Block 8 (Neuro) - L1, L5, L8 Flashcards
1
Q
What is the specialized zone between neurons at which communication takes place?
A
Synapse
2
Q
What are the two types of synapses?
A
- Electrical
2. Chemical
3
Q
What is an electrical synapse?
A
A low resistance, high conductance channel utilizing direct connections between cells called gap junctions
4
Q
What is a chemical synapse?
A
Chemical NT are released from synaptic vesicles in the presynaptic cell and diffuse across the synaptic cleft and bind to specialized receptors in the postsynaptic cell
5
Q
Compare the distance between pre- and post-synaptic cell membranes of electric and chemical synapses.
A
Electrical: shorter (3.5 nm)
Chemical: longer (20-40 nm)
6
Q
Which type of synapse maintains cytoplasmic continuity between pre- and post-synaptic cells?
A
Electrical
7
Q
Compare the ultrastructural components of electric and chemical synapses.
A
Electrical: gap junctions
Chemical: presynaptic vesicles and active zones; postsynaptic receptors
8
Q
Compare the agent of transmission of electric and chemical synapses.
A
Electrical: ion current
Chemical: chemical transmitter
9
Q
Compare the synaptic delay of electric and chemical synapses.
A
Electrical: virtually absent
Chemical: significant
10
Q
Compare the direction of transmission of electric and chemical synapses.
A
Electrical: usually bidirectional
Chemical: unidirectional
11
Q
Where do synapses occur within cells?
A
Active zones - specialized regions that function as docking sites for synaptic vesicles
12
Q
Describe the mechanism of NT release from the presynaptic terminal.
A
- NT is synthesized and stored in vesicles
- An AP invades the presynaptic terminal
- Depolarization of presynaptic terminal causes opening of voltage-gated Ca2+ channels
- Influx of Ca2+ through channels
- Ca2+ causes vesicles to fuse with the presynaptic membrane
- NT is released into synaptic cleft via exocytosis
- NT binds to receptor molecules in the postsynaptic membrane
- Opening or closing of postsynaptic channels
- Postsynaptic current causes excitatory or inhibitory postsynaptic potential that changes the excitability of the postsynaptic cell
- Removal of NT by glial uptake or degradation
- Retrieval of vesicular membrane from plasma membrane
13
Q
What two factors determine the grade of chemical synapses?
A
- Amount of NT released
2. Number of receptors available
14
Q
What determines the action of a NT?
A
The properties of the receptor (NOT the NT)
15
Q
What are the two common features of all chemical receptors?
A
- Membrane-spanning proteins
2. Carry out an effector function in the postsynaptic cell by directly or indirectly gating some type of response
16
Q
Describe the structure and function of a directly gated channel.
A
This channel is typically a single macromolecule made up of several protein subunits that form both the receptor and the ion channel.
17
Q
What is an ionophoric receptor?
A
Single macromolecule that forms both the receptor and the ion channel
18
Q
Directly gated responses are ___ (speed) but ___ (time). What types of responses do they tend to mediate?
A
Fast-acting; short-lived; behavioral types of responses
19
Q
Describe the structure and function of an indirectly gated channel.
A
The receptor complex is separate from the effector complex (ion channel). Communication between the receptor and the channel is accomplished by G proteins and second messengers.
20
Q
Which component of an indirectly gated receptor complex is NOT loosely bound to the postsynaptic membrane?
A
Second messengers (this allows them to affect distant sites within the cell)
21
Q
Indirectly gated responses are ___ (speed) but ___ (time). What types of responses do they tend to mediate?
A
Slow-acting; long-lasting or permanent; responses related to learning and memory
22
Q
___ of synaptic input occurs at the axon hillock. In the CNS, no single synaptic event is usually sufficient to produce an AP. Therefore, you need to ___ many potentials.
A
Integration; summate
23
Q
What factors affect the production of synaptic potentials?
A
- Size of the cell
- Location of the synapse (axon, dendrite, soma)
- Shape
- Proximity
- Strength (time and length constants)
- Sign (EPSP vs. IPSP) of the input
24
Q
At the axon hillock, the membrane potential is greatly reduced. Why and what effect does this have on threshold?
A
Due to higher density of voltage-gated sodium channels; increases the likelihood of surpassing threshold
25
At all sites within the cell beside the axon hillock, neuronal integration depends on what two passive properties of the membrane?
1. Time constant
| 2. Length constant
26
A long time constant means a better chance for integration via ___ summation.
Temporal (multiple inputs from a single source)
27
A long length constant means a better chance for integration via ___ summation.
Spacial (simultaneous single inputs from multiple sources)
28
What are the three types of synapses?
1. Axosomatic
2. Axodendritic
3. Axoaxonic
29
Axosomatic synapses are typically ___ and occur via ___ channels.
Inhibitory; chloride
30
Axodendritic synapses are typically ___.
Excitatory
31
Axoaxonic synapses are typically ___ and control the amount of ___ released.
Modulatory; NT
32
Which synapses affect the production of an AP and which do not?
Axosomatic and axodendritic are mediating, occur before the axon hillock, and can aid in the production of an AP. Axoaxonic synapses are modulatory and have no influence on the production of an AP. They can modulate its effectiveness at the presynaptic terminal.
33
The propagation of the AP to the presynaptic terminal requires what types of channels? At the terminal, the presence of these channels is not essential to NT release. What ion is essential?
Na; K
Ca
34
The opening of the voltage-gated Ca channels has a slower activation kinetics than that of Na. What is the implication of this?
There is some synaptic delay between the arrival of the AP and the opening of the Ca channels (this opening occurs near the peak of the AP, a 0.2ms delay)
35
___ of the AP is critical to the calcium influx.
Duration
36
Changes in the levels of calcium do NOT affect the amount of NT in a vesicle. What does it affect?
The probability of release of that vesicle from the presynaptic terminal
37
What are omega figures?
Deformations in the presynaptic membrane seen during active transmission - they are the vesicles releasing NT via exocytosis
38
What are the 7 basic steps for synaptic release and retrieval and what is required for almost every phase?
1. Translocation
2. Attachment to active zone
3. Contact to the docking protein at the presynaptic membrane via calcium-dependent proteins
4. Fusion to the membrane protein
5. Opening of the vesicle (exocytosis) and extrusion of contents into synaptic cleft
6. Collapse of the vesicle into the plasm membrane
7. Retrieval of the vesicle via calcium-dependent proteins
39
What two toxins can affect the SNARE proteins associated with NT release and lead to paralysis?
Botulinum and tetanus
40
What mediates endocytosis of vesicles?
Clathrin
41
What are 3 diseases leading to a defect in ACh resynthesis or packaging?
1. Familial infantile myasthenia
2. Congenital paucity of presynaptic vesicles and reduced quantal release
3. Black widow spider venom
42
What are 3 diseases leading to a defect in ACh release?
1. Lambert-Eaton myasthenic syndrome
2. Botulism
3. Aminoglycoside antibiotics
4. Magnesium intoxication
5. Snake venom
43
What 4 criteria define a NT?
1. Synthesized in a neuron
2. Present in the presynaptic terminal and released in amounts sufficient to exert its intended action on the postsynaptic cell
3. If applied exogenously in reasonable concentrations, it mimics exactly the action of the endogenously released substance.
4. A specific mechanism exists for its removal from the synaptic cleft
44
What are the major categories of small molecule NTs?
1. ACh
2. Biogenic amines
3. Amino acids
45
How is ACh built?
Acetyl CoA + choline
NB: choline is derived only from your diet
46
Where is ACh used?
1. All NMJs
2. All preganglionic synapses
3. Parasympathetic postganglionic synapses
4. Nucleus basalis (CNS)
47
What are the 3 biogenic amines?
1. Catecholamines
2. Indolamine
3. Imidazole
48
How are catecholamines derived?
Tyrosine + O2 -> L-DOPA -> dopamine + CO2 -> NE -> EPI
49
Dopamine is the essential NT switch for the ___.
Basal ganglia
50
Where is NE used?
1. All sympathetic postganglionic synapses
2. Hypothalamus
3. Limbic system
51
NE typically acts via ___ receptors.
Alpha-adrenergic
52
Where is EPI used?
1. Peripherally
| 2. Adrenal medulla
53
EPI typically acts via ___ receptors.
Beta-adrenergic
54
How is indolamine derived?
Tryptophan -> 5-HTP -> 5-HT (serotonin)
55
Serotonin is an essential NT in the ___ and ___.
Brainstem and limbic system
56
How is imidazole derived?
Histidine -> histamine
57
Where does histamine act?
Used as a local hormone - it acts on the cell which released it to limit the peripheral effects; found in the hypothalamus
58
What are some important amino acid NTs?
Glutamate, aspartate, glycine, GABA
59
Amino acid transmitters are derived from universal cellular compartments and must be protected from degradation for other cellular processes - how is this done?
Compartmentalized and isolated from the rest of the cell by placing them in a synaptic vesicle - once in a vesicle, they are not able to be returned to the cell
60
What are secretory proteins processed by the ER and Golgi apparatus, packaged, and sent to the terminal via fast axonal transport mechanisms?
Neuroactive peptides (NAPs)
61
Where does processing of NAP's take place?
In the vesicle
62
How are NT removed from the synapse?
1. Reuptake
2. Glial cell uptake
3. Enzymatic breakdown
63
What factors determine total synaptic conductance at a synapse?
1. N = total number of channels in the cell
2. P0 = probability that a channel is open
3. Gamma = conductance of an open channel
4. Vm - E(epsp) = driving forces acting on the ions
64
What factor affects the total synaptic conductance most significantly?
Probability that a channel is open
65
What factor most directly affects whether a channel is open?
Concentration of available NT at that synapse
66
How do central synapses differ from the NMJ?
NMJ:
1. Individual muscle fibers are innervated by a single motor neuron.
2. The synapse is excitatory only.
3. Transmitter is always ACh via nicotinic receptors
4. Synapse is highly effective, leading to a 70 mV depolarization and an AP in the sarcolemma ~100% of the time
vs.
CNS:
1. Central synapses have multiple connections/cell
2. Synapses can be excitatory OR inhibitory.
3. Many NT used singly and in combination
4. Effectiveness of the synapse is variable but typically small and thus depends on the integration of many synapses to reach threshold
67
What disease causes a defect in AChR density?
1. Myasthenia gravis
| 2. Congenital end-plate AChR deficiency
68
What disease causes a defect in AChR channel kinetics?
1. Slow-channel syndrome
| 2. High-conductance, fast-channel syndrome
69
What disease causes a defect in AChE?
1. Congenital end-plate deficiency
| 2. Organphosphates
70
What disease causes a defect in binding of ACh to its receptor?
1. Congenital myasthenic syndrome with abnormal interaction
2. Curare, succinylcholine, etc.
3. Snake venom
71
Excitatory synapses generally open what channels? What is the major NT?
Na and Ca
Glutamate
72
What types of receptors can be activated by glutamate?
1. AMPA
2. NMDA
3. Quisqualate-B
73
Inhibitory synapses generally open what channels? What are the major NTs?
K and Cl
GABA and glycine
74
Describe the scheme of second messenger pathways.
1. NT binds to receptor
2. REceptor binds to and activates a transducer (G-protein)
3. G-protein translocates and activates the primary effector
4. Primary effector produces a second messenger
5. Second messenger activates the secondary effector
6. This produces a change in the membrane potential of the post-synaptic cell
75
What are the three major systems of second messengers?
1. cAMP
2. Phosphoinositol
3. Arachidonic acid
76
Most protein kinases have what two segments?
1. Regulatory subunit
| 2. Catalytic subunit
77
What is the regulatory subunit?
Binding site or switch which activates/inactivates kinase
78
What is the catalytic subunit?
Interacts with other proteins
79
Describe the cAMP system.
1. NE binds to a beta-adrenergic receptor.
2. The receptor activates a Gs protein (transducer).
3. The Gs protein activates AC (primary effector)
4. AC leads to the production of cAMP (second messenger)
5. cAMP activates a cAMP-dependent protein kinase (secondary effector)
80
Describe the phosphoinositol system.
1. ACh binds to a muscarinic ACh receptor.
2. The receptor activates a Gq protein (transducer).
3. The Gs protein activates PLC (primary effector)
4. PLC leads to the production of IP3 and DAG (second messenger)
5. DAG activates a PKC (secondary effector) and IP3 diffuses into the ER, activating intracellular Ca2+ release.
81
Describe the arachidonic acid system.
1. Histamine binds to a histamine receptor.
2. The receptor activates a G protein (transducer).
3. The G protein activates PLA2 (primary effector)
4. PLA2 leads to the production of arachidonic acid (second messenger) by cleaving inositol phosphate
5. Arachidonic acid activates 5-lipoxygenase, 12-lipoxygenase, and cyclo-oxygenase (prostaglandins, thromboxanes, leukotrienes)
82
How is kinase activity terminated?
Phosphoprotein phosphatases
83
Slow synaptic mechanisms ___ cellular responses; fast synaptic mechanisms ___ cellular responses.
Modulate; mediate
84
True or false - G-proteins can act directly on channels without going through a second messenger cascade.
True - it also still a form of indirect transmission because the receptor is not part of the channel.
85
What is pain?
An unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage
86
What are the responses to superficial pain?
1. Orientation toward stimulus
2. Increase CO
3. Shut down digestion
4. Increase blood flow to skeletal muscle
5. Withdraw or escape
87
What are the responses to deep/chronic pain?
1. Social withdrawal
2. Anorexia
3. Decrease HR
4. Decrease blood flow to digestive tract
5. Decrease blood flow to skeletal muscle
6. Motor immobility
88
What are the types of nociceptors, the fiber group/name, and the modality?
1. Mechanical - A-delta, III, sharp/pricking pain
2. Thermal-mechanical - A-delta, III, burning pain
3. Thermal-mechanical - C, IV, freezing pain
4. Polymodal - C, IV, slow, burning pain
89
Compare the information transmitted via the DC and STT pathways.
DC: discriminative touch, proprioception, vibration
STT: pain, temperature, crude touch
90
Compare the fiber size and myelination of the DC and STT pathways.
DC: large fibers, heavily myelinated
STT: small fibers, thin or unmyelinated
91
Compare the point of decussation of the DC and STT pathways.
DC: decussate after ascending
STT: decussate before ascending
92
What is the difference between pain and nociception?
Pain: perception of aversive sensations originating from a specific area
Nociception: transduction and conveyance of signals from specialized sensory receptors concerning tissue damage
93
What type of nociceptors convey sharp pain?
Thermal or mechanical
94
What type of nociceptors convey dull or diffuse pain?
Polymodal
95
What type of nociceptors are found in viscera and only respond to inflammation or extreme stretch?
Silent
96
What is hyperalgesia?
Increased response to a stimulus which is normally painful
97
What causes hyperalgesia?
Lowering of the nociceptor's threshold by peripheral or central mechanisms, resulting in an increase in the number of action potentials sent to the CNS
98
What is primary hyperalgesia?
Occurs at the site of the lesion
99
What is secondary hyperalgesia?
Occurs during severe or persistent injury - nociceptors fire repeatedly, increasing the firing of neurons in the dorsal horn, leading to long-term changes in the overall excitability of these cells or the target neurons
100
What is central sensitization?
The resulting long-term changes in excitability/sensitivity of the dorsal horn neurons undergoing secondary hyperalgesia
101
Stimulation of the pain pathway results in inhibition of ___ and excitation of ___, resulting in the perception of pain.
Inhibitory interneurons; Projection neurons
102
By stimulating the ___ of the somatosensory system, you can excite the ___, resulting in a decreased output of the projection fiber and a suppression of the pain.
Non-nociceptive AB fibers; inhibitory interneurons
103
What is analgesia?
Modulation or reduction of pain
104
What is the gate control theory?
A balance exists between myelinated and unmyelinated fibers in the dorsal horn
105
What are the 4 primary classes of spinal neurons which can interact to modulate pain?
1. Unmyelinated nociceptive afferents (pain fibers)
2. Myelinated non-noceiceptive afferents (somatosensory fibers)
3. Projections neurons to the CNS
4. Spontaneously active inhibitory interneurons
106
What is allodynia?
Pain due to a stimulus which does not normally provoke pain
107
What is analgesia?
Absence of pain in response to stimulation which would normally be painful
108
What is causalgia?
A syndrome of sustained burning pain, allodynia, and hyperpathia after a traumatic nerve lesion, often combined with vasomotor and sudomotor dysfunction and later trophic changes
109
What is central pain?
Pain initiated or caused by a primary lesion of dysfunction in the CNS
110
What is CRPS?
Complex Regional Pain Syndrome
111
What is CRPS I?
Reflex sympathetic dystrophy - develops after an initiating noxious event
112
What is CRPS II?
Causalgia - develops after a nerve injury
113
What is hyperalgesia?
Increased pain from a stimulus that normally provokes pain
114
What is primary hyperalgesia?
Occurs at the site of injury when the nociceptive fiber is sensitized or directly stimulated by chemical agents released by the damaged tissue and nearby cells or the neuron itself
115
What is secondary hyperalgesia?
Occurs during severe or persistent injury, leads to long-term changes in sensitivity (central sensitization)
116
What is hyperpathia?
A painful syndrome characterized by an abnormally painful reaction to a stimulus, especially a repetitive stimulus, as well as an increased threshold
117
What is hypoalgesia?
Diminished pain in response to a normally painful stimulus
118
What is neuralgia?
Pain in the distribution of a nerve or nerves
119
What is neurogenic pain?
Pain initiated or caused by a primary lesion, dysfunction, or transitory perturbation in the peripheral or central nervous system
120
What are the two types of neurogenic pain?
1. Deafferentation pain
| 2. Sympathetically maintained pain
121
What is deafferentation pain?
May be a complication of any injury anywhere along the course of the somatosensory pathway
122
What is sympathetically maintained pain?
Simultaneous occurrence of pain, local autonomic dysregulation, and trophic changes in skin, soft tissue, and bone
123
What is neuropathic pain?
Pain caused by a lesion of the somatosensory nervous system
124
What is a neuropathy?
Disturbance or function or pathological change in a nerve
125
What is nociceptive pain?
Pain that arises from actual or threatened damage to non-neural tissue and is due to the activation of nociceptors
126
What is a pain threshold?
Minimum intensity of a stimulus that is perceived as painful
127
What is paresthesia?
An abnormal sensation, whether spontaneous or evoke
128
What is dysesthesia?
An unpleasant abnormal sensation, whether spontaneous or evoked
129
What is sensitization?
Increased responsiveness of nociceptive neurons to their normal input and/or recruitment of a response to normally subthreshold inputs
130
What are the two major cell types of the nervous system?
1. Neurons
| 2. Glia
131
True or false - the vast majority of neurons do not divide in the adult CNS.
True
132
Describe the cell body of a neuron.
1. Large euchromatic nucleus with a prominent nucleolus
2. Nissl bodies (rough ER for storage of Ca2+)
3. Other organelles
4. Neuropil
133
What is the neuropil?
Fibrous intercellular network surrounding cells of the CNS consisting of processes of neurons and glial cells
134
What are the main signal reception and processing sites of the nervous system?
Dendrites
135
What conducts action potentials in the nervous system?
Axons
136
What is the plasma membrane of an axon?
Axolemma
137
What are the contents of an axon?
Axoplasma
138
What is the region of the cell body where the axons originate?
Axon hillock
139
In neurons, cellular components are continuously synthesized in the soma and moved to the axon and dendrites by a process of ___. At the same time, worn-out materials are returned to the soma by ___ for degradation in lysosomes. ___ are the structures which support this process.
Anterograde transport; retrograde transport; microtubules
140
What are the 4 types of neurons (structure)?
1. Unipolar
2. Bipolar
3. Pseudounipolar
4. Multipolar
141
What are the 3 types of neurons (function)?
1. Sensory (afferent)
2. Motor (efferent)
3. Interneuron
142
What are the neuroglia of the periphery?
1. Schwann cell
| 2. Satellite cell
143
What is the function of Schwann cell?
Myelinate axons
144
What is the function of satellite cells?
Surround neuronal cell bodies to insulate, nourish, and regulate the local microenvironment
145
What are unmyelinated axons?
Axons with just a neurolemma
146
What is a ganglion?
Cluster of neuronal cell bodies outside the CNS
147
What is the role of the oligodendrocytes?
Myelinate CNS axons
148
What is the role of astrocytes?
Control ionic environment (buffer K+), form scar tissue, and help form BBB
149
What is the role of microglia?
Phagocytic and immune
150
What is the role of ependymal cells?
Line CNS cavities
151
A peripheral nerve is surrounded by ___.
Epineurium
152
A fascicle is surrounded by ___.
Perineureum
153
A nerve fiber is surrounded by ___.
Endoneurium
