Module 5 Flashcards
(115 cards)
1
Q
Given what you have learned about excitatory and inhibitory neurotransmitters in section 4.16 of your textbook, which of the following neurotransmitters was the excitatory substance released by sympathetic nerve stimulation in Otto Loewi’s experiments (i.e., acceleranstoff)?
acetylcholine
epinephrine/adrenaline
glycine
GABA
A
epinephrine/adrenaline
2
Q
The substances responsible for increasing and decreasing heart rate in Otto Loewi’s experiments belong to which of the following classes of neurotransmitters, respectively?
catecholamines; unconventional neurotransmitters
catecholamines; amino acids
catecholamines; acetylcholine
indolamines; acetylcholine
A
catecholamines; acetylcholine
3
Q
Which of the following processes is primarily responsible for breaking down the neurotransmitter released by stimulation of the vagus nerve innervating the heart?
enzymatic degradation
reuptake by transporters
diffusion
none of the above
A
enzymatic degradation
4
Q
Acetylcholine has an inhibitory effect on cardiac tissue, but it has an excitatory effect in other tissues (e.g., at the neuromuscular junctions). Which of the following factors explains the dual effects of this transmitter?
the quantity of transmitter released at axon terminals
the way the transmitter is removed from the synaptic cleft
the receptor subtypes to which the transmitter binds
the number of receptors available for transmitter binding
A
the receptor subtypes to which the transmitter binds
5
Q
Which of the following best describes an endorphin?
neurotransmitter
neuromodulator
neurohormone
neurosteroid
A
neuromodulator
6
Q
Where can you find receptors for estradiol within neurons?
the plasma membrane
the cytoplasm
the nucleus
all of the above
A
all of the above
7
Q
Which of the following is NOT a test for learning and memory in rodents?
the Morris water maze
the radial arm maze
the elevated plus-maze
the social recognition test
A
the elevated plus-maze
8
Q
Which of the following is NOT a component of a metabotropic receptor?
a signal protein that traverses the plasma membrane 5 times
a signal protein that traverses the plasma membrane 7 times
a ligand binding site
a G protein with α, β, and γ subunits
A
a signal protein that traverses the plasma membrane 5 times
9
Q
The motor symptoms of Parkinson’s disease are attributed to degeneration of neurons producing which of the following neurotransmitters?
Acetylcholine
Serotonin
Dopamine
GABA
A
dopamine
10
Q
Which neurotransmitter is primarily involved in alertness and arousal?
Norepinephrine
Serotonin
Dopamine
GABA
A
Norepinephrine
11
Q
Which of the following is the primary neurotransmitter at neuromuscular junctions?
Dopamine
Acetylcholine
Glutamate
GABA
A
Acetylcholine
12
Q
The drug DNQX is a selective antagonist for a particular subtype of the glutamate receptor. What will be the result of applying DNQX to a neuron prior to applying glutamate to the same neuron?
The effect of glutamate will be amplified
The effect of glutamate will be diminished or blocked
The effect of glutamate will be unchanged
The neuron will be depolarized
A
The effect of glutamate will be diminished or blocked
13
Q
The acetylcholinesterase inhibitor Donepezil is used to treat:
Depression
Parkinson’s disease
Alzheimer’s disease
Epilepsy
A
Alzheimer’s disease
14
Q
As we discussed, excessive levels of dopamine (DA) are involved in schizophrenia. Thus, this disorder is typically treated with DA antagonists. Which of the following may be an unintended consequence (i.e., side effect) of these drugs?
muscle tremors
pain
mania
hyperactivity
A
muscle tremors
15
Q
Which of the following drug classes are typically used to treat depression?
selective serotonin reuptake inhibitors (SSRIs)
norepinephrine reuptake inhibitors (NRIs)
serotonin–norepinephrine reuptake inhibitors (SNRIs)
all of the above
A
all of the above
16
Q
What is an axodendritic synapse?
A
A synapse of an axon terminal button onto a dendrite.
17
Q
Many axodendritic synapses terminate on ___________ (nodules of various shapes that are located on the surfaces of many dendrites)
A
dendritic spines
18
Q
What are axosomatic synapses?
A
Synapses of axon terminal buttons on somas (cell bodies).
19
Q
Many axodendritic synapses terminate on ___________ (nodules of various shapes that are located on the surfaces of many dendrites)
A
dendritic spines
20
Q
An astrocyte is situated at the ________.
A
synapse.
21
Q
Most synapses in the brain form a tripartite synapse. What is a triparte synapse?
A
A synapse that involves two neurons and an astroglial cell. All three cells communicate with one another through synaptic transmission.
22
Q
How do signals travel within neurons? How do signals travel between neurons?
A
Signals travel within neurons through changes in electrical charge across the plasma membrane.
In contrast, signals between neurons (i.e., across synapses) travel through the release of specialized chemicals.
23
Q
In 1914, Henry Dale showed that acetylcholine affected visceral organs in ways that mimicked activation of the parasympathetic nervous system. How?
A
Both parasympathetic nervous system activation and intravenous administration of acetylcholine slow the heartbeat.
Dale also showed that the effects of acetylcholine were mimicked by injections of muscarine and nicotine, later found to be agonists for acetylcholine receptors. Based on these discoveries, Dale proposed that acetylcholine is naturally synthesized within the body and released by neurons.
24
Q
Flip to see Otto Loewi’s study in detail.
A
1) Loewi placed two freshly excised, beating frog hearts in perfusion chambers containing Ringer’s solution (a solution of salts and water that mimics body fluid, used to maintain excised tissues).
2) The two chambers were connected so that perfusion fluid could flow between them.
3) The first frog’s heart (frog A) was connected to the vagus nerve, a parasympathetic cranial nerve responsible for lowering the heart rate.
4) The second frog’s heart (frog B) was denervated (disconnected from its nerves).
5) Electrical stimulation of the vagus nerve attached to the first heart quicklv caused this heart to beat more slowly. Shortly after the first heart’s vagus nerve was stimulated, the second heart also began to beat more slowly, as though its own vagus nerve had been stimulated! The only explanation for this was that some component of the perfusion medium from the first chamber entered the second chamber and acted on the second heart.
25
Loewi’s simple, but elegant experiment confirmed that nerve impulses affect cardiac activity through chemical transmission. The chemical responsible for inhibiting the heartbeat, which Loewi called ____________, remained unidentified for several years until Henry Dale and colleagues isolated acetylcholine from mammalian organs.
"Vagusstoff"
26
In the 1930’s, work from Dale’s laboratory showed that acetylcholine was released by nerve stimulation and that injection of acetylcholine mimicked the effects of nerve stimulation.
Dale proposed that acetylcholine is an _________chemical responsible for signal transmission within the autonomic nervous system.
endogenous
27
Loewi also performed similar experiments in which he stimulated sympathetic nerves innervating a frog’s heart. Sympathetic nerve stimulation resulted in the release of an excitatory substance that increased the beating of a denervated heart in a connected perfusion chamber. Loewi called this excitatory substance _____________.
“acceleranstoff”.
28
Flip to see a summary of Module 5.1.
Although acetylcholine was first synthesized in the 1800s, its role as a neurotransmitter in the parasympathetic nervous system was not established until the 1900s following the experimental work of Otto Loewi and Henry Dale.
Electrical stimulation of parasympathetic and sympathetic nerves innervating the heart results in decreased and increased heart rate, respectively, effects which are mediated by different chemical neurotransmitters.
29
Neural signals are transmitted by a wide range of neurotransmitters, but not all chemicals that alter neural activity are neurotransmitters. A number of criteria have been established that identify a chemical substance as a neurotransmitter at a given synapse. These criteria distinguish neurotransmitters from other signalling molecules that alter nervous system activity, such as hormones.
What are the 3 main criteria that a chemical must meet in order to be considered a neurotransmitter?
1) Presence within the presynaptic neuron - The neuron must contain the enzymes and precursors needed to synthesize the neurotransmitter chemical, or it must take up the chemical upon release by nearby cells.
2) Activity-dependent release - The neurotransmitter chemical must be released by the presynaptic neuron in response to arrival of an action potential at the axon terminal AND The chemical release should be Ca2+-dependent.
3) Action at postsynaptic receptors - Receptors for the neurotransmitter chemical must exist on the postsynaptic membrane AND Application of the chemical to the postsynaptic neuron should mimic the effects of endogenous activation of the presynaptic neuron.
30
What is the difference between a neurotransmitter and a neuromodulator?
Neurotransmitter - is a chemical that is released from the axon terminal of one neuron that either excites (depolarizes) or inhibits (hyperpolarizes) a nearby postsynaptic neuron.
Neuromodulator - is a chemical that is released from one neuron and alters the activity of a population of neurons. Neuromodulators tend to be released diffusely into the extracellular fluid, rather than at a particular synapse.
31
Neuromodulators act diffusely to alter the strength of neural activity across ______________, rather than transmitting excitatory or inhibitory signals directly from one neuron to another.
a population of neurons
32
The postsynaptic neurons affected by neuromodulators may be relatively ________ from the presynaptic (i.e., the releasing) neuron compared to the distances reached by neurotransmitters.
far
33
Neuromodulators tend to exert their effects by binding to ________________ receptors, rather than fast-acting ionotropic receptors.
slow-acting metabotropic
34
Owing to the different classes of receptors to which each neurochemical binds, the effects of neuromodulators tend to take _________ to develop and last longer compared to the effects of neurotransmitters.
longer
(The longer-lasting action of neuromodulators is due to the fact that their re-uptake and/or enzymatic breakdown is often significantly slower when compared to neurotransmitters.)
35
Flip to see the action of neurotransmitter (red) at ionotropic receptor:
Ligand binding at an ionotropic receptor causes the associated ion channel to rapidly open or close, inducing membrane depolarization or hyperpolarization.
36
Flip to see action of neuromodulator (yellow) at metabotropic receptor:
Ligand binding at a metabotropic receptor causes dissociation of the alpha subunit of the associated G protein (signalling molecule), leaving it free to act on nearby ion channels or induce the synthesis of second messengers.
37
The distinction between a neurotransmitter and a neuromodulator is not based on the chemical itself (e.g., its structure) but, rather, on the nature of the _______________________.
chemical’s release and binding to postsynaptic receptors.
38
Does the feature "fast-acting" describe a neurotransmitter or a neuromodulator?
Neurotransmitter
39
Does the feature "slow-acting" describe a neurotransmitter or a neuromodulator?
Neuromodulator
40
Does the feature "volume conduction within the extracellular space" describe a neurotransmitter or a neuromodulator?
Neuromodulator
41
Does the feature "diffuse actions on populations of neurons" describe a neurotransmitter or a neuromodulator?
Neuromodulator
42
Does the feature "long-lasting effects" describe a neurotransmitter or a neuromodulator?
Neuromodulator
43
Does the feature "binds to ionotropic receptors" describe a neurotransmitter or a neuromodulator?
Neurotransmitter
44
Does the feature "short-lasting effects" describe a neurotransmitter or a neuromodulator?
Neurotransmitter
45
Does the feature "binds to metabotropic receptors" describe a neurotransmitter or a neuromodulator?
Neuromodulator
46
Does the feature "directed action at postsynaptic neurons" describe a neurotransmitter or a neuromodulator?
Neurotransmitter
47
Does the feature "rapid break-down and reuptake" describe a neurotransmitter or a neuromodulator?
Neurotransmitter
48
What are some common neurotransmitters?
The amino acid transmitters glutamate, GABA, aspartate, and glycine.
Common neuromodulators include opioid peptides (e.g., enkephalins and endorphins). Interestingly, according to features listed above, several common neurotransmitters, such as serotonin, dopamine, histamine, and acetylcholine, are also technically neuromodulators.
49
What are some common neuromodulators?
Opioid peptides (e.g., enkephalins and endorphins).
(Interestingly, according to features listed above, several common neurotransmitters, such as serotonin, dopamine, histamine, and acetylcholine, are also technically neuromodulators.)
50
Flip notes on a the Module 5.2 Video about the (lesser-known) neuromodulator: The neurosteroid estradiol.
Neurosteroids: 17B-estradiol (E2)
Most biologically active of three major forms of estrogen.
E2 is primarily synthasized in the ovaries BUT it is also produced in a number of non-endocrine tissues in the brain, within the brain, it's E2 is synthesized mainly in regions involved in so-called neuroendoctrine functions. These include the hypothalamus and the preoptic area. E2 is also synthesized in a number of regions not primarily involved in endocrine functions such as the hippocampus
Important roles in nervous system development, neurogenesis, neuroprotection, and modulation of neuron activity, physiology, and plasticity.
Evidence suggests E2 is synthesized in neurons for both females and males in a wide range of vertabrate species. So it is not appropriate to view it as solely as a female steroid hormone but as a steroid that plays an important roles in both females and males.
We can't assess the concentration of E2, because it crosses the blood-brain barrier. Instead they assess the presence in those neurons of enzymes that we know to be necessary for E2 synthesis (ie: aromatase).
There can be lateralized effects of E2 on auditory signal processing and learning (because the birds only showed the effect when FAD was injected in the left hemisphere).
E2 enhances auditory neuron activity, signal processing, and learning and memory for salient acoustic inputs.
E2 may modulate neuron activity and signal processing, in part, by altering glutamate receptor activity
51
What are neurosteriods?
Neurosteroids (e.g., estrogens, testosterone, progesterone, glucocorticoids) are steroids that are produced within the nervous system and alter neural activity.
If we hear about chemicals such as estrogens and testosterone, we typically think about sex hormones that are released by endocrine glands located in the body, such as the ovaries and testes. Surprisingly, however, these steroid hormones also act in the central nervous system where they can function very much like a typical neuromodulator.
52
Flip to see a summary of Module 5.2
1) Neurotransmitters are distinguished from other signalling molecules by:
-their synthesis/presence within presynaptic neurons
-their release from the presynaptic neuron upon activation
-their activation of receptors to excite or inhibit nearby postsynaptic neurons
2) Neuromodulators are released diffusely into the extracellular space to affect multiple neurons and exert relatively delayed and long-lasting effects compared to neurotransmitters.
3) Neurosteroids such as estradiol and testosterone represent an important class of neuromodulators:
-Estradiol alters neuron activity and a range of cognitive processes, including learning and memory
53
Within the brain, neurotransmitters and neuromodulators have pronounced effects on a range of processes. Name a few of these processes.
Cognition, learning, memory, attention, mood, emotion, wakefulness, pain perception, and reward processing.
54
A neurotransmitter can be considered __________, ____________ or _____________ depending on its effects on postsynaptic neurons.
excitatory, inhibitory, or modulatory.
55
Glutamate - what are its receptor types and functions?
Receptor Type: Both ionotropic and metabotropic receptors
Functions: Primary excitatory transmitter in the CNS.
Involved in learning and memory.
56
γ-aminobutyric acid (GABA) - what are its receptor types and functions?
Receptor Type: Both ionotropic and metabotropic receptors
Functions: Primary inhibitory transmitter in the CNS
Involved in mood, learning, memory; and regulation of the sleep-wake cycle.
57
Acetylcholine
(ACh)- what are its receptor types and functions?
Receptor Type: Both ionotropic and metabotropic receptors
Functions: Involved in attention, learning, memory, and regulation of the sleep-wake cycle.
Within the peripheral nervous system, major transmitter at neuromuscular junctions; stimulates muscle contractions (except at the heart, where it has inhibitory effects; see section 5.1)
58
Dopamine
(DA) - what are its receptor types and functions?
Receptor Type: Metabotropic receptors
Functions: Involved in learning, memory, motivation, reward processing, and motor control.
Dopamine is released upon exposure to rewarding stimuli like drugs of abuse.
59
Norepinephrine (NE)/Noradrenaline (NA) - what are its receptor types and functions?
Receptor Type: Metabotropic receptors
Functions: Most common transmitter in the sympathetic nervous system.
Involved in alertness, attention, wakefulness, and stress (“fight or flight” processes).
60
Serotonin
(5-HT) - what are its receptor types and functions?
Receptor Type: Metabotropic receptors, with one exception
Functions: Involved in learning, memory, mood, emotion, pain, perception, and regulation of the sleep-wake cycle.
61
Histamine - what are its receptor types and functions?
Receptor Type: Metabotropic receptors
Functions: Involved in alertness, attention, learning, memory, pain perception, stress response, regulation of the sleep-wake cycle.
62
Each neurotransmitter binds to specific receptors in what is commonly referred to as a “lock-and-key” fashion (i.e., the transmitter fits its own receptor like a key fits its lock).
Flip to see explanations of this process from the Module 5.3 interactive diagram.
(Go back to module 5.3 for a diagram of this)
63
Re: the Module 5.3 Video:
What will be the effects of:
1) antagonizing acetylcholine receptors
and
2) inhibiting the breakdown of acetylcholine on spatial learning and memory in rats?
1. The selective acetylcholine receptor antagonist Scopolamine impaired spatial memory formation
2. The scopolamine-induced spatial memory impairment was prevented by inhibiting cholinesterase activity
What is the clinical relevance of these finsings?
* Cholinesterase inhibitors are used to treat the cognitive symptoms of Alzheimer's disease (Alzheimer's is related to low levels of of acetylcholine in the brain. Neurons that produce acetylcholine degenerate and die off in Alheimer's diseases.
* Behavioural tests in rodents can be used to assess the effects and utility of drugs developed to treat human diseases and disorders
64
Flip to see a summary of Module 5.3.
The effects of neurotransmitters are determined by the effects of their receptor activation; transmitters may excite, inhibit, or modulate postsynaptic neuron activity.
The role of individual neurotransmitters in a wide variety of psychological states and behaviours has been determined in part by the effects of manipulating neurotransmitter receptors.
An agonist is drugs that mimics the effects of a neurotransmitter at a particular receptor, whereas an antagonist is a drug that blocks or dampens the effects of a neurotransmitter at a particular receptor.
65
Several drugs commonly prescribed to treat neuropsychological conditions are agonists and antagonists of particular receptors. Although each receptor is specific to a particular chemical, each neurotransmitter may bind to multiple receptor subtypes. For example, serotonin binds to ________ different receptor subtypes!
15
(As we learn about the different effects that a single neurotransmitter can have depending on the receptor to which it binds, we can develop increasingly selective agonists and antagonists to treat conditions with fewer side effects.)
66
A variety of conditions are also commonly treated using drugs that prevent the ________ or _________ of particular neurotransmitters, rather than targeting receptors directly.
break down or reuptake
(These drugs prolong the time that neurotransmitters remain in the synaptic cleft upon release from the presynaptic neuron. If a neurotransmitter remains in the cleft for a longer period of time, it will bind to and activate a greater number of postsynaptic receptors and exert larger effects. These drugs may thus counteract low neurotransmitter levels.)
67
Describe the Neurotransmitter Imbalances associated with Alzheimer’s disease.
Alzheimer’s disease is a neurodegenerative disorder characterized by progressive impairments in learning and memory. Alzheimer’s disease is associated with reduced acetylcholine levels in the brain, resulting from degeneration of cholinergic (acetylcholine-producing) neurons in the basal forebrain.
Cholinesterase inhibitors (also called acetylcholinesterase inhibitors) are the primary drug type used to treat the symptoms of Alzheimer’s disease. These drugs work by inhibiting the enzyme (cholinesterase) that is responsible for the break-down of acetylcholine, thereby prolonging the presence of acetylcholine within the synaptic cleft.
68
Describe the Neurotransmitter Imbalances associated with Parkinson's Disease.
Parkinson’s disease is a neurodegenerative disorder characterized by severe motor impairments such as muscle tremors, bradykinesia (slowness of movement), and impaired posture, balance, and coordination. Parkinson’s disease is associated with reduced dopamine levels in the brain, resulting from degeneration of dopaminergic neurons in the basal ganglia (i.e., the substantia nigra).
The most common medication used to treat Parkinson’s disease is Levodopa (L-Dopa), the natural precursor to produce dopamine. Levodopa crosses the blood brain barrier, which allows it to be taken up by neurons and converted into dopamine.
69
Describe the Neurotransmitter Imbalances associated with Scizophrenia.
Schizophrenia is a serious condition characterized by a range of mental, emotional, and behavioural changes. The hallmark feature of schizophrenia is an abnormal perception of reality (e.g., hallucinations, delusions, and disordered thinking).
Schizophrenia has been linked to excessive levels of dopamine in the brain, particularly in the mesolimbic and prefrontal regions. Schizophrenia is commonly treated with antipsychotic medications that selectively antagonize particular dopamine receptors.
Recent research has also implicated alterations in other small-molecule neurotransmitters in schizophrenia (e.g., serotonin and norepinephrine) and combination drug therapies include compounds that alter the activity of these neurotransmitters in addition to dopamine.
70
Describe the Neurotransmitter Imbalances associated with depression.
Depression is a common mood disorder associated with persistent feeling of sadness and loss of interest. Depression has been linked to imbalances in multiple monoamines including serotonin, norepinephrine, and dopamine in the brain. Serotonin has received the most attention in depression research, with research indicating that depression may result from serotonin depletion in the brain.
Tricyclic antidepressants increase levels of serotonin and norepinephrine, but also have effects on other small-molecule neurotransmitters such as histamine and acetylcholine. Due to the side-effects associated with action across these transmitter systems, tricyclic antidepressants have been largely replaced by more selective drugs including selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs).
71
Describe the Neurotransmitter Imbalances associated with anxiety disorders.
Anxiety disorders are a collection of conditions characterized by excessive and persistent worry and fear, in the absence of threatening stimuli. Anxiety disorders include generalized anxiety disorder, social anxiety disorder, and post-traumatic stress disorder.
Like depression, various neurotransmitters are involved in anxiety, including GABA, glutamate, serotonin, and norepinephrine. Anxiety disorders may be treated using the same classes of drugs effective in depression, including SSRIs and SNRIs. Anxiety is also treated using anxiolytic (anxiety-reducing) drugs such as benzodiazepines, a type of GABA receptor agonist.
72
Describe the Neurotransmitter Imbalances associated with epilepsy.
Epilepsy is a common neurological condition characterized by the occurrence of repeated seizures. Seizures result from an excessive, uncontrolled excitation of large populations of neurons, which can spread throughout large parts of the brain, resulting in a loss of consciousness. It is thought that epilepsy results from an imbalance between excitatory and inhibitory neurotransmission (i.e., excessive excitation/insufficient inhibition).
A wide range of drugs may be prescribed to treat seizure disorders, including drugs that reduce glutamate (excitatory) activity and boost GABA (inhibitory) activity (e.g., GABA receptor agonists and GABA reuptake inhibitors). Seizure disorders may also be treated using drugs that block voltage-dependent sodium and calcium channels to reduce neuronal excitability (see Module 4).
73
A common theme pertaining to the clinical relevance of neurotransmitters is ____________.
balance.
Both excessive and insufficient amounts of neurotransmitters can result in serious neuropsychological conditions.
74
Flip to see a summary of Module 5.4.
Healthy nervous system function requires optimal neurotransmitter levels; both increases and decreases in the activity of particular neurotransmitters can have devastating effects.
Drugs used to treat diseases and disorders involving altered neurotransmitter levels include receptor agonists and antagonists, reuptake inhibitors, and drugs that prevent enzymatic transmitter degradation.
Non-selective agonists and antagonists can have many off-target (side) effects due to the presence of multiple receptor subtypes for most neurotransmitters.
75
Although axodendritic and axosomatic synapses are the most common synaptic arrangements, there are many others. List 3 of these.
Dendrodendritic synapses - which are interesting because they are often capable of transmission in either direction.
Axoaxonic synapses - these are particularly important because they can mediate presynaptic facilitation and inhibition. An axoaxonic synapse on or near a terminal button can selectively facilitate or inhibit the effects of that button on the post-synaptic neuron.
Axomyelenic synapses - in the central nervous system - where an axon synapses on the myelin sheath of an oligodendrocyte. This newly discovered type of synapse represents yet another form of neuron– glia communication.
76
What is the advantage of presynaptic facilitation and inhibition compared to PSPs?
They can selectively influence one particular synapse rather than the entire presynaptic neuron.
77
What are directed and non-directed synapses?
Directed synapses—synapses at which the site of neurotransmitter release and the site of neurotransmitter reception are in close proximity. This is a common arrangement, but there are also many nondirected synapses in the mammalian nervous system.
Nondirected synapses - are synapses at which the site of release is at some distance from the site of reception. In this type of arrangement, neurotransmitter molecules are released from a series of varicosities (bulges or swellings) along the axon and its branches and thus are widely dispersed to surrounding targets. Because of their appearance, these synapses are often referred to as string-of-beads synapses.
78
Describe how neurotransmitter molecules are synthesized and packaged in vesicles.
There are two basic categories of neurotransmitter molecules: large and small.
All large neurotransmitters are neuropeptides. Neuropeptides are short amino acid chains composed of between 3 and 36 amino acids; in effect, they are short proteins. Like other proteins, are assembled in the cytoplasm of the cell body on ribosomes; they are then packaged in vesicles by the cell body’s Golgi complex and transported by microtubules to the terminal buttons at a rate of about 40 centimeters (about 16 inches) per day. The vesicles that contain neuropeptides are usually larger than those that contain small-molecule neurotransmitters, and they do not usually congregate as closely to the presynaptic membrane as the other vesicles do.
Small-molecule neurotransmitters are typically synthesized in the cytoplasm of the terminal button and packaged in synaptic vesicles by the button’s Golgi complex. Once filled with neurotransmitter, the vesicles are stored in clusters next to the presynaptic membrane.
79
True or False?
Each neuron synthesizes and releases only one neurotransmitter.
False.
Many neurons contain two neurotransmitters— a situation generally referred to as coexistence. The button illustrated in Figure 4.7 contains synaptic vesicles of two sizes. This suggests that it contains two neurotransmitters: a neuropeptide in the larger vesicles and a small-molecule neurotransmitter in the smaller vesicles. There is also coexistence of multiple small-molecule neurotransmitters in the same neuron.
80
How does the release of small-molecule neurotransmitters differs from the release of neuropeptides?
Small-molecule neurotransmitters are typically released in a pulse each time an AP triggers a momentary influx of Ca2+ ions into the pre- synaptic membrane.
In contrast, neuropeptides are typically released gradually in response to general increases in the level of intracellular Ca2+ ions, such as might occur during a general increase in the rate of neuron firing.
81
Explain the process of neurotransmitter exocytosis.
It is the process of neurotransmitter release.
When a neuron is at rest, synaptic vesicles that contain small-molecule neurotransmitters tend to congregate near sections of the presynaptic membrane that are particularly rich in voltage-gated calcium channels.
When stimulated by APs, these channels open, and Ca2+ (calcium) ions enter the button. The entry of the Ca2+ ions triggers a chain reaction that ultimately causes synaptic vesicles to fuse with the presynaptic membrane and empty their contents into the synaptic cleft.
82
How does the release of small-molecule neurotransmitters differ from the release of neuropeptides?
Small-molecule neurotransmitters are typically released in a pulse each time an AP triggers a momentary influx of Ca2+ ions into the pre- synaptic membrane;
in contrast, neuropeptides are typically released gradually in response to general increases in the level of intracellular Ca2+ ions, such as might occur during a general increase in the rate of neuron firing.
83
84
Once released, neurotransmitter molecules produce signals in postsynaptic neurons by binding to ________ in the postsynaptic membrane.
receptors
Each receptor is a protein that contains binding sites for only particular neurotransmitters; thus, a neurotransmitter can influence only those cells that have receptors for it. Any molecule that binds to another is referred to as its ligand, and a neurotransmitter is thus said to be a ligand of its receptor.
85
True or False?
Not all vesicles fuse with the presynaptic membrane.
True.
Some vesicles are released as intact packages into the extracellular space. These extracellular vesicles often carry larger molecules (e.g., proteins, RNA molecules) between different neurons and glia in the central nervous system. Some of these transmitted molecules can induce persistent changes in the expression of genes through epigenetic mechanisms.
86
Once released, neurotransmitter molecules produce signals in postsynaptic neurons by binding to ____________ in the postsynaptic membrane.
receptors
Each receptor is a protein that contains binding sites for only particular neurotransmitters; thus, a neurotransmitter can influence only those cells that have receptors for it. Any molecule that binds to another is referred to as its ligand, and a neurotransmitter is thus said to be a ligand of its receptor.
87
Most neurotransmitters bind to several different types of receptors. The different types of receptors to which a particular neurotransmitter can bind are called the _____________ for that neurotransmitter.
receptor subtypes
(The various receptor subtypes for a neurotransmitter are typically located in different brain areas, and they typically respond to the neurotransmitter in different ways.)
88
What is an advantage of receptor subtypes?
They enable one neurotransmitter to transmit different kinds of messages to different parts of the brain.
89
Describe the differences between ionotropic and metabotropic receptors.
Ionotropic receptors are associated with ligand-activated ion channels;
VS:
metabotropic receptors are typically associated with sig- nal proteins and G proteins (guanosine-triphosphate−sensitive proteins).
When a neurotransmitter molecule binds to an iono- tropic receptor, the associated ion channel usually opens or closes immediately, thereby inducing an immediate post- synaptic potential.
VS:
Metabotropic receptors are more prevalent than ionotropic receptors, and their effects are slower to develop, longer-lasting, more diffuse, and more varied. There are many different kinds of metabotropic receptors, but each is attached to a serpentine signal protein that winds its way back and forth through the cell membrane seven times. The metabotropic receptor is attached to a portion of the signal protein outside the neuron; the G protein is attached to a portion of the signal protein inside the neuron.
90
What happens when a neurotransmitter binds to a metabotropic receptor?
A subunit of the associated G protein breaks away. Then, one of two things happen, depending on the particular G protein:
1) The subunit may move along the inside surface of the membrane and bind to a nearby ion channel, thereby inducing an EPSP or IPSP; or
2) It may trigger the synthesis of a chemical called a second messenger (neurotransmitters are considered to be the first messengers). Once created, a second messenger diffuses through the cytoplasm and may influence the activities of the neuron in a variety of ways—for example, it may enter the nucleus and bind to the DNA, thereby influencing genetic expression. Thus, a neurotransmitter’s binding to a metabotropic receptor can have radical, long-lasting effects.
91
True or False:
Only metabotropic receptors can produce second messengers.
False.
There is now evidence that ionotropic receptors can also produce second messengers that can have enduring effects.
92
One type of metabotropic receptor— autoreceptors—warrants special mention. What are autoreceptors?
They are are metabotropic receptors that have two unconventional characteristics:
1) They bind to their neuron’s own neurotransmitter molecules, and
2) they are located on the presynaptic, rather than the postsynaptic, membrane.
Their usual function is to monitor the number of neurotransmitter molecules in the synapse, to reduce subsequent release when the levels are high, and to increase subsequent release when they are low.
93
True or False?
Epigenetic mechanisms can act on both ionotropic and metabotropic receptors.
True.
There is strong evidence that the structures of both types of receptors (and thus their functionality) can be altered through epigenetic mechanisms. Moreover, certain disorders may be the result of modifications to receptor structure via epigenetic mechanisms.
94
Differences between small-molecule and peptide neurotransmitters in patterns of release and receptor binding suggest that they serve different functions. How?
Small-molecule neurotransmitters tend to be released into directed synapses and to activate either ionotropic receptors or metabotropic receptors that act directly on ion channels.
In contrast, neuropeptides tend to be released diffusely, and virtually all bind to metabotropic receptors that act through second messengers. Consequently, the function of small-molecule neurotransmitters appears to be the transmission of rapid, brief excitatory or inhibitory signals to adjacent cells; and the function of neuropeptides appears to be the transmission of slow, diffuse, long- lasting signals.
95
If nothing intervened, a neurotransmitter molecule would remain active in the synapse, in effect clogging that channel of communication. What 2 mechanisms (that terminate synaptic messages) keep that from happening?
1) Reuptake by transporters
2) Enzymatic degradation
Reuptake - is the more common of the two deactivating mechanisms. The majority of neurotransmitters, once released, are almost immediately drawn back into the pre-synaptic buttons by transporter mechanisms.
In contrast, other neurotransmitters are degraded (broken apart) in the synapse by the action of enzymes— proteins that stimulate or inhibit biochemical reactions without being affected by them. For example, acetylcholine, one of the few neurotransmitters for which enzymatic degradation is the main mechanism of synaptic deactivation, is broken down by the enzyme acetylcholinesterase.
Terminal buttons are models of efficiency. Once released, neurotransmitter molecules or their breakdown products are drawn back into the button and recycled, regardless of the mechanism of their deactivation. Even the vesicles, once they have done their job, are drawn back into the neuron from the presynaptic membrane and are used to create new vesicles.
96
Describe the roles of glia and gap junctions in synaptic transmission.
Glia - astrocytes have been shown to release chemical transmitters, to con- tain receptors for neurotransmitters, to conduct signals, and to influence synaptic transmission between neurons
Gap Junctions - are narrow spaces between adjacent cells that are bridged by fine, tubular, cytoplasm-filled protein channels, called connexins. Consequently, gap junctions connect the cytoplasm of two adjacent cells, allowing electrical signals and small molecules (e.g., second messengers) to pass from one cell to the next. Gap junctions are responsible for the existence of electrical synapses, which can transmit signals much more rapidly than chemical synapses.
Cerebral gap junctions occur between all classes of cerebral cells; however, the majority of them seem to occur between cells of the same kind. For example, many gap junctions link astrocytes together. into networks of glial cells. Also, gap junctions between neurons are particularly prevalent between inhibitory interneurons of the same type. Accordingly, one function of gap junctions appears to be to synchronize the activities of like cells in a particular area. One aspect of astrocytic organization suggests that they too play a role of synchronizing activities of like cells in a particular area.
97
Unlike neurons, astrocytes are distributed _____________ throughout a particular area, with only one astrocyte per location and little overlap between the projections of adjacent astrocytes.
evenly
(This suggests that each astrocyte coordinates the activity of neurons in its domain, and with as many as 40,000 processes, each astrocyte has a great potential to coordinate activity. Gap junctions on astrocytes tend to occur at the end of each process, where it comes in contact with processes from adjacent astrocytes.)
98
Go back and do "Scan Your Brain" matching activity on page 113 of textbook.
99
Name the major classes of neurotransmitters.
classes of conventional small- molecule neurotransmitters: the amino acids, the monoamines, and acetylcholine.
A fourth group of various small-molecule neurotransmitters are often referred to as unconventional neurotransmitters because their mechanisms of action are unusual.
In contrast to the small-molecule neurotransmitters, there is only one class of large-molecule neurotransmitters: the neuropeptides.
100
Identify the class, and discuss at least one function, of AMINO ACID NEUROTRANSMITTERS.
The neurotransmitters in the vast majority of fast-acting, directed synapses in the central nervous system are amino acids— the molecular building blocks of proteins.
The four most widely studied amino acid neurotransmitters are: glutamate, aspartate, glycine, and gamma-aminobutyric acid (GABA). The first three are common in the proteins we consume, whereas GABA is synthesized by a simple modification of the structure of glutamate.
Glutamate is the most prevalent excitatory neurotransmitter in the mammalian central nervous system. GABA is the most prevalent inhibitory neurotransmitter; however, it has excitatory effects at some synapses
101
Identify the class, and discuss at least one function, of MONOAMINE NEUROTRANSMITTERS.
Each is synthesized from a single amino acid—hence the name monoamine (one amine). Monoamine neurotransmitters are slightly larger than amino acid neurotransmitters, and their effects tend to be more diffuse. The monoamines are present in small groups of neurons whose cell bodies are, for the most part, located in the brain stem. These neurons often have highly branched axons with many varicosities (string- of-beads synapses), from which monoamine neurotransmitters are diffusely released into the extracellular fluid.
There are four monoamine neurotransmitters: dopamine, epinephrine, norepinephrine, and serotonin.
They are subdivided into two groups, catecholamines and indolamines, on the basis of their structures.
Dopamine, norepinephrine, and epinephrine are catecholamines. Each is synthesized from the amino acid tyrosine. Tyrosine is converted to l-dopa, which in turn is converted to dopa- mine. Neurons that release norepinephrine have an extra enzyme (one that is not present in dopaminergic neurons), which converts the dopamine in them to norepinephrine. Similarly, neurons that release epinephrine have all the enzymes present in neurons that release norepinephrine, along with an extra enzyme that converts norepinephrine to epinephrine (see Figure 4.15). In contrast to the other monoamines, serotonin (also called 5-hydroxytryptamine, or 5-HT) is synthesized from the amino acid tryptophan and is classified as an indolamine.
Neurons that release norepinephrine are called noradrenergic; those that release epinephrine are called adrenergic. There are two reasons for this naming. One is that epinephrine and norepinephrine used to be called adrenaline and noradrenaline, respectively, by many scientists, until a drug company registered Adrenalin as a brand name. The other reason will become apparent if you try to say norepinephrinergic.
102
Identify the class, and discuss at least one function, of ACETYLCHOLINES.
Acetylcholine (abbreviated Ach) is a small-molecule neurotransmitter that is, in one major respect, like a professor who is late for a lecture: It is in a class by itself. It is created by adding an acetyl group to a choline molecule.
Acetylcholine is the neurotransmitter at neuromuscular junctions, at many of the synapses in the autonomic nervous system, and at synapses in several parts of the central nervous system. Recall that acetylcholine is broken down in the synapse by the enzyme acetylcholinesterase. Neurons that release acetylcholine are said to be cholinergic.
103
Identify the class, and discuss at least one function, of UNCONVENTIONAL NEUROTRANSMITTERS.
They act in ways that are different from those that neuroscientists have come to think of as typical for such substances.
One class of unconventional neurotransmitters, the soluble-gas neurotransmitters, includes nitric oxide and carbon monoxide. These neurotransmitters are produced in the neural cytoplasm and immediately diffuse through the cell membrane into the extracellular fluid and then into nearby cells. They easily pass through cell membranes because they are soluble in lipids. Once inside another cell, they stimulate the production of a second messenger and in a few seconds are deactivated by being converted to other molecules. They are difficult to study because they exist for only a few seconds.
Soluble-gas neurotransmitters have been shown to be involved in retrograde transmission. At some synapses, they transmit feedback signals from the postsynaptic neuron back to the presynaptic neuron. The function of retrograde transmission seems to be to regulate the activity of pre-synaptic neurons.
Another class Endocannabinoids - are neurotransmitters that are similar to delta-9-tetrahydrocannabinol (THC), the main psychoactive constituent of marijuana. So far, two endocannabinoids have been discovered: The most widely studied is anandamide (from the Sanskrit word ananda, which means “eternal bliss”). Like the soluble gases, the endocannabinoids are produced immediately before they are released. Endocannabinoids are synthesized from fatty compounds in the cell membrane; they tend to be released from the dendrites and cell body; and they tend to have most of their effects on presynaptic neurons, inhibiting subsequent synaptic transmission.
104
Identify the class, and discuss at least one function, of NEUROPEPTIDES.
There are 100s. 5 categories (the first 3 show how neuropeptides often function in multiple capacities, not just as neurotransmitters):
1) Pituitary peptides - contains neuropeptides that were first identified as hormones released by the pituitary;
2) hypothalamic peptides - contains neuropeptides that were first identified as hormones released by the hypothalamus
3) Brain–gut peptides - contains neuropeptides that were first discovered in the gut.
4) opioid peptides - contains neuropeptides that are similar in structure to the active ingredients of opium.
5) Miscellaneous peptides - is a catch-all category that contains all of the neuropeptide transmitters that do not fit into one of the other four categories.
105
Drugs have two fundamentally different kinds of effects on synaptic transmission. They either ___________ it or they ______________ it.
They facilitate it or they inhibit it.
106
What is an agonist?
Drugs that facilitate the effects of a particular neurotransmitter.
107
What is an antagonist?
Drugs that inhibit the effects of a particular neurotransmitter.
108
What are the 7 general steps common to most neurotransmitters?
(1) synthesis of the neurotransmitter,
(2) storage in vesicles,
(3) breakdown in the cytoplasm of any neurotransmitter that leaks from the vesicles,
(4) exocytosis,
(5) inhibitory feedback via autoreceptors,
(6) activation of postsynaptic receptors, and
(7) deactivation.
109
Some agonists of a particular neurotransmitter bind to postsynaptic receptors and activate them, whereas some antagonistic drugs, called ______________ , bind to postsynaptic receptors without activating them and, in so doing, block the access of the usual neurotransmitter.
receptor blockers
110
It was originally assumed that there was one kind of receptor for each neurotransmitter, but how was this notion dispelled by research on acetylcholine receptors?
Some acetylcholine receptors bind to nicotine (a CNS stimulant and the major psychoactive ingredient of tobacco), whereas other acetylcholine receptors bind to muscarine (a poisonous substance found in some mushrooms). These two kinds of acetylcholine receptors thus became known as nicotinic receptors and muscarinic receptors.
Nicotinic and muscarinic receptors are distributed differently in the nervous system, have different modes of action, and consequently have different behavioral effects. Both nicotinic and muscarinic receptors are found in the CNS and the PNS. In the PNS, many nicotinic receptors occur at the junctions between motor neurons and muscle fibers, whereas many muscarinic receptors are located in the autonomic nervous system (ANS). Nicotinic and muscarinic receptors are ionotropic and metabotropic, respectively.
111
Go back and take notes from page 118-119 on drugs/plant extracts.
112
What is Atropine?
The main active ingredient of belladonna, is a receptor blocker that exerts its antagonist effect by binding to muscarinic receptors, thereby blocking the effects of acetylcholine on them.
113
In the 1970s, it was discovered that opioid drugs such as morphine bind effectively to receptors in the brain. These receptors were generally found in the hypothalamus and other limbic areas, but they were most concentrated in the area of the brain stem around the cerebral aqueduct, which connects the third and fourth ventricles; this part of the brain stem is called the _______________.
periaqueductal gray (PAG).
114
The existence of selective opioid receptors in the brain raised an interesting question: Why are they there? They are certainly not there so that once humans discovered opium, opioids would have a place to bind. The existence of opioid receptors suggested that ________________________.
opioid chemicals occur naturally in the brain, and that possibility triggered an intensive search for them.
Several families of endogenous (occurring naturally within the body) opioids have been discovered.
1) Enkephalins (meaning “in the head”)
2) Endorphins (a contraction of “endogenous morphine”).
All endogenous opioid neurotransmitters are neuropep- tides, and their receptors are metabotropic.
115
In the 1950s, largely by chance, two drugs were found to have antipsychotic effects; that is, they reduced the severity of psychosis—the major symptom of schizo- phrenia. Although these two drugs were not related struc- turally, they both produced a curious pattern of effects: Neither drug appeared to have any antipsychotic activity until patients had been taking it for about 3 weeks, at which point the drug also started to produce mild Parkinsonian symptoms (e.g., tremor-at-rest).
Researchers put this result together with what two other findings?
(1) Parkinson’s disease is associated with the degeneration of a main dopamine pathway in the brain, and
(2) dopamine agonists (e.g., cocaine and amphetamines) produce a tran- sient condition that resembles schizophrenia. Together, these findings suggested that schizophrenia might be caused by excessive activity at dopamine synapses and thus that potent dopamine antagonists would be effective in its treatment.
