vesicle

A vesicle is a membrane-enclosed sac that stores or transports substances. Vesicles fuse with the cell membrane of the presynaptic neuron to release stored neurotransmitters into the synaptic cleft.

Receptor

This is a protein molecule within a cell membrane that has specific binding sites for select neurotransmitters or drugs and which produces a specific physiological effect.

Dopamine and Dopamine Receptors

One basic concept to note when we talk about neurotransmitters like dopamine, serotonin, and norepinephrine is that they don’t just float around inside the brain and make things happen. Each of these three neurotransmitters must be matched up with the proper receptor, the receiving unit that allows the neurotransmitter to bind. The binding creates some type of reaction in the receptor. Sometimes it is responsible for a new event, such as moving the leg. Other times it may slow or stop those actions. But in all 3 cases, in order to work, the neurotransmitter has to bind to a specific receptor.

Dopamine is an important neurotransmitter involved in the pathophysiology of schizophrenia and major depressive disorder (MDD) and is involved in four different neural pathways: mesocortical, mesolimbic, nigrostriatal, and tuberoinfundibular.

There are two major types of dopamine receptors. The neurotransmitter receptor proteins are integral components in the communication between adjacent cells of the nervous system, spanning the width of the postsynaptic membrane and protruding into the synaptic cleft and cell cytoplasm. They mediate the effects of neurotransmitters between adjacent neurons.

Although it was initially believed that each neurotransmitter interacted with a single type of receptor, it is now clear that there exists a family of neurotransmitter receptors for each neurotransmitter, called subtypes. Thus, depending on which receptor subtype the neurotransmitter binds with on the postsynaptic neuron, dopamine can increase or decrease cellular activity.

Select the image of the brain to learn more about the four dopaminergic pathways.

Serotonin and Serotonin Receptors

Serotonin—also known as 5-HT—is a neurotransmitter that is found throughout the body.

There are multiple receptor subtypes for serotonin; the roles of these receptor subtypes are not fully elucidated. Serotonergic neurons project widely throughout the brain from their origin in the brain stem.

The wide dispersal of serotonergic neurons throughout the brain enables serotonin to be involved in modulating diverse body functions.

High concentrations of serotonin are found in the CNS, platelets, and certain cells in the gastrointestinal tract.

The raphe nuclei are the group of nuclei in the brain stem that releases serotonin into the brain.

Select the brain to learn more about serontonin pathways and body functions.

Norepinephrine and Norepinephrine Receptors

There is another term you may hear that also means norepinephrine—noradrenaline. In the United States we typically use norepinephrine, but you may hear noradrenaline used if you are speaking with a healthcare professional who trained in Europe.

Norepinephrine Pathways

Prefrontal cortex

Some noradrenergic projections to the prefrontal cortex are thought to help regulate mood; others are thought to mediate attention.

The noradrenergic projection to the limbic cortex is thought to mediate emotions, energy, fatigue, and psychomotor agitation/retardation.

Cerebellum

The noradrenergic projection to the cerebellum is thought to mediate motor movements, especially tremor.

Spinal cord

The noradrenergic projection to the brain stem controls blood pressure.

Select each of the three norepinephrine pathway labels to learn more.

Receptor Subtypes

Dopamine Dopaminergic receptors (D1-5 subtypes)
Serotonin 5-HT receptors (5-HT1A-F, 5-HT2A-C, 5-HT3-7 subtypes)
Noradrenaline α-adrenergic receptors (α1A-C, α2A-C subtypes)
Glutamate β-adrenergic receptors (β1-3 subtypes)
GABA Ionotropic receptors: non-NMDA (AMPA, kainate), NMDA receptors

Neurotransmitters are released and diffuse across the synapse and bind to structures called receptors located within the cell membrane of the dendrite of the adjacent nerve cell. The table shown on this screen shows the types of receptors—and receptor subtypes—to which the major neurotransmitters bind. Note that for each neurotransmitter there are several important receptor subtypes. Keep this in mind as you learn about how an imbalance in neurotransmitters plays a role in MDD and schizophrenia and the rationale for the design of various drugs to treat these disorders.

The neurotransmitters act as chemical messengers, which transmit information from one neuron to another. The binding of a neurotransmitter to its receptor on the postsynaptic neuron triggers specific downstream physiological consequences, such as increasing neurotransmitter release to the next neuron in the pathway or increasing the production of functional proteins in the cell. These downstream events are mediated either through a change in electrical properties of the neuron and/or through a series of interactions between intracellular proteins—second messengers.

Drug-Receptor Interaction

These are some of the important basic principles that apply to many different types of drugs that are used by mental health specialists such as psychiatrists. Learn these functions now so you will be better able to understand how specific classes of drugs and individual drugs act.

Select the forward arrow to see the next type of interaction.

Drug Classifications

The classification of a drug as an agonist, antagonist, or partial agonist is based on the characteristic activity of the receptor after the drug binds to the receptor. This classification is determined in vitro.

Select the forward arrow to see what happens with an agonist.

Agonist Full Activation

An agonist binds with the receptor and increases downstream activity.

Select the forward arrow to see what happens with an antagonist.

Antagonist Inhibits Activation

An antagonist binds with the receptor and inhibits downstream activity of receptor stimulation by an agonist.

Select the forward arrow again to see the actions of a partial agonist.

Partial Agonist and Partial Activation

But sometimes an agent can act as an agonist to a certain extent that produces less than the maximal response of a full agonist. This kind of drug is called a partial agonist. In other words, after a partial agonist binds to the receptor, the receptor functions at a preset level—not fully activated but not fully blocked. For example, a partial agonist with 20% intrinsic activity allows the receptor to function at a preset level of 20% activity, or agonism, whereas a partial agonist with an intrinsic activity of 40% allows the receptor to function at a preset level of 40% activity, or agonism. The partial agonist with the higher intrinsic activity—40%—functions more like an agonist than the partial agonist with lower intrinsic activity. Importantly, a drug with lower intrinsic activity functions more like an antagonist than a drug with higher intrinsic activity.

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Agonism, Antagonism, and Partial Agonism

Full Agonist

Select the arrow to advance to another type of agent.

Partial Dopamine Agonist

Select the arrow to advance to another type of agent.

Partial Dopamine Agonist

Select the arrow to advance to another type of agent.

Another Partial Dopamine Agonist

Select the arrow to advance to another type of agent.

Full Dopamine Antagonist

 

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Progress Check Questions

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