chapter 22 - Signal Transduction Mechanisms: I. Electrical and Synaptic Signaling in Neurons Flashcards

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1
Q

Q: What is the most dramatic example of regulation of electrical properties in cell membranes?

A

action potential

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2
Q

Q: What allows cell membranes to regulate ion flow?

A

A: Their ability to control the passage of ions between the interior and exterior of the cell.

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3
Q

Q: What are the two main divisions of the vertebrate nervous system?

A

A:
Central Nervous System (CNS): Brain and spinal cord.
Peripheral Nervous System (PNS): Sensory and motor components.

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4
Q

Q: What are the two main types of cells in the nervous system?

A

A:
Neurons: Send and receive electrical impulses.
Glial cells: Support various functions and are the most abundant in the CNS.

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5
Q

Q: What are the 3 types of neurons?

A

A:
Sensory neurons
Motor neurons
Interneurons

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6
Q

Q: What are the types of glial cells and their functions?-

A

A:
- Microglia: Fight infections and remove debris.
- Oligodendrocytes and Schwann cells: Form myelin sheaths around CNS and peripheral nerves.
- Astrocytes: Regulate access of blood-borne components into the extracellular fluid, forming the blood-brain barrier.

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7
Q

Q: What are the structural components of a neuron?

A

A:
- Cell body: Contains the nucleus and endomembrane components.
Processes:
- Dendrites: Receive signals.
- Axons: Conduct signals.

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8
Q

Q: What is axoplasm?

A

A: The cytosol within an axon.

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9
Q

Q: What is a nerve?

A

A: A tissue composed of bundles of axons.

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10
Q

Q: What is the role of the myelin sheath?

A

A: Insulates axons, separating segments with nodes of Ranvier.

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11
Q

Q: What distinguishes motor neurons?

A

A:
- Multiple branched dendrites.
- A single, long axon.
- Terminal structures called synaptic boutons (or terminal bulbs).

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12
Q

Q: What is the function of synaptic boutons?

A

A: Transmit signals to neurons, muscles, or gland cells.

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13
Q

Q: What is a synapse?

A

A: The junction between a nerve cell, gland, or muscle cell.

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14
Q

Q: Where do synapses typically occur?

A

A:
Between axons and dendrites.
Between two dendrites.

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15
Q

Q: What is membrane potential (Vm)?

A

A: A fundamental property where cells at rest have excess negative charge inside and positive charge outside.

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16
Q

Q: What is resting membrane potential?

A

A: The electrical potential resulting from the charge distribution.

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17
Q

Q: What are the principles of ion transport?

A

A:
1. Diffusion: Solutes move from high to low concentration.

Example: Potassium ions diffuse out due to the potassium ion gradient.

  1. Electroneutrality: Ions in solution are paired with oppositely charged ions.

Example:
Inside the cell: K+ pairs with trapped anions.
Outside the cell: Na+ pairs with Cl-.

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18
Q

What is electrical potential (voltage)?

A

A:
- Local separation of charges where one region has more positive charges, and another has more negative charges.
- It requires work to create this separation.

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19
Q

Q: Must a solution maintain electroneutrality?

A

A: Yes, but charges can be separated locally to create electrical potential.

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20
Q

Q: What is current in the context of ion transport?

A

A:
- The movement of ions (positive or negative).
- Measured in amperes (A).

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21
Q

Q: Why are squid giant axons significant for research? (year)

A

A:
- Their large size allows for easy insertion of microelectrodes.
- Used since the 1930s to study nerve transmission and measure/control electrical potentials.

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22
Q

Q: What is the resting membrane potential of the squid giant axon?

A

A: About –60 mV.

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23
Q

Q: Which cells exhibit electrical excitability?

A

A: Nerve, muscle, and certain other cell types.

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24
Q

Q: What is an action potential?

A

A:
A rapid change in membrane potential in electrically excitable cells triggered by certain stimuli.
The membrane potential changes from negative to positive and back to negative in a short time.

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25
Q

Q: What does the resting membrane potential depend on?

A

A:
- Ion concentrations:
Extracellular fluid: Mostly sodium chloride (NaCl).
Cytosol: Contains trapped macromolecules like
proteins and RNA.
- Selective membrane permeability: Specific ion channels help maintain resting potential.

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26
Q

Q: What are leak channels?

A

A:
Ion channels that form pores through the lipid bilayer.
Characteristics:
Always open (not gated).
Allow potassium and sodium to diffuse
based on ion concentration and
membrane voltage.

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27
Q

Q: Why is the resting potential negative?

A

A:
Potassium leak channels allow K+ to diffuse out of the cell.
This leaves behind anions without counterions, creating a negative charge inside the cell.

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28
Q

Q: What is the role of the Na+/K+ pump?

A

A:
Compensates for ion leakage by pumping Na+ out and K+ into the cell.

Key features:
- ATP-dependent process.
- Pumps 3 Na+ ions out for every 2 K+ ions in.
- Maintains the large potassium ion gradient across the membrane.

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29
Q

Q: What is the relationship between ion leak and the Na+/K+ pump?

A

A: The pump continuously works to restore ionic gradients that are disrupted by ion leakage.

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30
Q

Q: Why do potassium ions leave the cell through leak channels?

A

A: Due to the concentration gradient of potassium being higher inside the cell than outside.

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31
Q

Q: How does the composition of ions differ between the cytosol and extracellular fluid?

A

A:
Cytosol: High in K+ with macromolecules like proteins and RNA.
Extracellular fluid: High in Na+ and Cl-.

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32
Q

Q: What is the Nernst equation used for?

A

A: It describes the relationship between membrane potential and ion concentration, specifically at equilibrium.

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33
Q

Q: What is electrical equilibrium?

A

A: The state where a chemical gradient is balanced by electrical potential, resulting in an equilibrium (or reversal) potential.

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34
Q

Q: What does the Nernst equation assume when simplified?

A

A:
- A temperature of 293K.
- A monovalent ion with a valence of 1.

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35
Q

Q: How does the Nernst equation relate membrane potential to ion gradients?

A

A: For every tenfold increase in the cation gradient, the membrane potential changes by approximately -58 mV.

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36
Q

Q: Why is the simplified Nernst equation incomplete?

A

A: It does not account for anions or the unequal distribution of multiple ions like Na+, K+, and Cl-.

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37
Q

Q: How do individual ions affect membrane potential?

A

A:
- K+: Diffuses out of the cell, making the membrane potential more negative
.
- Na+: Flows into the cell, driving the potential in the positive direction (depolarization).

  • Cl-: Diffuses into the cell but is repelled by the negative membrane potential unless accompanied by positive ions.
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38
Q

Q: What happens when membrane permeability to Cl- increases?

A

A:
- Hyperpolarization: Net entry of Cl- without a matching cation makes the membrane potential more negative.

  • Cl- enters with Na+ during increased sodium permeability, further decreasing excitability.
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39
Q

Q: What does the Goldman equation describe?

A

A: The combined effects of multiple ions (Na+, K+, Cl-) on membrane potential, accounting for their relative permeabilities.

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40
Q

Q: How is the Goldman equation different from the Nernst equation?

A

A: It includes terms for the permeability of each ion, while the Nernst equation deals with only one ion at a time.

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41
Q

Q: What are steady-state ion movements across the plasma membrane?

A

A:
- K+ only permeability: Membrane potential equals K+ equilibrium potential.

  • Slight Na+ permeability: Causes partial depolarization as Na+ leaks in.
  • Result: K+ diffuses outward, balancing the inward Na+ movement.
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42
Q

Q: What are the contributions of Goldman, Lloyd, and Katz?

A

A: They described how gradients of multiple ions contribute to membrane potential and developed the Goldman equation.

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43
Q

Q: How does the Goldman equation estimate resting membrane potential in a squid axon?

A

A:
Uses relative permeabilities:
- K+: 1.0

  • Na+: 0.04 (4%)
  • Cl-: 0.45 (45%)
  • The estimated potential is -60.3 mV, aligning with the typical measured value of -60 mV.
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44
Q

Q: How does the Goldman equation simplify to the Nernst equation?

A

A: When the relative permeability of one ion is very high, the Goldman equation reduces to the Nernst equation for that ion.

45
Q

Q: When can Cl- effects be ignored in the Goldman equation?

A

A: When the permeability of Na+ (Pna) is much greater than that of K+ (Pk).

46
Q

Q: What is required for an electrically excitable cell to generate an action potential?

A

A:
Resting potential: Established by ion gradients and permeability.
Depolarization: Stimulus causing a rapid response.
Voltage-gated channels: Present in addition to leak channels and Na+/K+ pumps.

47
Q

Q: What is patch clamping?

A

A:
A method to record ion currents passing through single channels.
Developed by Erwin Neher and Bert Sakmann.
Used in neurobiology to study ion channel function.

48
Q

Q: How are frog oocytes used in ion channel research?

A

A:
Channel proteins are synthesized in large amounts.
Studied in lipid bilayers or frog eggs.
Mutations or modifications help determine specific channel regions’ roles.

49
Q

Q: What is optogenetics?

A

A: A technique using genetically engineered, light-sensitive channel proteins to manipulate neuronal ion concentrations.

50
Q

Q: What are the tools used in optogenetics, and their functions?

A

A:
Bacteriorhodopsin: Inhibits neurons.
Channelrhodopsins: Activates neurons.

51
Q

Q: How is optogenetics applied?

A

A: Channel proteins are expressed in neuronal cell cultures or transgenic animals, and responses are observed under a microscope.

52
Q

Q: How do voltage-gated ion channels respond to changes in voltage?

A

A: They open or close based on voltage changes across the membrane.

53
Q

Q: What are ligand-gated ion channels?

A

A: Channels that open when a specific molecule binds to them.

54
Q

Q: Which voltage-gated ion channels are responsible for action potential?

A

A: Voltage-gated Na+ and K+ channels.

55
Q

Q: What are the structural categories of voltage-gated ion channels?

A

A:
1. Potassium Channels: Multimeric proteins with four subunits.
2. Sodium Channels: Large monomeric proteins with four domains.

56
Q

Q: What is common in the structure of both sodium and potassium voltage-gated channels?

A

A:
Each domain or subunit contains six transmembrane α-helices.

57
Q

Q: What determines the specificity of ion channels?

A

A:
1. Size of the central pore.
2. Interaction between ions and oxygen atoms in the amino acids of the selectivity filter.

58
Q

Q: How do oxygen atoms in the selectivity filter contribute to specificity?

A

A: They are positioned to interact with ions as they pass through, ensuring the correct ions are selected.
Channel Gating and Inactivation

59
Q

Q: What is channel gating in voltage-gated sodium channels?

A

A: The process where channels open rapidly in response to a stimulus and then close again.

60
Q

Q: Is channel gating all-or-none or partial?

A

A: All-or-none; channels are either fully open or fully closed.

61
Q

Q: What acts as a voltage sensor in voltage-gated sodium channels?

A

A: The fourth transmembrane helix, S4.

62
Q

Q: What is channel inactivation?

A

A: A state where the channel cannot reopen immediately, even if stimulated, due to an inactivating particle blocking the channel opening.

63
Q

Q: What is an action potential?

A

A: A rapid, large depolarization and repolarization of the neuronal plasma membrane caused by:
Inward movement of Na+.
Outward movement of K+.

64
Q

Q: How does an action potential propagate?

A

it travels along the cell membrane, moving away from its point of origin. This movement occurs through a process known as propagation.

65
Q

Phases of Action Potential
Q: What happens during the depolarizing phase?

A

A:
Membrane potential rises rapidly after crossing the threshold potential.
Significant Na+ channels activate, causing the potential to peak at approximately +40 mV.

66
Q

Q: What happens during the repolarizing phase?

A

A:
Sodium channels inactivate, and voltage-gated K+ channels open.
The membrane repolarizes as K+ exits the cell.

67
Q

Q: What is the hyperpolarizing phase (undershoot)?

A

A:
Temporary drop of the membrane potential below the resting level due to increased K+ permeability.
As K+ channels close, the membrane potential returns to the resting level.

68
Q

Q: What is the absolute refractory period?

A

A: A phase immediately after an action potential when:
Na+ channels are inactivated.
No action potential can be triggered, regardless of the stimulus.

69
Q

Q: What is the relative refractory period?

A

A: A phase during the undershoot when:
Na+ channels recover, but K+ channels are still open.
Membrane potential is below the threshold, requiring a stronger stimulus to trigger another action potential.

70
Q

Q: What is the Hodgkin Cycle?

A

A: A positive feedback loop where:
Depolarization opens Na+ channels.
Increased Na+ flow causes further depolarization, opening more channels.

71
Q

Q: What is subthreshold depolarization?

A

A:
A small membrane depolarization that does not reach the threshold potential.
No action potential occurs as the membrane potential recovers through K+ leak channels.

72
Q

Q: How much do ion concentrations change during an action potential?

A

A: Cellular concentrations of Na+ and K+ hardly change because the ions involved are a small fraction of the total ions in the cell.

73
Q

Q: What happens during intense neuronal activity?

A

A: Significant changes in ion concentration can occur with sustained activity.

74
Q

Q: How is a signal propagated along the axon?

A

A:
Depolarization spreads passively but decreases in magnitude.
Active regeneration of the action potential ensures it does not lose strength as it travels.

75
Q

Q: What are the steps of action potential propagation in a nonmyelinated nerve cell?

A

A:
- Depolarization: Stimulation causes Na+ to rush into the cell, reversing polarity locally.

  • Spread: Depolarization spreads to adjacent regions, reaching the threshold.
  • Repolarization Initiation: Original region becomes permeable to K+, which exits to restore resting potential
    .
  • Resetting: The membrane at the original site returns to its resting state.
  • Continuation: Depolarization triggers the same sequence in the next region, actively propagating the action potential.
76
Q

Q: What is the function of the myelin sheath?

A

A:
Acts as an electrical insulator, reducing membrane capacitance.
Allows nerve impulses to spread farther

77
Q

Q: What is saltatory propagation?

A

A: A process where action potentials “jump” between nodes of Ranvier, making conduction more rapid than in nonmyelinated axons.

78
Q

Q: Where are action potentials renewed in myelinated axons?

A

A: At the nodes of Ranvier, which are spaced close enough to ensure propagation continuity.

79
Q

Q: What is found at the nodes of Ranvier?

A

A:
Voltage-sensitive Na+ channels concentrated in the node.
Adhesive proteins between axonal and glial membranes in paranodal regions.
K+ channels in juxtaparanodal regions.

80
Q

Q: What are synapses?

A

: Points of contact where signals are transmitted between neurons or to other cell types.

81
Q

Q: How do electrical synapses work?

A

A: The presynaptic and postsynaptic neurons are connected by gap junctions, allowing ions to pass directly without delay.

82
Q

Q: What is a chemical synapse?

A

A: A type of synapse where presynaptic and postsynaptic neurons are separated by a synaptic cleft, and the signal is transmitted chemically.

83
Q

Q: How are neurotransmitters released and transmitted?

A

A:
1. Stored in synaptic boutons of the presynaptic neuron.

  1. Released when an action potential reaches the bouton.
  2. Diffuse across the synaptic cleft to bind receptors on the postsynaptic membrane.
  3. Converted into an electrical signal to excite or inhibit the postsynaptic cell.
84
Q

Q: What are the two classes of neurotransmitter receptors?

A

A:
Ionotropic receptors: Ligand-gated ion channels.
Metabotropic receptors: Indirectly affect the cell via messenger systems.

85
Q

Q: What effects do neurotransmitters have on the postsynaptic neuron?

A

A:
Excitatory: Cause depolarization (e.g., acetylcholine, glutamate, serotonin).
Inhibitory: Cause hyperpolarization (e.g., GABA, glycine).

86
Q

Criteria for Neurotransmitters
Q: What are the criteria for a molecule to qualify as a neurotransmitter?

A

A:
Natural presence in the presynaptic neuron.
Released when the neuron is stimulated.
Appropriate response elicited in the synaptic cleft.

Common Neurotransmitters
Acetylcholine:
Most common in vertebrate neuromuscular junctions.
Excitatory.
Used in cholinergic synapses.
Catecholamines (dopamine, norepinephrine, epinephrine):
Tyrosine derivatives.
Synthesized in the adrenal gland.
Used in adrenergic synapses.
Amino Acids and Derivatives:
Excitatory: Glutamate, serotonin.
Inhibitory: GABA, glycine.
Neuropeptides:
Act on groups of neurons with long-lasting effects.
Example: Enkephalins inhibit pain perception.
Endocannabinoids:
Lipid derivatives that inhibit presynaptic neurons.
THC from cannabis stimulates these receptors

87
Q

Q: How does calcium regulate neurotransmitter secretion?

A

A:
Action potential depolarizes the bouton.
Voltage-gated calcium channels open, increasing Ca²⁺ concentration.
Neurotransmitters stored in neurosecretory vesicles are released.
Calcium and Vesicle Dynamics

88
Q

Q: How does calcium influence vesicle release in the synaptic bouton?

A

A:
Mobilizes vesicles held in storage for rapid release.
Causes docked vesicles to fuse with the plasma membrane, releasing neurotransmitters via exocytosis.

89
Q

Q: What proteins mediate docking and fusion of vesicles with the plasma membrane?

A

A:
t-SNAREs and v-SNAREs facilitate vesicle fusion.
Synaptotagmin binds calcium, undergoes a conformational change, and promotes efficient SNARE interactions.

90
Q

Q: What is the “active zone” in the synaptic bouton?

A

A:
The site where vesicles dock and fuse, located near calcium channels for efficient neurotransmitter release.

91
Q

Q: What is kiss-and-run exocytosis?

A

A: A transient release method where a vesicle briefly fuses with the plasma membrane, releases neurotransmitter, and reseals.

92
Q

Q: How are neurotransmitters detected by postsynaptic neurons?

A

A: Each neurotransmitter binds to specific receptors on the postsynaptic cell membrane, triggering excitatory or inhibitory effects.

93
Q

Q: What type of receptor is nAchR, and what happens when it binds acetylcholine?

A

A:
It is a ligand-gated Na⁺ channel.
Binding of two acetylcholine molecules opens the receptor, allowing Na⁺ to enter and depolarize the cell.

94
Q

Q: What neurotoxins affect nAchR?

A

A:
α-bungarotoxin and cobratoxin covalently bind to nAchRs.
Curare (contains d-tubocurarine) and some snake venoms compete with acetylcholine, preventing depolarization.

95
Q

Q: What are antagonists and agonists in cholinergic systems?

A

A:
Antagonists: Block acetylcholine binding, preventing depolarization.
Agonists: Mimic acetylcholine, causing depolarization, but are not rapidly inactivated.

96
Q

Q: How does the GABA receptor function, and what is its effect?

A

A:
It is a ligand-gated Cl⁻ channel.
When open, it allows Cl⁻ to enter the cell, causing hyperpolarization and reducing action potential likelihood.

97
Q

Q: How do benzodiazepines interact with GABA receptors?

A

A: They enhance GABA’s effects, promoting increased hyperpolarization.
NMDA Receptor

98
Q

Q: What is the NMDA receptor, and why is it significant?

A

A:
It is an ionotropic receptor for glutamate, permeable to Na⁺ and Ca²⁺ when glutamate binds.
Plays a critical role in memory and neuronal plasticity.

99
Q

Q: What is a common use for NMDA receptor antagonists?

A

A: They are frequently used as anesthetics.

100
Q

Q: Why must neurotransmitters be inactivated after release?

A

A: To prevent prolonged stimulation or inhibition of the postsynaptic neuron.

101
Q

Q: What are the two primary mechanisms of neurotransmitter inactivation?

A

A:
Degradation (e.g., enzymatic breakdown).
Reuptake into the presynaptic cell or nearby support cells.

102
Q

Q: How does acetylcholinesterase function?

A

A:
Hydrolyzes acetylcholine into acetic acid and choline.
Inhibited by compounds like carbamoyl esters, nerve gases (e.g., sarin), and certain insecticides.

103
Q

Q: What is the role of neurotransmitter reuptake?

A

A:
Pumps neurotransmitters back into the presynaptic neuron or nearby support cells within milliseconds.
Antidepressants like Prozac block reuptake to prolong neurotransmitter action.

104
Q

Q: What are PSPs, and how do they work?

A

A:
Postsynaptic potentials are incremental changes in membrane potential caused by neurotransmitter binding.
PSPs can be excitatory (EPSP) or inhibitory (IPSP) depending on the neurotransmitter.

105
Q

S
Q: What is temporal summation?

A

A:
Occurs when rapid successive action potentials sum up EPSPs over time, pushing the postsynaptic cell past its threshold.

106
Q

Q: What is spatial summation?

A

A:
Occurs when multiple action potentials from different synapses release neurotransmitters simultaneously, increasing the likelihood of reaching the action potential threshold.

107
Q

Sensory neurons:

A

Detect stimuli.
.

108
Q

Motor neurons:

A

Transmit signals from the CNS to muscles and glands.

109
Q

Interneurons:

A

Process signals and transmit information within the nervous system