Neuro: 2:00-3:00Scribe: Kristina Hixson

Monday, January 25 , 2010

Principles of Sensory TransductionPage1 of 6

Principles of Sensory Transduction [S1]
It is a hard act to follow the epilepsy lecture. So I’m going to start at the sensory component of the next series of lectures by giving you an overview of sensory transduction.
Table 21-1 [S2]
So every organism has to sense various things in the environment. Hopefully you are listening to my voice, hopefully you can see the screen and I think everybody in grade school learns the various 5 senses (touch, smell) we all learned those senses. Some organism have specialized senses such as electroreception which we won’t be talking about. Some animals can sense infrareds, such as rattle snakes and we won’t talk about that. What we are going to talk about are the very basic principles of sensory transduction that affects us and to give you some idea we can basically talk today briefly, you will get more details on this, vision, hearing, balance. We will then be talking about somatosensory and that will be broken down into different components, touch proprioception, temperature, and pain. Then gustatory which is taste and olfactory which is smell. Those are the basic ones. As you can see you can describe themodality of the sensory system. We can also discuss the stimulus energy that is required for example vision requires photons of light, sound requires sound pressure. The receptor classes and then receptor cell types. This is going to be basically this slide or tablelays out overview of what we are going to do for the next 40 minutes or so.
4 Attributes of a Stimulus [S3]
We are going to make it even easier for us if possible and tell us that really we need to remember that there are only really 4 attributes of a stimulus that you need to remember or need to know. The modality. So for example is it visual, somatosensory or auditory. You want to know the intensity of the stimulus especially if it is painful and others as well. But how loud is it, how bright is it, how painful is it, those are all measures of intensity. Duration, how long is it going to go on for, about 40 minutes. Or even shorter. And then location, you want to know for example where the object is in your visual field especially if it is a predator for example. You want to know where the sound source is located, and you also want to know where that bug is that is crawling on your skin that somatosensory location. So these are the four attributes that we are goingto talk about. The modality here is being how within the somatosensory system and we are not going to talk too much about those details today. Location is going to lead us to what is called the concept of a receptive field which we will talk about and we will talk about how we code for intensity and time course as we go on.
4 Attributes of a Stimulus: Modality [S4]
Clicker question: back to modality attributes
Table 21-1 [S5]
skipped
Figure 2 [S6]
The modality as I said would be vision, hearing, balance, somatosensory, and to give you some idea of the types of peripheral receptors for these different types of modalities they arefunctionally quite different. For example somatosensory receptors whereby the peripheral nerve ending is in the skin and the cell body is in the dorsal root ganglia and they have a central projection into the spinal cord the ganglion cell here is in the dorsal root ganglion. The sensation, the touch or painful sensation is detected by this end of the axon and it projects centrally into the spinal cord. So a single cell both detects it and signals and relays to the spinal cord. In contrast in the auditory system you have a specialized (and this is also true for the vestibular system) you have specialized cells which are called hair cells which have these little stereocilia sticking out and as we will see shortly when they deflect this cell will either depolarize or hyperpolarize and will then either increase or decrease neurotransmitter release and that will then affect this second order neuron which signals to the brain. And in other cases such as the visual system you have specialized photoreceptors which transduce photons of energy into membrane potential changes through a cascade that we will talk about very briefly and you will hear more about later. There is an interneuron and then a ganglion cell that projects to the rest of the brain is located here. So there are different morals for transducing peripheral stimuli into neural activity.
Figure 3: Labeled Line Concept [S7]
Within modalities there is a concept called the labeled line concept. For example the labeled line concept relates to the idea that receptors in the periphery project through specific pathways to the cortex so for example somatosensory receptors will eventually project to somatosensory cortex and the ganglion cells in the retina will project through a number of relays to visual cortex which is like a labeled line and auditory cells will project to auditory cortex in the cortex, a little simplistic but that is the way it is. So for example if I poke you in the eye, you will see light, you will feel pressure as well, but what will happen is potentially the small amount of increase in the pressure of the eye will cause ganglion cells to fire extra action potentials and you will perceive that because it activates cells in the visual cortex as being a light flash. So the concept of a labeled line is if I activate the peripheral cells that feed through the labeled line you will perceive whatever it is that I stimulate. If I stimulated for example this pathway here (orange) which is a pain pathway you would feel pain. If on the other hand I stimulated this pathway you would feel light touch. So depending on how you stimulate the receptors in the periphery you can either activate pain or light touch. Perceived very differently by the brain and each one has its own labeled line. So the concept of the labeled line is that a peripheral cell sort of has access to this almost private phone line up to the cortex and if you activate it here it will produce the sensation that it is suppose to. So if I electrically stimulate cells in the cochlea of the ear you would hear a sound, if you stimulate ganglion cells you will tend to see a flash of light and if I stimulate the pain receptors you will feel some pain. It is a labeled line. That is basically how the brain keeps track of it. It interprets electrical activity in these parts of the cortex as reflecting activity in the periphery in that particular modality.
Figure 23-7 S8]
Now these modalities transduce energy in a number of different ways. There are some basic principles that will hold true. Mechanoreceptors are important in the somatosensory system for touch and they are also very important in auditory and vestibular system. The basic principle is quite straightforward. You can imagine a mechanoreceptor is a channel in the membrane. It is generally a non-specific cation channel such that when the membrane is in deflected or stimulated the channel is closed. If somehow when you deform the membrane slightly the channel opens up which is what happens then ions will flow into the cell, depolarizing it and potentially generating action potentials in some cells or in hair cells it will just depolarize them. 1 mechanism of sensory transductions is some sort of deformation of the membrane will cause mechanoreceptors to open up and that will cause ionic fluxes which will depolarize the membrane. That is one mechanism.
Another major principle is chemoreceptors and these can actually both (chemoreceptors and vertebrae photoreceptor) use a second messenger cascade to signal the changes. In the chemoreceptors it is cyclic AMP second messenger cascade which you should hear more about later on. This is a little bit slower in some cases these cascades then the direct activation but they give you a lot of amplification of signals. So the cascades allow you amplify 1 or a few molecules of a chemical can be sensed with this system. For example there are some moths that can detect singlemolecules of pheromones using a chemoreceptor system and this amplification system and can detect potential mates with chemoreception. I don’t know if that works for humans, but that is true for moths.
The vertebrate photoreceptor also uses a cascade and this is actually a cyclic GMP cascade. In this case a photon of light is absorbed by a specific moleculewhich undergoes a change in its structure leading to a cascade. Here is the cascade going on here causing a decrease in intracellular cyclic GMP and strangely vertebrate photoreceptors actually close in response to light and we will talk a little bit more about that. But the vertebrate photoreceptor is unusual in the sense that it hyperpolarizes in response to light
Sensory Transduction by Mechanoreceptors [S9]
Let’s talk a little bit more about the easy one which is mechanoreceptors. This is a cartoon, very much a cartoon of a muscle spindle, a stretch receptor. These stretch receptors are modified muscle fibers that are interfusal muscle fibers that are sensitive to muscle stretch and we will talk about these when we talk about spinal reflexes. The main thing to note is that the central part of the muscle spindle is sensitive to muscle stretch and it has these afrind* axons that come in, wrap around the sensory spindle like this and if you look at the membrane of the axons they have stretch sensitive channels. This is a cartoon showing these stretch sensitive channels. Basically whenever there is a stretch on the muscle spindle then the stretchsensitivechannels are deformed and you see what is called a receptor potential, the greater the stretch of the muscle spindle the greater the depolarization of the axon in this region. And if you could record from these patches in this case a single channel undergoing different pressures and you can actually record from individual stretch receptors channels and you could apply increasing pressures to them and this is done as a path clamp experiment. What happens is as the pressureincreases on these stretch sensitive channels they stay open more frequently and this going in this case with no pressure it is open very briefly and as you increase the pressure it is open more frequently and for longer. So the more the pressure the more the channel stays open and the longer it tends to stay open and therefore that tends to increase the overall flow of ions which causes this membrane to depolarize proportionally to the amount of stretch. This is a relatively straightforward sensory transduction system. This basically arranged around stretch sensitive channels that are non-specific cation ion channels
Figure 29 [S10]
The same sort of principle is used by the auditory and vestibular system.
Came back to this slide. So now if we go back to the hair cells here we can see that when the stereocilia moves toward the kinocilium the tip-links are all stretched and the cells will depolarize. In contrast when the stereocilia move away from the kinocilium the tip-links are no longer stretched and no arms flowing so the cell is hyperpolarized. Now as I said this is not the sensory cell that transmits information to the rest of the brain. There it is compounded actually by an axon where the cell body sits in the spiral ganglia. What happens is this cell just depolarizes and hyperpolarizes and using probably glutamate as its neurotransmitter, when it depolarizes it tends to release more glutamate and that will cause the postsynaptic membrane to depolarize more and when it hyperpolarizes it releases less glutamate and that will cause the postsynaptic membrane to hyperpolarize. So the net result is that with this system when the stereocilia is moved towards thekinocilium the hair cell depolarizes, it increases glutamate release which ceases the membrane postsynaptic membrane to depolarize and then that axon will generate increase firing rate. So an increase firing rate as the result of that and on the flip side when the stereocilia move away from the kinocilium the hair cell hyperpolarizes, decreased neurotransmitter release, postsynaptic membrane hyperpolarizes and there is a decrease in the rate of action potentials. You are going to see this pattern repeated in retina as well. So here the hair cell is basically producing what are called graded potentials, it produces no action potentials. The action potentials are generated in the second order cell that projects into either the auditory of the cochlear nuclei or the vestibular nuclei
The firing of afferent…. [S11]
So the hair cells in the auditory and vestibular system which are drawn in a cartoon like this have little short cilia called stereocilia and then one large slightly heavier duty cilia called the kinocilia and when you deflect these stereocilia like this towards the kinocilium then hair cells depolarize. And when you move the stereocilia away from the kinocilium they tend to hyperpolarize. Now we now know in fact that the way this occurs, it was originally thought that the channels, the mechanosensitive channels were at the base of the cilia but they are not, it turns out that the stretch sensitive channels were actually the very tips of these cilia and they are in these areas at what are called locations where the cilia are connected with what are called tip-link, this is a tip-link. So if you can see when the cilium moves, just imagine this is a kinocilia and this is a stereocilia, when they move in this direction this little tip-link is no longer pulling on the membrane and so channels are closed. And then when it stretches to this position you can see the tip-links are stretched and they pull on the mechanosensitive channels and those channels open. So basically going from this position to this position you could have all the channels closed and all the channels open so the cell will either be hyperpolarized in this position or depolarized in this position. The other thing you should note is how this occurs over about 1 micron of displacement. It’s a very exquisitelysensitive mechanical system. It is sensitive to only 1 micron of movement of the stereocilia and it uses this (this is basically a lever type concept) so that you are basically using a small amount of movement with a lever to amplify the mechanical signal. So this is using a mechanical lever concept to amplify small movements of the stereocilia. (went back to slide 10)
Figure 21-3 [S12]
This gets a little more complicated. Chemoreceptors and photoreceptors signal through second messenger cascades. And the basic principle, here is the unstimulated condition where there is no odorant molecules. Here is the condition where there are odorantmolecules. Even when there are things that smell they will bind to a receptor, but that then activates this cyclic AMP cascade causing these channels to open. You are going tofind that there is a large and heterogeneous variety of olfactory receptors. The specificity in your olfactory system is produced by this receptor. You could detect millions of different smells. Sometimes good, sometimes not. The ability to detect different smells is produced through a variety of different receptors here.
Now photoreceptors come in less variety then the chemosensory receptors. Really there are only 2 major classes of photoreceptors, rods and they are sensitive to about 510nm wavelength and are used in relative darkness and dusk, and cones that are sensitive to short medium or long wavelengths of light, so they give you color vision. If we look at the rod and we willtalk about rod transduction. We can see that we can zoom in on these rods and there are all these discs lining the rod, repeated disc in a rod outer segment. Within the rod outer segments if you look at one of these discs you will see that there is a rhodopsin molecule sitting on the intracellular discs and that is sensitive to light. It is essential that you have a second messenger cascade because in fact the light sensitive molecule, rhodopsin which is on the intracellular discs, has to signal to the channels in the membrane of the outer segments. So how does it do that? Well basically in darkness there is an increased production of cyclic GMP and these cyclic GMP gated channels are open. When light comes along, rhodopsin absorbs the photon of energy, undergoes basically a change in structure which we will hear more about later. Second messenger cascade there is a hydrolysis of cyclic GMP reduces intracellular cyclic GMP levels and then channels close. Basically this membrane potential will hyperpolarize in response to light being absorbed by discs in the outer segments. So that is another basic sensory transduction. The whole principle is that youare taking energy in the form of light which the nervous system can’t use and transducing it into graded potential changes in the nervous system which can be interpreted by the rest of the brain.
Figure 1 [S13]
So I don’t usually ask people to memorize this because you are going to hear about it in other lectures so I can seem like a good guy.