1
Q
What are the 3 hypotheses for how axons find their targets?
A
- Mechanical guidance
- Resonance
- Chemoaffinity
2
Q
What is Mechanical guidance?
A
growing axons follow track
3
Q
What is resonance?
A
growing and connecting axons induce identity of postsynaptic cell
4
Q
What is chemoaffinity?
A
pre and post synaptic cells have ligand/receptor pair
5
Q
Which hypothesis for how axons find their targets has the most evidence?
A
chemoaffinity
6
Q
What are 2 points of evidence for chemoaffinity?
A
- taking eye out of frog + rotating it (Roger Sperry’s experiment)
- guidance cues that are either short or long range attraction/repulstion
7
Q
What happens in Roger Sperry’s frog experiment?
A
- frog sticks out the tongue when fly is in the wrong direction
- temporal and nasal parts rotated-temporal retina still projecting to the anterior tectum
- the nasal parts projecting to the posterior tectumï
- shows axons already know where to go and can’t adapt
8
Q
What interaction is coming into play in the retinal tectal system?
A
short range interactions
9
Q
What are short range interactions?
A
- temporal retinal axons grow only on anterior membranes (not posterior) where as nasal axons don’t discriminate
10
Q
What experiment shows short range interactions in the retinal tectal system?
A
- boiled membranes from anterior or posterior tectum to see which one contained the activity.
- boiling posterior tectum membranes eliminated preference by temporal axons
- cues were repulsive.
11
Q
What is the cue in short range interactions in the retinal tectal system?
A
ephrin
receptor is eph
12
Q
- How are neurons which are developing attracted from the roof plate to the floor plate?
A
netrin is acting as a long range attractive cue
13
Q
How do we know that netrin acts as a long range attractive cue?
A
knock out netrin and you don’t get the attraction
14
Q
Name the attractive and repulsive long range and short range cues
A
Attraction: Short range (collagen) and long range (netrins)
Repulsion: Short range (ephrins) and long range (slit)
15
Q
What is required for midline crossing?
A
Slit repulsion
16
Q
What is slit repulsion?
A
- knock out slit and the repulsion is not turned on so
- axons stay in the midline and do not cross
17
Q
What is required for the movement of the growth cone?
A
- Polymerization of actin causes movement of the growth cone
- lamelapodium is tubulin rich and filopodia are actin rich
18
Q
What regulates the dynamics of the growth cone?
A
Ca2+
19
Q
What is the matching problem?
A
- Neurons require target-derived trophic factor for survival
- Target generates limiting quantities of factor
20
Q
How is matching of neuron to one target (muscle) achieved?
A
- Neurons compete
- those that get enough, survive; those that don’t die
21
Q
What are the 2 most important events for the post synaptic changes at the NMJ?
A
- Immediate redistribution of ACH receptor
2. Increase in expression at synapse and decrease in expression in non synaptic regions
22
Q
What molecules are involved in immediate redistribution of ACH receptor?
A
agrin signals through MuSK
23
Q
What molecules are involved in the increase in expression at synapse and decrease in expression in non synaptic regions?
A
Neureglin (also called ARIA).
24
Q
What are the four basic divisions in somatosensation?
A
- Touch
- Proprioception (not detected by the skin)
- Pain (nociception)
- Temperature
25
Where are the sensory neurons located?
In the Dorsal root ganglia or the trigeminal ganglion for the face
26
What is special about sensory neurons?
They are pseudounipolar (2 axons and no dendrite)
27
Each ganglion innervates a _______ called a ______
- single region of the body
| - dermatome
28
For touch, what are the four basic receptors?
1. Merkel Receptors
2. Messiner receptors
3. Ruffini
4. Pacinian
29
What are Merkel Receptors?
small receptive field, slow adapting, medium threshold for mechanical stretch, edges and points and fine texture, braille
30
What are Messiner receptors?
medium receptive field, rapid adapting, small threshold for mechanical stretch, motion and grip
31
What are Ruffini receptors?
large receptive field size, slowly adapting, very large threshold for mechanical stretch, skin stretch and finger position
32
What are Pacinian receptors?
large (entire finger) receptive field size, rapidly adapting, and very small threshold for mechanical stretch, vibration and grasping
33
What are the 4 somatosensory response characterizations?
1. Speed of conduction
2. Adapting or non adapting
3. Receptive field size
4. Threshold of activation
34
Where in the body is the best two-point discrimination? (smallest receptive field size)
In the fingers
35
How do we respond to mechanical deformations?
- At level of nerve endings there are ion channels that exist in the closed state prior to the mechanical change and then
- when stretched Na+ is allowed in
36
What is an example of a mechanical deformation?
piezo1 and piezo2 are essential components of distinct mechanically activated cation channels
37
What is the general pathway for touch sensation?
ascend ipsilaterally and don’t synapse until the brainstem
38
What is the pathway for touch sensation?
1. Mechanosensory input ascends ipsilaterally through the dorsal columns
2. synapse and cross at the midline near the brain
3. (gracile and cuneate nucleus extends through the medial lemniscus to the thalamus and then the cortex)
39
What do proprioceptors detect?
- change in muscle length
| - tension in on the muscle to detect body positioning
40
Proprioceptors are part of _______
local circuit in the spinal cord that underlies the knee jerk reflex
41
Why should you practice the piano?
Expansion of a cortical representation by a repetitive behavioral task
42
The cells that mediate pain and temperature are cells that terminate in what?
Free nerve endings
43
What is congenital insensitivity to pain and what is happening in individuals who have this disorder?
-Individuals with this disorder cannot feel pain but can feel normal touch
44
What is the cause of congenital insensitivity to pain?
-Due to a mutation in a Na+ channel that is specific to nociceptors
45
What are the 2 types of nerve fibers that detect pain and what kind of pain?
Alpha delta = sharp pain
| C fibers = slow dull pain
46
Which afferents are the slowest for pain nerve fibers?
skinniest afferents are the slowest
47
What are the 3 molecules of temperature and pain?
1. TRPV1- heat and chili peppers
2. TRPM8- cold and menthol
3. TRPA1-pain and mustard
48
What was the experimental method for isolating the TRPV1 or capsaicin receptor?
- Used cloning:
- isolated total mRNA from DRG
- introduced to tissue culture that don’t normally respond to capsaicin
- measured influx of calcium with intracellular calcium imaging
49
What can an isolated single mRNA generate?
-response to capsaicin (calcium ion channel) and determine receptor amino acid sequence
50
What is the TRPV1 receptor opened by?
This receptor is opened by heat, capsaicin, and acidification
51
What does knocking out TRPV1 do?
causes inability to taste chili peppers and less sensitive to hot temperatures
52
What happens with a knockout of TRPA1?
- injecting formalin into the paw of a mouse
- measuring the time spent licking the paw,
- see that with knockout all phases of the pain response are decreased.
53
What else does TRPA1 also respond to?
carbonation
54
What happens in an inflammatory reaction?
- Inflammatory mediators (NGF) up regulates TRPV1 activity causing channels to open at lower temperature
- cells fire at lower temp
55
What are inflammatory mediator cells?
NGF
56
What is the result/example of an inflammatory reaction?
warm shower feels hot
57
What tract do nociceptor afferents ascend through?
-anteriolateral tract
58
Where does the anteriolateral tract cross?
-crosses at same level of spinal cord where axons enter
59
What happens when you have a lesion of the spinal cord?
- won't feel pain on opposite side of body
| - won't feel touch on same side of body in regions lower than region
60
What do we mean by saying that pain has descending control?
- descending fibers synapse on pain afferents
| - block incoming pain signals
61
What are the 3 chemical senses?
1. smell
2. taste
3. vomeronasal (not in humans)
62
There are odor primaries (T/F)
False
63
What is the general pathway for olfaction?
1. Olfactory sensory neurons in the olfactory epithelium send axons that pass through the cribiform plate to the olfactory bulb
2. Odorants are detected on sensory cilia that project into the olfactory mucosa
3. sensory response initiates in cilia
64
What kind of current is the olfaction sensory response?
- inward current
| - action potential depolarizaiton
65
3 reasons why humans have lower ability to smell than other animals
1. humans have fewer receptor neurons than dogs
2. humans have fewer receptor genes than mice
3. humans have ~300 genes each encoding different receptor, mice have ~1000
66
What is the olfactory sensory transduction pathway? (5)
1. Receptor binds ligand
2. G protein exchanges GDP for GTP
3. Adenylate cyclase makes cAMP from ATP
4. cAMP opens a CNG (cyclic-nucleotide gated) ion channel
5. Na+ and Ca2+ comes into cell causing depolarization
67
What is the olfactory sensory transduction pathway? (5)
1. Receptor binds ligand
2. G protein exchanges GDP for GTP
3. Adenylate cyclase makes cAMP from ATP
4. cAMP opens a CNG (cyclic-nucleotide gated) ion channel
5. Na+ and Ca2+ comes into cell causing depolarization
68
What provides specificity in the olfactory system?
Each receptor binds a different constellation of odorants
69
What are 4 characterisits of odorant receptors?
1. They are -7 TM G protein coupled
2. encoded in intronless genes
3. scattered throughout the genome
3. number in the hundreds (we have 388 functional receptors)
70
How many genes for odorant receptors?
hundreds
71
How many receptors per neuron/
1 receptor/neuron
72
What kind of distribution of olfactory sensory neurons?
random distribution in olfactory epithelium
73
Each neuron responds to _______ and each odorant activates _______
subset of odorants, several receptors
74
________ in olfactory bulb of axons from olfactory sensory neurons that express same receptor
convergence
75
What are our five tastes?
1. Bitter: toxins (from plants) aversive
2. Sweet: nutritious (can detect at only high concentrations)
3. Umami: amino acids
4. Sour: protons, citrus.
5. Salty: NaCl
76
How are different tastes detected?
- specific receptors detect tastants
| - specific subsets of cells respond to each class of tastants
77
What was the experiment used to identify the sweet receptor?
- cloned from mouse based on identification of mouse that cannot taste sweet
- respond to sweet using calcium imaging
78
In the mouse used to identify sweet receptor, what was the role of calcium?
Ca2+ elevation in response to sweet
79
What are the 2 sweet response receptors?
T1R2 and T1R3 coupled to PLCB2 and TRPM5
80
What is the umami receptor composed of?
T1R1 + T1R3
81
What are the bitter receptors?
-T2Rs
82
What are 2 qualities of bitter receptors?
1. family of 30 GPCRs-all expressed in same cells
| 2. cannot distinguish different bitter tastes
83
What is the transduction pathway for bitter taste?
1. T2R/T1R receptors are GPCRs, activate G protein, which is coupled to PLCB2
2. PLCB2 breaks down PIP2 to generate IP3
3. IP3 binds to IP3 receptors to release intracellular stores Ca2+
4. open a Ca2+ gated TRPM5 channel
84
Can TPRM5 and PLCB2 Knockouts taste bitter or sweet taste?
no
85
What determines whether something tastes good or bad?
-Cell type, not receptor
86
What experiment showed what determines whether something tastes good/bad?
- inserted unnatural receptor (RASSL) into T2R expressing cells
- animals avoid agonist
87
What happens when human specific bitter receptor is put into T2R cell?
-animal avoid biter agonist
88
What happens if human bitter receptor in T1R cell?
-animal attracted to bitter
89
How are genetic changes made?
promoters
90
What is the T1R1 promoter?
-T1R1 promoter directs gene to be expressed in umami cell
91
What is the T1R2 promoter?
-directs gene to be expressed in sweet cell
92
What is the T2R promoter?
-directs genes to be expressed in bitter cell
93
What is so interesting about PTC?
-There is polymorphism of whether or not people can taste it.
94
Where is the variation for PTC?
• Tas2R38 gene (PAV is taster and AV1 is non taster)
95
What is evidence for balancing selection?
- both tasters and nontasters are found in equal proportions in the populations
- both alleles must have some selective advantage
96
Why can’t cats taste sweet?
-T1R2 is a pseudogene in cats meaning it contains inactivating mutations
EX: cats are obligate carnivores
97
What are sour and salty receptors?
- Both are ion channels
| - do not use PLCB2 or TRPM5.
98
What are pheromones?
- chemicals released by animals
| - elicit stereotyped behavioral/endocrine response in another animal of same species
99
What do pheromones involve?
-vomeronasal system (no cortical representation)
100
How many types of VNO receptors are there?
-2 V1Rs have about 200 members and V2Rs have about 70
101
What is the transduction pathway for pheromones?
1. The VNO receptor interacts with PLC through a G protein coupled receptor
2. TRPC2 channel (express in VNO microvilli) opens
102
1. What knockout eliminates electrical response to pheromones?
TRPC2 knock out-responsible for response of neurons to pheromones
103
What happens when the VNO is silenced in males? (normal/castrated)
- male mouse (intruder) introduced to established mouse, resident attacks intruder (normal)
- attacks occur less frequently (castrated)
104
What happens is castrated intruder is swabbed with pheromones from urine?
-he will again be attacked by resident
105
Do TRPC2 KO mice attack intruders? why/why not?
- no
| - consistent with the idea that they cannot sense the pheromones on the intruders
106
What do TRPC2 KO do?
-mate with intruders
107
Why do TRPC2 KO try to mate with intruders?
- detection of pheromones by the VNO is necessary to allow male mice to discriminate gender
- in the absence of this information the default is to mate
108
What do female TRPC2 KO show?
- male typical mating behavior
| - seems like the lack of inputs somehow “masculinizes the brain.”
109
Why don’t humans have pheromones?
-TRPC2 in humans is a pseudogene probably lost when trichromacy appeared
110
What experiment figured out that we must have a central circadian clock?
- Had people sleep with and without cues a
- found that in the absence of cues humans still showed a sleep wake cycle, but the cycle was more than 24 hours (about 25 hrs)
111
1. What other daily cycles do we have besides sleep/wake? (3)
1. Melatonin levels
2. Body temp
3. Serum control
112
Where is the central clock?
-In the SCN (suprachiasmatic nucleus)
113
How do we know where central clock is?
- neurons in the SCN fire action potentials in a 24 hour rhythm
- isolated SCN neurons continue to keep this rhythm
114
What happens during ablation of SCN?
disrupts wake/sleep cycle in mice
115
What happens if SCN is transplanted?
transplanted SCN confers time keeping of host to recipient
116
What is per?
-central component of the clock, which when mutated leads to altered circadian rhythms
117
How do per mRNA and protein cycle?
with a 24 hour rhythm
118
per is a ______ factor which means that it controls _______
- transcription
| - expression of other genes
119
What do per and cry form? What is the function?
- heterodimer
| - together they inhibit their own expression
120
What are per and cry turned on by?
- Bmal
| - Clk
121
How is the central clock maintained?
a ~24 hr of cycle of per transcription, translation, degradation
-controlled by negative feedback of per on its own expression
122
What is the non-visual input to the SCN?
-retinal ganglion cells that express the visual pigment melanopsin can detect light (even in the absence of photoreceptor input)
123
What are the cells of the non-visual input to the SCN?
- intrinsically photosensitive RGCs
| - (ipRGCs)
124
Where do Melanopsin cells/ipRGCs project? How is this determined?
- SCN
| - by expressing lacZ gene
125
What does the lacZ gene generate?
-blue color under melanopsin promoter
126
What happens when you genetically kill melanopsin cells?
-animals lose entrainment to light
127
Does melanopsin KO produce the same results as genetically killing melanopsin cells?
- no
| - ipRGC can also receive input from photoreceptors in abscence of melanopsin
128
What kind of cells are essential for circadian entrainment?
ipRGCs(melanopsin cells)
129
ipRGCs(melanopsin cells) are essential for ________
circadium entrainment
130
What is familial advanced sleep phase syndrome?
-people go to sleep very early and wake very early
131
What is familial advanced sleep phase syndrome associated with?
- associated with mutation in the per gene
- causes it to accumulate more quickly
- shortening the clock
132
What is the definition of sleep? (4)
1. naturally recurring state
2. reduced/absent consciousness
3. relatively suspended sensory activity
4. inactivity of nearly all voluntary muscles
133
What is the pattern of sleep cycle?
- Sleep cycle is about 90 minutes
| - Each cycle has longer REM stages
134
How many sleep stages?
5
135
What is REM?
- rapid eye movements
| - dreaming, muscle paralysis
136
What is stage 4 of sleep?
- deepest sleep
| - most restful (2 per night)
137
How was it shown that sleep is essential?
- take 2 rats and allow one to fall asleep and not the other
| - The one that isn’t allowed to sleep dies and loses body weight
138
What is the sleep center and how is it activated and inactivated?
- If you stimulate the Reticular activating system the animal is awakened
- If you stimulate the thalamus the animal falls asleep.
139
What is the effect of antihistamines on sleep?
- cause sleepiness
- histamine is used as a neurotransmitter by a brain area that promotes arousal (TMN)
- if this is inhibited, sleep is promoted
140
What are 3 sleep disorders?
1. Narcolepsy
2. Sleep apnea
3. Delayed sleep phase syndrome
141
What is narcolepsy?
- recurring short episodes of sleep accompanied by cataplexy-mutation in orexin receptor gene leads to narcolepsy in mice and dogs
- in humans it is thought to be an autoimmune response that leads to loss of orexin neurons
142
What is sleep apnea
obstruction of upper airways due to loss of muscle tones leads to frequent awakening
143
What are the 3 association areas?
1. Anterior or prefrontal involved in planning motor output
2. Posterior links information from several sensory modalities for perception and language
3. Limbic emotion and memory
144
What are the two major language areas?
1. Brocas
| 2. Wernicke's
145
What is Broca's area?
- left frontal lobe (posterior inferior frontal gyrus)
| - known as motor or expressive aphasia cant get the words out
146
What is Wernicke's area?
- left superior temporal gyrus where temporal and parietal lobes meet
- Sensory or receptive asphasia-problem in language comprehension so speech is meaningless
147
What does it mean to say we are split brained?
- Different brain functions are localized to different sides of the brain
- Each hemibrain can operate independently despite fragmented system for processing information
148
What are the 2 theories of emotion?
- James Lange theory
| - Cannon-bard Theory
149
What is the James Lange theory of emotion?
-physiological response to a perceived threat precedes and causes an emotional response
150
What is are 4 pieces of evidence of the James lange Theory?
1. Subjects given muscle instructions for facial expression without being told what emotion they are imitating show a change in automatic response appropriate to that expression
1. Paraplegics show lessoned emotion responses
3. Adrenaline injection produces fear sensation
4. Block facial expression, reduced emotion response
151
What is the cannon-bard theory?
- physiological and emotional response occur simultaneously
- sensory information travels both to the cortex where we have a conscious subjective experience of the emotion and to the hypothalamus which then triggers visceral responses and facial expressions
152
What brain centers control emotion? How do we know?
- hypothalamus
- if cortex is removed + leave posterior hypothalamus, animals act enraged
- cortex not necessary for emotional response
153
What is Kluver Bucy syndrome?
- Removal of medial temporal lobes (including limbic lobes) from monkey
- found that the monkey became tame.
154
How can Kluver Bucy syndrome be observed in humans?
- temporal lobectomy
| - see similar changes with removal of amygdala alone
155
What is wrong with patient SM?
- genetic mutation that leads to calcification of bilateral amygdala
- cannot recognize facial expression of fear, but recognize other emotions
- fearless
156
What region of the brain is involved with perceptual awareness and attention?
-posterior parietal cortex
157
What does the posterior association cortex do?
-links information from several sensory modalities for perception + language
158
What is the temporal region used for?
face recognition
159
What is a problem associated with unilateral lobe lesions?
Contralateral neglect syndrome (lesions on right side neglect left side)
160
What are the 2 types of memory?
1. declarative - what you know
| 2. non declarative - what you do
161
What are the 2 parts of declarative memory?
1. Long term storage- not well understood
| 2. Short term memories-hippocampus
162
What are 3 parts of non declarative memory?
1. Procedural memory doesn’t require hippocampus- HM can do procedural memories
2. Long term storage- not known
3. Short term- widespread
163
What are the two types of amnesia?
1. Anterograde
| 2. Retrograde
164
What is anterograde amnesia? What portion of the brain is affected?
- inability to establish new memories
| - HM-hippocampal damage and medial temporal lobe
165
What is retrograde amnesia?
-difficulty retrieving memories established beforehand
BISC 421 - Module II
flashcards
Decks in class (14)
# Cards
-
Lecture 14 - Brain Structure58
-
Lecture 15 - Spinal Cord + Motor Cortex46
-
Lecture 16 - Cerebellum49
-
Lecture 17 - Basal Ganglia35
-
Lecture 18 - Eye Movement10
-
STUDY GUIDE146
-
STUDY GUIDE MODULE III165
-
Sensory Biology30
-
Nociception/Pain29
-
Olfactory System19
-
Taste34
-
Pheromones16
-
Circadian Rhythms43
-
Sex Differences20
