Chapter 11 I. Organization of the nervous system A. The two main branches: Central Nervous System (CNS)- brain and spinal cord Peripheral Nervous System (PNS)- the rest. Originates from major nerves (bundles of neurons) coming out of the brain (cranial nerves) and spinal cord (spinal nerves) B. The PNS branches 1. Afferent vs. Efferent Divisions Afferent- "sensory." Brings information to the CNS about sensation (olfaction, audition, etc), "state of the body" (position of joints & muscles, stretch of organs, etc), pressure, pain, etc. Efferent- Brings messages out of the CNS to muscles and glands (called "effectors") 2. The Efferent Division a. Somatic vs. Autonomic Systems Somatic (SNS)- messages sent to skeletal muscle (that's what we talked about in muscle physiology) Autonomic (ANS)- messages sent to cardiac & smooth muscle, and glands b. The Autonomic Nervous System Parasympathetic- "normal" state of being; really- conserve energy, digest and excrete Sympathetic- "emergency"; really- mobilize energy, prepare for exercise or fasting * The para- and sympathetic systems have opposing effects to one another (ex. paradecreases heart rate, sympathetic increases heart rate). The quick & dirty introduction to them makes it sound like either one or the other is functioning, depending on whether there's an emergency or not. Really, both are typically influencing different parts of the body to varying extents at any given time. II. Histology of nervous tissue A. Neurons 1. Some characteristics With few exceptions (olfactory neurons and hippocampus), cannot divide, so are very long-lived High metabolic rate; that is, they use a lot of energy. Prefer glucose as the energy source. Consist of a cell body, dendrites, and an axon 2. Structure a. Cell body- large nucleus & nucleoli. Elaborate cytoskeleton which extend into axon. This is where neurotransmitters are made, and are sent down the axon to synaptic terminals. Lots of ribosomes and extensive ER: Nissl bodies (clumps of cell bodies appear gray because of Nissl bodies- "gray matter") b. Dendrites- highly branched extensions (branches- "dendritic spines"). Primary area of reception from other neurons (receive neurotransmitters). c. Axon- long extension that branches at the end (branches"telodendria," end at synaptic terminals) -axoplasm, axolemma -axon hillock- thickened area where axon merges with cell body -no Golgi or Nissl bodies -materials move between the cell body and synaptic terminals along microtubules ("neurotubules"). ATP is required (review microtubules from Chapter 3). Anterograde & retrograde flow. -the axon carries action potentials from the axon hillock to synaptic terminals. An action potential arriving at the synaptic terminals triggers the release of neurotransmitters. -axons of many neurons are myelinated (see "neuroglia," below). 3. Classification a. By structureBipolar- cell body between dendrites and axon. Rare, in sense organs. Unipolar- cell body bulges out to the side, axon and dendrites are continuous. Common in PNS, especially sensory. Multipolar- the "representative" neuron. The most common type. b. By function 1) Sensory/Afferent neurons- most are unipolar; brings info to the CNS; types-Exteroceptors- info about the outside world: touch, temperature, senses -Proprioceptors- info about position/movement of skeletal muscles & joints -Interoceptors- info about organ systems & pain 2) Motor neurons- efferent, multipolar 3) Interneurons- in CNS. Coordinate information, for instance, between sensory and motor neurons; multipolar B. Neuroglia- support cells of the nervous system 1. Support cells in the CNS a. Ependymal cells- line central cavities of brain and spinal cord, produce and circulate Cerebrospinal Fluid. b. Astrocytes -Wrap around capillaries and control which substances enter the CNS: blood-brain barrier -Extensive cytoskeleton gives support and structure to the CNS -Aid in repair of neural tissue -Absorb substances from interstitium (ex., neurotransmitters) c. Oligodendrocytes- numerous extensions "reach out" and wrap around axons, myelinating them. One oligodendrocyte adds myelination to many neurons. Myelinated CNS appears whitish and constitutes white matter. d. Microglia- derived from immune cells. Phagocytize debris and any pathogens that happen to invade. 2. PNS support cells a. Satellite cells- surround cell bodies, regulate interstitial fluid (help to maintain ions, etc). b. Schwann cells- surround axons -Some Schwann cells completely myelinate axons. The entire cell wraps itself around a segment of the axon. Unlike oligodendrocytes, each Schwann cell surrounds only one axon. Each axon has several Schwann cells wrapped around its length. -Some Schwann cells send a whimpy covering around many axons, and don't really wrap around them completely. Axons with this whimpy covering are considered unmyelinated. Many sensory neurons are unmyelinated. *Myelination affects the speed of conduction: myelinated neurons conduct signals MUCH faster (~250 miles/hour vs. ~2 mph). III. Neurophysiology A. Background: types of membrane channels we’ll be looking at: 1. Chemically regulated (“ligand-gated”): open/close in response to the binding of a chemical, like the Na+ channels of a muscle cell at the motor end plate. Facilitated diffusion. 2. Voltage regulated: open/close in response to a specific change in voltage, like the Na+ channels of a muscle cell along the rest of its membrane, and the Ca2+ channels in the SR. Facilitated diffusion 3. Mechanically regulated: open/close in response to some sort of mechanical stimulus, like pressure or vibration. We'll get to these later on. Facilitated diffusion. 4. Leak channels- always open; there are many more K+ leak channels than Na+, and this helps to create the electrochemical gradients that exist. Facilitated diffusion. 5. Sodium-potassium exchange pump- pumps 3 Na+ out and 2 K+ in; constantly working; helps to establish and maintain the electrochemical gradients that exist. Active transport. B. The nerve cell at rest 1. Leak channels: the membrane of a neuron contains leak channels for both Na+ and K+. However, it contains MANY more K+ leak channels. Since more K+ is in the cell than out, K+ passively diffuses down its concentration gradient through these leak channels to the exterior of the cell (the opposite is true for Na+). Since there are more K+ channels, more K+ ions leave the cell than Na+ ions enter. Therefore, more positive charges leave the cell than enter. This is partially responsible for creating the slight negative interior of the cell compared with the exterior. 2. Sodium-Postassium Exchange pumps- constantly work to pump Na+ out and K+ in, against their concentration gradients. It's not an even trade though. 3 Na+ are pumped out for every 2 K+ pumped in. Again, more positive charge goes out than comes in, helping to create the relative negative interior of the cell. 3. The resting potential of the average nerve cell is -70mV. *Keep in mind that the electrochemical gradient of sodium (the combination of electrical attraction and a concentration gradient) means sodium REALLY "wants" to get in, if it could. *Take a minute to draw a cell with several K+ leak channels, a few Na+ leak channels, and some Na+-K= exchange pumps. Draw an ion at each of these channels, and draw an arrow to indicate which direction each ion travels through. This will help you to visualize the uneven movement of positive charges. C. Introduction to action potential generation/propagation, and release of neurotransmitter 1. Local/graded potential- Neurotransmitters from the presynaptic cell binds to receptors in the postsynaptic cell, causing chemically-gated Na+ channels to open, and Na + rushes in. The interior of the cell becomes less negative, or depolarized (the voltage increases). If enough Na+ enters that the voltage around the axon hillock reaches threshold (-60 - -55 mV), an action potential will be generated. 2. Action potential a. Voltage-regulated Na+ channels at the base of the axon (adjacent to the hillock) respond to threshold voltage. At resting potential, the activation gate of these channels is closed, while the inactivation gate is open. At threshold, the activation gate opens. Now the channel is completely open and Na+ ions enter the cell, following their electrochemical gradient. As Na+ enter, the voltage increases (becomes less negative). When voltage reaches +30 mV, the inactivation gate closes, preventing further movement by Na+. Inactivation gates will reopen when voltage returns to around resting potential by the efflux of K+ (see below). *Side note: Na+ continues to enter the cell even after the voltage has hit zero because a concentration gradient for Na+ still exists. That is, even though the total charges have been balanced, there are still more Na+ outside than inside the cell, so Na+ will continue to move down its concentration gradient. b. Around the same time (+30mV), voltage-regulated K+ channels open. K+ then rushes out, following its electrochemical gradient. (Remember that there are more K+ inside than outside the cell, and at +30 mV, the exterior of the cell is actually negative compared with the interior). We are now in a phase where voltage is being restored by K+: repolarization. c. When enough K+ have left the cell that the voltage hits -70 again, K+ channels start to close, but some K+ still sneak through and voltage will peak around -90mV. At this point the cell is hyperpolarized. A hyperpolarized cell is less sensitive to stimuli, because a larger change in voltage is required to hit threshold. d. Sodium-Potassium exchange pumps will return the cell to its normal ion concentrations. *Keep in mind that each of these changes in voltage is a local event; that is, depolarization occurs first at the base of the axon. It causes an influx of Na+ through neighboring channels. That influx affects neighboring channels, which open; that effects the next neighbors down, and so-on. So depolarization (and all subsequent events) occurs sequentially down the axon, toward the synaptic terminals. e. Absolute refractory period: From the time the Na+ activation gate opens until the time the INactivation gate reopens, the cell cannot fire another action potential. Relative refractory period: After the inactivation gate reopens until the cell has restored resting ion distributions. The cell CAN fire another action potential during this time. 3. An action potential reaches a synaptic terminal -Voltage-gated Ca++ channels in the membrane open, Ca++ pours in from the extracellular fluid. -Ca++ triggers the release of Nt (neurotransmitters) from synaptic vesicles -Ca++ is actively pumped back out, and Nt are broken down by enzymes and the remnants are reabsorbed into the presynaptic cell (as in Ach); or, the Nt are taken up by the presynaptic cell whole (“reuptake,” as in serotonin). D. Other factors involved with Action Potentials and Synapses 1. Graded potentials a. Typically, one delivery of Nt onto a postsynaptic cell is not enough to trigger an AP. It will cause some depolarization, but not to threshold. More than one depolarization events are typically required to reach threshold and generate an AP. What can bring a cell to threshold? Spatial summation- many stimuli (ex. Nt) arrive at once Temporal summation- many stimuli arrive in rapid succession b. Excitatory Post-Synaptic Potentials (EPSP) and Inhibitory PostSynaptic Potentials (IPSP) An EPSP is a change in membrane potential that will make a neuron more likely to reach threshold. That is, it is a depolarized potential. A neuron that experiences an EPSP is "excited," or needs less stimulation to reach threshold. For example, in an EPSP, a few chemically-gated Na+ channels are opened. An IPSP is a change in membrane potential that will make a neuron less likely to reach threshold. That is, a hyperpolarized potential. A neuron that experiences an IPSP is "inhibited," or needs more stimulation to reach threshold. For example, in an IPSP, chemically-gated K+ or Cl- channels are opened. *Please read "Summation by the Post-Synaptic Neuron” *Take a minute to draw a neuron with chemically gated Na+, K+, and Cl- channels. Draw where these ions are in a resting cell (in or out of the cell). Now show yourself, with arrows, which direction each would travel if its channels were open. What effect will the movement of each have on the voltage (will the interior become more positive or more negative)? 2. Synaptic Potentiation-please read *Take a minute to draw three neurons: the presynaptic cell and the postsynaptic cell as usual. Now, draw the third neuron. This third neuron should have its synaptic terminal synapse with the synaptic terminal of the presynaptic neuron. Use arrows to indicate serotonin coming from that 3rd cell onto the presynaptic cell. Now draw Ca++ channels opening on the presynaptic cell, and Nt being released from it to the postsynaptic cell. 4. Speed of AP conduction (how fast an Action Potential travels down an axon) affected by two factors a. Diameter of axon- larger diameter = faster b. Myelination- myelinated axons = faster. In a myelinated axon, only the nodes of Ranvier contain ion channels, so the movement of ions seems to "jump" from node to node. This type of conduction is called saltatory (saltation- jumping). *Conduction in non-myelinated axons called continuous c. Axon types based on diameter & myelination Type A- large, myelin; up to ~300mph; ex. motor fibers to skeletal muscle Type B- medium, myelin; up to ~40 mph; ex. some fibers to smooth muscle, some from sensory Type C- small, no myelin; ~2 mph; ex. many sensory, many interneurons, some motor to smooth muscle III. Neurotransmitters A. Actions- *Keep in mind that the action of a neurotransmitter (whether it's excitatory or inhibitory, and whether it's direct or indirect) depends on the receptors of the postsynaptic cell. For instance, skeletal muscle contains receptors that open Na+ channels (excited) in response to Ach; while cardiac muscle contains receptors that open K+ or Cl- channels (inhibited) in response to Ach. *Please read "chemical synapses" under heading “The Synapse” 1. Direct- cause Na+, K+, or Cl- channels to open in response to binding of Nt. These have fast, short-term effects. 2. Indirect- cause the postsynaptic cell to change in some way, making it more or less sensitive to direct Nt (for example, could cause the postsynaptic cell to build more Na+ channels, so that each EPSP would be stronger because more sodium would enter with ONE stimulus). Indirectly acting Nt initiate a cascade of chemical reactions that include "secondmessenger" chemicals: when the Nt binds, chemicals within the cell "respond" and "send messages" to the nucleus (ex, we need more Na+ channels). B. Specific Nt; know structural class, whether it acts directly, indirectly or both; whether it is excitatory, inhibitory or both; whether it is used by the CNS, PNS or both; and general function. Keep in mind the function/s listed are oversimplified and often not the only function/s. 1. Ach- direct & indirect, excitatory(E) to skeletal muscle, inhibitory(I) to cardiac. Used in PNS and CNS. 2. Biogenic Amines (amino acid derivatives) a. NorEpinephrine (NE)- indirect, usually E, PNS & CNS. Among other functions- emergency response. b. Serotonin- indirect & direct, I, CNS. Mood regulation. c. Dopamine- indirect, I or E, CNS & PNS. Mood regulation, postural muscle control. 4. Glutamate- an amino acid. direct, E, CNS. Learning and memory. Overrelease kills neurons and is associated with stroke. 5. Opioids- a peptide. (incl. endorphins)- indirect, I, CNS. Pain reduction. 6. CO (carbon monoxide)-a gas. not well understood, may be involved with memory and concentration. *This is a VERY short list, and not all Nt have been discovered. IV. Neuronal Pools- Groups of interconnected interneurons. Can communicate in a number of different ways, which are not necessarily mutually exclusive: A. Divergence B. Convergence C. Serial processing D. Parallel Processing E. Reverberation