Ppt Chap 3


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Ppt Chap 3

  1. 1. Chapter 3 Synapses
  2. 2. The Concept of the Synapse <ul><li>Neurons communicate by transmitting chemicals at junctions called “synapses” </li></ul><ul><li>In 1906, Charles Scott Sherrington coined the term synapse to describe the specialized gap that existed between neurons. </li></ul><ul><li>Sherrington conducted his research investigating how neurons communicate with each other by studying reflexes (automatic muscular responses to stimuli). </li></ul>
  3. 4. The Concept of the Synapse <ul><li>Sherrington observed three important points about reflexes: </li></ul><ul><ul><li>Reflexes are slower than conduction along an axon. </li></ul></ul><ul><ul><li>Several weak stimuli presented at slightly different times or slightly different locations produces a stronger reflex than a single stimulus does. </li></ul></ul><ul><ul><li>As one set of muscles relaxes, another set becomes excited. </li></ul></ul>
  4. 5. The Concept of the Synapse <ul><li>Sherrington observed a difference in the speed of conduction in a reflex arc from previously measured action potentials. </li></ul><ul><li>He believed the difference must be accounted for by the time it took for communication between neurons. </li></ul><ul><li>Evidence validated the idea of the synapse. </li></ul>
  5. 7. The Concept of the Synapse <ul><li>Sherrington observed that repeated stimuli over a short period of time produced a stronger response. </li></ul><ul><li>Led to the idea of temporal summation or that repeated stimuli can have a cumulative effect and can produce a nerve impulse when a single stimuli is too weak. </li></ul>
  6. 8. The Concept of the Synapse <ul><li>Sherrington also noticed that several small stimuli on a similar location produced a reflex when a single stimuli did not. </li></ul><ul><li>This led to the idea of spatial summation or that synaptic input from several locations can have a cumulative effect and trigger a nerve impulse. </li></ul>
  7. 11. The Concept of the Synapse <ul><li>Presynaptic neuron – the neuron that delivers the synaptic transmission </li></ul><ul><li>Postsynaptic neuron – the neuron that receives the message </li></ul><ul><li>Excitatory postsynaptic potential (EPSP) is a graded potential that decays over time and space. </li></ul><ul><li>The cumulative effect of EPSPs are the basis for temporal and spatial summation. </li></ul>
  8. 12. The Concept of the Synapse <ul><li>Sherrington also noticed that during the reflex that occurred, the foot of a dog that was pinched retracted while the other three feet were extended. </li></ul><ul><li>He suggested that an interneuron in the spinal cord sent an excitatory message to the flexor muscles of one leg and an inhibitory message was sent to the other three legs. </li></ul>
  9. 14. The Concept of the Synapse <ul><li>This led to the idea of inhibitory postsynaptic potential or the temporary hyperpolarization of a membrane. </li></ul><ul><li>An ISPS occurs when synaptic input selectively opens the gates for positively charged potassium ions to leave the cell or negatively charged chloride ions to enter the cells. </li></ul><ul><li>Serves as an active “brake”, that suppresses excitation. </li></ul>
  10. 16. The Concept of the Synapse <ul><li>Neurons can have thousands of synapses. </li></ul><ul><li>Both temporal and spatial summation can occur within a neuron. </li></ul><ul><li>The likelihood of an action potential depends upon the ratio of IPSPs to EPSPs at a given moment. </li></ul>
  11. 18. The Concept of the Synapse <ul><li>The spontaneous firing rate refers to the periodic production of action potentials despite synaptic input. </li></ul><ul><li>EPSPs increase the number of action potentials above the spontaneous firing rate. </li></ul><ul><li>IPSPs decrease the number of action potentials below the spontaneous firing rate. </li></ul>
  12. 19. Chemical Events at the Synapse <ul><li>German physiologist Otto Loewi was the first to convincingly demonstrate that communication across the synapse occurs via chemical means. </li></ul><ul><li>Neurotransmitters are chemicals that travel across the synapse and allow communication between neurons. </li></ul>
  13. 21. Chemical Events at the Synapse <ul><li>The major sequence of events allowing communication between neurons across the synapse: </li></ul><ul><ul><li>The neuron synthesizes chemicals that serve as neurotransmitters. </li></ul></ul><ul><ul><li>Neurons store neurotransmitters in axon terminals or transport them there. </li></ul></ul><ul><ul><li>An action potential triggers the release of neurotransmitters into the synaptic cleft. </li></ul></ul>
  14. 22. Chemical Events at the Synapse (cont.) <ul><li>The neurotransmitters travel across the cleft and attach to receptors on the postsynaptic neuron. </li></ul><ul><li>The neurotransmitters separate from the receptors. </li></ul><ul><li>The neurotransmitters are taken back into the presynaptic neuron, diffuse away, or are inactivated by chemicals. </li></ul><ul><li>The postsynaptic cell may send negative feedback to slow the release of further neurotransmitters. </li></ul>
  15. 24. Chemical Events at the Synapse <ul><li>Major categories of neurotransmitters include the following: </li></ul><ul><ul><li>Amino acids. </li></ul></ul><ul><ul><li>Neuropeptides. </li></ul></ul><ul><ul><li>Acetylcholine. </li></ul></ul><ul><ul><li>Monoamines. </li></ul></ul><ul><ul><li>Purines. </li></ul></ul><ul><ul><li>Gases. </li></ul></ul>
  16. 25. Chemical Events at the Synapse <ul><li>Neurons synthesize neurotransmitters and other chemicals from substances provided by the diet. </li></ul><ul><ul><li>Acetylcholine synthesized from choline found in milk, eggs, and nuts. </li></ul></ul><ul><ul><li>Tryptophan serves as a precursor for serotonin. </li></ul></ul><ul><li>Catecholimines contain a catechol group and an amine group. (epinephrine, norepinephrine and dopamine) </li></ul>
  17. 27. Chemical Events at the Synapse <ul><li>Smaller neurotransmitters are synthesized in the presynaptic terminal and held there for release. </li></ul><ul><ul><li>Example: acetylcholine </li></ul></ul><ul><li>Larger neurotransmitters are synthesized in the cell body and transported down the axon. </li></ul><ul><ul><li>Example: neuropeptides </li></ul></ul>
  18. 29. Neurotransmitters Amino Acids: glutamate, GABA, glycine, aspartate, maybe others A Modified Amino Acid: acetylcholine Monoamines (also modified from amino acids): indoleamines: serotonin catecholamines: dopamine, norepinephrine, epinephrine Peptides (chains of amino acids): endorphins, substance P, neuropeptide Y, many others Purines: ATP, adenosine, maybe others Gases: NO (nitric oxide), maybe others
  19. 30. Chemical Events at the Synapse <ul><li>Vesicles are tiny spherical packets located in the presynaptic terminal where neurotransmitters are held for release. </li></ul><ul><li>MAO (monoamine oxidase) is a chemical that breaks down excess levels of some neurotransmitters </li></ul><ul><li>Exocytosis refers to the excretion of the neurotransmitter from the presynaptic terminal into the synaptic cleft. </li></ul><ul><ul><li>Triggered by an action potential arriving fro the axon. </li></ul></ul>
  20. 31. Chemical Events at the Synapse <ul><li>Transmission across the synaptic cleft by a neurotransmitter takes fewer than .01 microseconds. </li></ul><ul><li>Most individual neurons release at least two or more different kinds of neurotransmitters. </li></ul><ul><li>Neurons may also respond to more types of neurotransmitters than they release. </li></ul>
  21. 33. Chemical Events at the Synapse <ul><li>Proteins tether neurons together and guide neurotransmitter molecules to receptors. </li></ul><ul><li>An ionotropic effect refers to when a neurotransmitter attaches to receptors and immediately opens ion channels. </li></ul><ul><li>Most effects occur very quickly and are very short lasting. </li></ul><ul><li>Most ionotropic effects rely on glutamate or GABA. </li></ul>
  22. 34. Chemical Events at the Synapse <ul><li>Metabotropic effects occur when neurotransmitters attach to a receptor and initiates a sequence of slower and longer lasting metabolic reactions. </li></ul><ul><li>Metabotropic events include such behaviors as hunger, fear, thirst, or anger. </li></ul><ul><li>When neurotransmitters attach to a metabotropic receptor, it bends the rest of the protein . </li></ul><ul><li>Bending allows a portion of the protein inside the neuron to react with other molecules. </li></ul>
  23. 36. Chemical Events at the Synapse <ul><li>The portion inside the neuron activates a G-protein –one that is coupled to guanosine triphosphate (GTP), an energy storing molecule. </li></ul><ul><li>G-protein increases the concentration of a “second-messenger”. </li></ul><ul><li>The second messenger communicates to areas within the cell. </li></ul><ul><ul><li>May open or close ion channels, alter production of activating proteins, or activate chromosomes. </li></ul></ul>
  24. 38. Chemical Events at the Synapse <ul><li>Metabotropic effects utilize a number of different neurotransmitters </li></ul><ul><li>Neuropeptides are often called neuromodulators </li></ul><ul><ul><li>Release requires repeated stimulation </li></ul></ul><ul><ul><li>Released peptides trigger other neurons to release same neuropeptide </li></ul></ul><ul><ul><li>Diffuse widely and affect many neurons via metabotropic receptors </li></ul></ul>
  25. 39. Chemical Events at the Synapse <ul><li>A hormone is a chemical secreted by a gland or other cells that is transported to other organs by the blood where it alters activity. </li></ul><ul><li>Endocrine glands are responsible for the production of hormones. </li></ul><ul><li>Hormones are important for triggering long-lasting changes in multiple parts of the body. </li></ul>
  26. 40. Chemical Events at the Synapse <ul><li>Protein hormones and peptide hormones are composed of chains of amino acids and attach to membrane receptors where they activate second messenger systems. </li></ul><ul><li>Hormones secreted by the brain can control the release of other hormones. </li></ul>
  27. 42. Chemical Events at the Synapse <ul><li>The pituitary gland is attached to the hypothalamus and consists of two distinct glands that each release a different set of hormones: </li></ul><ul><li>Anterior pituitary- composed of glandular tissue and synthesizes six hormones. </li></ul><ul><li>Posterior pituitary- composed of neural tissue and can be considered an extension of the hypothalamus </li></ul>
  28. 44. Chemical Events at the Synapse <ul><li>Neurons in the hypothalamus synthesize the hormones oxytocin and vasopressin which migrate down axons to the posterior pituitary. </li></ul><ul><ul><li>Also known as antidiuretic hormones </li></ul></ul><ul><li>The hypothalamus secretes releasing hormones . </li></ul><ul><ul><li>flow through the blood and stimulate the anterior pituitary to release a number of other hormones. </li></ul></ul>
  29. 46. Chemical Events at the Synapse <ul><li>The hypothalamus maintains a fairly constant circulating level of hormones through a negative-feedback system. </li></ul><ul><ul><li>Example : TSH- releasing hormone </li></ul></ul>
  30. 48. Chemical Events at the Synapse <ul><li>Neurotransmitters released into the synapse do not remain and are subject to either inactivation or reuptake . </li></ul><ul><li>Reuptake refers to when the presynaptic neuron take sup most of the neurotransmitter molecules intact and reuses the. </li></ul><ul><li>Transporters are special membrane proteins that facilitate reuptake. </li></ul><ul><ul><li>Example: Serotonin is taken back up into the presynaptic terminal. </li></ul></ul>
  31. 49. Chemical Events at the Synapse <ul><li>Examples of inactivation and reuptake include: </li></ul><ul><ul><li>Acetylcholine is broken down by acetylcholinesterase into acetate and choline. </li></ul></ul><ul><li>Some serotonin and catecholamine molecules are converted into inactive chemicals: </li></ul><ul><ul><li>COMT and MAO are enzymes that convert catecholamine transmitters into inactive chemicals. </li></ul></ul>
  32. 50. Chemical Events at the Synapse <ul><li>Negative feedback in the brain is accomplished in two ways: </li></ul><ul><li>Autoreceptors are receptors that detect the amount of transmitter released an inhibit further synthesis and release. </li></ul><ul><li>Post synaptic neurons respond to stimulation by releasing chemicals that travel back to the presynaptic terminal where the inhibit further release </li></ul>
  33. 51. Synapses, Drugs and Addiction <ul><li>The study of the influence of various kinds of drugs has provided us with knowledge about many aspects of neural communication at the synaptic level. </li></ul><ul><li>Drugs work by mimicking our own neurochemistry. </li></ul><ul><ul><li>Example: receptors in the brain respond to LSD and cocaine </li></ul></ul><ul><li>Drugs alter various stages of synaptic processing. </li></ul>
  34. 53. Substance Abuse and Addictions <ul><li>Addictive substances increase dopamine activity in certain areas of the brain. </li></ul><ul><li>Olds and Milner (1954) placed rats in a Skinner box that allowed self-stimulation of the brain by the pressing of a lever. </li></ul><ul><li>Rats sometimes pressed the lever 2000 times per hour to stimulated the release of dopamine in the nucleus accumbens. </li></ul>
  35. 55. Substance Abuse and Addictions <ul><li>Other behaviors that release dopamine include sexual excitement, gambling, and video games. </li></ul><ul><li>fMRI research indicates dopamine is released during viewing of “attractive” people. </li></ul>
  36. 56. Substance Abuse and Addictions <ul><li>Berridge and Robinson (1998) suggest an important distinction be made between “liking” and “wanting” behaviors. </li></ul><ul><li>Activity in the nucleus accumbens seems to be related to “wanting”. </li></ul><ul><ul><li>Results in a monopolization of attention. </li></ul></ul>
  37. 58. Drugs and the Synapse <ul><li>Drugs either facilitate or inhibit activity at the synapse. </li></ul><ul><ul><li>Antagonistic drugs block the effects of neurotransmitters. </li></ul></ul><ul><ul><li>Agonist drugs mimic or increase the effects of neurotransmitters. </li></ul></ul>
  38. 59. Drugs and the Synapse <ul><li>Drugs work by doing one or more of the following to neurotransmitters: </li></ul><ul><ul><li>Increasing the synthesis. </li></ul></ul><ul><ul><li>Causing vesicles to leak. </li></ul></ul><ul><ul><li>Increasing release. </li></ul></ul><ul><ul><li>Decreasing reuptake. </li></ul></ul><ul><ul><li>Blocking the breakdown into inactive chemical. </li></ul></ul><ul><ul><li>Directly stimulating or blocking postsynaptic receptors. </li></ul></ul>
  39. 60. Drugs and the Synapse <ul><li>A drug has an affinity for a particular type of receptor if it binds to that receptor. </li></ul><ul><ul><li>Can vary from strong to weak. </li></ul></ul><ul><li>The efficacy of the drug is its tendency to activate the receptor. </li></ul><ul><li>Drugs can have a high affinity but low efficacy. </li></ul>
  40. 61. Drugs and the Synapse <ul><li>Almost all abused drugs stimulate dopamine release in the nucleus accumbens, </li></ul><ul><ul><li>small subcortical area rich in dopamine receptors </li></ul></ul><ul><ul><li>an area responsible for feelings of pleasure </li></ul></ul><ul><li>Sustained bursts of dopamine in the nucleus accumbens inhibit cells that release the inhibitory neurotransmitter GABA </li></ul>
  41. 62. Drugs and the Synapse <ul><li>Drugs are categorized according to their predominant action or effect upon behavior </li></ul><ul><li>Stimulant drugs increase excitement, alertness, motor activity and elevate mood. </li></ul><ul><li>Examples: amphetamines, cocaine, methylphenidate (Ritalin), MDMA (Ecstasy), nicotine </li></ul>
  42. 63. Drugs and the Synapse <ul><li>Amphetamine stimulate dopamine synapses by increasing the release of dopamine from the presynaptic terminal. </li></ul><ul><li>Cocaine blocks the reuptake of dopamine, norepinephrine, and serotonin. </li></ul><ul><li>Methylphenidate (Ritalin) also blocks the reuptake of dopamine but in a more gradual and more controlled rate. </li></ul><ul><ul><li>Often prescribed for people with ADD </li></ul></ul>
  43. 64. Drugs and the Synapse <ul><li>MDMD (ecstasy) increases the release of dopamine at low doses that account for its stimulant properties. </li></ul><ul><li>Increases the release of serotonin at higher doses accounting for its hallucinogenic properties. </li></ul><ul><li>Research indicates damage to neurons that contain serotonin. </li></ul><ul><li>Degree of risk to humans is not clear. </li></ul>
  44. 65. Drugs and the Synapse <ul><li>Nicotine is the active ingredient in tobacco. </li></ul><ul><li>Nicotine stimulates one type of acetylcholine receptor known as the nicotinic receptor . </li></ul><ul><li>Nicotinic receptors are found in the central nervous system, the nerve-muscle junction of skeletal muscles and in the nucleus accumbens. </li></ul><ul><li>Nicotinic receptors are also abundant in the nucleus accumbens and facilitate dopamine release. </li></ul>
  45. 66. Drugs and the Synapse <ul><li>Opiate drugs are those that are derived from (or similar to those derived from) the opium poppy. </li></ul><ul><li>Opiates decrease sensitivity to pain and increase relaxation by attaching to endorphin receptors in the brain. </li></ul><ul><li>Examples: morphine, heroin, methadone. </li></ul>
  46. 67. Drugs and the Synapse <ul><li>The brain produces peptides called endorphins. </li></ul><ul><li>Endorphin synapses may contribute to certain kinds of reinforcement by inhibiting the release of GABA indirectly. </li></ul><ul><li>Endorphin synapses inhibit ventral tagmental neurons that release GABA </li></ul><ul><li>Inhibiting GABA indirectly releases dopamine. </li></ul>
  47. 68. Drugs and the Synapse <ul><li>Tetrahydocannabinol (THC) is the active ingredient in marijuana. </li></ul><ul><li>THC attaches to cannabinoid receptors throughout the brain but especially the cerebral cortex, cerebellum, basal ganglia, and hippocampus. </li></ul><ul><li>Anandamide and 2-AG are the endogenous chemicals that attach to these receptors. </li></ul>
  48. 69. Drugs and the Synapse <ul><li>The location of the receptors in the brain may account for the subjective effects of loss of time, an intensification of sensory experience, and also memory impairment. </li></ul><ul><li>The cannabinoid receptors are located on the presynaptic neuron and inhibit the release of glutamate and GABA. </li></ul>
  49. 70. Drugs and the Synapse <ul><li>Hallucinogenic drugs cause distorted perception. </li></ul><ul><li>Many hallucinogenic drugs resemble serotonin in their molecular shape. </li></ul><ul><li>Hallucinogenic drugs stimulate serotonin type 2A receptors (5-HT 2A ) at inappropriate times or for longer duration than usual thus causing their subjective effect. </li></ul>
  50. 72. Drugs Main Behavioral Effects Main Synaptic Effects Amphetamine Excitement, alertness, elevated mood, decreased fatigue Increases release of dopamine and several other transmitters Cocaine Excitement, alertness, elevated mood, decreased fatigue Blocks reuptake of dopamine and several other transmitters Methylphenidate (Ritalin) Increased concentration Blocks reuptake of dopamine and others, but gradually
  51. 73. Drugs Main Behavioral Effects Main Synaptic Effects MDMA (“ecstasy”) Low dose: stimulant Higher dose: sensory distortions Releases dopamine Releases seratonin, damages axons containing seratonin Nicotene Mostly stimulant effects Stimulates nicotinic-type acetylcholine receptor, which (among other effects) increases dopamine release in nucleus accumbens Opiates (e.g., heroin, morphine) Relaxation, withdrawal, decreased pain Stimulates endorphin receptors
  52. 74. Drugs Main Behavioral Effects Main Synaptic Effects Cannabinoids (marijuana) Altered sensory experiences, decreased pain and nausea, increased appetite Excites negative-feedback receptors on presynaptic cells; those receptors ordinarily respond to anandamide and 2AG Hallucinogens (e.g., LSD) Distorted sensations Stimulates seratonin type 2A receptors (5-HT 2A )
  53. 75. Drugs and the Synapse <ul><li>Alcohol is a drug that has a long historical use and is used widely throughout the world. </li></ul><ul><li>In moderate amounts, alcohol is associated with relaxation. </li></ul><ul><li>In greater amounts it impairs judgment and damages the liver and other organs. </li></ul><ul><li>Alcoholism/alcohol dependence is the continued use of alcohol despite medical or social harm even after one has decided to quit or decrease drinking. </li></ul>
  54. 76. Drugs and the Synapse <ul><li>Alcohol has a number of diverse physiological effects including: </li></ul><ul><ul><li>Inhibition of sodium across the membrane. </li></ul></ul><ul><ul><li>Expansion of the surface of membranes. </li></ul></ul><ul><ul><li>Decreased serotonin activity. </li></ul></ul><ul><ul><li>Enhanced response by the GABA A receptor. </li></ul></ul><ul><ul><li>Blockage of glutamate receptors. </li></ul></ul><ul><ul><li>Increased dopamine activity. </li></ul></ul>
  55. 77. Drugs and the Synapse <ul><li>The genetic basis for early-onset alcoholism is stronger than for later-onset, especially in men. </li></ul><ul><li>Researchers distinguish between two types of alcoholism </li></ul><ul><ul><li>Type I/Type A </li></ul></ul><ul><ul><li>Type II/Type B </li></ul></ul>
  56. 78. Substance Abuse and Addictions <ul><li>Type I/Type A characteristics include: </li></ul><ul><ul><li>Later onset. </li></ul></ul><ul><ul><li>Gradual onset. </li></ul></ul><ul><ul><li>Fewer genetic relatives with alcoholism. </li></ul></ul><ul><ul><li>Equal quantity between men and women. </li></ul></ul><ul><ul><li>Less severe. </li></ul></ul>
  57. 79. Substance Abuse and Addictions <ul><li>Type II/Type B characteristic include: </li></ul><ul><ul><li>Earlier onset (usually before 25). </li></ul></ul><ul><ul><li>More rapid onset. </li></ul></ul><ul><ul><li>More genetic relatives with alcoholism. </li></ul></ul><ul><ul><li>Men outnumber women. </li></ul></ul><ul><ul><li>Often severe. </li></ul></ul><ul><ul><li>Often associated with criminality. </li></ul></ul>
  58. 80. Drugs and the Synapse <ul><li>Various factors contribute to continued substance abuse: </li></ul><ul><li>Tolerance develops </li></ul><ul><li>Cravings in response to cues </li></ul><ul><li>Brain reorganization (nucleus accumbens and prefrontal cortex) </li></ul>
  59. 81. Drugs and the Synapse <ul><li>Genes influence the likelihood of alcoholism in various ways: </li></ul><ul><ul><li>Sensitivity of Dopamine type 4 receptor </li></ul></ul><ul><ul><li>Control of COMT enzyme that breaks down dopamine </li></ul></ul>
  60. 83. Drugs and the Synapse <ul><li>Medications used to combat alcoholism include: </li></ul><ul><ul><li>Antabuse. </li></ul></ul><ul><ul><li>Methadone. </li></ul></ul><ul><ul><li>Many do not respond to other treatments so medications have been used to reduce cravings. </li></ul></ul>
  61. 84. Drugs and the Synapse <ul><li>Antabuse (disulfiram) works by antagonizing the effects of acetaldehyde dehydrogenase. </li></ul><ul><li>After alcohol consumption, enzymes in the liver metabolize it into a poisonous substance called acetaldehyde . </li></ul><ul><li>Acetaldehyde is converted by the enzyme acetaldehyde dehydrogenase into acetic acid , a chemical that the body can use as a source of energy. </li></ul><ul><li>Accumulation of acetaldehyde results in sickness. </li></ul>
  62. 85. Drugs and the Synapse <ul><li>Most studies suggest that Antabuse has been only moderately effective. </li></ul><ul><li>When effective, it supplements the alcoholic’s own commitment to quit. </li></ul><ul><li>Daily routine of pill ingestion may reaffirm commitment not to drink. </li></ul><ul><li>Many quit taking the pill and continue to drink. </li></ul>
  63. 86. Drugs and the Synapse <ul><li>Methadone is an opiate similar to heroin and morphine but is absorbed and metabolized slowly. </li></ul><ul><li>Perceived to be less harmful than other drugs. </li></ul><ul><li>Assumed to satisfy the cravings associated with the previous drug use and allow the person to carry on with their life. </li></ul>