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State the neuron doctrine in a single sentence. To whom is this insight credited?
Ch2
- The neuron doctrine is the idea that the neurons are not continuous with one
- another but are discrete cells that communicate by contact and not by continuity. This
- insight is credited to Cajal.
-
Which parts of a neuron are shown by a Golgi stain and are not shown by a Nissl stain?
Ch2
- The Golgi stain shows the neuronal cell body with the dendrites and the axon.
- The Nissl stain shows only the cell body.
-
What are the three physical characteristics that distinguish axons from dendrites?
Ch2
i) The cell body usually gives rise to a single axon while many dendrites extend from the cell body.
ii) The axon is of uniform diameter throughout its length while dendrites rarely extend more than 2 mm in length.
iii) The branches of an axon generally extend at right angles while dendrites generally taper to a fine point.
-
Among the following structures, state those which are unique to neurons and the ones that are not: nucleus, mitochondria, rough ER, synaptic vesicle, and Golgi apparatus.
Ch2
The synaptic vesicle is unique to neurons whereas the nucleus, the mitochondria, the rough ER, and Golgi apparatus are not unique to neurons.
-
What are the steps by which the information in the DNA of the nucleus directs the synthesis of a membrane-associated protein molecule?
Ch2
Protein synthesis, the assembly of protein molecules, occurs in the cytoplasm. The DNA never leaves the nucleus. The intermediary that carries the genetic message to the sites of protein synthesis in the cytoplasm is a long molecule called messenger ribonucleic acid, mRNA. The process of assembling a piece of mRNA that contains the information of a gene is called transcription and the resulting mRNA is called the transcript. Messenger RNA transcripts emerge from the nucleus through pores in the nuclear envelope and travel to ribosomes, the sites of protein synthesis in the cytoplasm. At these sites, protein molecules are assembled by linking individual amino acids into a chain. Amino acids of 20 different kinds are the building blocks for protein. Amino acids are brought to the ribosome by transfer RNA (tRNA). The assembling of proteins from amino acids under the direction of the mRNA is called translation.
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Colchicine is a drug that causes microtubules to break apart or depolymerize. What effect would this drug have on anterograde transport? What would happen in the axon terminal?
Ch2
Vesicles containing molecules needed at the axon terminal "walk down" the microtubules within the axon on "legs" provided by a protein called kinesin. The process is fueled by ATP. Kinesin moves material only from the soma to the terminal. Movement in this direction is called anterograde transport. The application of colchicines causes microtubules to disintegrate and when applied to the axon disrupts the path for anterograde transport. As a result, all movement of material from the soma to the terminal (anterograde transport) ceases. If the colchicines application does notkill the whole cell, then the material to be transported will accumulate on the side of the axon closest to the soma.
-
What is myelin and what does it do? Which cells provide myelin to the central nervous system?
Ch2
Myelin refers to layers of glial membrane that insulate axons. Myelin speeds the propagation of nerve impulses down the axon. The oligodendroglial cells provide myelin in the central nervous system.
-
What are the two functions that the proteins perform in the neuronal membrane to establish and maintain the resting membrane potential?
Ch3
- Proteins in the neuronal membrane:
- 1) Provide channels that control the movement of specific ions across the neuronal membrane and
- 2) Pump sodium and potassium ions across the membrane against their concentration gradient to maintain the resting membrane potential.
-
On which side of the neuronal membrane are Na+ ions more abundant?
Ch3
The neuronal membrane potential depends on the ionic concentrations on either side of the membrane. K+ is more concentrated on the inside of the neuronal membrane, whereas Na+ and Ca2+ are more concentrated on the outside.
-
When the membrane is at the potassium equilibrium potential, in which direction (in or out) is there a net movement of potassium ions?
Ch3
The potassium equilibrium potential represents a balance between the chemical and electrical forces driving potassium across the membrane through potassium channels. There is no net movement of potassium ions at potassium’s equilibrium potential, which is –80mV.
-
There is a much greater potassium K+ concentration inside the cell than outside. Why, then, is the resting membrane potential negative?
Ch3
The resting membrane potential is negative because the neuron is filled with negatively charged molecules, such as proteins, that do not traverse the cell membrane through channels the way ions do.
-
When the brain is deprived of oxygen, the mitochondria within the neurons cease to produce ATP. What effect would this have on the membrane potential and why?
Ch3
The neuronal membrane potential depends on different concentrations of sodium and potassium on either side of the membrane. Ionic concentration gradients are established by the action of the sodium-potassium ion pump, an enzyme that requires ATP. Without ATP, the pump will not function. As a result, the resting membrane potential will not exist and the brain will not function.
-
Define membrane potential (Vm) and sodium equilibrium potential (ENa). Which of these, if any, changes during the course of action potential?
Ch4
The membrane potential (Vm) is the voltage across the neuronal membrane at any moment in time. The potential of the resting membrane is –75 mV. The sodium equilibrium potential (ENa) is the steady equilibrium potential achieved when the membrane is permeable only to sodium ions. The value of ENa is 62 mV. However, in its resting state, the membrane is not permeable to sodium. During the application of action potential, sodium channels open and sodium rushes into the cell. The large sodium current takes the membrane potential from its negative resting state toward ENa. Sodium channels are deactivated after 1 msec, and the membrane repolarizes due to potassium efflux, which takes the membrane potential back toward the equilibrium potential of potassium.
-
Which ions carry the early inward and late outward currents during the action
potential?
Ch4
During the early part of the action potential, the influx of sodium ions across the membrane briefly depolarizes the membrane. The brief inward sodium current is a consequence of opening the voltage-gated sodium channels for only 1 msec. Membrane repolarization is the result of potassium efflux, which is the outward potassium current because of opening voltage-gated potassium channels after a delay of 1 msec.
-
Why is the action potential referred to as “all-or-none”?
Ch4
Action potential is termed “all-or-none” because no partial action potentials exist. A physical or electrical event opens sodium permeable channels, but the resulting influx of sodium ions and the resulting depolarization – called a generator potential — must reach acritical level before the axon generates an action potential. The critical level is called a threshold. After achieving threshold depolarization, the cell fires an action potential.
-
Some voltage-gated K+ channels are known as delayed rectifiers because of the timing of their opening during an action potential. What would happen if these channels took much longer than normal to open?
Ch4
Voltage-gated potassium channels open 1 msec after membrane depolarization. The resulting potassium conductance rectifies, or resets, the membrane potential. This conductance is called the delayed rectifier because of the 1 msec delay in rectifying the membrane potential. If these channels took longer than normal to open, the action potential would be wider, which means that it would take longer to restore the resting membrane potential.
-
Imagine you have labeled tetrodotoxin (TTX) to be able to see it with a microscope. If we wash the TTX on to a neuron, what parts of the cell would you expect labeled? What would be the consequence of applying TTX to the neuron?
Ch4
TTX is a natural toxin that interferes with the function of voltage-gated sodium channels. TTX blocks the sodium permeable pore by binding tightly to a specific part outside the channel and blocking all the sodium-dependent action potentials. Applying TTX to a neuron would block all impulses in that nerve, preventing it from firing any action potential, regardless of input. Labeled TXX could be visualized on the cell’s axon, where voltage-gated sodium channels are concentrated.
-
How does the conduction velocity of action potential vary with axonal diameter? Why?
Ch4
The speed of action potential depends on how far depolarization spreads ahead of action potential. This, in turn, depends on the physical characteristics of axons. The two paths that a positive charge can take are inside an axon and across the axonal membrane. When the axon is narrow with many open pores, more of the current flows across the axonal membrane and is lost. When the axon is wide with a few open pores, the current flows inside the axon. The farther down the axon the current flows, the farther ahead of the action potential the membrane will be depolarized and the faster the action potential will propagate. As a result, the conduction velocity of axons increases with the diameter of axons.
-
What is meant by quantal release of neurotransmitter?
Ch5
- The elementary unit of a neurotransmitter release is the content of one synaptic vesicle.
- Each vesicle contains several thousand transmitter molecules. The total amount of transmitter released at a synapse is a multiple of this number, depending on how many vesicles release
- their contents into the synaptic cleft. The amplitude of postsynaptic EPSP is a multiple of the response to the contents of one vesicle. It reflects the number of transmitter molecules in one synaptic vesicle and the number of postsynaptic receptors available at the synapse.
-
You apply ACh and activate nicotinic receptors on a muscle cell. Which way will current flow through the receptor channels when Vm = –60 mV? When Vm = 0 mV? When Vm = 60 mV? Why?
Ch5
Nicotonic ACh receptors are permeable to both sodium and potassium. When Vm = –60 mV, net current flow through ACh-gated ion channels is inward, toward the equilibrium potential of sodium, causing depolarization. At Vm = 60 mV, the direction of net current flow through the ACh-gated ion channels is outward, toward the equilibrium potential of potassium, causing the membrane potential to become less positive. The critical value of membrane potential at which the direction of current flow reverses is called the reversal potential. In this case, the reversal potential is 0 mV because this is the value between the equilibrium potentials of sodium and potassium. At 0 mV, no current flows.
-
In this chapter, we discussed a GABA-gated ion channel that is permeable to Cl–. GABA also activates a G-protein-coupled receptor called the GABAB receptor, which causes potassium-selective channels to open. What effect would GABAB receptor activation have on the membrane potential? CH5
-
Activated GABA-gated Cl– ion channels bring the membrane toward the equilibrium potential for Cl–, which is –65 mV. If the membrane potential was less negative than –65 mV when the transmitter was released, activation would cause hyperpolarization. The activation of GABAB receptors causes potassium-selective channels to open. As a result, GABAB activation brings membrane potential toward the equilibrium potential of potassium, which is –80 mV. If the membrane potential was less negative than –80 mV when the transmitter was released, activation would also cause hyperpolarization. This channel might also impact the neuron by shunting inhibition, allowing a depolarizing current from an excitatory synapse to leak out. This, in turn, decreases the likelihood of action potential. The action of a G-protein-coupled receptor is, however, slower than that of the GABA-gated Cl– ion channel or a typical excitatory synapse. Therefore, its effects would be slower to occur and would last longer.
-
You think you have discovered a new neurotransmitter, and you are studying its effect on a neuron. The reversal potential for the response caused by the new chemical is –60 mV. Is this substance excitatory or inhibitory? Why?
Ch5
If the new chemical has a reversal potential of –60 mV, the substance is likely to be inhibitory. The reversal potential reflects the types of ions the membrane is permeable to after the application of the neurotransmitter. A reversal potential of –60 mV suggests that the neurotransmitter activates ion channels that make the membrane more negative. If a neurotransmitter causes the membrane to move toward a value that is more negative than the action potential threshold, the neuron becomes less likely to fire an action potential, which means it is inhibited.
-
A drug called strychnine, isolated from the seeds of a tree native in India and commonly used as rat poison, blocks the effects of glycine. Is strychnine an agonist or an antagonist of the glycine receptor?
Ch5
Strychnine is an antagonist of glycine at its receptor. Mild strychnine poisoning enhances the startle and other reflexes and resembles hyperekplexia. High doses can eliminate glycine-mediated inhibition in circuits of the spinal cord and the brain stem. This leads to uncontrollable seizures and unchecked muscular contractions, spasms, and paralysis of respiratory muscles. It might ultimately result in painful, agonizing death from asphyxiation.
-
How does nerve gas cause respiratory paralysis?
Ch5
Nerve gases interfere with synaptic transmission at the neuromuscular junction by inhibiting AChE. Uninterrupted exposure to high concentrations of ACh for several seconds leads to a process called desensitization. In this process, transmitter-gated channels close despite the continued presence of ACh. Normally, the rapid destruction of ACh by AChE prevents desensitization. However, if AChE is inhibited by nerve gas, ACh receptors will be desensitized and neuromuscular transmission will fail, causing respiratory paralysis.
-
Why is an excitatory synapse on the soma more effective in evoking action potentials in the postsynaptic neuron than an excitatory synapse on the tip of a dendrite?
Ch5
A current entering the sites of synaptic contact must spread to the spike-initiation zone and this zone must be depolarized beyond its threshold to generate an action potential. In addition, depolarization decreases as a function of distance along a dendrite. As a result, the effectiveness of an excitatory synapse for triggering an action potential depends on how far the synapse is from the spike-initiation zone. Because the soma is closer to the spikeinitiation zone, an excitatory synapse on the soma is more effective for evoking action potentials than an excitatory synapse on the tip of a dendrite.
-
What are the steps that lead to increased excitability in a neuron when NE is released presynaptically? Ch5
- 1. The NE receptor bound to a b receptor activates G-protein in the membrane.
- 2. G-protein activates the adenylyl cyclase enzyme.
- 3. Adenylyl cyclase converts ATP into the second messenger cAMP.
- 4. cAMP activates a protein, kinase.
- 5. Kinase causes a potassium channel to close by attaching a phosphate group to it. This produces little change in membrane potential but increases the membrane resistance and increases the length constant of dendrites. This enhances the response that a weak or a distant
- excitatory synapse produces. This effect can last longer than that of the presence of the
- transmitter.
-
If you could place microelectrodes into both a presynaptic and a postsynaptic neuron, how would you determine whether the synapse between them was chemically or electrically mediated?
Ch6
A microelectrode placed in the presynaptic and postsynaptic neuron would show different results for electrical and chemical transmission. For electrical transmission, the two electrodes would show identical or similar changes in electrical activity, i.e., the action potential in the presynaptic membrane would produce an action potential in the postsynaptic membrane. Chemically mediated synapses operate differently. An action potential in the presynaptic membrane causes neurotransmitter release in the synaptic cleft, and the postsynaptic membrane might respond to the neurotransmitter with changes in conduction, but not an action potential. An action potential is generated in the postsynaptic neuron of a chemically mediated synapse only if the whole neuron is sufficiently depolarized. This action potential would not be evident in a postsynaptic dendrite or cell body (typical synaptic sites); you would have to record for the axon of the postsynaptic neuron.
-
List the criteria that are used to determine whether a chemical serves as a neurotransmitter. What are the various experimental strategies you could use to show that ACh fulfills the criteria of a neurotransmitter at the neuromuscular junction?
Ch6
- 1) The molecule must be synthesized and stored in the presynaptic neuron.
- 2) The molecule must be released by the presynaptic axon terminal upon stimulation.
- 3) The molecule, when experimentally applied, must produce a response in the postsynaptic cell that mimics the response produced by the release of the neurotransmitter from the presynaptic neuron. Immunohistochemistry shows where specific molecules are localized, and in situ hybridization shows where specific mRNA transcripts for specific proteins are located. These methods could be used to demonstrate the presence of ACh in the presynaptic terminal at the neuromuscular junction. It would be useful to show that the synthesizing enzyme is present as well.
-
What are three methods that could be used to show that a neurotransmitter receptor is synthesized or localized in a particular neuron? CH6
Three methods are used to study the receptors of various neurotransmitters: neuropharmacological analysis of synaptic transmission, ligand-binding methods, and molecular analysis of receptor proteins. Neuropharmacological analysis studies the actions of different drugs. Ligand-binding methods can be used to identify the location of receptors by labeling ligands that bind to them, such as specific agonists, antagonists, or chemical neurotransmitters. Molecular analysis studies the protein molecules and the subunits that form the neurotransmitter receptors, such as transmitter-gated ion channels and G-proteincoupled receptors. This method may also be used to examine the genes that encode these proteins and the consequences of altering the genes or the gene products.
-
Compare and contrast the properties of (a) AMPA and NMDA receptors, and (b) GABAA and GABAB receptors. Ch6
- (a) AMPA and NMDA are glutamate receptor subtypes; both are activated by glutamate, but the drug AMPA acts only on the AMPA receptor and the drug NMDA acts only on the NMDA receptor. AMPA and NMDA are chemical agonists used to differentiate the glutamate receptor subtypes. Their antagonists can also distinguish receptor subtypes, forexample, the antagonist for AMPA is CNQX and the antagonist for NMDA is AP5. The differences in the receptors are related to slight differences in the protein. An important property of the NMDA receptor is that it is only active in the presence of glutamate and sufficient depolarization in the postsynaptic neuron.
- (b) GABAA and GABAB are GABA receptor subtypes; both respond to GABA but muscimol is the agonist for the GABAA receptor, and the agonist for GABAB is baclofen. The antagonist for GABAA is bicuculline whereas the antagonist for GABAB is phaclofen.
-
Synaptic inhibition is an important feature of the circuitry in the cerebral cortex. How would you determine whether GABA or Gly, or both, or neither, is the inhibitory neurotransmitter of the cortex? Ch6
Synaptic inhibition is represented by inhibitory postsynaptic potentials in the postsynaptic neuron of an inhibitory synapse. To determine whether GABA or Gly or both are inhibitory neurotransmitters, you could record IPSPs in response to GABA or Gly application in an in vitro preparation. You might also examine the nature of the postsynaptic receptors. Both GABA and Gly receptors gate a chloride channel, which when opened, would help hyperpolarize the postsynaptic cell and make that neuron less likely to fire an action potential.
-
Glutamate activates a number of different metabotropic receptors. The consequence of activating one subtype is the inhibition of cAMP formation. A consequence of activating a second subtype is activation of protein kinase C. Propose mechanisms for these different effects. CH6
The subtype of glutamate metabotropic receptor that inhibits cAMP formation may activate Gi. This is the mechanism used by the NE receptor subtype called a2, which inhibits adenylyl cyclase and, consequently, inhibits cAMP formation. The other subtype of glutamate metabotropic receptor might activate a G-protein that stimulates the enzyme phospholipase C (PLC). PLC splits the membrane phospholipids PIP2 into two parts: DAG and IP3. DAG stays in the plane of the membrane and activates the downstream enzyme protein kinase C (PKC). (IP3, on the other hand, diffuses away and causes organelles to discharge their calcium stores.)
-
Do convergence and divergence of neurotransmitter effects occur in single neurons?
Ch6
Diverging neurotransmitter effects are represented by the multitude of consequences a single neurotransmitter may have because it affects many different receptor subtypes in postsynaptic neurons. This effect may occur in a single neuron that possesses G-proteincoupled receptors with two or more intracellular functions or, potentially, single neurons that elaborate different types of receptors in different parts of the neuron. Convergence occurs when several transmitters affect a single effector system. This can occur in a single cell at the level of the G-protein, the second messenger cascade, or the type of ion channel. Neurons integrate divergent and convergent signaling systems, resulting in a complex map of chemical effects.
-
Ca2+ ions are considered to be second messengers. Why? CH6
Ca2+ ions are considered to be second messengers because elevations of Ca2+ ions in the cytosol can have widespread and long-lasting effects on the neuron. An example of this is Ca2+ activation of the enzyme calcium-calmodulin-dependent protein kinase (CaMK), which is important in molecular mechanisms of memory.
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