1. Chapter 3 Synapses

2. Synaptic Transmission Overview
Link to Animated Video

3. The Concept of the Synapse
Synapse: gap between one neuron’s presynaptic terminal and another receiving neuron
Discovered by Santiago Ramon y Cajal in the late 1800s

4. The Concept of the Synapse
In 1906, Charles Scott Sherrington:
coined the term synapse and proposed that neurons communicate by transmitting chemicals at synapses
conducted research on synaptic communication by studying reflexes (automatic muscular responses to stimuli).

5. Reflex arc: the complete circuit from sensory neuron to muscle response
Figure 3.1: A reflex arc for leg flexion.
The anatomy has been simplified to show the relationship among sensory neuron, intrinsic neuron, and motor neuron.
Fig. 3-1, p. 52

6. Sherrington deduced three properties of reflexes:
Reflexes are slower than conduction along a single axon.

7. Sherrington deduced three properties of reflexes:
2. Several weak stimuli presented at slightly different times or slightly different locations produces a stronger reflex than a single stimulus does.

8. Sherrington deduced three properties of reflexes:
3. As one set of muscles relaxes, another set becomes excited.

9. John Eccles (1964) Postsynaptic neuron: receives the message
Presynaptic neuron: delivers the synaptic potential

10. Spatial summation: synaptic input from several locations can have a cumulative effect and trigger a nerve impulse
Temporal summation: repeated stimuli can have a cumulative effect and can produce a nerve impulse when a single stimuli is too weak.
Link to animation of Summation of Postsynaptic Potentials
Figure 3.4: Temporal and spatial summation.
Fig. 3-4, p. 54

11. Graded potentials
either depolarize (excite) or hyperpolarize (inhibit) the postsynaptic neuron
decay over time and space

12. The Concept of the Synapse
Excitatory postsynaptic potential (EPSP) depolarizes neuron’s membrane
is a graded (excitatory) potential that decays over time and space.
The cumulative effect of EPSPs are the basis for temporal and spatial summation.
Inhibitory postsynaptic potential (IPSP): hyperpolarizes membrane.
Serves as an active “brake”, that suppresses excitation.

13. The Concept of the Synapse
The spontaneous firing rate refers to the periodic production of action potentials despite synaptic input.
EPSPs increase the nerve cell’s spontaneous firing rate.
IPSPs decrease the nerve cell’s spontaneous firing rate.

14. Chemical Events at the Synapse
Otto Loewi (1920): Discovered that transmission of a message across the synapse occurs by chemical means.

15. Neuroanatomy Handout #2: The Synapse and Neurotransmitters
Synaptic cleft (E)
Axon membrane (A)
Presynaptic membrane (A1)
Synaptic vesicles (B): tiny spherical packets located in the presynaptic terminal where neurotransmitters are held for release
Neurotransmitters (C): chemicals that travel across the synapse and allow communication between neurons
Neurotransmitter fragments (C1)

16. Neurotransmitters Approx. 100 different kinds
Neurons synthesize neurotransmitters and other chemicals from substances provided by the diet.
Acetylcholine is synthesized from choline found in milk, eggs, and nuts.
Serotonin is synthesized from tryptophan found in turkey and soy. =

17. Major sequence of events for neurotransmitters:
The neuron synthesizes chemicals that serve as neurotransmitters.
Neurons store neurotransmitters in axon terminals or transport them there (transportation from cell body can take hours or days).
An action potential triggers the release of neurotransmitters into the synaptic cleft.

18. Major sequence of events for neurotransmitters:
Exocytosis (D) refers to the excretion of the neurotransmitter from the presynaptic terminal into the synaptic cleft.
Triggered by an action potential arriving from the axon.

19. Major sequence of events for neurotransmitters:
The neurotransmitters travel across the cleft and attach to the postsynaptic membrane (F) at the postsynaptic receptor sites (G).
The neurotransmitters separate from the receptors.
The neurotransmitters are taken back into the presynaptic neuron, diffuse away, or are inactivated by chemicals.

20. Major sequence of events for neurotransmitters:
Reuptake (endocytosis) (H) refers to the presynaptic neuron taking up most of the neurotransmitter molecules intact and reusing them.

21. Chemical Events at the Synapse
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.
Endocrine glands are responsible for the production of hormones.
Hormones are important for triggering long-lasting changes in multiple parts of the body.

22. Pituitary Gland
Attached to the hypothalamus and consisting of two distinct glands that each release a different set of hormones:
Anterior pituitary- composed of glandular tissue and synthesizes six hormones.
Posterior pituitary- composed of neural tissue and can be considered an extension of the hypothalamus

23. Drugs and the Synapse
Drugs work by doing one or more of the following to neurotransmitters:
Increasing the synthesis.
Causing vesicles to leak.
Increasing release.
Decreasing reuptake.
Blocking the breakdown into inactive chemical.
Directly stimulating or blocking postsynaptic receptors.

24. Table 3-3, p. 76

25. Link to Mouse Party

26. Drugs and the Synapse
Drugs either facilitate or inhibit activity at the synapse.
Antagonistic drugs block the effects of neurotransmitters.
Agonist drugs mimic or increase the effects of neurotransmitters.

27. Drugs and the Synapse
A drug has an affinity for a particular type of receptor if it binds to that receptor.
Can vary from strong to weak.
The efficacy of the drug is its tendency to activate the receptor.
Drugs can have a high affinity but low efficacy.

28. Drugs and the Synapse
Almost all abused drugs stimulate dopamine release in the nucleus accumbens,
small subcortical area rich in dopamine receptors
an area responsible for feelings of pleasure

29. Drugs and the Synapse
Drugs are categorized according to their predominant action or effect upon behavior
Stimulant drugs increase excitement, alertness, motor activity and elevate mood.
Examples: amphetamines, cocaine, methylphenidate (Ritalin), MDMA (Ecstasy), nicotine
Stimulant drugs directly stimulate dopamine receptor types D2, D3, and D4.

30. Drugs and the Synapse
Amphetamines stimulate dopamine synapses by increasing the release of dopamine from the presynaptic terminal.
Cocaine blocks the reuptake of dopamine, norepinephrine, and serotonin.
Methylphenidate (Ritalin) also blocks the reuptake of dopamine but in a more gradual and more controlled rate.
Often prescribed for people with ADD

31. Drugs and the Synapse MDMA (Ecstasy):
increases the release of dopamine at low doses that account for its stimulant properties
increases the release of serotonin at higher doses accounting for its hallucinogenic properties.
Research indicates ecstasy use may contribute to higher incidences of anxiety and depression as well as memory loss and other cognitive deficits.

32. Drugs and the Synapse Nicotine: active ingredient in tobacco
stimulates an acetylcholine receptor known as the nicotinic receptor, found in
central nervous system
nerve-muscle junction of skeletal muscles
nucleus accumbens

33. Drugs and the Synapse Opiate drugs: derived from opium poppy
decrease sensitivity to pain and increase relaxation
Examples: morphine, heroin, methadone.

34. Drugs and the Synapse Endorphins: naturally produced neurotransmitters
ease pain
inhibit GABA, allowing dopamine to exert its effect
attach to the same receptors to which opiates attach.

35. Drugs and the Synapse Tetrahydocannabinol (THC):
active ingredient in marijuana
attaches to cannabinoid receptors, especially in the cerebral cortex, cerebellum, basal ganglia, and hippocampus.
Cannabinoids: chemicals related to THC, typically used medically
Anandamide and 2-AG are the endogenous chemicals that attach to these receptors.

37. Drugs and the Synapse Hallucinogenic drugs: cause distorted perception
may resemble serotonin in their molecular shape
stimulate serotonin type 2A receptors (5-HT2A) at inappropriate times or for longer duration than usual thus causing their subjective effect.

38. Alcohol and Alcoholism
is associated with relaxation
in greater amounts impairs judgment and damages the liver and other organs
dependence (alcoholism) is the habitual use of alcohol despite medical or social harm

39. Alcohol and Alcoholism
Alcohol has a number of diverse physiological effects, including:
Enhanced response by the GABAA receptor
Blockage of glutamate receptors
Increased dopamine activity

40. Alcohol and Alcoholism
Strong influence of genetics on alcoholism
The genetic basis for early-onset alcoholism is stronger than for later-onset, especially in men
Researchers distinguish between two types of alcoholism
Type I/Type A
Type II/Type B

41. Alcohol and Alcoholism
Type I/Type A characteristics include:
Later onset (usually after 25)
Gradual onset
Fewer genetic relatives with alcoholism
Equal quantity between men and women

42. Alcohol and Alcoholism
Type II/Type B characteristics include:
Earlier onset (usually before 25)
More rapid onset
More genetic relatives with alcoholism
Men outnumber women

43. Alcohol and Alcoholism
Genes influence the likelihood of alcoholism in many ways, such as:
being more sensitive and needing more alcohol to provide reinforcement
being linked with impulsivity
influencing responses to stress and anxiety-inducing experiences
likelihood of prenatal exposure to alcohol

44. Alcohol and Alcoholism
Research on sons of alcoholic fathers shows:
Less average intoxication after one drink
Stress decreases more than for the average person
Smaller than normal amygdala

45. Addiction Various factors contribute to continued substance abuse:
Tolerance: The body’s decrease in response to a drug with repeated use
Withdrawal: Uncomfortable/painful symptoms once drug use is discontinued
Cravings develop in response to cues
Brain reorganization (nucleus accumbens and prefrontal cortex)

46. Medications to Combat Alcohol Abuse
Revia (naloxone) blocks opiate receptors, thereby decreasing the pleasure from alcohol.
Antabuse (disulfiram) works by making user sick (only moderately effective)
= 

47. Medications to Combat Opiate Abuse
Methadone is an opiate similar to heroin and morphine but is absorbed and metabolized slowly
Perceived to be less harmful than other drugs
Assumed to satisfy cravings associated with previous drug use
Levomethadyl acetate (LAAM) is similar to morphine but can be taken three times a week rather than daily