2Synaptic Transmission Overview Link to Animated Video
3The Concept of the Synapse Synapse: gap between one neuron’s presynaptic terminal and another receiving neuronDiscovered by Santiago Ramon y Cajal in the late 1800s
4The Concept of the Synapse In 1906, Charles Scott Sherrington:coined the term synapse and proposed that neurons communicate by transmitting chemicals at synapsesconducted research on synaptic communication by studying reflexes (automatic muscular responses to stimuli).
5Reflex 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
6Sherrington deduced three properties of reflexes: Reflexes are slower than conduction along a single axon.
7Sherrington 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.
8Sherrington deduced three properties of reflexes: 3. As one set of muscles relaxes, another set becomes excited.
9John Eccles (1964) Postsynaptic neuron: receives the message Presynaptic neuron: delivers the synaptic potential
10Spatial summation: synaptic input from several locations can have a cumulative effect and trigger a nerve impulseTemporal 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 PotentialsFigure 3.4: Temporal and spatial summation.Fig. 3-4, p. 54
11Graded potentialseither depolarize (excite) or hyperpolarize (inhibit) the postsynaptic neurondecay over time and space
12The Concept of the Synapse Excitatory postsynaptic potential (EPSP) depolarizes neuron’s membraneis 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.
13The 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.
14Chemical Events at the Synapse Otto Loewi (1920): Discovered that transmission of a message across the synapse occurs by chemical means.
15Neuroanatomy 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 releaseNeurotransmitters (C): chemicals that travel across the synapse and allow communication between neuronsNeurotransmitter fragments (C1)
16Neurotransmitters 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.=
17Major 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.
18Major 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.
19Major 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.
20Major sequence of events for neurotransmitters: Reuptake (endocytosis) (H) refers to the presynaptic neuron taking up most of the neurotransmitter molecules intact and reusing them.
21Chemical 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.
22Pituitary GlandAttached 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
23Drugs and the SynapseDrugs 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.
26Drugs and the SynapseDrugs either facilitate or inhibit activity at the synapse.Antagonistic drugs block the effects of neurotransmitters.Agonist drugs mimic or increase the effects of neurotransmitters.
27Drugs and the SynapseA 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.
28Drugs and the SynapseAlmost all abused drugs stimulate dopamine release in the nucleus accumbens,small subcortical area rich in dopamine receptorsan area responsible for feelings of pleasure
29Drugs and the SynapseDrugs are categorized according to their predominant action or effect upon behaviorStimulant drugs increase excitement, alertness, motor activity and elevate mood.Examples: amphetamines, cocaine, methylphenidate (Ritalin), MDMA (Ecstasy), nicotineStimulant drugs directly stimulate dopamine receptor types D2, D3, and D4.
30Drugs and the SynapseAmphetamines 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
31Drugs and the Synapse MDMA (Ecstasy): increases the release of dopamine at low doses that account for its stimulant propertiesincreases 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.
32Drugs and the Synapse Nicotine: active ingredient in tobacco stimulates an acetylcholine receptor known as the nicotinic receptor, found incentral nervous systemnerve-muscle junction of skeletal musclesnucleus accumbens
33Drugs and the Synapse Opiate drugs: derived from opium poppy decrease sensitivity to pain and increase relaxationExamples: morphine, heroin, methadone.
34Drugs and the Synapse Endorphins: naturally produced neurotransmitters ease paininhibit GABA, allowing dopamine to exert its effectattach to the same receptors to which opiates attach.
35Drugs and the Synapse Tetrahydocannabinol (THC): active ingredient in marijuanaattaches to cannabinoid receptors, especially in the cerebral cortex, cerebellum, basal ganglia, and hippocampus.Cannabinoids: chemicals related to THC, typically used medicallyAnandamide and 2-AG are the endogenous chemicals that attach to these receptors.
37Drugs and the Synapse Hallucinogenic drugs: cause distorted perception may resemble serotonin in their molecular shapestimulate serotonin type 2A receptors (5-HT2A) at inappropriate times or for longer duration than usual thus causing their subjective effect.
38Alcohol and Alcoholism is associated with relaxationin greater amounts impairs judgment and damages the liver and other organsdependence (alcoholism) is the habitual use of alcohol despite medical or social harm
39Alcohol and Alcoholism Alcohol has a number of diverse physiological effects, including:Enhanced response by the GABAA receptorBlockage of glutamate receptorsIncreased dopamine activity
40Alcohol and Alcoholism Strong influence of genetics on alcoholismThe genetic basis for early-onset alcoholism is stronger than for later-onset, especially in menResearchers distinguish between two types of alcoholismType I/Type AType II/Type B
41Alcohol and Alcoholism Type I/Type A characteristics include:Later onset (usually after 25)Gradual onsetFewer genetic relatives with alcoholismEqual quantity between men and women
42Alcohol and Alcoholism Type II/Type B characteristics include:Earlier onset (usually before 25)More rapid onsetMore genetic relatives with alcoholismMen outnumber women
43Alcohol and Alcoholism Genes influence the likelihood of alcoholism in many ways, such as:being more sensitive and needing more alcohol to provide reinforcementbeing linked with impulsivityinfluencing responses to stress and anxiety-inducing experienceslikelihood of prenatal exposure to alcohol
44Alcohol and Alcoholism Research on sons of alcoholic fathers shows:Less average intoxication after one drinkStress decreases more than for the average personSmaller than normal amygdala
45Addiction Various factors contribute to continued substance abuse: Tolerance: The body’s decrease in response to a drug with repeated useWithdrawal: Uncomfortable/painful symptoms once drug use is discontinuedCravings develop in response to cuesBrain reorganization (nucleus accumbens and prefrontal cortex)
46Medications 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)=
47Medications to Combat Opiate Abuse Methadone is an opiate similar to heroin and morphine but is absorbed and metabolized slowlyPerceived to be less harmful than other drugsAssumed to satisfy cravings associated with previous drug useLevomethadyl acetate (LAAM) is similar to morphine but can be taken three times a week rather than daily