NROB60 S2024 Lecture 3: Development of the Nervous System PDF

NROB60 S2024 Lecture 3 Week 3: Development of the Nervous System Agenda 1. Evolution and brain development 2. Neurodevelopment in humans 3. Gross anatomy of the human brain Evolution and Brain Development MacLean’s Triune Brain Theory Probably the best known model for understanding th...

NROB60 S2024 Lecture 3 Week 3: Development of the Nervous System Agenda 1. Evolution and brain development 2. Neurodevelopment in humans 3. Gross anatomy of the human brain Evolution and Brain Development MacLean’s Triune Brain Theory Probably the best known model for understanding the structure of the brain in relation to its evolutionary history is the famous triune brain theory, which was developed by Paul MacLean and became very influential in the 1960s. Over the years since, however, several elements of this model have had to be revised in light of more recent neuroanatomical findings. Therefore, it isn’t a fully accurate model, however it does illustrate how different parts of the brain developed as cognitive complexity of the organism develops, and that the development of the cerebral hemispheres, and the neocortex in particular, is what defines the primate and human brain from other species. Here’s a run down of the theory: Mammalian Brains Notice how all mammalian brains have a level of similarity. For example you can see how they all have a brainstem, cerebellum, and then a cortex. One main difference is the presence or absence of gyri and sulci o Here, rodents have a smooth cortex. We call this lissencephalic. There are no bumps and ridge. o In comparison, all the other brains have different amounts of gyri and sulci. These brains are termed as gyrencephalic. o Typically the degree of folds in the cortex correlates to the degree of cognitive development of a species. So for example you can see that a cat has less gyri compared to a chimpanzee. And we view chimpanzees as having higher order cognitive functioning compared to cats. NROB60 S2024 Lecture 3 o Another point of comparison is the size of different regions. Look how large the cerebellum is relative to the cortex in a rat compared to a human! o This also applies to the olfactory bulbs! o The idea is that specific areas would have evolved with the specific species needs in mind. So animals that have strong senses of smell, like rodents, will have larger olfactory bulbs relative the overall size of their brain compared to species that don’t heavily rely on that sense, like humans. Instead, humans have a much larger relative visual cortex since most humans rely most on our visual senses. Neurodevelopment in Humans Some additional anatomical terminology If you remember from last week, we used a bunch of terms which I did not explicitly define, but which all related to common names for describing collections of neurons, the primary cells that make up the nervous system which include the cells body, and axons, the extended part of the cell that makes up what we referred to last week as the nerves. As we get into today’s lecture, it will be important to understand the subtle differences between all these terms. Next week we will move away from gross anatomy, that is looking at larger brain structures, and zone into brain cells. For now, here are the terms you should be familiar with: NROB60 S2024 Lecture 3 Embryonic Development The entire CNS is derived from the walls of a fluid-filled tube called the neural tube that is formed at an early stage in embryonic development. The inside of the tube becomes the adult ventricular system. Thus, by examining how this tube changes during the course of fetal development, we can understand how the brain is organized and how the different parts fit together. So what we’re going to do for this next part of today’s lecture is use embryonic development as a way to understand the structural organization of the brain Formation of the Neural Tube The embryo begins as a flat disk with three distinct layers of cells called endoderm, mesoderm, and ectoderm. The endoderm ultimately gives rise to the lining of many of our internal organs. From the mesoderm arise the bones of the skeleton and the muscles. Whereas the nervous system and the skin derive entirely from the ectoderm. Therefore, our focus is on changes in the part of the ectoderm that give rise to the nervous system: the neural plate. At this early stage (about 17 days from conception in humans), the brain consists only of a flat sheet of cells. NROB60 S2024 Lecture 3 The next event of interest is the formation of a groove in the neural plate that runs rostral to caudal, called the neural groove. The walls of the groove are called neural folds, which then move together and fuse dorsally, forming the neural tube. The entire central nervous system develops from the walls of the neural tube. As the neural folds come together, some neural ectoderm is pinched off and comes to lie just lateral to the neural tube. This tissue is called the neural crest. All neurons with cell bodies in the peripheral nervous system derive from the neural crest. The neural crest develops in close association with the underlying mesoderm. The mesoderm at this stage in development forms prominent bulges on either side of the neural tube called somites. From these somites, the 33 individual vertebrae of the spinal column and the related skeletal muscles will develop. The nerves that innervate these skeletal muscles are therefore called somatic motor nerves. The process by which the neural plate becomes the neural tube is called neurulation. Neurulation occurs very early in embryonic development, about 22 days after conception in humans. A common birth defect is the failure of appropriate closure of the neural tube. Fortunately, recent research suggests that most cases of neural tube defects can be avoided by ensuring proper nutrition during pregnancy around this time. o Specifically, it is related to a deficiency of the vitamin folic acid (or folate) o Typically, neural defects occur in approximately 1 out of every 500 live births. o But it has been estimated that dietary supplementation of folic acid during this period could reduce the incidence of neural tube defects by 90% At the molecular level, successful neurulation depends on specific sequences of gene expression that are controlled, in part, by the position and local chemical environment of the cell. This explains why something like a vitamin deficiency can result in drastic effects. Here is a lovely microscope photo of what neurulation really looks like. There’s also another angle for what the folding looks like. NROB60 S2024 Lecture 3 The fusion of the neural folds to form the neural tube occurs first in the middle, then anteriorly and posteriorly. Failure of the anterior neural tube to close results in anencephaly, a condition characterized by degeneration of the forebrain and skull It is always fatal. Failure of the posterior neural tube to close results in a condition called spina bifida. o Bifida is from the Latin word meaning “cleft in two parts” o In its most severe form, spina bifida is characterized by the failure of the posterior spinal cord to form from the neural plate. o Less severe forms are characterized by defects in the meninges and vertebrae overlying the posterior spinal cord. o Spina bifida is typically not fatal, but it does result in permanent disability. Differentiation Primary Brain Vesicles The process by which structures become more complex and functionally specialized during development is called differentiation The first step in the differentiation of the brain is the development of three swellings called the primary vesicles. This occurs at the rostral end of the neural tube. The entire brain derives from the three primary vesicles of the neural tube! The rostral-most vesicle is called the prosencephalon. o Pro is Greek for “before” o Encephalon is derived from the Greek for “brain.” NROB60 S2024 Lecture 3 o Thus, the prosencephalon is also called the forebrain. Behind the prosencephalon lies another vesicle called the mesencephalon, or midbrain. Caudal to this is the third primary vesicle, the rhombencephalon, or hindbrain. o The rhombencephalon connects with the caudal neural tube, which gives rise to the spinal cord. Forebrain: The next important developments occur in the forebrain, where two sets of secondary vesicles sprout off on both sides of the prosencephalon. The secondary vesicles are the optic vesicles and the telencephalic vesicles. The central structure that remains after the secondary vesicles have sprouted off is called the diencephalon, or “between brain” Thus, the forebrain at this stage consists of the two optic vesicles, the two telencephalic vesicles, and the diencephalon. The optic vesicles grow and fold in to form the optic stalks and the optic cups, which will ultimately become the optic nerves and the two retinas in the adult. NROB60 S2024 Lecture 3 The important point is that the retina is at the back of the eye, and the optic nerve, which contains the axons that connect the eye to the diencephalon and midbrain, are part of the brain, and not the PNS! You can see from the diagram how the two telencephalon cerebral hemispheres lie above and on either side of the diencephalon, and that the ventral–medial surfaces of the hemispheres have fused with the lateral surfaces of the diencephalon. You can also see how these structures leave room for fluid-filled spaces within the cerebral hemispheres. These are called the lateral ventricles, and the space at the center of the diencephalon is called the third ventricle. The paired lateral ventricles are a key landmark in the adult brain: Whenever you see paired fluid-filled ventricles in a brain section, you know that the tissue surrounding them is in the telencephalon. The elongated, slit-like appearance of the third ventricle in cross section is also a useful feature for identifying the diencephalon. If you look at the walls of the telencephalic vesicles, they appear swollen. This is because during this stage of development, there is a proliferation of new neurons. NROB60 S2024 Lecture 3 These neurons form two different types of gray matter in the telencephalon: the cerebral cortex and the basal telencephalon. Likewise, the diencephalon differentiates into two structures: the thalamus and the hypothalamus. o The thalamus is nestled deep inside the forebrain and so it gets its name from the Greek word for “inner chamber.” The neurons of the developing forebrain extend axons to communicate with other parts of the nervous system. These axons bundle together to form three major white matter systems: the cortical white matter, the corpus callosum, and the internal capsule. o The cortical white matter contains all the axons that run to and from the neurons in the cerebral cortex. o The corpus callosum is continuous with the cortical white matter and forms an axonal bridge that links cortical neurons of the two cerebral hemispheres. o The cortical white matter is also continuous with the internal capsule, which links the cortex with the brain stem, particularly the thalamus. We’re going to use the example of the thalamus to describe how these white matter tracts work: o The forebrain is the seat of perceptions, conscious awareness, cognition, and voluntary action. All this depends on extensive interconnections with the sensory and motor neurons of the brain stem and spinal cord. o Cortical neurons receive sensory information, form perceptions of the outside world, and command voluntary movements. o Neurons in the olfactory bulbs receive information from cells that sense chemicals in the nose (odors) and relay this information caudally to a part of the cerebral cortex for further analysis. Information from the eyes, ears, and skin is also brought to the cerebral cortex for analysis. However, each of the sensory pathways serving vision, audition (hearing), and somatic sensation relays (i.e., synapses upon neurons) in the thalamus in route to the cortex. Thus, the thalamus is often referred to as the gateway to the cerebral cortex. NROB60 S2024 Lecture 3 o Thalamic neurons send axons to the cortex via the internal capsule. As a general rule, the axons of each internal capsule carry information to the cortex about the contralateral side of the body. Therefore, if a thumbtack entered the right foot, it would be relayed to the left cortex by the left thalamus via axons in the left internal capsule. o But how does the right foot know what the left foot is doing? One important way is by communication between the hemispheres via the axons in the corpus callosum. o Cortical neurons also send axons through the internal capsule, back to the brain stem. Some cortical axons course all the way to the spinal cord, forming the corticospinal tract. This is one important way cortex can command voluntary movement. o Another way is by communicating with neurons in the basal ganglia, a collection of cells in the basal telencephalon. We’ll talk more about the basal ganglia later in the semester. Midbrain The midbrain serves as a conduit for information passing from the spinal cord to the forebrain and vice versa. It contains axons descending from the cerebral cortex to the brain stem and the spinal cord. For example, the corticospinal tract goes through the midbrain on the way to the spinal cord. Damage to this tract in the midbrain on one side produces a loss of voluntary control of movement on the opposite side of the body. Unlike the forebrain, the midbrain is mostly already developed by this point and differentiates relatively little. The dorsal surface of the mesencephalic vesicle becomes a structure called the tectum (Latin for “roof”). o The tectum differentiates into two structures: the superior colliculus and the inferior colliculus. o The superior colliculus receives direct input from the eye, so it is also called the optic tectum. One function of the optic tectum is to control eye movements, which it does via synaptic connections with the motor neurons that innervate the eye muscles. Some of the axons that supply the eye muscles originate in the midbrain, bundling together to form cranial nerves III and IV. The floor of the midbrain becomes the tegmentum. o The tegmentum is one of the most colorful regions of the brain because it contains both the substantia nigra (meaning the black substance) and the red nucleus. o The substantia nigra is literally black when you look at it. This is because cells in this region produce melanin. o We’ll come back to this again later in the semester. That’s all you need to know about it for now. The CSF-filled space in between constricts into a narrow channel called the cerebral aqueduct. NROB60 S2024 Lecture 3 The aqueduct connects rostrally with the third ventricle of the diencephalon. Because it is small and circular in cross section, the cerebral aqueduct is a good landmark for identifying the midbrain. Hindbrain The hindbrain differentiates into three important structures: the cerebellum, the pons, and the medulla oblongata—also simply called the medulla. o The cerebellum and pons develop from the rostral half of the hindbrain. o The medulla develops from the caudal half. o The CSF-filled tube becomes the fourth ventricle, which is continuous with the cerebral aqueduct of the midbrain. At the three-vesicle stage, the rostral hindbrain is just a simple tube. But in subsequent weeks, the tissue along the dorsal–lateral wall of the tube, called the rhombic lip, grows dorsally and medially until it fuses with its twin on the other side. The resulting flap of brain tissue grows into the cerebellum. The ventral wall of the tube differentiates and swells to form the pons. NROB60 S2024 Lecture 3 During the differentiation of the caudal half of the hindbrain, we see the development of the medulla. The ventral and lateral walls of this region swell, leaving the roof covered only with a thin layer of non-neuronal ependymal cells. Along the ventral surface of each side of the medulla runs a major white matter system. Cut in cross section, these bundles of axons appear somewhat triangular in shape, explaining why they are called the medullary pyramids. Like the midbrain, the hindbrain is an important conduit for information passing from the forebrain to the spinal cord, and vice versa. NROB60 S2024 Lecture 3 In addition, neurons of the hindbrain contribute to the processing of sensory information, the control of voluntary movement, and regulation of the autonomic nervous system. The cerebellum is also known as the “little brain,” and is an important movement control center. It receives massive axonal inputs from the spinal cord and the pons. The spinal cord inputs provide information about the body’s position in space. We’ll discuss more about the cerebellum later in the semester. Of the descending axons passing through the midbrain, over 90%—about 20 million axons in the human—synapse on neurons in the pons. The pontine cells relay all this information to the cerebellum on the opposite site. Thus, the pons serves as a massive switchboard connecting the cerebral cortex to the cerebellum. (The word pons is from the Latin word for “bridge.”) Spinal Cord Development from the caudal neural tube into the spinal cord is straightforward compared to the differentiation of the brain. With the expansion of the tissue in the walls, the cavity of the tube constricts to form the tiny CSF-filled spinal canal. If you look at a cross section, the gray matter of the spinal cord (where the neurons are) looks like a butterfly shape. The upper part of the butterfly’s wing is the dorsal horn, and the lower part is the ventral horn. That’s all you need to be able to identify from the spinal cord. NROB60 S2024 Lecture 3 Summary Remember that imagining things in 3D space an in relation to each other is the best way to guarantee you can localize yourself within the brain. Here’s a diagram from a different angle which shows you the developed sections we just discussed: Gross Anatomy of the Human Brain This last part of the lecture today will be going over gross anatomy. This should feel very similar to the identification of brain structures you are doing during your labs, but for human brain instead of sheep brain. You’ll notice that there are many, many similarities for identification across sheep and human, but everything will look slightly different. Again here, the best strategy is to locate yourself in 3D space by using the anatomical terminology of dorsal/ventral, medial/lateral, etc. This is because while structures look different across sheep and human, they are generally located in similar locations and so this strategy helps you learn things in the same way across the lab and lecture. Hopefully this will reduce the amount you need to study. Lateral Surface Gross features + gyri/sulci Gross inspection reveals the three major parts: the large cerebrum, the brain stem that forms its stalk, and the rippled cerebellum. NROB60 S2024 Lecture 3 Now if we go one step further in detail, we can start to identify noteworthy bumps or gyri and grooves or sulci. If a sulcus is especially deep, they are called fissures. You should be able to identify: The postcentral gyrus, which lies immediately posterior to the central sulcus. o The neurons of the postcentral gyrus are involved in somatic sensation (or touch) The precentral gyrus, which lies immediately anterior to it. o The neurons of the precentral gyrus control voluntary movement Both these gyri are separated by the central sulcus On the lower part of the cortex, you can easily identify the lateral or sylvian fissure. Just below, is the superior temporal gyrus. o Neurons in the superior temporal gyrus are involved in audition. Lobes and Insula By convention, the cerebrum is subdivided into lobes and named after the bones of the skull that lie over them. NROB60 S2024 Lecture 3 The central sulcus divides the frontal lobe from the parietal lobe. The temporal lobe lies immediately ventral to the lateral fissure. The occipital lobe lies at the very back of the cerebrum, bordering both parietal and temporal lobes. A buried piece of the cerebral cortex, called the insula (Latin for “island”), is revealed if the margins of the lateral fissure are gently pulled apart. The insula borders and separates the temporal and frontal lobes. Lateral Cortical Areas This next view of the lateral surface is not going to be on the test so don’t spend time memorizing it but I wanted to show you how these lobes get broken down further into sections based on their function. You can see motor areas, sensory areas, visual areas etc. NROB60 S2024 Lecture 3 New Motor Cortex Findings Interestingly, it may seem like we neuroscientists have it all figure out but actually, determining the specific function of a small patch of brain tissue is difficult. We’ll get into this more in the second half of the course when we really dive into some major brain regions and what their functions are and how we figure that out. But for now, I wanted to share a quick little update from a paper that was published last month. I’m sure many of you have seen the “motor omunculus” which is that goofy picture you see below of the primary motor cortex. It’s often shown in psychology 101 classes to explain how specific areas of the primary motor cortex is responsible for specific movement of body parts. However, we know it is inaccurate. At it wasn’t until last month that a researcher published an updated version showing a more accurate specificity! So what I personally love about the field of neuroscience is just how much there is still left to confirm or discover. And FYI I’m showing a twitter post from the paper author because I wanted to give you all a science academia tip. For some reason, profs LOVE twitter for posting all their new research and interacting with each other. If you want to be “in the know,” Twitter is the best place to be! It’s a great spot for scoping out labs you might be interesting in working in as well. NROB60 S2024 Lecture 3 Link to the original journal article by Gordon et al., 2023 You can see from the comparative diagram I pulled from the original journal article that on the left, the original homunculus from 1948 looks quite different from the updated version on the right. So while scientists were right about each area of the motor cortex corresponding to a specific motor action, they were wrong about specifying what that map actually looked like. Medial Surface Brain Stem Structures Splitting the brain down the middle exposes the medial surface of the cerebrum. This view also shows the midsagittal, cut surface of the brain stem, consisting of the diencephalon (thalamus and hypothalamus), the midbrain (tectum and tegmentum), the pons, and the medulla You should also be able to locate the tiny pineal body NROB60 S2024 Lecture 3 Forebrain Structures Now we are looking at the important forebrain structures that can be observed by viewing the medial surface of the brain. Notice the cut surface of the corpus callosum, a huge bundle of axons that connects the two sides of the cerebrum. The fornix (Latin for “arch”) is another prominent fiber bundle that connects the hippocampus on each side with the hypothalamus. Make sure you can also identify the cingulate gyrus, and the optic chiasm Ventral Surface Just like in the sheep, the underside of the brain has a lot of distinct anatomical features. Notice the X-shaped optic chiasm, just anterior to the hypothalamus. o The chiasm is the place where many axons from the eyes decussate (cross) from one side to another. The bundles of axons anterior to the chiasm, which emerge from the backs of the eyes, are the optic nerves. The bundles lying posterior to the chiasm, which disappear into the thalamus, are called the optic tracts. The paired mammillary bodies are a prominent feature of the ventral surface of the brain. o These nuclei of the hypothalamus are part of the circuitry that stores memory Notice also the olfactory bulbs and the midbrain, pons, and medulla. NROB60 S2024 Lecture 3 Dorsal Surface Cerebellum If we were to remove the entire cerebrum, this is what our view of the cerebellum would look like. You can identify the middle vermis along with the two left and right hemispheres. Brainstem If we now remove the cerebellum, we are left with the brainstem. You’ll be identifying all these areas on the sheep brain so hopefully this gives you a heads start. It looks very similar across species. The major divisions of the brain stem are labeled on the left side of the image, and some specific structures are labeled on the right side. The pineal body, lying atop the thalamus, secretes melatonin and is involved in the regulation of sleep and sexual behavior. NROB60 S2024 Lecture 3 The superior colliculus receives direct input from the eyes and is involved in the control of eye movement, while the inferior colliculus is an important component of the auditory system. The cerebellar peduncles are the large bundles of axons that connect the cerebellum and the brain stem Final notes and study tips Again, please, please, please don't just straight up memorize from the diagrams provided. I know this is a lot to learn and it will help in the long run to visualize in 3D space! I may not provide the exact diagram on your exam, I may provide a completely different cut of the tissue but if you can locate yourself in space, you should know where you are.