Okay, I think we're ready to switch gears here, in talking about how the brain changes across the lifespan. I'd like to turn our attention to a couple of specific contexts. Beginning first with the plasticity of sensory and motor maps in the brain where these plastic phenomena have been best studied and best understood. So, what we know is that the somatic sensory and somatic motor maps can undergo a fairly dramatic reorganization across the life span. We used to think that this kind of plasticity was limited quite stringently by a critical period in early life. But we now know that it's possible to absorb plasticity in these somatotopic maps, even into adulthood. And this was shown rather dramatically by a series of experiments led by Michael Morsnick at the university of California in San Francisco in the 1980's and then years since then. And many experiments have led to similar kinds of observations. And here is an experiment that was done on an owl monkey. And the experiment involved the surgical removal of a digit in the contralateral hand following a mapping of the somatic sensory cortex. And so the question was, how would that somatic sensory cortex change in the months following the surgical amputation of a digit? And so, here on the left hand side of this figure, is a map of the hand region in the somatic sensory cortex in area 3b, adjacent area 1. And what we see are the territories that contain neurons that were responsive to stimulation of each of the five digits on the monkey's hand. Then, following the amputation of digit number 3, what was seen after several months of recovery, is that the cortical area that responded to the digit number 3 before the surgery has now come to represent the adjacent digits 2 and 4. So, now this part of the brain seems to have been taken over by circuits that were either already there in silent, or represented the growth of new synaptic connections into this region of the hand representation. Well, I would invite you to refer to an interesting box in the text book, if you have a copy of the textbook, that considers the phenomena of, of phantom limbs. phantom sensations generally we now think are generated at the level of the cerebral cortex. And it reflects this kind of plasticity that follows injury to a nerve, whether or not there's actual removal of a body part. Well, this is a subject that I don't mind telling you that I've come to know quite a bit about not of my own choosing. But because of a condition that I developed some years ago that required the surgical removal of a portion of my right jaw. I'm not sure if you've noticed that I tend to be a little bit weak here on the right side of my face, maybe just slightly asymmetrical. It's because the right side of my jaw is now comprised of titanium and hip bone and in the process of undergoing surgical interventions for a condition that led me to this state, I've had severe damage to the mandibular division of the trigeminal nerve. So, this has led to the experience of phantom sensations around the region of the right side of my face, and into the oral structures. And over the years they have changed somewhat, and I suspect they reflect something like this process that's being outlined here. Where there is now invasion into a region that has been [UNKNOWN] by this surgery. And in my case, it reflects the cutaneous surfaces, as well as the oral surfaces, on the right interior portion of my face. Well, sometimes these phantoms are a bit distressful. But oftentimes they are somewhat entertaining, I suppose, so like the man who knew too much in the Hitchcock film having some information in mind can both be troubling and also at sometimes somewhat entertaining. Well, enough about me. let's get back to the subject of cortical plasticity in life, following some kind of modulation of body structure or function. Well, one does not have to have amputation or nerve section in order to induce plasticity in the regions of our sensory and motor maps. We know this from experimental studies in animals, and now studies in human subjects where it's possible to relate the relevant map to some particular experience of the body. And in this case, monkeys were subject to cortical mapping. In order to represent the distribution of receptive fields in the somatic sensory cortex as they relate to each of the five digits on the contralateral hand. And in this case monkeys were trained in a task that especially activated digits 2 and 3, and to a lesser extent, digit 4. And after some period of differential stimulation of these digits, what we see is a fairly significant expansion in the amount of the somatic sensory cortex that's representing these three stimulated digits. Perhaps at the expense of the adjacent representations of digits 1 and 5. So, this is generally the case for all kinds of different sorts of manipulations. For example, it's been studied in the somatic sensory and motor maps of violin players. That typically the right central region of the central sulcus cortex is enlarged structurally and functionally compared to the corresponding region in the left hemisphere. And if one considers the act of practicing the violin, I think we gain some insight as to why that might be the case. Consider the fingerings of the left hand along the neck of the violin. It requires incredible skill to fractionate the movements of the digits of the left hand. perhaps a qualitatively and quantitatively greater amount of skill and experience than does it take to bow with the right hand. If one is playing the instrument in the conventional way. Well, when the somatic sensory motor maps of these violin players have been studied, again one sees evidence for an exuberant growth of the corresponding region in the right central sulcus compared to the left. Perhaps reflecting the kind of neurobiological change that we see illustraed in this experimental study using this non human primate model. Well, what kind of mechanisms then might be responsible for these kinds of changes in the somatic sencory and motor maps? Well hopefully you will recall the mechanisms of synaptic plasticity that we discussed in unit 2. That would include long term potentiation, long term depression, the consequences of these physiological changes for the growth or the pruning of synaptic connections. and one might imagine that in this particular case where we see in it, overall expansion in the dimensions of the cortical areas that are representing the experienced functions. We imagine that perhaps long term potentiation has been especially prominent leading to the growth of new synaptic connections along dendrites. So, if indeed that has been the case this would occupy more volume, and potentially account for these larger representations. Well what kind of circuits in the cortex might actually be responsible for these kinds of synaptic changes that might lead to an expansion in cortical circuitry volume? Well I would suggest that one interesting circuit arises from these pyramidal cells, that we find in the upper layers of the cortex. Now I will remind you that the thalamic input comes into the middle layers of the cortex. And then from there these stellate cells and small pyramidal cells relay information up to cortical layers 2 and 3. And in cortical layers 2 and 3, we see the computation of new functional properties, but we also see the extension of long ranging connections that allow for one cortical column to communicate with nearby columns within the cortical area. And even to communicate with distant columns in adjacent cortical areas. So, this computational function of the cortical microcircuit together with the dissemination. Or the communication of the signals to other cortical columns is an important function of these pyramidal cells that we find in the upper layers of the cortex. Well, in studies that my colleagues and I have done looking at the organization of the cerebral cortex. We've had occasion to study these long ranging connections that are grown out by these cortical pyramidal cells in the horizontal dimension. And the way we've typically studied these connections is by making an injection of a tracer substance into a local [SOUND] volume of the cerebral cortex above cortical layer 4. that substance then is taken up by the neurons that are present at the site of the injection. And the tracer substances transported along the axons that grow out from these cells. And what I'd like to show you is some data from my own lab that, that I generated with the help of my colleagues. that illustrate this cortical network. So, we're looking at a tracing of axons, following one such experiment, where, the injection of the tracer was made, right here in the middle. It's as if we are now looking down upon the cortex from above. And so, this is where we would find the cell bodies that have taken up the tracer. And all of these short line segments that you see represent the axons that have grown out away from these cells. There is a bit of a halo here in the middle where I did not trace the axons, because they are simply so dense close to the cell bodies. It's difficult to differentiate the labelled axons from the dendrites at that point, so I simply omitted them from this tracing. And what we see then, is that these axons extend for several millimeters across the cerebral cortex. Now, I'll just remind you that each [SOUND] hypercolumn within the cortical circuit is about a millimeter or so in diameter. That's probably actually an upper boundary for the size of the human hypercolumn. We don't quite know precisely what it is, but it's somewhere a millimeter or less. So, what we see is evidence of connections that are extending well beyond the typical hypercolumn. And the implication is that these are connections, that are connecting multiple hypercolumns together. And so, these connections provide then for a substratum that potentially might mediate plasticity, in the brain. Well, let's take a closer look at, these data, I'd like to actually show you what these cells look like. So, if we were to focus in now on the region of the injection site, right in the middle, here's what we would see. This is a dark field photo-micrograph, showing you a cluster of about a dozen or so neurons, and what we're looking at is mainly the cell bodies, these small little brown spots and their dendrites, these thick tufts that are proceeding out from, from these cells. And then these finer thread like structures, here's one right there, there's another one over here. These are, these are axons that are extending over some distance across the cortical mantle. And if we were to look at it in a more remote site, for example out here what we would see is a terminal cluster. So, all of these bright little line segments here, these are all portions of axons, where we have terminals of the axons that arose from cells that were several hypercolumns removed from the location where we find this terminal cluster. Now, the anatomy is interesting in and of itself, but what makes this really fascinating is to relate the anatomy to the physiology. And we can do this in this particular study, because we made injections into the visual cortex after we mapped the distribution of columns that are representing different orientations of visual stimuli. And what, we, and, actually several other groups, ahead of us have done in other model systems, is demonstrated that there is a principle of like connecting to like. When it comes to these long ranging horizontal connections in the cerebral cortex. And what I mean by that is that if one were to inject, let's say a region of the visual cortical map, that has a preference for near vertical orientations. What we find is a clustering of connections that has a preference for overlying other columns that likewise represent near vertical orientations. And so this now suggests that what we're seeing here is a capacity within this cortical network to represent different regions of visual space that are responding preferentially to the same stimulus. Well, why am I telling you this about these horizontal connections in the cerebral cortex? It's because this horizontal network very likely mediates the plastic reorganization of functional maps in sensory, and motor regions of the cerebral cortex. we know this from a variety of studies that had looked at how does this horizontal network in the somatic sensory cortex respond to nerve injury or to immobilization of a joint that alters the way that musculoskeletal unit can be used by the animal. And in such instances, we see really a tremendous amount of exuberant growth, within the cerebral cortex. involving these kinds of horizontal connections. And it suggests that there is a dynamical sequence of events that must take place following the perturbation. that leads to the growth of these connections. It presumably involves perhaps the awakening of silent synapses that are already present in this network. and that might then be followed by the growth of new axonal collaterals that extend the range and the density of synaptic connections. Now, we'll say more about the growth of axons in the brain, or lack thereof, following injury to the brain itself. But at least with injury to peripheral structures, or to the structured use of the peripheral structures. We think that this horizontal network is an important mediator of the adaptive plasticity that can follow in, in the consequence of that kind of disturbance.
