What we want to be able to account for is how is it that when sperm and egg unite to give rise zygote, it eventually gives rise to something as complicated as the human brain and this is a multi-dimensional view of what the brain looks like in the adult in all its various configurations. So what I\u2019m going to do is start with going through some of the stages of brain development and having established that then turn to what it is that we know about the role of experience and influence in brain development. So just briefly I will summarize in outline form and then describe each in detail the various stages. <\/p>\n\n\n\n
The neurulation essentially refers to the construction of the neural tube. Some of you will know that errors in neurulation lead to neural tube defects. Spina bifida is an example of that. Once the tube is formed there\u2019s a stage of proliferation where immature cells are being produced on a huge scale. <\/p>\n\n\n\n
Cell migration refers to the actual construction of the cortex where cells, these primitive cells migrate in an outward fashion and basically build the brain. Differentiation means once the cells have gone to their correct location the analogy being you take the subway or the tube from one stop to another and when you get off at that stop you mature. And that\u2019s the process of differentiation. Some of you have that experience I\u2019m sure. The now mature neurons set up shop, they form connections between one another. This is synaptogenesis. And the last stage of brain development is myelination, which is simply the laying down of myelin on certain axons in the brain to speed up information. <\/p>\n\n\n\n
So let me go back to the first stage of neurulation. Right after conception, between the 18th and the 24th day after conception the embryo is divided into three layers, an inner layer, middle layer and an outer layer. And the outer layer, the ectoderm of the embryo begins to thicken and form a pear-shaped neural plate and I\u2019ll illustrate this in just a moment. And on that plate a groove starts to form down a longitudinal axis and gradually the groove deepens so a tube forms and the tube then closes up at the bottom and top ends and the part at the top end will become the top of your head. Your brain here and the bottom end will become the bottom of your spinal cord. <\/p>\n\n\n\n
So this is an electron micrograph that illustrates this. On your right you will see from top to bottom the plate thickening and a groove forming and then the groove deepens and then now the groove has become a tube and then the tube seals up at both ends. This is a cartoon version of this. So once that\u2019s happened what you see on your right is what says forebrain, midbrain and hindbrain. And so those areas differentiate out to give rise to – fore brain would be basically your neocortex, mid brain would be structures down one step below that involved in various autonomic functions and then the hind brain and the rest of this becomes your spinal cord. Now what\u2019s essential about this is this is occurring very, very early in pre-natal life. It\u2019s essentially done by about the 24th pre-natal day and as I tell my undergraduates when I lecture on this, many women have no idea they are even pregnant at this point in time. And we know from epidemiological studies now that some forms of neural tube. Defects have been tied to deficiencies of folic acid and in fact now in the United States folic acid is routinely given. There has been a drop in the neural tube defects. So once your neural tube forms, neurogenesis is this next stage. <\/p>\n\n\n\n
So now we have immature neurons and immature glial cells. Glial cells are the other major form of brain cell in the brain. In most regions of the brain neurogenesis is complete pre-natally. That is we assume that the newborn brain has all the cells it\u2019s ever going to have. Thus unlike scratching yourself or getting a bad sunburn when you repair yourself, if you damage a brain cell you don\u2019t make a new brain cell, which is very unfortunate. However there is very recent work now that starts to question the notion that neurogenesis is completely complete at birth. And in fact over the last several years using some very new methods in neuroscience it\u2019s been discovered that in some regions of the brain, notably the hippocampus there is a process of post-natal neurogenesis that goes on through at least midlife. And so we are essentially creating new neurons throughout mid-life. Somebody may have this feeling, a little pop in your head; it\u2019s probably a new neuron that was being made. And most importantly we know that this post-natal neurogenesis can be up regulated or down regulated by experience, meaning that in a learning environment there\u2019s an increase in the production of new cells. In an environment that\u2019s highly stressful there\u2019s a decrease in the production of these new cells. Once you have these cells we have this process of cell migration. <\/p>\n\n\n\n
So the neural tube is closed, there is this proliferation of cells that lines the neural tube and then some of the cells get connected to one another and they climb along a fiber to another location. We have six layers of our cortex. The cortex is just that thin layer with convolutions in it and the way it gets constructed is that a cell will migrate what\u2019s called a radial glial fiber to its target destination. <\/p>\n\n\n\n
So to go back to the subway analogy, you get on it at Bloor St. and you know you have to make three stops and you get off there. And once you get off is once again, as I said before, mature. The cortex forms in an inside out fashion meaning the earliest formed layers are formed first and each subsequent layer is formed by cells moving past that layer to the next layer. So we have not only 6 lamina but we have columns of related cells by virtue of this process. And so the next slide illustrates this as well. <\/p>\n\n\n\n
So you can see here, if you look at the left side where it says subventricular zone at the bottom, this would be the point of origin of some types of cells. The long blues lines are the radial glial fibers and what you see as the yellow part is the cell attaching to a radial glial fiber and traveling up. And typical migration time is about 21 hours. Now the next slide is going to illustrate this in real time. <\/p>\n\n\n\n
What you\u2019re looking at here, this is a video of migration in the ferret brain. And what you\u2019re looking at here is this cell, moving at a non-radial direction, moving away. Now to go back to something Dr. Rutter said, what\u2019s important about this is that the point of origin of this primitive cell determines in part where the cell will wind up in the cortex. But Susan McConnell whose data these are has elegantly shown that if at a certain point in development you transplant the cell to a different location in the subventricular zone it will actually wind up going to a different part of the cortex and being a perfectly normal cell. But if you wait too long you can\u2019t do that. So even at this early point in development we have a strong genetic propensity for cells to move in a certain direction, but that genetic propensity in fact can be influenced by experience. <\/p>\n\n\n\n
So we have a plastic process, very, very early in life; between roughly the 12th and the 24th week. So most cells migrate by the end of the 25th week pre-natally. At this point in time the cells have not differentiated, meaning that they have not matured. So it\u2019s a little tiny cell; it hasn\u2019t yet developed a cell body or axons or dendrites, which means it\u2019s very small. The reason our brains are convoluted, have that pattern to it is that the brain grows over onto itself. <\/p>\n\n\n\n
This is what the brain looks like at about 23 to 24 weeks gestation. Notice that there really are no sulci and gyra in this brain and some of you will also know that babies are now being delivered at this age. So those of you who spent time in an intensive care unit know that a baby delivered at 23, 24 weeks essentially has a brain that looks like this. I won\u2019t belabor that. <\/p>\n\n\n\n
So once the cells reach their target destination several things can happen. The cell body can develop, the cell can die, which is referred to as apoptosis and that\u2019s a perfectly normal developmental process. At least 50% of all the cells that are originally born wind up dying. Processes like axons and dendrites can develop and then synapses can form and this is what goes on during the latter stages. <\/p>\n\n\n\n
So this is a brief cartoon of what a synapse would look like \u2026 \u201cthe action potential, red dots propagate along the axon of neuron 2, leading to an excitatory post synaptic potential in the target zone. The depolarization spreads passively within the target cell until it reaches the axon hillock. Since the depolarization is lower than the excitation threshold an action potential is not generated and resting potential is resumed. Successive activation of neurons 2 at short intervals brings to summation of the excitation in the target cell a process known as temporal summation. If at a given moment the depolarization at the axon hillock exceeds the excitation threshold an action potential is generated.\u201d <\/p>\n\n\n\n
So that was just to illustrate how this would work in a real brain; how a synapse would connect and cause an action potential to occur. <\/p>\n\n\n\n
So let me briefly get through synapses. There\u2019s massive over production of synapses and so the newborn brain has many, many more synapses than the adult brain. So over production is followed by a period of retraction in which now we cull back the number of synapses to adult levels. In the human this rate of retraction varies from area to area. For example in the visual cortex the peak of over production occurs between the 3rd and 4th post-natal month, and by about 4, 5, 6 years of age there\u2019s a retraction to adult levels of synapses. <\/p>\n\n\n\n
In contrast synapses in the middle, frontal gyrus in the frontal cortex peak at around a year of age and are not retracted to adult levels until mid to late adolescence. So here\u2019s a slide that illustrates that. So the solid line are synapses in the visual cortex, the dash line are synapses in the frontal cortex. And what you can see is the peak occurs much earlier in visual cortex and then the retraction is over by about four or five years. And in contrast middle frontal cortex is a much later period of retraction. <\/p>\n\n\n\n
So why do we over produce synapses? This is Monday morning quarterbacking, we don\u2019t really know, but this is our best speculation. Captures experience thereby pruning or cultivating synapses. It can be adaptive for the organism; a period of opportunity; it can also be maladaptive or a period of vulnerability depending on the nature of the experience. And thus plasticity can be thought of as cutting both ways. <\/p>\n\n\n\n
And finally myelin is a lipid protein substance that is produced depending if you\u2019re in the autonomic or peripheral or central nervous system, wraps itself around an axon, speeds up the conduction of a nervous impulse along that axon that has implications for serial and parallel processing. It occurs in ways beginning in the last part of gestation, in the full term pregnancy. The next wave occurs in the first months or year or so post-natal life, and the final wave which largely affects the hippocampus and the frontal cortex\u2026when I do this I\u2019m trying to point at the hippocampus and the frontal cortex…as late as middle age. In fact Francine Dennis at Harvard has demonstrated continual myelination in the hippocampus as late as midlife. When you go back to what I said about post-natal neurogenesis it is no accident then that we\u2019re continuing to make new cells in the hippocampus and new cells seem to be being myelinated. What Francine has not demonstrated is whether the cells that are being myelinated are 45 years old or 4 days old, and that\u2019s an impossible thing to tell at this point with technology. <\/p>\n\n\n\n
The summary of functional brain development; most aspects of language and memory are established fairly early in life. However prefrontal functions, cognitive flexibility, working memory and things like that have a much later developmental trajectory. We know that these are functions that are typically not obtained until mid to late adolescence and anyone who know teenagers recognize this. In fact some of you may wonder will it ever happen. But it typically does and these are then fine-tuned much later on. Those of you who teach undergraduates know that even some undergraduates still suffer from difficulties in some of these areas, like planning behavior. But then as you get to be older you do this better because you have to plan your behavior because otherwise you would never remember what you were going to do. This is an overview of human brain development. This is a slide that I made for a book that was published by the National Academy of Sciences last year, Neurons to Neighborhood, and in brief you can see, if you just look at the timeline it underscores the point that Dr. Rutter made. It is na\u00efve to think that brain development ends at the age of three or even five because <\/p>\n","protected":false},"excerpt":{"rendered":"
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