Lessons from Studies of Orientation and Direction Preference, part 2

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Medical Neuroscience

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Duke University

Medical Neuroscience

995 оценки

Medical Neuroscience explores the functional organization and neurophysiology of the human central nervous system, while providing a neurobiological framework for understanding human behavior. In this course, you will discover the organization of the neural systems in the brain and spinal cord that mediate sensation, motivate bodily action, and integrate sensorimotor signals with memory, emotion and related faculties of cognition. The overall goal of this course is to provide the foundation for understanding the impairments of sensation, action and cognition that accompany injury, disease or dysfunction in the central nervous system. The course will build upon knowledge acquired through prior studies of cell and molecular biology, general physiology and human anatomy, as we focus primarily on the central nervous system. This online course is designed to include all of the core concepts in neurophysiology and clinical neuroanatomy that would be presented in most first-year neuroscience courses in schools of medicine. However, there are some topics (e.g., biological psychiatry) and several learning experiences (e.g., hands-on brain dissection) that we provide in the corresponding course offered in the Duke University School of Medicine on campus that we are not attempting to reproduce in Medical Neuroscience online. Nevertheless, our aim is to faithfully present in scope and rigor a medical school caliber course experience. This course comprises six units of content organized into 12 weeks, with an additional week for a comprehensive final exam: - Unit 1 Neuroanatomy (weeks 1-2). This unit covers the surface anatomy of the human brain, its internal structure, and the overall organization of sensory and motor systems in the brainstem and spinal cord. - Unit 2 Neural signaling (weeks 3-4). This unit addresses the fundamental mechanisms of neuronal excitability, signal generation and propagation, synaptic transmission, post synaptic mechanisms of signal integration, and neural plasticity. - Unit 3 Sensory systems (weeks 5-7). Here, you will learn the overall organization and function of the sensory systems that contribute to our sense of self relative to the world around us: somatic sensory systems, proprioception, vision, audition, and balance senses. - Unit 4 Motor systems (weeks 8-9). In this unit, we will examine the organization and function of the brain and spinal mechanisms that govern bodily movement. - Unit 5 Brain Development (week 10). Next, we turn our attention to the neurobiological mechanisms for building the nervous system in embryonic development and in early postnatal life; we will also consider how the brain changes across the lifespan. - Unit 6 Cognition (weeks 11-12). The course concludes with a survey of the association systems of the cerebral hemispheres, with an emphasis on cortical networks that integrate perception, memory and emotion in organizing behavior and planning for the future; we will also consider brain systems for maintaining homeostasis and regulating brain state.

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The Changing Brain: The Brain Across the Lifespan

This module represents another turning point in Medical Neuroscience. Now that we have surveyed human neuroanatomy and our sensory and motor systems, we are ready to take a step back and consider how this magnificent central nervous system came to be the way that it is. We will also learn how the brain re-wires itself across the lifespan as genetic specification, experience-dependent plasticity and self-organization continue to interact, re-shaping the structure and function of neural circuits throughout the central nervous system.

Lessons from Studies of Ocular Dominance Columns, part 121:03

Lessons from Studies of Ocular Dominance Columns, part 211:21

Lessons from Studies of Orientation and Direction Preference, part 115:01

Lessons from Studies of Orientation and Direction Preference, part 210:41

Lessons from Studies of Orientation and Direction Preference, part 316:01

Neurotrophins In Developmental Plasticity12:59

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Leonard E. White, Ph.D.
Associate Professor
Department of Neurology, Department of Neurobiology, Duke University School of Medicine; Department of Psychology & Neuroscience, Trinity College of Arts & Sciences; Director of Education, Duke Institute for Brain Sciences; Duke University

Well, I tell you all this so that I can describe for you some experiments that my

colleagues and I have done to look at how the experience of the animal in early

life impacts the self-organization of these cortical networks that perform

these computations that account for orientation selectivity.

And direction selectivity. And we began by simply looking at the

emergence of these orientation preference maps in the visual cortex of animals

beginning from just before the time they naturally opened their eyes, and then on

through the phase of normal cortical development.

And so if one looks at an animal soon after it has open its eyes, one can

indeed find that their is a system of orientation columns that are organized

into a map of orientation preference. So, this has been known since really, the

early 90s, when it was first possible to apply these methods to the developing

visual cortex. And, what was discovered is that these

columns do indeed self-organize. They appear pretty early in postnatal

life, and those animals that are born with their eyes closed, they seem to

emerge prior to the time of eye opening but they rapidly develop in the days to

weeks that follow the onset of normal visual experience.

So we thought an obvious experiment to test whether vision had an important role

to play in the maturation of this system, was to raise animals in total darkness.

And, thus removing visual experience from the life history of the animals.

And when we did that experiment, what we found was that sure enough.

The circuits for orientation selectivity and preference do self-organize.

It's possible to recognize. It's possible to recognize columns and

the response maps, and in the selectivity maps that we generate from these animals.

And the signals are sufficiently robust. That we can assign color values and

create an orientation preference map. With the proper analysis applied to these

maps, indeed, these maps from animals that never saw any photons of light until

the experiment, do indeed self organize and develop.

Pinwheels with a density of Pi. However, I think, perhaps, even your eye

can pick this out. the contrast of the images that we

recorded from these animals that lacked vision seemed to be sig, significantly

less than what we observed from animals that had normal vision.

Throughout the period of brain maturation that we study.

So, while these cortical networks do indeed self-organize without the benefit

of vision, vision does seem to contribute to the refinement of these maps, and an

increase in the selective responses. Of the neurons, whose signals we're

recording with this method. Well, just because these circuits

self-organize, and are present in animals that have never experienced vision does

not mean that this process. Cannot be influenced by experiment.

So we thought it was important to do a complementary experiment.

Rather than just taking away vision we thought we should make vision abnormal.

And a fairly straightforward way to do that is to raise animals keeping their

eyelids shut. And that's very much like what your eye

might do if we were to close our eyes and then look around.

The visual scene, if I look up towards the florecent lights in the ceiling I can

tell that I'm looking up. And seeing an incease in illumination

compared to if I were to look away. But I see no form.

I see no structure. I see no shape to what.

Eye, eye view, simply an increase or a decrement in light intensity.

So this is the nature of visual experience that we imposed on the set of

animals, and when we did this, what we discovered is that there were some pretty

significant impacts on the development of the circuits that compute orientation

preference. Now this manipulation did not produce

cortical blindness. And we know that because when we looked

at the response maps in the visual cortex, we saw robust activation of the

visual cortex. The problem however, is that we failed to

see the robust development of columnar structure It's as if the very same

circuits in the brain responded to the presentation of a horizontal stimulus and

the presentation of a vertical stimulus. So when these images were subtracted,

what we found was virtually no evidence of columnar structure that was organized

into a map of orientation preference. So, I want to notice the implication of,

this finding here. What this shows us is that when we made

vision abnormal, what we found was actually more significant imparement of

the visual cortex then when we simply deprived the animal of vision.

Now, this reminds me, at least, of a famous, aphorism.

That was suggested by, one of our, seminal neurosurgeons of the 20th

century. Dr.

Wilder Penfield. Who said that no brain is better than bad

brain. Well, that justified some neurosurgical

procedures aimed at the removal of bad brain.

In this case, I would suggest that bad experience is worse.

More detrimental to the development of visual cortical circuits, than is no

experience. So what have we learned from these

studies? I think we can make some provisional

conclusions based on these experiments looking at the development of orientation

preference.`` I think what we've learned is that normally circuits in the visual

cortex self-organize. And they operate synergistically with

normal sensorimotor experience. And this synergy promotes the full

maturation of these circuits. However, when experience is rendered to

be abnormal, then this synergy is broken. And self-organization goes awry.

[INAUDIBLE]. The neural circuits that develop as a

consequence are functionally impaired. Now, these neural circuits, they

self-organize to adapt to the quality of the incoming sensory signals.

So, by self-organization going awry, I mean relative to the synergy that our

brain has evolved to anticipate From the world in which we live.

But when that synergy is aggregated by some kind of ocular impediment, in our

case, keeping the eyelids closed or perhaps in clinical populations

congenital cataract, for example. would be one human condition that we

would model through this method of keeping the eyelids shut.

well, such conditions. Keeping the eyelids shut or congenital

cataract. Are those that, would provide for the

adaptive influence over the circuity of the visual cortex that would then

develop. So consequently, not only do these neural

circuits under these conditions fail to benefit from normal visual experience.

And as a result, they're actually, developing along a trajectory that

instantiates functional impairment. So now I'd like to turn our attention to

the property of direction selectivity and direction preference.

So we can think of this as a further differentiation of the circuitry for

orientation selectivity and orientation preference Where those circuits begin to

specialize for the representation of motion in just one direction or other,

with the preferred direction of motion being orthogonal to the preferred

orientation. That is to say, circuits might develop a

preference, let's say, for vertical stimulus.

but there might be a differentiation of one side of the orientation domain to

prefer vertical moving to the right. Whereas, the other side of that

orientation column might differentiate preference for vertical moving to the

left. Now we can resolve this with the same

method I have just described for you this optical imaging of intrinsic signal

methods. One can even resolve it to the cellular

level using a method known as two photon imaging of calcium signals which is what

here is represented here to the right. So it's now possible to do studies where,

for example, we can, zoom in on a small region of the visual cortex and recognize

that, with this more low-resolution method, we can define a region that

responds, let's say, mainly to downward motion And that region representing

downward motion seems to be separated by some kind of barrier condition from an

adjacent region that represents upward motion.

We imagine that within this hyper column here, there is an orientation column that

represents horizontal. But it has subdivided into these two

adjacent domains that represent opposite directions of motion.

And then, zooming into this region with this method that provides cellular

resolution, we see, indeed, there is a population of cells, each cell being

represented by an arrow here that has a preference.

And the upper right region of this field seems to show a predominant preference

for upward motion, whereas the lower left region of the field shows a predominance

of cells that prefer downward motion.

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