Chapter 5 Non MCQ questions Flashcards
1
Q
What type of experiments revealed how Neurons communicate?
A
Experiments on heart beats.
2
Q
What does acetylcholine (ach) do?
A
acetylcholine (ach) first neurotransmitter discovered in the peripheral and central nervous systems; activates skeletal muscles in the somatic nervous system and may either excite or inhibit internal organs in the autonomic system.
3
Q
What does epinephrine (eP, or adrenaline) do?
A
epinephrine (eP, or adrenaline) Chemical messenger that acts as a hormone to mobilize the body for fight or flight during times of stress and as a neurotransmitter in the central nervous system.
Accelerayes heart rate in frogs.
Adrenaline (Latin) and epinephrine (Greek) are the same substance, produced by the adrenal glands located atop the kidneys. Adrenaline is the name more people know, in part because a drug company used it as a trade name, but EP is common parlance in the neuroscience community
4
Q
What does norepinephrine (ne, or noradrenaline) do?
A
norepinephrine (ne, or noradrenaline) Neurotransmitter found in the brain and in the sympathetic division of the autonomic nervous system; accelerates heart rate in mammals.
trade name, but EP is common parlance in the neuroscience community. Further experimentation eventually demonstrated that the chemical that accelerates heart rate in mammals is norepinephrine (NE, also noradrenaline), a chemical closely related to EP. The results of Loewi’s complementary experiments showed that ACh from the vagus nerve inhibits heartbeat, and EP from the accelerator nerve excites it.
5
Q
What is a Neurotransmitter?
A
neurotransmitter: Chemical released by a neuron onto a target with an excitatory or inhibitory effect.
Outside the central nervous system, many of the same chemicals, EP among them, circulate in the bloodstream as hormones. Under control of the hypothalamus, the pituitary gland directs hormones to excite or inhibit targets such as the organs and glands in the autonomic nervous system. In part because hormones travel through the bloodstream to distant targets, their action is slower than that of CNS neurotransmitters prodded by the lightning-quick nerve impulse
6
Q
Under control of (1) the (2) directs hormones to excite or inhibit targets such as the organs and glands in the autonomic nervous system.
A
(1) Hypothalamus.
(2) Pituitary Gland.
7
Q
How many neurotransmitters are there?
A
How many transmitters there are is an open question, with the number of 100 given for the maximum number and the number 50 given for the confirmed number. Whether a chemical is accepted as neurotransmitter depends on the extent to which it meets certain criteria.
8
Q
What are the symptoms of Parkinson’s disease?
A
Disorder of the motor system correlated with a loss of dopamine in the brain and characterized by tremors, muscular rigidity, and reduction in voluntary movement.
shaking was usually the first symptom, and it typically began in a hand. over a number of years, the shaking spread to include the arm and then other parts of the body.
as the disease progressed, patients had a propensity to lean forward and walk on the balls of their feet. They also tended to run forward to prevent themselves from falling. in the later stages of the disease, patients had difficulty eating and swallowing. They drooled and their bowel movements slowed. eventually, the patients lost all muscular control and were unable to sleep because of the disruptive tremors.
Jean-martin Charcot named the condition Parkinson’s disease
n 1919, Constantin Tréatikoff studied the brains of nine Parkinson patients on autopsy and found that the substantia nigra, a small nucleus in the midbrain, had degenerated. in the brain of one patient who had experienced symptoms of Parkinson’s disease on one side of the body only, the substantia nigra had degenerated on the side opposite that of the symptoms.
- Chemical examination of the brains of Parkinson patients showed that symptoms of the disease appear when the level of dopamine, then a proposed neurotransmitter, was reduced to less than 10 percent of normal in the basal ganglia.
3Confirming the role of dopamine in a neural pathway connecting the substantia nigra to the basal ganglia, urban ungerstedt found in 1971 that injecting a neurotoxin called 6-hydroxydopamine into rats selectively destroyed these dopamine-containing neurons and produced the symptoms of Parkinson’s disease. researchers have now linked the loss of dopamine neurons to an array of causes, including genetic predisposition, the flu, pollution, insecticides and herbicides, and toxic drugs. Dopamine itself has been linked not only to motor behavior but also to some forms of learning and to neural structures that mediate reward and addiction. Thus, this remarkable series of discoveries initiated by James Parkinson has been a source of more insight into the function of the brain than has the investigation of any other disease.
9
Q
What does Dopamine do?
A
dopamine (Da) is an amine neurotransmitter that plays a role in coordinating movement, in attention and learning, and in behaviors that are reinforcing
10
Q
What is Synaptic Vesicle?
A
synaptic vesicle organelle consisting of a membrane structure that encloses a quantum of neurotransmitter.
11
Q
What is the Synaptic Cleft?
A
gap that separates the presynaptic membrane from the postsynaptic membrane.
The synaptic Cleft is central to synapse function because Neurotransmitter chemicals must bridge this gap to carry a message from one neuron to the next.
12
Q
What are glial cells role in neurotransmitters?
A
The surrounding glia contribute to chemical neurotransmission in a number of ways—by supplying the building blocks for the synthesis of neurotransmitters or by mopping up excess neurotransmitter molecules, for example.
13
Q
What is a Gap Junction?
A
gap junction (electrical synapse) fused prejunction and postjunction cell membrane in which connected ion channels form a pore that allows ions to pass directly from one neuron to the next.
. Gap junctions are found in the mammalian brain, where in some regions they allow groups of interneurons to synchronize their firing rhythmically. Gap junctions also allow glial cells and neurons to exchange substances
14
Q
What are the benefits of a chemical synapse over electrical synapse?
A
Why, if chemical synapses transmit messages more slowly, do mammals rely on them more than on gap junctions? The answer is that chemical synapses are flexible in controlling whether a message is passed from one neuron to the next, they can amplify or diminish a signal sent from one neuron to the next, and they can change with experience to alter their signals and so mediate learning
15
Q
What is a chemical synapse?
A
chemical synapse Junction at which messenger molecules are released when stimulated by an action potential.
16
Q
What are the four steps in Neurotransmission?
A
The four-step process of transmitting information across a chemical synapse is illustrated in Figure 5-4 and explained in this section. In brief, the neurotransmitter must be
1. synthesized and stored in the axon terminal.
- transported to the presynaptic membrane and released in response to an action potential.
- able to activate the receptors on the target-cell membrane located on the postsynaptic membrane.
- inactivated, or it will continue to work indefinitely.
17
Q
What are the two ways Neurotransmitters can be derived?
A
Neurotransmitters are derived in two general ways, and these origins define two broad classes of neurotransmitters.
1: Some Synthezised in cells.
2: Some Derived from food
1: Some are synthesized in the cell body according to instructions contained in the neuron’s DNA, packaged in membranes on the Golgi bodies and transported on microtubules to the axon terminal. Cell-derived neurotransmitters may also be manufactured within the presynaptic terminal from mRNA that is transported to the terminal.
2: Other neurotransmitters are synthesized in the axon terminal from building blocks derived from food. Transporters, protein molecules that pump substances across the cell membrane, absorb the required precursor chemicals from the blood supply. (Sometimes transporter proteins absorb the neurotransmitter ready-made.) Mitochondria in the axon terminal provide the energy needed both to synthesize precursor chemicals into the neurotransmitter and to wrap them in membranous vesicles.
Regardless of their origin, neurotransmitters in the axon terminal can usually be found in three locations, depending on the type of neurotransmitter. Some vesicles are warehoused in granules, some are attached to microfilaments in the terminal, and still others are attached to the presynaptic membrane. These sites represent the steps in which a transmitter is transported from a granule to the membrane, ready to be released into the synaptic cleft.
18
Q
What is a transporter?
A
transporter: Protein molecule that pumps substances across a membrane.
19
Q
What is a Storage Granule?
A
storage granule membranous compartment that holds several vesicles containing a neurotransmitter.
20
Q
What chemical plays a role in action potentials on the presynaptic membrane?
A
Calcium cations (Ca21) play an important role. The presynaptic membrane is rich in voltage-sensitive calcium channels, and the surrounding extracellular fluid is rich in Ca21. As illustrated in Figure 5-5, the action potential’s arrival opens these calcium channels, allowing an influx of calcium ions into the axon terminal. The incoming Ca21 binds to the protein calmodulin, and the resulting complex takes part in two chemical reactions: one releases vesicles bound to the presynaptic membrane, and the other releases vesicles bound to microfilaments in the axon terminal.
21
Q
How does receptor site activation work?
A
After the neurotransmitter has been released from vesicles on the presynaptic membrane, it diffuses across the synaptic cleft and binds to specialized protein molecules embedded in the postsynaptic membrane. These
transmitter-activated receptors have binding sites for the transmitter substance. Through the receptors, the postsynaptic cell may be affected in one of three ways, depending on the type of neurotransmitter and the kind of receptors on the postsynaptic membrane. The transmitter may 1. depolarize the postsynaptic membrane and so have an excitatory action on the postsynaptic neuron. 2. hyperpolarize the postsynaptic membrane and so have an inhibitory action on the postsynaptic neuron. 3. initiate other chemical reactions that modulate either effect, inhibitory or excitatory, or that influence other functions of the receiving neuron.
22
Q
How much neurotransmitter is needed to send a message?
A
Bernard Katz was awarded a Nobel Prize in 1970 for providing an answer.
Recording electrical activity from the postsynaptic membranes of muscles, he detected small, spontaneous depolarizations now called miniature postsynaptic potentials. The potentials varied in size, but each size appeared to be a multiple of the smallest potential.
Katz concluded that the smallest postsynaptic potential is produced by the release of the contents of just one synaptic vesicle.
This amount of neurotransmitter is called a quantum. To produce a postsynaptic potential that is large enough to initiate a postsynaptic action potential requires the simultaneous release of many quanta from the presynaptic cell.
The results of subsequent experiments show that the number of quanta released from the presynaptic membrane in response to a single action potential depends on two factors:
(1) the amount of Ca2 + (calcium)that enters the axon terminal in response to the action potential and (2) the number of vesicles docked at the membrane, waiting to be released.
23
Q
How are neurotransmitters deactivated?
A
Deactivation is accomplished in at least four ways:
- Diffusion: Some of the neurotransmitter simply diffuses away from the synaptic cleft and is no longer available to bind to receptors.
- Degradation by enzymes in the synaptic cleft
- Reuptake: Membrane transporter proteins specific to that transmitter may bring the transmitter back into the presynaptic axon terminal for subsequent reuse. The by-products of degradation by enzymes also may be taken back into the terminal to be used again in the cell.
- Glial uptake: Some neurotransmitters are taken up by neighboring glial cells. Potentially, the glial cells can also store transmitters for re-export to the axon terminal.
24
Q
What is a Quantum?
A
quantum (pl. quanta): amount of neurotransmitter, equivalent to the contents of a single synaptic vesicle, that produces a just observable change in postsynaptic electric potential.
25
What is reuptake?
reuptake Deactivation of a neurotransmitter when membrane transporter proteins bring the transmitter back into the presynaptic axon terminal for subsequent reuse.
26
How many different type of synapses are there?
1: Dendrodendritic: Dendrites send messages to other dendrites.
2: Axodendritic: Axon terminal of one neuron synapses on dendritic spine of another.
3: Axoextracellular: Terminal with no specific target. Secretes transmitter into extracellular fluid.
4: Axosomatic: Axon terminal ends on cell body.
5: Axosynaptic: Axon terminal ends on another terminal.
6: Axoaxonic: Axon terminal ends on another axon.
7: Axosecretory: Axon terminal ends on tiny blood vessel and secretes transmitter directly into blood.
27
Where are type 1 and type 2 synapses located?
Type I (excitatory) synapses are typically located on the shafts or the spines of dendrites, whereas Type II (inhibitory) synapses are typically located on a cell body. In addition, Type I synapses have round synaptic vesicles, whereas the vesicles of Type II synapses are flattened. The material on the presynaptic and postsynaptic membranes is denser in a Type I synapse than it is in a Type II, and the Type I synaptic cleft is wider. Finally, the active zone on a Type I synapse is larger than that on a Type II synapse. The different locations of Type I and Type II synapses divide a neuron into two zones: an excitatory dendritic tree and an inhibitory cell body. You can think of excitatory and inhibitory messages as interacting from these two different perspectives.
This wide variety of connections makes the synapse a versatile chemical delivery system. Synapses can deliver transmitters to highly specific sites or diffuse locales. Through connections to the dendrites, cell body, or axon of a neuron, transmitters can control the actions of the neuron in different ways. Through axosynaptic connections, they can also provide exquisite control over another neuron’s input to a cell. By excreting transmitters into extracellular fluid or into the blood, axoextracellular and axosecretory synapses can modulate the function of large areas of tissue or even the entire body. Recall that many transmitters secreted by neurons act as hormones circulating in your blood, with widespread influences on your body. Gap junctions, shown in Figure 5-3, further increase the diversity of signaling between one part of a neuron and another part of the same neuron. Intraneuronal communication may occur via dendrodendritc and axoaxonic gap junctions. Gap junctions also allow neighboring neurons to synchronize their signals through somasomatic (cell body to cell body) connections, and they allow glial cells, especially astrocytes, to pass nutrient chemicals to neurons and to receive waste products from them.
28
What are the four steps in identifying a Neuron?
The chemical must be synthesized in the neuron or otherwise be present in it.
2. When the neuron is active, the chemical must be released and produce a response in some target.
3. The same response must be obtained when the chemical is experimentally placed on the target.
4. A mechanism must exist for removing the chemical from its site of action after its work is done.
29
What is a suspected neurotransmitter called?
A suspect chemical that has not yet been shown to meet all the criteria is called a putative (supposed) transmitter.
30
What are the criteria for identifying a neurotransmitter?
Researchers trying to identify new CNS neurotransmitters can use microelectrodes to stimulate and record from single neurons. A glass microelectrode is small enough to be placed on specific targets on a neuron. It can be filled with a chemical of interest and, when a current is passed through the electrode, the chemical can be ejected into or onto the neuron to mimic the release of a neurotransmitter onto the cell.
The criteria for identifying a neurotransmitter are fairly easy to apply when examining the somatic nervous system, especially at an accessible nerve–muscle junction with only one main neurotransmitter, acetylcholine.
But identifying chemical transmitters in the central nervous system is not so easy. In the brain and spinal cord, thousands of synapses are packed around every neuron, preventing easy access to a single synapse and its activities.
Consequently, a number of techniques, including staining, stimulating, and collecting, are used to identify substances thought to be CNS neurotransmitters.
31
What was the first substance identified as an Acetylcholine?
Acetylcholine was not only the first substance identified as a neurotransmitter but also the first substance identified as a CNS neurotransmitter. A logical argument that predicted its presence even before experimental proof was gathered greatly facilitated the process. As you know, all motor-neuron axons leaving the spinal cord use ACh as a transmitter. Each of these axons has an axon collateral within the spinal cord that synapses on a nearby CNS interneuron. The interneuron, in turn, synapses back on the motor neuron’s cell body. This circular set of connections, called a Renshaw loop after the researcher who first described it, is shown in Figure 5-9. Because the main axon to the muscle releases acetylcholine, investigators suspected that its axon collateral also might release ACh. For two terminals of the same axon to use different transmitters seemed unlikely. Knowing what chemical to look for made it easier to find and obtain the required proof that ACh is in fact a neurotransmitter in both locations. The loop made by the axon collateral and the interneuron in the spinal cord forms a feedback circuit that enables the motor neuron to inhibit itself from becoming overexcited if it receives a great many excitatory inputs from other parts of the CNS. Follow the positive and negative signs in Figure 5-9 to see how the Renshaw loop works. If the Renshaw loop is blocked, as can be done with the toxin strychnine, motor neurons become overactive, resulting in convulsions that can choke off respiration and so cause death.
32
What are the three classes of Neurotransmitters
chemical composition: (1) small-molecule transmitters, (2) peptide transmitters, and (3) transmitter gases.
33
What are small molecule transmitters?
One of the three classes of Neurotransmitters.
Because small-molecule transmitters or their main components are derived from the food that we eat, their level and activity in the body can be influenced by diet. This fact is important in the design of drugs that act on the nervous system. Many neuroactive drugs are designed to reach the brain by the same route that smallmolecule transmitters or their precursor chemicals follow: the digestive tract.
34
What are some example of small molecule transmitters?
acetylcholine (aCh) histamine (h)
amines
Dopamine (Da) Norepinephrine (Ne, or noradrenaline, Na) epinephrine (eP, or adrenaline) serotonin (5-hT)
amino acids glutamate (glu) gamma-aminobutyric acid (gaBa) glycine (gly)
35
What is Histamine?
Histamine is an example of a small molecule neurotransmitter.Among its many functions, which include the control of arousal and of waking, the transmitter histamine (H) can cause the constriction of smooth muscles. When activated in allergic reactions, histamine contributes to asthma, a constriction of the airways. You are probably familiar with antihistamine drugs used to treat allergies.
Neurotransmitter that controls arousal and waking; can cause the constriction of smooth muscles and so, when activated in allergic reactions, contributes to asthma, a constriction of the airways.
36
What is a Renshaw Loop?
All motor-neuron axons leaving the spinal cord use ACh (Acetycholoine) as a transmitter. Each of these axons has an axon collateral within the spinal cord that synapses on a nearby CNS interneuron. The interneuron, in turn, synapses back on the motor neuron’s cell body. This circular set of connections, called a Renshaw loop
37
What two substances is Acetycholine made up of?
Choline and acetate. Choline is among the breakdown products of fats in foods such as egg yolk, avocado, salmon, and olive oil; acetate is a compound found in acidic foods, such as vinegar and lemon juice. As depicted in Figure 5-10, inside the cell, acetyl coenzyme A (acetyl CoA) carries acetate to the synthesis site, and the transmitter is synthesized as a second enzyme, choline acetyltransferase (ChAT), transfers the acetate to choline to form ACh. After ACh has been released into the synaptic cleft and diffuses to receptor sites on the postsynaptic membrane, a third enzyme, acetylcholinesterase (AChE), reverses the process by detaching acetate from choline. These breakdown products can then be taken back into the presynaptic terminal for reuse.
38
What is a rate limiting factor?
Any chemical in limited supply that restricts the pace at which another chemical can be synthesized. Eg dopamine, Epinephrine and norepinepherine.
39
What chemical is converted sequentially into dopamine, norepinephrine, and, finally, epinephrine.
The enzyme tyrosine hydroxylase (enzyme 1 in Figure 5-11) changes tyrosine into l-dopa, which is sequentially converted by other enzymes into dopamine, norepinephrine, and, finally, epinephrine. An interesting fact about this biochemical sequence is that the supply of the enzyme tyrosine hydroxylase is limited. Consequently, so is the rate at which dopamine, norepinephrine, and epinephrine can be produced, regardless of how much tyrosine is present or ingested. This rate-limiting factor can be bypassed by the oral administration of l-dopa, which is why l-dopa is a medication used in the treatment of Parkinson’s disease
40
Why is L-dopa medication used in the treatment of Parkinson's disease?
The supply of the enzyme tyrosine hydroxylase is limited.Consequently, so is the rate at which dopamine, norepinephrine, and epinephrine can be produced, regardless of how much tyrosine is present or ingested. This rate-limiting factor can be bypassed by the oral administration of l-dopa, which is why l-dopa is a medication used in the treatment of Parkinson’s disease
41
What role does Serotonin play?
Amine neurotransmitter that plays a role in regulating mood and aggression, appetite and arousal, the perception of pain, and respiration. Serotonin is derived from the amino acid tryptophan, which is abundant in turkey, milk, and bananas, among other foods
42
What do Glutamate and Gaba do?
glutamate (Glu) amino acid neurotransmitter that excites neurons. gamma-aminobutyric acid (GaBa) amino acid neurotransmitter that inhibits neurons
43
How do Glutamate and Gaba work?
In the forebrain and cerebellum, glutamate is the main excitatory transmitter and GABA is the main inhibitory transmitter. Type I excitatory synapses thus have glutamate as a neurotransmitter, and Type II inhibitory synapses have GABA as a neurotransmitter. So the appearance of a synapse provides information about the neurotransmitter and its function (review Figure 5-7). Interestingly, glutamate is widely distributed in CNS neurons, but it becomes a neurotransmitter only if it is appropriately packaged in vesicles in the axon terminal. The amino acid transmitter glycine (Gly) is a much more common inhibitory transmitter in the brainstem and spinal cord, where it acts within the Renshaw loop, for example
44
What are peptide neurotransmitters?
Multifunctional chain of amino acids that acts as a neurotransmitter; synthesized from mrNa on instructions from the cell’s DNa. Peptide neurotransmitters can act as hormones and may contribute to learning.
In some neurons, peptide transmitters are made in the axon terminal, but most are assembled on the neuron’s ribosomes, packaged in a membrane by Golgi bodies transported by the microtubules to the axon terminals.
The entire process of neuropeptide synthesis and transport is relatively slow compared with the nearly ready-made formation of small-molecule neurotransmitters.
Consequently, peptide transmitters act slowly and are not replaced quickly.
Neuropeptides, however, perform an enormous range of functions in the nervous system, as might be expected from the large number that exist there. They act as hormones that respond to stress, enable a mother to bond with her infant, regulate eating and drinking and pleasure and pain, and probably contribute to learning.
Opium and related synthetic chemicals such as morphine, long known to both produce euphoria and reduce pain, appear to mimic the actions of three natural brain neurotransmitter peptides: met-enkephalin, leu-enkephalin, and beta-endorphin. (The term enkephalin derives from the phrase “in the cephalon,” meaning “in the brain or head,” whereas the term endorphin is a shortened form of “endogenous morphine.”) A part of the amino acid chain in each of these three peptide transmitters is structurally similar to the others, as illustrated for two of these peptides in Figure 5-13. Presumably, opium mimics this part of the chain. The discovery of naturally occurring opium-like peptides suggested that one or more of them might take part in the management of pain. Opioid peptides, however, appear in a number of locations and perform a variety of functions in the brain, including the inducement of nausea. Therefore opiumlike drugs are still preferred for pain management.
45
What are some examples of peptide neurotransmitters?
opioids: enkephaline, dynorphin
Neurohypophyseals: Vasopressin, oxytocin
secretins: gastric inhibitory peptide, growth-hormone-releasing peptide
insulins: insulin, insulin growth factors
gastrins: gastrin, cholecystokinin
somatostatins: Pancreatic polypeptides
Corticosteroids: glucocorticoids, mineralocorticoids
46
What does Carbon monoxide do?
carbon monoxide (co) gas that acts as a neurotransmitter in the activation of cellular metabolism.
Both NO (Nitric Oxide) and CO activate metabolic (energy expending) processes in cells, including processes modulating the production of other neurotransmitters.
47
What does nitric Oxide do?
nitric oxide (no) gas that acts as a chemical neurotransmitter—for example, to dilate blood vessels, aid digestion, and activate cellular metabolism
Both NO (Nitric Oxide) and CO activate metabolic (energy expending) processes in cells, including processes modulating the production of other neurotransmitters.
Nitric oxide serves as a chemical messenger in many parts of the body. It controls the muscles in intestinal walls, and it dilates blood vessels in brain regions that are in active use, allowing these regions to receive more blood. Because it also dilates blood vessels in the sexual organs, NO is active in producing penile erections. Viagra, a drug used to treat erectile dysfunction in men, acts by enhancing the chemical pathways influenced by NO. Note that NO does not of itself produce sexual arousal.
48
When a neurotransmitter is released from any of the wide varieties of synapses onto a wide variety of targets, as illustrated in Figure 5-6, it crosses the synaptic cleft and binds to a receptor. What happens next?
What happens next depends on the receptor type. There are two receptor types Ionotropic and metabotropic.
Each of the two general classes of receptor proteins has a different effect. One directly changes the electrical potential of the postsynaptic membrane (Ionotropic); the other induces cellular change indirectly (metabotropic).
Ionotropic receptors allow the movement of ions such as Na1, K1, and Ca21, across a membrane (the suffix tropic means “to move toward”). As Figure 5-14 illustrates, an ionotropic receptor has two parts: (1) a binding site for a neurotransmitter and (2) a pore, or channel.
When the neurotransmitter attaches to the binding site, the receptor changes shape, either opening the pore and allowing ions to flow through it or closing the pore and blocking the flow of ions. Because the binding of the transmitter to the receptor is quickly followed by the opening or closing of the receptor pore that affects the flow of ions, ionotropic receptors bring about very rapid changes in membrane voltage.
Ionotropic receptors are usually excitatory: they trigger an action potential.
embedded membrane protein that acts as (1) a binding site for a neurotransmitter and (2) a pore that regulates ion flow to directly and rapidly change membrane voltage
49
What are the type of receptors?
There are two receptor types Ionotropic and metabotropic.
Each of the two general classes of receptor proteins has a different effect. One directly changes the electrical potential of the postsynaptic membrane (Ionotropic); the other induces cellular change indirectly (metabotropic).
50
What does Ionotropic receptors do?
One directly changes the electrical potential of the postsynaptic membrane (Ionotropic); the other induces cellular change indirectly (metabotropic).
Ionotropic receptors allow the movement of ions such as Na1, K1, and Ca21, across a membrane (the suffix tropic means “to move toward”). As Figure 5-14 illustrates, an ionotropic receptor has two parts: (1) a binding site for a neurotransmitter and (2) a pore, or channel.
When the neurotransmitter attaches to the binding site, the receptor changes shape, either opening the pore and allowing ions to flow through it or closing the pore and blocking the flow of ions. Because the binding of the transmitter to the receptor is quickly followed by the opening or closing of the receptor pore that affects the flow of ions, ionotropic receptors bring about very rapid changes in membrane voltage.
Ionotropic receptors are usually excitatory: they trigger an action potential.
embedded membrane protein that acts as (1) a binding site for a neurotransmitter and (2) a pore that regulates ion flow to directly and rapidly change membrane voltage.
51
What do Metatropic receptors do?
metabotropic receptor embedded membrane protein, with a binding site for a neurotransmitter but no pore, linked to a g protein that can affect other receptors or act with second messengers to affect other cellular processes
a metabotropic receptor has a binding site for a neurotransmitter but lacks its own pore through which ions can flow. Through a series of steps, activated metabotropic receptors indirectly produce changes in nearby ion channels or in the cell’s metabolic activity
When activated, these embedded membrane proteins trigger associated G proteins, thereby exerting indirect effects (A) on nearby ion channels or (B) in the cell’s metabolic activity.
52
What is the relationship between receptor sites and neurotransmitters?
No one neurotransmitter is associated with a single receptor type. A neurotransmitter may bind either to an ionotropic receptor and have an excitatory effect on the target cell or to a metabotropic receptor and have an inhibitory effect. Recall that acetylcholine has an excitatory effect on skeletal muscles. Here it activates an ionotropic receptor. You know that ACh has an inhibitory effect on the heart rate. Here it activates a metabotropic receptor. In addition, each transmitter may bind with several different kinds of ionotropic or metabotropic receptors. Elsewhere in the nervous system, for example, acetylcholine may activate a wide variety of either receptor type.
53
Neurotransmitters are identified using four experimental criteria: (1), (2) (3) and (4).
(1) Synthesis
(2) Release
(3) Receptor
(4) Action
54
The three broad classes of chemically related neurotransmitters are (1), (2) and (3). all three classes, encompassing the approximately 100 likely neurotransmitters active in the nervous system are associated with both (4) and (5) receptors.
(1) Small Molecule transmitters
(2) Peptide transmitters
(3) Gaseous Transmitters
(4) Ionotropic
(5) Metatropic
55
Contrast the major characteristics of ionotropic and metabotropic receptors.
An Ionotropic receptor's pore or channel can be opened or closed to regulate the flow through of ions, directly effecting rapid and usually excitatory voltage changes on the cell membrane.
Metatropic receptors which are generally inhibitory and slow acting, activate second messengers to directly produce changes in cell function and structure.
56
What are second messengers?
Chemical that carries a message to initiate a biochemical process when activated by a neurotransmitter (the first messenger). to a receptor can activate an escalating sequence of events called an amplification cascade. The cascade effect causes many downstream proteins (second messengers or channels or both) to be activated or deactivated. Ionotropic receptors do not have such a widespread “amplifying” effect.
57
Why can't you implicate just one neurotransmitter to a behavior?
There are many different combinations of neurotransmitters and receptors.
A single neuron may use one transmitter at one synapse and a different transmitter at another synapse. Moreover, different transmitters may coexist in the same terminal or synapse. Neuropeptides have been found to coexist in terminals with smallmolecule transmitters, and more than one small-molecule transmitter may be found in a single synapse. In some cases, more than one transmitter may even be packaged within a single vesicle.
58
What are Motor Neurons also called?
Cholinergic neuron Neuron that uses acetylcholine as its main neurotransmitter. The term cholinergic applies to any neuron that uses aCh as its main transmitter.
Motor neurons are also called cholinergic neurons because acetylcholine is their main neurotransmitter. At a skeletal muscle, cholinergic neurons are excitatory and produce muscular contractions. Just as a single main neurotransmitter serves the SNS, so does a single main receptor, an ionotropic, transmitter-activated channel called a nicotinic ACh receptor (nAChr). When ACh binds to this receptor, its pore opens to permit ion flow, thus depolarizing the muscle fiber. The pore of a nicotinic receptor is large and permits the simultaneous efflux of K1 and influx of Na1. The molecular structure of nicotine, a chemical found in tobacco, activates the nAChr in the same way that ACh does, which is how this receptor got its name. The molecular structure of nicotine is sufficiently similar to ACh that nicotine acts as a mimic, fitting into acetylcholine-receptor binding sites. Although acetylcholine is the primary neurotransmitter at skeletal muscles, other neurotransmitters also are found in these cholinergic axon terminals and are released onto the muscle along with ACh. One of these neurotransmitters is a neuropeptide called calcitonin-gene-related peptide (CGRP) that acts through CGRP metabotrophic receptors to increase the force with which a muscle contracts.
59
What neurotransmitter controls both divisions of the Autonomic nervous system?
Both ANS divisions are controlled by acetylcholine neurons that emanate from the CNS at two levels of the spinal cord. The CNS neurons synapse with parasympathetic neurons that also contain acetylcholine and with sympathetic neurons that contain norepinephrine.
In other words, ACh neurons in the CNS synapse with sympathetic NE neurons to prepare the body’s organs for fight or flight. Cholinergic (ACh) neurons in the CNS synapse with autonomic ACh neurons in the parasympathetic division to prepare the body’s organs to rest and digest.
Whether acetylcholine synapses or norepinephrine synapses are excitatory or inhibitory on a particular body organ depends on that organ’s receptors. During sympathetic arousal, norepinephrine turns up heart rate and turns down digestive functions because NE receptors on the heart are excitatory, whereas NE receptors on the gut
are inhibitory. Similarly, acetylcholine turns down heart rate and turns up digestive functions because its receptors on these organs are different. Acetylcholine receptors on the heart are inhibitory, whereas those on the gut are excitatory. The activity of neurotransmitters, excitatory in one location and inhibitory in another, mediate the sympathetic and parasympathetic divisions to form a complementary autonomic regulating system that maintains the body’s internal environment under differing circumstances.
60
What are the four activating systems in the Central Nervous System?
Each of four small-molecule transmitters participates in its own neural activating system—the cholinergic, dopaminergic, noradrenergic, and serotonergic systems
For each of the four activating systems that we describe here, a relatively small number of neurons grouped together in one or a few brainstem nuclei send axons to widespread CNS regions, suggesting that these nuclei and their terminals play a role in synchronizing activity throughout the brain and spinal cord. You can envision an activating system as analogous to the power supply to a house. The fuse box is the source of the house’s power and from it, lines go to each room. Just as in the ANS, the precise action of the CNS transmitter depends on the region of the brain that is innervated and on the types of receptors on which the transmitter acts at that region. To continue our analogy, precisely what the activating effect of the power is in each room depends on the electrical devices in the room.
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What is an activating system?
Activating system: Neural pathways that coordinate brain activity through a single neurotransmitter; cell bodies are located in a nucleus in the brainstem and axons are distributed through a wide region of the brain
Each system’s cell bodies are gathered into nuclei in the brainstem. The axons project diffusely through the brain and synapse on target structures. Each activating system is associated with one or more behaviors or diseases.
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What does the Cholingernic system do?
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Cholinergenic system (Acetycholine)
Active in maintaining attention and waking EEG pattern
• Thought to play a role in memory by maintaining neuron excitability
• Death of cholinergic neurons and decrease in ACh in the neocortex are thought to be related to Alzheimer’s disease
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Basal Forebrain Nuclei and Midbrain Nuclei are it's main cell bodies through which it transmits Acetycholine through it's axons to rest of brain.
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What does the Dopaminergic system do?
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Dopaminergic system (dopamine) j has two pathway:
Nigrostriatial pathways and Mesolimbic pathway.
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Nigrostriatial pathway:
• Active in maintaining normal motor behavior
• Loss of DA is related to muscle rigidity and dyskinesia in Parkinson’s disease
The nigrostriatial dopaminergic system plays a role in coordinating movement. As described throughout this chapter in relation to Parkinsonism, when DA neurons in the substantia nigra are lost, the result is a condition of extreme muscular rigidity
Associated with Caudate Nucleus.
Mesolimbic pathways
• Dopamine release causes feelings of reward and pleasure
• Thought to be the neurotransmitter system most affected by addictive drugs and behavioral addictions
• Increases in DA activity may be related to schizophrenia
• Decreases in DA activity may be related to deficits of attention
Associated with Nuclei in Ventral Tegmentum and Nucleus Accumbens in Basal Ganglia.
Dopamine in the mesolimbic dopaminergic system may be the neurotransmitter most affected in addiction—to food, drugs, and to other behaviors that involve a loss of impulse control. A common feature of addictive behaviors is that stimulating the mesolimbic DA system enhances responses to environmental stimuli, thus making the stimuli attractive and rewarding.
Excessive mesolimbic DA activity is proposed as well to play a role in schizophrenia, a behavioral disorder characterized by delusions, hallucinations, disorganized speech, blunted emotion, agitation or immobility, and a host of associated symptoms. Schizophrenia is one of the most common and debilitating psychiatric disorders, affecting 1 in 100 people.
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What does the Noradrengic system do?
Noradrenergic system (norepinephrine)
• Active in maintaining emotional tone
• Decreases in NE activity are thought to be related to depression
• Increases in NE are thought to be related to mania (overexcited behavior)
• Decreased NE activity is associated with hyperactivity and attention-deficit/hyperactivity disorder
The term noradrenergic neuron describes a neuron using noradrenaline as its transmitter. The term noradrenaline is derived from adrenaline, the Latin name for epinephrine. Norepinephrine (noradrenalin) may play a role in learning by stimulating neurons to change their structure. It may also facilitate normal development of the brain and play a role in organizing movements
In the main, behaviors and disorders related to the noradrenergic system concern the emotions. Some symptoms of major depression—a mood disorder characterized by prolonged feelings of worthlessness and guilt, the disruption of normal eating habits, sleep disturbances, a general slowing of behavior, and frequent thoughts of suicide—may be related to decreases in the activity of noradrenergic neurons. Conversely, some symptoms of mania (excessive excitability) may be related to increases in the activity of these same neurons. Decreased NE activity has also been associated both with hyperactivity and attention-deficit/hyperactivity disorder (ADHD).
Nuclei is Locus Coeruleus.
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What does the Serotonergic system do?
(serotonin)
• Active in maintaining waking EEG pattern
• Changes in serotonin activity are related to obsessive–compulsive disorder, tics, and schizophrenia
• Decreases in serotonin activity are related to depression • Abnormalities in brainstem 5-HT neurons are linked to disorders such as sleep apnea and SIDS
Raphe Nuclei.
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What is Alzheimer's disease?
alzheimer’s disease Degenerative brain disorder related to aging that first appears as progressive memory loss and later develops into generalized dementia.
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Why is it difficult to connect activating systems with particular disorders?
Each activating system is associated with a number of behaviors. With the exception of dopamine’s clear link to Parkinson’s disease, however, associations among activating systems, behavior, and brain disorders are far less certain.
All these relations are subjects of ongoing research. The difficulty in making definitive correlations between activating systems and behavior or activating systems and a disorder is that the axons of these systems connect to almost every part of the brain. They likely have both specific functions and modulatory roles.
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What helps Parkinson's disease patients
For Parkinson’s patients, rhythmic movement apparently helps to restore the balance between neural excitation and inhibition—between the loss and the release of behavior. Patients who attend dance classes, as pictured here, report that moving to music helps them regain muscle control. Exercise and music are helpful additions to treatments directed toward replacing depleted dopamine.
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What area of loss of neurons is associated with Parkinson's disease?
The death of dopamine neurons in the substania nigra, a basal ganglia structure located in the midbrain that plays an important role in reward and movement.
Parkinson’s disease can be induced by a toxin that selectively kills dopamine neurons
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What neurotransmitters is most associated with Dopamine and Scitzopherenia?
Dopamine in the mesolimbic dopaminergic system may be the neurotransmitter most affected in addiction—to food, drugs, and to other behaviors that involve a loss of impulse control. A common feature of addictive behaviors is that stimulating the mesolimbic DA system enhances responses to environmental stimuli, thus making the stimuli attractive and rewarding. Excessive mesolimbic DA activity is proposed as well to play a role in schizophrenia, a behavioral disorder characterized by delusions, hallucinations, disorganized speech, blunted
emotion, agitation or immobility, and a host of associated symptoms. Schizophrenia is one of the most common and debilitating psychiatric disorders, affecting 1 in 100 people.
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What is Schizopherena?
Schizophrenia Behavioral disorder characterized by delusions, hallucinations, disorganized speech, blunted emotion, agitation or immobility, and a host of associated symptoms
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What activating system is mainly associated with emotions?
In the main, behaviors and disorders related to the noradrenergic system concern the emotions. Some symptoms of major depression—a mood disorder characterized by prolonged feelings of worthlessness and guilt, the disruption of normal eating habits, sleep disturbances, a general slowing of behavior, and frequent thoughts of suicide—may be related to decreases in the activity of noradrenergic neurons. Conversely, some symptoms of mania (excessive excitability) may be related to increases in the activity of these same neurons. Decreased NE activity has also been associated both with hyperactivity and attention-deficit/hyperactivity disorder (ADHD).
noradrenergic neuron from adrenaline, latin for “epinephrine”; a neuron containing norepinephrine.
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What are depression and Mania?
major depression mood disorder characterized by prolonged feelings of worthlessness and guilt, the disruption of normal eating habits, sleep disturbances, a general slowing of behavior, and frequent thoughts of suicide. mania Disordered mental state of extreme excitement
Some symptoms of depression may be related to decreases in the activity of serotonin neurons, and drugs commonly used to treat depression act on serotonin neurons. Consequently, two forms of depression may exist, one related to norepinephrine and another related to serotonin.
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What activating system is associated with OCD and Scitzopherenia?
Likewise, the results of some research suggest that various symptoms of schizophrenia also may be related to increases in serotonin activity, which implies that there may be different forms of schizophrenia. Increased serotonergic activity is also related to symptoms observed in obsessive-compulsive disorder (OCD), a condition in which a person compulsively repeats acts (such as hand washing) and has repetitive and often unpleasant thoughts (obsessions). Evidence also points to a link between abnormalities in serotonergic nuclei and conditions such as sleep apnea and sudden infant death syndrome (SIDS).
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Although neurons can synthesize more than one (1) they are usually identified by the principal (2) in their axon terminals.
(1) Neurotransmitter
| (2) Neurotransmitter
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In the peripheral nervous system, the neurotransmitter at somatic muscles is (1);in the autonomic nervous system (2), neurons from the spinal cord connect to (3) neurons for parasympathic activity and with (4) neurons for sympathetic activity.
(1) Acetycholine (ACh)
(2) Acetycholine (ACh)
(3) )Acetycholine (ACh)
(4) Norepinephrine (NE)
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The four main activating systems of the brain are (1), (2), (3) and (4).
(1) Cholinergic
(2) Dopaminergic
(3) Noadrenergic
(4) Serotonergic
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How would you respond to the comment that a behavior is caused solely by a “chemical imbalance in the brain”?
This idea has been attractive for a long time because a clear relationship exists between Dopamine (DA) loss in the substania nigra and PArkinson disease and because Acetylcholine and norepinephrine are clearly related to somatic and autonomic behaviors.
But for other neurotransmitter systems in the brain, establishing clear one to one relationships has proved difficult.
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What is a requirement for learning? What is learning?
Relatively permanent change in behavior that results from experience.
Neuroplasticity is both a requirement for learning and memory and a characteristic not only of the mammalian brain but also of the nervous systems of all animals, even the simplest worms. Larger brains with more connections are more plastic, however, and thus likely to show more adaptability in neural organization. Greater adaptability happens because experience alters the synapse. Not only are synapses versatile in structure and function, they are also plastic: they can change. The synapse, therefore, provides a site for the neural basis of learning, a relatively permanent change in behavior that results from experience.
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What is Habituation?
Habituation learning behavior in which a response to a stimulus weakens with repeated stimulus presentations.
In habituation, the response to a stimulus weakens with repeated presentations of the stimulus. If you are accustomed to living in the country and then move to a city, you might at first find the sounds of traffic and people extremely loud and annoying. With time, however, you stop noticing most of the noise most of the time. You have habituated to it. Habituation develops with all our senses. When you first put on a shoe, you “feel” it on your foot, but very soon it is as if the shoe were not there. You have not become insensitive to sensations, however. When people talk to you, you still hear them; when someone steps on your foot, you still feel the pressure. Your brain simply has habituated to the customary “background” sensation of a shoe on your foot.
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What did Eric Kandel win a Nobel prize for?
Eric Kandel was awarded a Nobel Prize in 2000 for his descriptions of the synaptic basis of learning in a way that Donald Hebb envisaged: learning in which the conjoint activity of nerve cells serves to link them. Kandel’s subject, the marine snail Aplysia californica, is an ideal subject for learning experiments. Slightly larger than a softball and lacking a shell, Aplysia has roughly 20,000 neurons. Some are quite accessible to researchers, who can isolate and study circuits having very few synapses.
Kandel and his coworkers measured neurotransmitter output from a sensory neuron and verified that less neurotransmitter is in fact released from a habituated neuron than from a nonhabituated one.
As habituation takes place, that Ca2+ (calcium ions) influx decreases in response to the voltage changes associated with an action potential. Presumably, with repeated use, voltage-sensitive calcium channels become less responsive to voltage changes and more resistant to the passage of calcium ions. The neural basis of habituation lies in the change in presynaptic calcium channels. Its mechanism, which is summarized close up in the Results section of Experiment 5-2, is a reduced sensitivity of calcium channels and a consequent decrease in the release of a neurotransmitter. Thus, habituation can be linked to a specific molecular change, as summarized in the experiment’s Conclusion.
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What happens neurally to cause Habituation?
Electrical recordings from the motor neuron show that, as habituation develops, the excitatory postsynaptic potentials in the motor neuron become smaller. The most likely way in which these EPSPs decrease in size is that the motor neuron is receiving less neurotransmitter from the sensory neuron across the synapse. And if less neurotransmitter is being received, then the changes accompanying habituation must be taking place in the presynaptic axon terminal of the sensory neuron.
With habituation, the influx of calcium ions in response to an action potential decrease resulting in less neurotransmitter released at the presynaptic membrane
and less depolarization of the postsynaptic membrane
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What is Sensitization?
Sensitization learning behavior in which the response to a stimulus strengthens with repeated presentations of that stimulus because the stimulus is novel or because the stimulus is stronger than normal—for example, after habituation has occurred.
Sensitization occurs within a context. Sudden, novel stimulation heightens our general awareness and often results in larger-than-normal responses to all kinds of stimulation. If you are suddenly startled by a loud noise, you become much more responsive to other stimuli in your surroundings, including some to which you had been previously habituated
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What is Post Traumatic Stress Disorder?
In posttraumatic stress disorder (PTSD), physiological arousal related to recurring memories and dreams surrounding a traumatic event persist for months or years after the event. One characteristic of PTSD is a heightened response to stimuli, suggesting that the disorder is in part related to sensitization.
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What is the Neural basis of Sensitization?
The neural circuits participating in sensitization differ from those that take part in a habituation response. Sensitization, then, is the opposite of habituation at the molecular level as well as at the behavioral level. In sensitization, more Ca21 influx results in more transmitter being released, whereas in habituation, less Ca21 influx results in less neurotransmitter being released. The structural basis of cellular memory in these two forms of learning is different, however. In sensitization, the change takes place in potassium channels, whereas in habituation, the change takes place in calcium channels
An interneuron that receives input from a sensory neuron in the tail (and so carries information about the shock) makes an axoaxonic synapse with a siphon sensory neuron. The interneuron’s axon terminal contains serotonin. Consequently, in response to a tail shock, the tail sensory neuron activates the interneuron, which in turn releases serotonin onto the axon of the siphon sensory neuron. Information from the siphon still comes through the siphon sensory neuron to activate the motor neuron leading to the gill muscle, but the gill-withdrawal response is amplified by the interneuron’s action in releasing serotonin onto the presynaptic membrane of the sensory neuron. At the molecular level, shown close up in Experiment 5-3, the serotonin released from the interneuron binds to a metabotropic serotonin receptor on the axon of the siphon sensory neuron. This binding activates second messengers in the sensory neuron. Specifically, the serotonin receptor is coupled through its G protein to the enzyme adenyl cyclase. This enzyme increases the concentration of the second messenger cyclic adenosine monophosphate (cAMP) in the presynaptic membrane of the siphon sensory neuron. Through a number of chemical reactions, cAMP attaches a phosphate molecule (PO4) to potassium channels, and the phosphate renders the potassium channels less responsive.
In response to an action potential traveling down the axon of the siphon sensory neuron (such as one generated by a touch to the siphon), the potassium channels on that neuron are slower to open. Consequently, K1 ions cannot repolarize the membrane as quickly as is normal, so the action potential lasts longer than it usually would.
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What chemical ion is neccessary for Neurotransmitter release?
Calcium (Ca2+). More CA2 + release influences the influex of neurotransmitters.
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How are synapses responsible for the long term changes associated with learning and memory?
Repeated stimulation produces habituation and sensitization that can persist for months. Brief training produces short-term learning, whereas longer training periods produce more enduring learning. If you cram for an exam the night before you take it, you might forget the material quickly, but if you study a little each day for a week, your learning may tend to endure
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What happens at the neural level with learning?
Craig Bailey and Mary Chen (see Miniaci et al., 2008) found that the number and size of sensory synapses change in well-trained, habituated, and sensitized Aplysia. Relative to a control neuron, the number and size of synapses decrease in habituated animals and increase in sensitized animals, as represented in Figure 5-19. Apparently, synaptic events associated with habituation and sensitization can also trigger processes in the sensory cell that result in the loss or formation of new synapses. A mechanism through which these processes can take place begins with calcium ions that mobilize second messengers to send instructions to nuclear DNA. The transcription and translation of nuclear DNA, in turn, initiate structural changes at synapses, including the formation of new synapses and new experiment
xperimental evidence about structural changes in dendritic spines. The second messenger cAMP plays an important role in carrying instructions regarding these structural changes to nuclear DNA. The evidence for cAMP’s involvement comes from studies of fruit flies. In the fruit fly, Drosophila, two genetic mutations can produce the same learning deficiency. Both render the second messenger cAMP inoperative, but in opposite ways. One mutation, called dunce, lacks the enzymes needed to degrade cAMP, so the fruit fly has abnormally high cAMP levels. The other mutation, called rutabaga, reduces levels of cAMP below the normal range for Drosophila neurons. Significantly, fruit flies with either of these mutations are impaired in acquiring habituated and sensitized responses because their levels of cAMP cannot be regulated. New synapses seem to be required for learning to take place, and the second messenger cAMP seems to be needed to carry instructions to form them. Figure 5-20 summarizes these research findings. More lasting habituation and sensitization are mediated by relatively permanent changes in neuronal structure—by fewer or more synaptic connections—and the effects can be difficult to alter. As a result of sensitization, for example, symptoms of posttraumatic stress disorder can persist indefinitely.
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Experience alters the (1), the site of the neural basis of (2) a relatively permanent change in behavior that results from experience.
(1) Synapse
| (2) Learning
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Aplysia’s synaptic function mediates two basic forms of learning: (1) and (2).
(1) Habituation
| (2) Sensization
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Changes that accompany habituation take place within the(1) of the (2) neuron, mediated by (3) channels that grow (4) sensitive with use.
(1) Presynaptic Axon Terminal
(2) Sensory
(3) Calcium
(4) Less
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The sensitization response is amplified by (1) that release serotonin onto the presynaptic membrane of the sensory neuron, changing the sensitivity of presynaptic (2) channels and increasing the influx of (3) .
(1) Interneurons
(2) Potassium
(3) Calcium ions
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One characteristic of (1), defined as physiological arousal related to recurring memories and dreams surrounding a traumatic event that persist for months or years after the event, is a heightened response to stimuli. This suggests that the disorder is in part related to (2).
(1) Postraumatic stress disorder
| (2) Sensitization
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Describe the benefits and/or drawbacks of permanent habituation and sensitization
Permanent responses to frequently occuring stimuli are biologiclly (or behaviorally and or metaphorically) efficient but if stimuli changes suddenly, a lack of flexibilty becomes maladaptive.
