Exam 3 Flashcards
(107 cards)
1
Q
what is synaptic plasticity?
A
ability of the brain to change (learning, memory)
2
Q
what two main areas of the brain does synaptic plasticity occur?
A
hippocampus
cerebellum
3
Q
what is meant by neural plasticity? (i.e. how does the neuron change to become plastic)
A
changes in synaptic efficiency
- how much input it takes to activate postsynaptic neuron
- high efficiency = requires less input
4
Q
do you need a signal at both the presynapse and postsynapse to change efficiency?
A
YES!!!
- requires concurrent activity
5
Q
what increases efficiency of the synapse? what decreases it?
A
increase = LTP (less input needed)
decrease = LTD (more input needed)
6
Q
what type of frequency stimulation is needed to produce an LTP? (tested in hippocampus slices)
how long did the LTP last after the stimulation?
A
brief, high frequency stimulation (10hz for 10 sec)
- lasted for about 40 hours
- in intact animals, lasts about 1 yr
7
Q
what is the mechanism of an LTP?
A
- Glu binds AMPA receptor (Na+ enters cell, depo)
- depo ejects Mg2+ ion from NMDA receptor
- allows for Glu to bind to NMDA
- Ca2+ enters cell (2nd messenger system)
8
Q
what is a coincidence detector?
A
detects simultaneous activation of both pre and post synapse
9
Q
what is the coincidence detector of the LTP mechanism?
A
NMDA receptor
10
Q
what type of channel is the AMPA-R and NMDA-R?
A
AMPA = ligand-gated
NMDA = voltage & chemically gated
11
Q
what do NMDA antagonists act on?
A
block LTP (not EPSP) due to receptor being mediated by AMPA
- blocks Ca2+
11
Q
what happens to the LTP if there is a simultaneous signal? (more rapid APs)
A
longer LTP due to the longer ejection of Mg2+
12
Q
what are the Ca2+ intracellular effects of an LTP?
A
- Ca2+ enters and activates Protein Kinase C & CaMK2
- activate AMPA-R and other signaling molecules
- overall increase Glu release to start a LOOP
13
Q
what happens if you increase phosphorylation of the 2nd messenger system of the LTP?
A
increase LTP duration
- this occurs for a bit after Ca2+ is gone
14
Q
what happens during early LTP expression? (first 1-2 hrs)
A
- phosphorylation of targets increases conductance (signal more efficient)
- creates a strong EPSP
- increase AMPA-R amount (made by dendritic spines)
15
Q
what happens during late LTP expression? (several hours after induction)
A
dependent on gene expression and protein synthesis
1. initiated by Protein Kinase A
2. activates TFs, AMPA-R, kinases
3. increase number and size of synaptic connections through dendritic spine
- allows for faster response
16
Q
what is blocked to inhibit late LTP expression?
A
protein synthesis
17
Q
what are silent synapses?
A
synapses w/ NMDA-R but no AMPA-R (glu only binds NMDA)
- cannot get EPSP
18
Q
how does Nitric Oxide contribute to LTP?
A
- activated by Ca2+
- NO diffuses out of cell & goes to presynapse
- binds to cGMP-R to increase cGMP
- increase of NT release (including Glu)
- allows for a bigger LTP response
19
Q
what type of frequency stimulation does an LTD require?
A
low frequency stimulation (1hz over 10-15 min)
20
Q
what is the main mechanism of an LTD?
A
clathrin-dependent endocytosis pinches off part of the MB that contains AMPA-R
- decreases the number of receptors that respond to Glu
21
Q
what receptors does the hippocampus use for an LTD?
A
NMDA & AMPA
22
Q
what receptors does the cerebellum use for an LTD?
A
AMPA & mGlu
23
Q
what is the 3-cell interaction that occurs in the cerebellum for an LTD?
A
purkinje cell
climbing fibers (1000/synapse)
parallel fibers (1/synapse)
24
what in the 3-cell interaction serves as an error signal? (wrong movement) how does this work to stop the EPSP?
climbing fibers
- causes the active parallel fibers to decrease influence on the PC = decreases EPSP
25
what two things must be active in order to produce an LTD?
climbing fibers and parallel fibers
26
describe the mechanism of an LTD at the cerebellum
1. parallel fibers cause glu to bind to mGlu-R
2. activates phospholipase C
3. PIP2 -> IP3 & DAG
4a. IP3 releases Ca2+ internal stores
4b. DAG -> Protein Kinase C -> internalizes AMPA-R
5. climbing fibers cause Ca2+ to enter cell & release Ca2+ internal stores
27
which fibers produce a weak EPSP (depo)? what about strong EPSP?
weak = parallel fibers (AMPA)
strong = climbing fibers (AMPA)
28
what is the coincidence detector of an LTD?
Protein Kinase C
- detects activation of both fibers
29
what is protein kinase c main role in an LTD?
helps to decrease AMPA-R to cause less activation of parallel fibers & PC = decrease EPSP = LTD
30
what are the three main types of traumatic brain injuries?
- physical trauma: blunt force (closed, penetrating, falls, etc.)
- hypoxia: oxygen deficiency (occulsion, stroke)
- neurodegenerative disease: alz, parkinson's
31
what are the causes of a TBI? (traumatic brain injury)
- acceleration / deceleration
- blast waves, blunt force
- single movement or repeated contacts
32
what are the three classification of a TBI?
- closed head injury (blunt force trauma)
- focal blow injury (contusion)
- diffuse (wide-spread damage)
33
what causes a closed head injury?
shearing forces
- body & brain move in opposite directions
34
what causes a focal blow injury?
blow & counterblow
- two collisions
35
what causes a diffuse injury?
hypoxia, stroke
- macroscopic and microscopic damage
36
what are the two types of primary damage?
macroscopic
microscopic
37
what is some examples of macroscopic damage? (4)
- hematoma (subdural, epidural)
- white matter damage (shearing of axon tracts)
- focal contusions (bruising, increase in ICP)
- ischemic damage (hypoxia, micro occlusion, excitotoxicity)
38
what are some examples of microscopic damage? (6)
- axonal damage
- MB perforation (extra hole for molecules to go thru)
- leaky ion channels
- proteins in MB distort
- swelling of axon
- microhemorrhages (occur w/ high shear rates)
39
describe how axons can become damaged in a head injury
shearing of somas & axons
- cell bodies (gray matter) are more dense than fragile axons (white matter)
- detachment from soma
- disruption of synapses (pulls structures apart)
40
what are three types of secondary damage? when does this occur after injury?
hrs to days after injury
- cell death (apoptosis)
- mitochondrial disfunction
- excitoxicity
41
what happens if the mitochondria disfunctions?
decrease in ATP and O2 utilization in cells
42
what happens during excitoxicity?
increase in Glu due to disruption of MB proteins
- astrocytes also swell due to increase in ICP
43
how do you treat excitoxicity?
shut down Glu and lessen rate of apoptosis
- Memantine (partial NMDA ant)
- Progesterone, 17-beta estradiol (blocks Ca2+ channels, inhibits NMDA-R)
44
what acute symptoms of a head injury?
- loss of consciousness
- amnesia
- altered mental state (disorientation, confusion)
- neurologic deficits (diminished reflexes)
45
what is post-concussion syndrome (PCS)? describe the symptoms (physical, emotional, cognitive, bx)
occurs weeks to a year or more after injury
- physical: headaches, lethargy, dizziness
- emotional: depression, anxiety, mood swings
- cognitive: changes in personality, sensory perception, decreased attention & memory
- bx: impulsivity, irritability, PTSD
46
what are some long-term consequences of a head injury?
- permanent PCS symptoms
- early-onset dementia due to increased tau & neurofibrillary tangles
-chronic traumatic encephalophathy (CTE)
47
what are some brain responses to a head injury? (4)
cell death (apoptosis, necrosis)
inflammatory & immune responses
glial scarring
inhibition of axon growth
48
what is the difference b/w apoptosis and necrosis?
apoptosis: programmed, occurs intracellularly
necrosis: accidental, due to external events (infection, injury)
49
what is the mechanism of apoptosis?
1. initiated by excitoxicity (Glu) or binding of inflam. cytokines
2. blocks Bc12 genes (comes from synapse to inhibit CytC)
3. cytochrome C is released to activate Capase-3
4. cell is broken down (DNA fragmentation, changes cytoskeleton, MB blebbing (bulges and explodes)
50
what happens in the inflammatory response for a head injury?
activated microglia, astrocytes, and oligodendrocytes
- Ng2 cells are released (in addition to other chemical signals such as TGF, TNF-alpha, IL-1, IFN-gamma, etc)
forms glial scars (increase glial growth, decrease neuronal growth)
neutrophils, monocytes are activated (leukocytes)
51
what happens in the inhibition of axon growth due to a head injury?
glial scarring (physical barrier)
chemical inhibition (semaphorins, ephrins)
oligodendrocytes release NogoA to inhibit growth
- antiserum binds to NogoA to help form glial scar
51
what is functional reorganization? where in the brain was this studied?
no new cells are produced, only an expansion of intact neurons
- studied in M1 (primary motor cortex)
- neurons intact increased neurite branching & contralateral M1 activity
- still had synaptic efficiency (LTP/LTD)
52
what are some barriers to repair & regeneration?
- injury that causes neuronal death
- inhibition of axon growth (glial scars)
- stem cells decrease (differentiation, migration, division)
- glia-mediated immune responses
53
what are three types of repair of neurons?
- axon growth (PNS, motor fibers)
- restoration of damaged CNS neurons (glia-neuron interaction)
- genesis of new neurons (multipotent stem cells)
54
what did Henry Head do?
curious about how quickly PNS neurons regenerate
- cut his own radial n. (reattached thru surgery)
- 6-19 wks = regained pressure, touch
- 2 yrs = regained light touch, temp, fine motor control
55
what stimulates axon repair in the PNS?
- schwann cells in the ECM release trophic and tropic factors
- macrophages clear cellular debris to allow for growth of branches, growth cone develops, increase of integrin expression
56
where do the repair molecules work in location to the neuron injury?
distal end!!!
- towards the synapse
57
what neurotrophins help connect synapses in the PNS?
increase of NGF, BDNF
58
what neurotrophins help maintain intact synapses? (decrease inhibition, polyneuronal reinnervation: trimming back)
decrease of NT3, NT4
59
what stimulated axon repair in the CNS?
microglia clean up cellular debris
astrocytes, oligodendrocytes form glial scars
60
what method was used to determine that there are no new neurons produced or mitosis occurring in neurons?
neuronal birth-dating
- they did discover that new glia cells develop int he hippocampus!
61
describe the difference between embryonic stem cells and adult stem cells
embryonic: pluripotent, infinite self-renewal
adult: neurons don't have infinite self-renewal (but all other cells do)
62
what are characteristics of stem cells?
- form stem cell niches
- similar to astrocytes w/ cell-to-cell signaling
- located near blood vessels (get support molecules from blood)
63
where are stem cell niches located in the brain? (2)
subgranular zone of hippocampus
anterior subventricular zone of olfactory bulbs
- rostral stream
64
what do majority of neural stem cells turn into?
mainly glial fate or interneurons (no long-distance)
65
what are transit amplifying cells (TAC)?
progenitor cell that can differentiate
- stem -> TAC -> neuroblast -> neuron
- rapid, asymmetric mitosis
- combines w/ neuroblasts & glioblasts to make more of them
- limited # of divisions (need to be replenished by stem cells)
66
do humans have stem cell niches in the hippocampus?
NO!!!
- only in olfactory bulbs
67
what are the two hormone function types? describe them
organizational: permanent development of body
activational: short-lived, bx causes the release
68
genotype vs phenotype
genotype: genes present in DNA (on or off)
phenotype: only expressed genes
69
difference between sexual identity and sexual orientation
sexual identity: individuals perception of phenotype
sexual orientation: based on sexual attraction
70
what does the Y chromosome contain that makes the male phenotype?
SRY & TDF (testes determining factor)
- translocation of gene during meiotic recombination can lose the SRY in this process
- if SRY is present = MALE (does not matter if they are XX)
- absent SRY = FEMALE
71
what do all reproductive organs start out as? what week does differentiation occur? what does this entail?
starts off as primordial gonad
- differentiation happens at 6wks
- SRY: medulla becomes testes
- no SRY: cortex becomes ovaries
72
what are the two internal reproductive ducts? what is process of the differentiation of these ducts?
Mullerian system (female)
Wolffian system (male)
- differentiation occurs at 3rd month
- no SRY = female (male ducts wither w/o T)
- SRY = male (testes produce T to allow for wolffian to thrive, Mullerian inhibiting substance is produced to destroy mullerian)
73
what happens if T is given to a female at the 3rd month?
both systems develop b/c there is not MIS to inhibit the mullerian
74
what helps masculinize external genitalia during the critical period?
DHT
75
what regulates sexual dimorphisms of the brain (gonadotropins)? what releases them?
regulated by hypothalamus
- released by pituitary at the AVPV
76
what produces the male pattern at the sexually dimorphic nucleus (SDN) of rats?
estradiol
77
what happens to the SDN if T is given to a female?
masculinizes it
78
what gives the female pattern at the SDN?
alpha-fetoprotein binds estradiol to allow for the female pattern
79
who has a bigger SDN, males or females?
males
- masculinization prevents apoptosis at the SDN
80
where is the SDN located at in rats?
anterior hypothalamus
81
what produces hair at puberty in females?
adrostenedione from the adrenal cortex
- act at androgen-R
82
what produces hair at puberty in males?
testosterone
83
what is androgen insensitivity?
XY, 1/13K births
- genetic mutation on X chromosome
- SRY w/ T, but no androgen or MIS-R
- think they are female, except they have undescended testes
84
what is congenital adrenal hyperplasia (CAH)?
XX & XY, 1/16-20k births
- infant screening occurs for this due to high death rate
- prenatal adrenal cortex hyperactivity (too much androgens)
- creates partially masculinized external genitalia
85
what is 5-alpha reductase deficiency?
XY
- T is not converted into DHT
- feminized external genitalia
- raised as female, but feels like a male
- at puberty, T increases and forms partial male genitalia
- common the Dominican Republic
86
what is the pathway to produce DHT and estradiol?
1. cholesterol
2. progesterone
3. testosterone
4a. DHT (5alpha reductase)
4b. estradiol (aromatase)
87
what are the male bx in a rat? female bx? what hormones are responsible for these bx
male (T) = mounting, copulation
female (E) = attracts male, lordosis
88
what happens to the bx of castrated male rats if you give T as adults?
no mounting
89
what happens if you give castrated male rats E as adults?
lordosis
90
what happens if you give ovariectomy (with T) rats, E as adults?
no lordosis
91
what happens if you give ovariectomy (with T) rats, T as adults?
mounting
92
what happens if you castrate a male?
decrease in sexual bx
93
what happens if you perform an ovariectomy to a female?
no effect
- but if you increase T, they have increased intercourse frequency
94
where is the sexual bx in male rats located at?
SDN (medial preoptic area)
- if destroyed, no male bx, but still has attraction for females
95
where is the sexual bx in female rats located at?
ventromedial nucleus of hypothalamus
- if destroyed, no female bx
96
where in the brain does sexual orientation (attraction) come from?
anterior hypothalamus (INAH-3) and anterior commissure
97
who has a larger INAH-3, males or females?
males
98
who has a larger ant. commissure, males or females?
females
99
put in order from largest to smallest INAH-3...
hetero-F (+)
hetero-M (+)
hetero-F(-)
hetero-M (-)
homo-M (+)
hetero-M(-)
hetero-M(+)
homo-M(+)
hetero-F(-)
hetero-F(+)
100
who has a bigger INAH-3, hetero-M or transXY?
hetero-M
101
what area of the brain was studied when looking at the difference b/w cis and trans?
bed nucleus of stria terminalis (forebrain paraventricular area)
102
which stria terminalis was larger, cis-M or transXY?
cis-M
- cis-F was the smallest
103
which stria terminalis was larger, cis-M or transXX?
same size
104
what was the outcome of homo and hetero activity at the anterior hypothalamus of M & F when exposed to estrogen odor?
homo-F, hetero-M activated
- no change in hetero-F
105
what was the outcome of homo and hetero activity at the anterior hypothalamus of M & F when exposed to androgen odor?
hetero-F, homo-M activated
- no change in hetero-M
