What I plan to do for the next two or three classes is to briefly touch on a question you probably ask at some time or another--how does the whole nervous system work? That is, we've talked about how neurons generate action potentials and how two or a few neurons communicate, but we haven't really talked about how this all fits together into a functional nervous system. The general outlines of how things work are now known, but a great deal has yet to be discovered. While scientists are learning much about how incoming sensory information is processed and interpreted by the central nervous system and about how the brain decides and executes movements, much less is known about the "higher order functions" that most neuroscientists are most interested in. By this I mean such functions of the brain as judgment, reasoning, thinking (cognition), imagination, awareness, consciousness, and so forth. We know relatively little about where these activities take place in the brain, though brain imaging techniques are starting to reveal the answer to that question, and almost nothing about how these processes occur. A recent book claims that this may be unknowable and that these processes are destined to remain mysterious to us, though that's not the view of most neuroscientists.
The nervous systems of all animals seems designed to detect and interpret a variety of events taking place within or in the vicinity of the animal's body, to evaluate the significance of those events for the animal's well being, and to respond in appropriate ways that, at the most basic level, enhance the animal's chances for survival and reproduction. In other words the nervous system has a way to sense what's happening in an around the body (called the sensory arm), an arm to control movement (called the motor arm) and an analysis, integration, and decision making center somewhere between the two--input, output, and decisions. (See Fig. 1.6)
These different functions are reflected in the overall structure of the nervous system. If you recall our earlier discussions, sensory neurons are distributed throughout the body, but in vertebrates most have their cell body in clusters along the spinal cord called dorsal root ganglia, and whose axons enter the spinal cord in axon bundles called dorsal roots. (The exception to this is the 4 "special senses" whose sensory neurons are exclusively in the head--vision, hearing, taste and smell (olfaction)--and that connect directly into the brain, bypassing the spinal cord.). The output is achieved by motor neurons, consisting of two subsets. The somatic motor neurons, which mostly have cell bodies in the ventral horn of the spinal cord, innervate skeletal (or striated) muscle. The autonomic nervous system, consisting of sympathetic and parasympathetic motor neurons, innervates heart muscle, glands, and smooth muscles (e.g., in the iris, bladder, gut, blood vessels, etc.) (See Box 1A.)
All sensory systems are organized in more or less the same way, so I'll first introduce some general principles of how the sensory nervous system works and then focus on the kinds of sensation that are detected by the somatic sensory (or somatosensory) system. Throughout an animal's body are specialized nerve cells that can respond to events occurring within or near the body. These cells are called sensory receptors (which are very different from the transmitter receptor proteins we've been talking about); the events that activate them are called stimuli (singular = stimulus). Examples of receptors are the rod cells in the retina (for light), hair cells in the inner ear (for sound), taste buds in the tongue (chemicals), blood gas (O2 and CO2) sensors in blood vessels, proprioceptors in muscles and joints, etc. These receptors are sometimes called the primary or first order sensory neurons; as you might guess, there are secondary (second order), tertiary (third order) sensory neurons, etc. The stimuli that activate these receptors have detectable physical properties associated with them--for example, temperature, light (wavelength), air pressure, mechanical deformation of the skin, etc. The physical property of a stimulus that activates a receptor is called its modality. Stimuli are characterized both by a modality and by an amplitude (or intensity). Thus red light may be weak or intense, pressure may be light or heavy, sounds may be soft or loud, etc.
Each receptor responds primarily to a single kind of stimulus--i.e., is specific, and receptor neurons are often classed into four categories:
Mechanoreceptors--touch, hearing, joint position.
Thermoreceptors--heat, cold
Chemoreceptors--odors (airborne chemicals), blood COs concentration, blood glucose
Photoreceptors--light
Whatever their category, receptors that only respond to very intense stimuli (great heat or very sharp objects) are called nociceptors (which means receptors for noxious stimuli).
Receptors are also sometimes distinguished according to whether they detect events inside the body (interoceptors), outside the body (exteroceptors), or detect the position of the body in space (proprioceptors). For example, interoceptors detect heart rate, blood pressure, concentration of blood gases, etc. Exteroceptors detect light, heat, sound, smells, etc. And proprioceptors detect joint position, muscle stretch, etc. We are usually aware of input from exteroceptors, but not usually of information coming to the CNS from interoceptors or proprioceptors, although we can often get access to that information if we think about it. After a few seconds' thought you can tell where your hands, legs, nose, etc. are with respect to each other and your surroundings. That is, proprioception doesn't give a vivid sensation, the way sound or light do, but you can make yourself aware of what your proprioceptors are telling you. It's usually harder to detect input from interoceptors, but some people can detect their heart rate, and some can modify it at will.
How do receptor neurons work? As far as we know, all sensory cells respond to stimuli by alterations in their membrane potential, which often causes an action potential. And, as far as we know, the only way for a neuron to alter its membrane potential is to alter its membrane permeability to one or more ions. Thus, it's believed (and in many cases, known) that sensory cells contain ion channels whose conductance is changed in response to the sensory stimulus. These ion channels can be directly altered by the stimulus (stretch receptors are thought to have ion channels that increase their conductance for ions, especially sodium, when the cell's membrane is deformed). Or they can be indirectly altered as in the rod, which absorbs light with a protein called rhodopsin, which activates a lengthy second messenger system (destruction of cyclic GMP) that in turn alters ion channels in the rod cell membrane. These ion channels are not usually affected by tetrodotoxin or other drugs that block voltage-gated ion channels, so they are presumably distinct proteins from the voltage-gated ion channels and ligand-gated ion channels (although chemoreceptors might have ligand gated channels) that we have been discussing.
Typically a specific region of the sensory neuron contains a specialized structure that can respond to a stimulus with a change in membrane potential, and other regions do not. This specialized structure is called the receptive region of the neuron. In the touch, pain and temperature sensitive neurons in the skin, the receptive region is a specialized nerve ending right in the skin which is variously called an organ, a corpuscle, etc. If one touches the corpuscle, one gets an electrical response in the nerve cell, while if one touches the nerve cell body, no change in membrane potential is normally observed. So, just as there are specialized molecules located only in the presynaptic nerve terminal that are necessary for neurotransmission, there must be specialized molecules located only in the receptive region of the neuron that are necessary for detecting stimuli. Drawing here.
Conversion of energy from one form to another is called transduction by physicists. Since all sensory neurons convert one form of energy--concentration, light, air pressure, mechanical force--into electrical energy, they are transducers.
When a appropriate stimulus interacts with a sensory neuron, it causes a receptor potential (or generator potential) in the neuron. Like a synaptic potential, this is usually subthreshold at the receptive region, but it can spread to adjacent regions and cause depolarization there. The trigger zone of a neuron is the region with the lowest threshold for action potential firing, and the highest concentration of voltage gated sodium channels. In somatic sensory neurons, the trigger zone is usually adjacent to the receptive region of the neuron, so activation of the receptive region may cause an action potential that is then propagated all the way to the synapses that the sensory neurons make onto other neurons in the spinal cord. If, however, the intensity of the stimulus is too small to cause an action potential, then the central nervous system never becomes "aware" of the stimulus. Thus, a very dim light, soft sound, or weak touch (such as a mosquito landing on your skin) may never reach the level of your consciousness. Generally, the size (amplitude) of the receptor potential is roughly proportional to the intensity of the stimulus.
The size of the receptor potential also usually declines if the stimulus persists for a long time (this property is called "adaptation"; Fig. 8.2). For example, you notice your watchband when you put on your watch in the morning, but eventually lose awareness of it. That's because the pressure sensing neurons eventually adapt and stop sending information to your CNS. Adaptation can be rapid (the neuron ceases responding to the stimulus in less than a second) or slow (the neurons ceases to respond over several seconds; in some cases the neuron never completely adapts and continues to generate action potentials at regular intervals as long as the stimulus is present). The size of the receptor potential determines whether or not one or more action potentials is "fired" by the sensory neuron. If the stimulus is too small to bring the trigger zone to threshold, the stimulus is said to be subthreshold and is not "perceived" (Perception generally means that the sensory signal reaches the CNS, especially the brain. Thus, a signal might be generated in the sensory neuron but if the CNS doesn't become aware of it, it isn't perceived). If a stimulus is cause a response that is above the threshold for firing action potentials, then how many action potentials are generated depends on how long the membrane potential at the trigger zone stays above threshold (and, of course, on the refractory period for firing action potentials). A rapidly adapting receptor neuron might drop below threshold quickly, while a slowly adapting neuron's membrane potential will remain above threshold for a long time, causing a chain of action potentials. Usually the frequency of discharge (the rate at which the neuron "fires" action potentials) is roughly proportional to the intensity of the stimulus. It's thought that this fact serves as a kind of "coding" system. If you press gently on a touch receptor, it fires a few action potentials and then ceases. If you press hard, it fires many more. This difference in number and frequency of action potentials coming from the same kind of sensory neuron is somehow used by the brain to assess the intensity of the stimulus.
Further information about the nature of the stimulus is provided by the number of different receptor cells that are responding to a particular stimulus. Each receptor neuron is capable of responding to stimuli that impinge on a limited area of the body; this area is called its receptive field. For touch neurons, for example, I'd activate different sensory neurons by touching my finger tip than my palm or my elbow. Which particular receptors are being activated, of course, tells the brain about where on the body the stimulus is occurring. That's how you know if the pin is stuck in your hand or your foot. But if I touch my finger, I might actually activate two or more nearby sensory neurons. The brain uses the number of different active sensory neurons to evaluate how large the stimulus is--that is, a softball will activate more touch receptors than a golf ball, and thus I can tell, with my eyes closed, that a softball is the larger object. How well the brain can discriminate two closely spaced stimuli depends on the number and size of receptive fields present in a particular region of the body (as explained on pp. 151-2 of Purves et al.) Generally, the receptive fields for touch neurons are quite large in the skin of the back (i.e., there aren't many touch sensing neurons, so each one responds to touch of a large area of skin.) Thus two distinct stimuli that are close together might activate the same sensory neuron, and thus the brain would perceive them as one stimulus. But on the fingers or lips, the density of sensory neurons is high and receptive fields are small. Thus two closely spaced stimuli will probably activate two separate sensory neurons, and the brain will interpret them as separate events. (Fig. 8.4)
There's a kind of topological organization to the somatic sensory nervous system that the brain apparently uses to keep track of where things are happening in the body. As I mentioned earlier the sensory axons pass into the central nervous system through the dorsal roots of the spinal cord (see Fig. 1.13) Each segment of the spinal cord (defined as the area of one vertebra) has two dorsal roots, one on each side. Each dorsal root contains a large number of axons that carry sensory information. The sensory endings of the axons that enter a given dorsal root are normally clustered together on the surface of the body. The surface area of skin (cutaneous receptors) that generates the sensory information that enters the spinal cord through a single dorsal root is called its dermatome. In general the lower parts of the (human) body are innervated by sensory neurons that enter the lower part of the spinal cord (called the sacral and lumbar regions), the middle parts enter through the middle region of the spinal cord (called the thoracic region), and the upper body's innervation enters through the upper part of the spinal cord (called the cervical (neck) region). In addition sensory information from the right side of the body enters the dorsal roots on the right side of the spinal cord and vice versa. In other words there's a general correspondence between the surface area of the body (dermatome) and where its sensory information comes into the spinal cord; these inputs from different regions are kept separate in the spinal cord, all the way up to the brain. (see Box A, p. 155). This information allows neurologists to pinpoint where injury or disease is affecting the nervous system. For example, if someone is hit by a helmet in the back in a football game, and loses sensation in the right hip, but not above or below that area, then a neurologist would conclude that the damage to the spinal cord is around lumbar segments 2 or 3. (This correspondence between sensory area of the body surface and dorsal root isn't perfect because sensory neurons tend to scramble and reassort their sensory information That is, adjacent sensory cells send their axons into a bundle called a plexus, and different axons come out of the plexus into different dorsal roots.
So this means that there's considerable overlap in the dermatomes of adjacent dorsal roots. Thus damage to one dorsal root doesn't cause complete loss of sensation in a particular area of the skin, but rather a partial loss in sensation in a relatively large area.
When somatic sensory neurons enter the spinal cord, their axons branch and one branch up the spinal cord goes toward the brain while another branch goes down the spinal cord in the opposite direction. There's some jargon associated with this phenomenon. The branching of an axon is often called bifurcation. In the spinal cord, cells or information that move towards the brain are called "ascending" and those that move away from the brain are called "descending". Thus there are usually both ascending and descending branches of primary sensory neurons. The ascending branches carry information up to the brain, while the descending branches are usually involved in reflex arcs; they make synapses directly onto motor neurons that send axons back out to the periphery. In general, the sensory axons branch and travel up the same side of the spinal cord that they entered it--the axons of sensory inputs from the left half enter and remain on the left half of the spinal cord and vice versa. (Two objects or events on the same side (left/right) of the body are said to be ipsilateral; those on opposite sides are said to be contralateral. Thus the somatic sensory axons travel in the ipsilateral spinal cord.)
Fig. 8.6 in Purves shows what happens after the initial entry of the primary secondary neurons into the spinal cord. The axons travel in bundles, called tracts, (not " tracks") or columns. Moreover, the tracts are topologically organized. That is, axons that enter from lower parts of the body stay adjacent to each other, as do those that enter from the upper parts of the body; they don't intermix in the spinal cord. This topological segregation of sensory neurons according to where they originate in the body is maintained through several synapses all the way up the spinal cord to the cerebral cortex of the brain. Put another way, axons from leg sensory neurons stay together but are kept separate from axons from arm sensory neurons. When they reach the cerebral cortex therefore, there are separate parts of the cortex that receive sensory information from these different regions of the body. It's thought, of course, that this is how the brain "knows" where sensory information comes from. That is, if segment A of the cortex is active, that means that the information is from the leg; if it's segment B, the information is from the arm, etc.
The axons from the primary sensory neurons travel all the way up to the base of the brain in axon bundles in the white matter (which is white because it consists of myelinated axons) of the "dorsal columns" before they make a synapse onto groups of neuronal cell bodies in the medulla oblongata on the same side of the body. These "secondary" or "second order" neurons send their axons across the midline of the spinal cord to the contralateral side and then up to the thalamus. (When axons cross the midline of the body they are said to decussate). The thalamus is a region deep in the "forebrain" (which consists of most of what we think of as the brain, except the cerebellum and the brainstem (pons, medulla, and midbrain (see Fig. 1.7 in Purves et al.)). These neurons from the medulla make synapses on thalamic neurons in the ventral posterior part of the thalamus (i.e., the lower rear part); these thalamic neurons are the tertiary or third order sensory neurons. Essentially all sensory information passes through the thalamus--not only somatosensory information, but vision, smell, hearing, vestibular input, etc. Thus the thalamus seems to be an important "way station" for processing and integrating various kinds of sensory information coming into the brain. The thalamus "projects" its axons up to the cerebral cortex, the thin coating of neurons on the outside of the forebrain. There are six layers of neurons in the cerebral cortex of humans, and most somatosensory axons from the thalamus make synapses on the neurons of layer IV.
A particular area of the cerebral cortex receives inputs from the third order somatosensory neurons from the thalamus. This area, cleverly enough, is called the somatic sensory cortex. (Different regions of the cerebral cortex receive different kinds of sensory information--so there's also an auditory (sound) region of the cortex, olfactory (smell) cortex, visual cortex, etc.), It's pretty clear that sensory inputs from different parts of the body are channeled to different parts of the somatic sensory cortex, as shown in Figure 8.8 in Purves et al. This was figured out in the 1930s and later by Wilder Penfield and his coworkers. Penfield was a Canadian neurosurgeon who was performing neurosurgery on epileptics to remove damaged areas of their brain. He wanted to be sure he didn't remove some area of brain that would destroy some essential function (e.g., vision, reason), so he actually did the surgeries on awake patients. He used a local anesthetic on the scalp and then opened an incision in the scalp and skull exposing the brain underneath. He would locate the area of the epileptic activity (called the epileptic focus), and before he removed it, he would give the area a mild electrical stimulation and then ask the patient what they were perceiving. (The brain has no sensory receptors of its own, and thus the people didn't "feel" him touching or even carrying out surgery on their brains). Patients would say things like "something's tickling my leg" or "there's a hot spot in the middle of my back", when Penfield was stimulating the somatic sensory cortex. ("They'd "see" things when he stimulated the visual cortex, "smell" something if he stimulated the olfactory cortex, etc.) In this way, Penfield was able to map out which areas of the brain were responsible for interpreting which sensory (or motor) functions. Within the somatic sensory cortex, he found, as shown in Fig. 8.8, that different parts of the body were "perceived" when he stimulated different areas within that region. What's more the number of neurons (or size of the cortex) that interpreted information from different areas of the body were not proportional to the size of that part of the body; input from the hands and front of the head (i.e, the face) seemed to take up most of the somatic sensory cortex, while the rest of the body (except the genitals) had rather little input. That is, for humans the most important areas of the body, as far as the brains are concerned are the hands, and face (especially mouth), which in consistent with our knowing that we primarily use our hands to feel the world (rather than, say our feet or arms), we use our mouths and tongues to communicate, and our most vulnerable sensory organs--ears, nose and eyes--are in the front of the head. Thus, our nervous systems are organized in order to receive somatic sensory information preferentially from these vital areas.
In different animals the proportion of the somatic sensory cortex taken up by inputs from different areas of the body vary considerably. Rats, cats and other animals that use their whiskers to negotiate through space have, for example, very large areas of their somatic sensory cortex that receive whisker-derived inputs. It appears that the more important a particular portion of the body is for the successful functioning of a particular species, the larger the area of somatic sensory cortex that's devoted to interpreting information from that area of the body.
Purves et al. don't say, because no one knows, exactly how the cortex converts the incoming sensory information into perception. That is, Penfield showed that one could stimulate the cortex and get the same sensation as if you had touched a corresponding area of the body. That tells us that the cortex uses the topological segregation of the inputs to decide on where on the body the information is coming from, and the modality of the input (from heat rather than touch receptors, say) to decide whether it is feeling warmth or pressure, but no one yet knows how these individual inputs are assembled into the complex conscious awareness of the world around us that we experience. If you're looking for a topic that will keep you occupied in study throughout a career, that's one that will do.