Lecture 10 Notes PDF

The Retina In Bear et al. study Chapter 9. I. Introduction to SYSTEMS neuroscience A. Thus far the focus of the course has been on the cellular/molecular level. B. The rest of the course will be focused on systems level. We will apply what we have already learned to the systems level. C. Systems are...

The Retina In Bear et al. study Chapter 9. I. Introduction to SYSTEMS neuroscience A. Thus far the focus of the course has been on the cellular/molecular level. B. The rest of the course will be focused on systems level. We will apply what we have already learned to the systems level. C. Systems are circuits of neurons that interact to perform some function (for example the visual system, the auditory system, the pain sensing system, memory systems, motor systems, etc.). D. Problems in understanding systems. The unknowns are greater. The complexity is vastly greater. The operation of many systems is highly counterintuitive. E. Neural Codes: A fundamental concept. The essential idea is that the meaning of activity (e.g., action potentials) by a neuron depends on the system it is part of. Action potential by a neuron in a pain system would yield the perception of pain; action potential by a neurons in the visual system would yield the perception of sight; action potentials by a neuron in a motor systems would cause movement; action potential by a neuron in a system underlying emotion might cause the feeling of fear or another emotion. 1. Also, systems have subsystems and neurons in different subsystems code for different functions. For example, in the visual system, different areas and groups of neurons perform different functions. Some neurons are responsible for detecting the form of a visual object; others are responsible for detecting color (they code for color), other for movement (they code for movement), others for location (they code to location of an object in the visual field), etc. The action potential produced by these different neurons mean different things, i.e. they "code" for different perceptions/meanings etc. © Hongdian Yang. This content is protected and may not be shared, uploaded, or distributed. 2. What is a neuron coding? What attribute of the visual world is a neuron in the visual system encoding? All that you measure when you record membrane voltage is action potentials, but action potentials in different neurons mean different things. How do neuroscientists determine the function of a neuron or of a system of neurons? II. The Visual System: The retina A. The retina consists of several thin layers of cells distributed across the inside of the eye. B. The fovea is the portion of the retina where light falls from an object that you are looking directly at. It is the portion of the retina with the highest acuity, the ability to resolve fine detail and patterns of light. Note: Acuity and sensitivity are different. C. The optic disk is the retinal location where axons from a type of retinal cell collect and exit the eye and form the optic nerve. This is the blind spot because there are no photoreceptors in the optic disk. D. Below is a diagram depicting the eye and how a visual image is "mapped" onto the retina: © Hongdian Yang. This content is protected and may not be shared, uploaded, or distributed. Retina A a Fovea E. A neuron’s receptive field is the location in the environment (or the surface of the body) from which an appropriate stimulus will change that cell's activity. For example light at 'A' (the tip of the flame in the diagram above) will affect the activity of retinal cell in location 'a' in the retina. Cells in different locations in the retina have receptive fields in different locations in the visual field. F. There are five cell types in the retina. 1. Photoreceptors – The first stage in the visual system. a. Photoreceptors - the only cell type in the visual system that is directly sensitive to light. b. There are two types of photoreceptors: 1) Rods a) There are about 120 million rods in the human retina. © Hongdian Yang. This content is protected and may not be shared, uploaded, or distributed. b) Rods are highly sensitive to light and are responsible for vision in very dim light. c) Rods are bleached in bright light and thus unresponsive in bright light. d) Rods are not responsible for high acuity vision (not good for fine detail). e) Rods are achromatic (insensitive to colors). f) Rods only exist outside of the fovea. 2) Cones a) There are about 6 million cones in the human retina. b) Cones are less sensitive to light intensity and are inoperative in dim light. c) Cones are sensitive to color. There are three subtypes, selectively sensitive to red, blue, and green wavelengths of light. d) Cones are most concentrated in the fovea. c. Photoreceptors project to the bipolar cells. 2. Bipolar cells (BPs) 3. Retinal ganglion cells (RGCs) a. RGCs are the only output cell type in the retina. b. RGCs are the only means by which information from the eye gets to the rest of the visual system and their axons form the optic tract. 4. Horizontal cells (HCs) 5. Amacrine cells (ACs) See figures 9.11, 9.12 and 9.13 G. Why is it that only the RGCs have axons? 1. Axons are needed for long-distance transfer of information. In the retina, the cells are very close together and so don’t need action potentials or axons. Also, © Hongdian Yang. This content is protected and may not be shared, uploaded, or distributed. communication by PSPs may be able to convey information that is more subtle than can be conveyed by the AP frequency code (recall that PSPs are graded). 2. Only the RGCs and ACs generate action potentials. The rest of the cell types use graded depolarization to release neurotransmitter to the next cell. A depolarization increases neurotransmitter release. Small depolarizations cause small release of neurotransmitter; large depolarizations cause large release of neurotransmitter. H. The relationship between different cell types in the retina. 1. The retina is "inside-out" with the photoreceptors furthest away from the light (at the very back of the eye) and the RGCs the closest to the light. Thus light must pass through the other cell types to reach the photoreceptors. 2. This works because all the cells in the eye, except the photoreceptors, are translucent. 3. Also, at the foveal pit all cell types, except the photoreceptors, are pushed out of the way (see 9.15). III. How light is absorbed by photoreceptors A. Phototransduction is how light energy leads to a change in membrane potential. B. Below is a diagram depicting how light changes photoreceptor membrane potential. (Also, see Figure 9.17) © Hongdian Yang. This content is protected and may not be shared, uploaded, or distributed. DARK: RMP ~ -30 mV Photoreceptor membrane voltage Dim Moderate Bright -30mV Highest release Glutamate release < as light increases Lowest glutamate release -65mV Time (msec) 1. The resting membrane potential of photoreceptors is -30 mV and this is in the dark. 2. The maximum hyperpolarization is down to -65 mV and this is produced by bright light. 3. Glutamate is the neurotransmitter used by photoreceptors. The greater the intensity of light, the less neurotransmitter released. III. How does light produce the graded hyperpolarization? See Figure 9.19 A. The ligand-gated Na+ channels in the outer segment membrane are open in the dark, causing depolarization (to the “resting membrane potential” of -30 mV). B. These ligand-gated channels are like receptors, but they are "inside-out", meaning that they bind their ligand cGMP to a binding site on the intracellular face of the Na + channel and this opens the channel. © Hongdian Yang. This content is protected and may not be shared, uploaded, or distributed. IV. How does light decrease the concentration of cGMP? 1. The photopigment, which is highly concentrated in the membrane of the disks in the outer segment of the photoreceptors, is purple in the dark. When it absorbs light the photopigment is bleached to a pale yellow. 2. The photopigment is called rhodopsin, and it consists of two parts... a. Opsin is a protein. b. Retinal, which is the only light sensitive molecule anywhere in the visual system. The precursor of retinal is vitamin A. Retinal exists in 2 conformations: 1) In the dark it is 11-cis-retinal. 2) A photon of light will switch it to the all trans-retinal conformation. See Figure 9.18. 3. The steps in cGMP activation are as follows: a. Opsin passes through the membrane seven times (i.e. it is a metabotropic or Gprotein-coupled receptor). b. The release of retinal from opsin allows opsin to change shape and this activates a G-protein (transducin). See Figure 9.19. c. The G-protein (G) dissociates and travels along the membrane and activates an enzyme (cGMP phosphodiesterase). d. cGMP phosphodiesterase converts cGMP to GMP, and thus lowers the concentration of cGMP. © Hongdian Yang. This content is protected and may not be shared, uploaded, or distributed. e. In the dark, cGMP is bound to the Na+ channel. Light decreases the concentration of cGMP, causing cGMP to disassociate from the channel. Consequently, the channels close and the photoreceptor cells hyperpolarize. B. Why do we have this type of system (what is the advantage)? a. The increased surface area and increased photopigment produced by having the photopigment molecules on the stacked disks, instead of on the Na+ channels, increases the chance of the light being detected by a rod. This system is so sensitive that a single photon can produce a detectable change in membrane potential of a rod type photoreceptor. b. The use of G-proteins allows for amplification; each molecule of opsin can activate many G-proteins, each of which, in turn, can activate many enzymes of cGMP phosphodiesterase, each of which can, in turn, convert many molecules of cGMP into GMP. © Hongdian Yang. This content is protected and may not be shared, uploaded, or distributed.