Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Clinical Neuroscience > module 3 > Flashcards

module 3 Flashcards

1
Q

what is multiple sclerosis

A

autoimmune disorder with antibodies against myelin
- consequently damages neurons in the CNS

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

what are some symptoms of MS

A

optic neuritis
sensory loss
muscle weakness
pins&needles

(starts with sensory symptoms first)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

what are three ways MS is diagnosed

A

lesions seen in MRI
spinal tap (antibodies detected in the CSF)
electrical potentials to measure speed of AP

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

what are the 4 clinical courses of MS

A

relapsing remitting MS (RRMS)
secondary progressive MS (SPMS)
primary progressive MS (PPMS)
primary relapsing MS (PRMS)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

what is relapsing remitting MS (RRMS)

A

occurrence of relapses at irregular intervals with complete or incomplete neurological recovery
(~85% of patients)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

what is secondary progressive MS (SPMS)

A

progressive, irreversible disability that occurs independently of the presence of relapses

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

what is primary progressive MS (PPMS)

A

gradual worsening without relapses/attacks

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

what is primary relapsing MS (PRMS)

A

progressive disease from the onset, acute relapses and periods of continuing progression between relapses
(rare)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

is new myelin formed during remyelination as efficient as original myelin

A

no, remyelination produces thinner myelin sheaths

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

what is the relationship between epstein-barr virus and MS

A

EBV infection during 10yr-45yr increases MS risk 32 fold

several EBV antigens are the target of cross-reactive autoantibodies found in MS

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

where is myelin degenerated in MS

A

only myelin formed by oligodendrocytes (CNS)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

where do t cells develop and mature

A

develop in bone marrow and mature in thymus where they acquire specific receptors

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

what kinds of T cells are deleted during development

A

T cells with receptors that have a strong affinity for self antigens

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

what are T regulatory cells (Trergs)

A

inhibit T cells that have a strong affinity for self-antigens in the periphery

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

what are Treg cells crucial for

A

preventing autoimmunity

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

how are T cells and B cells activated

A
  1. naive helper T cells engage MHC II molecules on antigen presenting cells (APC) and become activated
  2. clones of activated helper T cell activate B cells and cytotoxic T cells
  3. cytotoxic T cells produce enzymes that lyse the infected cells
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

what is a CD4+ T cell

A

helper T cell

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

what is a CD8+ T cell

A

cytotoxic T cell

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

what kind of cells are antibody secreting cells

A

B cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

how many types of antibodies does a B cell make

A

one kind

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

what activates B cells to produce antibodies

A

activated helper T cells activate B cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

what are memory cells

A

a few T and B cells that remain after the infection

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

what 2 things are seen in the CSF of 95% of MS patients

A

clonal bands of IgG antibodies (against myelin antigens)

antibodies to glial proteins, aquaporins and potassium channels

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

what do some antibodies against myelin cross-react against

A

EBV antigens

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

have there been any specific antigens identified that are responsible for MS

A

no

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

what happens in MS if there is a depletion of B cells

A

helps symptoms

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

what is a consequence of demyelination in MS

A

action potentials decay before reaching the presynaptic terminal because they have to cross stretches of demyelinated axons

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

what causes organelles to aggregate (blebs) in MS

A

axonal transport along microtubules is disrupted in demyelinated axons which can cause organelles to aggregate

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

what are 5 treatments that can be done to help the immune system in MS

A
  1. glucocorticoids
  2. interferons: alter the balance of T helper and T reg cells
  3. rituximab: destroys B cells in circulation
  4. plasmapheresis: remove plasma, deplete antibodies, put it back
  5. reduce T/B cells in circulation
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

what are two other treatments (not to do with immune system) for MS

A

compete with myelin for binding sites on immune cells

block potassium channels

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

what are the two centers of the brain that are considered upper motor neurons

A

motor cortex: voluntary movements
brainstem centers: movements, posture control

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
32
Q

what are the two brain areas that modulate and fine tune movement

A

basal ganglia: initiation of intended movement and suppression of unwanted movement

cerebellum: coordination of ongoing movement

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
33
Q

where are lower motor neurons found

A

ventral horn of spinal cord

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
34
Q

what does a lower motor neuron look like

A

one alpha motor neuron branches and innervates many muscle fibers

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
35
Q

what is a motor unit

A

one alpha motor neuron (in ventral horn of spinal cord) and the muscle fibers it innervated

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
36
Q

what is a motor neuron pool

A

all the motor neurons innervating a muscle

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
37
Q

what is the order of events that occurs at the neuro-muscular junction

A
  1. ACh released from presynaptic terminal
  2. nAChRs (ion channels) are activated
  3. muscle is depolarizes and fires AP
  4. muscle contracts
    (DRAW)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
38
Q

what is muscle tone

A

the basal level of contraction maintained at all times that allows the muscle to both stretch and contract

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
39
Q

what is the neuromuscular spindle

A

a sensory receptor (organ) that senses the length/stretch of muscle fibers

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
40
Q

what is myasthenia gravis

A

autoantibodies against postsynaptic nAChRs

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
41
Q

what is lambert eaton myotonia

A

autoantibodies against presynaptic voltage-gated calcium channels

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
42
Q

what is spinal muscular atrophy (SMA)

A

rapid degeneration of lower motor neurons

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
43
Q

what are the genetics of SMA

A

autosomal recessive
deletion or loss of function mutations in survival of motor neuron (SMN) gene

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
44
Q

what does the survival of motor neuron (SMN) gene do

A

encodes a protein involved in the assembly of snRNPs
- mutations result in splicing defects especially in lower motor neurons

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
45
Q

what are symptoms of SMA

A

severely reduced muscle tone
(affected children never sit/stand)
respiratory failure before age 2

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
46
Q

what is the treatment for SMA

A

antisense drug that modulates alternate splicing of the SMN2 gene, functionally converting it into SMN1gene, thus increasing the level of SMN protein in the CNS

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
47
Q

what are Betz cells

A

large pyramidal neurons that are found in layer V of the motor cortex
- largest neurons in the brain

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
48
Q

what connections do Betz cells form

A

direct connections with alpha motor neurons in the spinal cord
(other connections are mainly to interneurons in the spinal cord)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
49
Q

what is the function of Betz cells

A

initiate and modulate voluntary movement by activating lower motor neurons that supply distal limbs
- essential for fine motor control

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
50
Q

what is the ventral corticospinal tract

A

cortex to brain stem to spinal cord
- fibers do not decussate
- terminate bilaterally in medial spinal cord and over many segments
- control posture

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
51
Q

what is the corticobulbar tract

A

from cortex to cranial nerve nuclei in midbrain, pons, and medulla

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
52
Q

what is the lateral corticospinal tract

A

direct pathway from cortex to spinal cord
- decussate in medulla
- terminate laterally
- control limbs and fine movement

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
53
Q

what are the strength effects of LMN and UMN syndrome

A

LMN: weakness or paralysis
UPN: weakness

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
54
Q

what are the muscle bulk effects of LMN and UMN syndrome

A

LMN: severe atrophy
UMN: mild to no atrophy

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
55
Q

what are the reflex effects of LMN and UMN syndrome

A

LMN: hypoactive superficial and deep reflexes
UMN: hyperactive deep reflexes after initial period of spinal shock

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
56
Q

what are the special signs and symptoms of LMN syndrome

A

initial signs/symptoms persist
fasciculations and fibrillations
geographic distribution of impairment
impairment of reflexive and gross and/or fine voluntary movements

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
57
Q

what are the special signs and symptoms of UMN syndrome

A

initial period of spinal shock, then spasticity ensues
babinski sign and clonus
more widespread (nongeographic) distribution of impairment
impairment of fine voluntary movements; gross movements relatively unimpaired

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
58
Q

what is ALS

A

heterogeneous disorder with degeneration of both upper motor neurons and lower motor neurons

brain loses its ability to initiate and control voluntary movements

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
59
Q

what are the early symptoms of ALS

A

muscle weakness with flaccidity (LMN damage)
sometimes difficulty speaking and dysphagia

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
60
Q

what are later symptoms of ALS

A

muscles gradually weaken, fibrillations, fasciculations, atrophy

gradually all voluntary muscles are affected and lose ability to speak, eat, move, breathe

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
61
Q

what is amyotrophic mean

A

muscle wasting

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
62
Q

what are the 4 main genes associated with ALS

A

SOD1 (transcription factor)
FUS (RNA binding protein)
TDP-43 (RNA binding protein)
C9orf72 (open reading frame gene that can cause a repeat expansion in interon)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
63
Q

what is SOD1

A

a transcription factor

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
64
Q

what can TDP-43 mislocalization cause

A

aggregate formation in motor neurons of the spinal cord of ALS

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
65
Q

how does SOD1 regulate expression

A
  1. upon activation, it is phosphorylated
  2. phosphorylated SOD1 accumulated in nucleus
  3. SOD1 binds to promoters and regulates expression of genes involved in oxidative stress responses (ex. antioxidants and DNA repair proteins)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
66
Q

what happens to SOD1 in ALS

A

it is misfolded and aggregated
- aggregates are found in nucleus and cytoplasm where phosphorylation is disrupted

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
67
Q

what is the role of chaperone proteins

A

help proteins fold into correct 3D structure

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
68
Q

what happens to misfolded proteins

A

they are shunted to degradation pathways

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
69
Q

what is the sequence of events that occurs in the ubiquitin proteasome pathway for degradation of misfolded proteins

A
  1. misfolded protein is tagged with ubiquitin
  2. the proteosome complex (filled with enzymes) destroy the target protein
  3. ubiquitin that was attached is released to be recycled
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
70
Q

what are autophagosomes

A

membranes that fold around proteins or mitochondria that need to be degraded

  • then fuses with a lysosome that contains enzymes to destroy targets
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
71
Q

what is an ALS mutation that affects degradation

A

C9orf72 - regulator of autophagy initiation

  • mutation results in diminished ability to degrade misfolded proteins
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
72
Q

what two genes are substrates of autophagy and are involved in ALS

A

SOD1 and TPD43
- suggest that defective autophagy contributes to the toxic accumulation of these proteins in ALS

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
73
Q

what are 6 cellular deficits associated with ALS

A
  1. protein homeostasis (disturbances in protein quality control)
  2. hyperactivation of microglia
  3. diminished energy supply
  4. excitotoxicity from reduced glutamate uptake
  5. disturbances in RNA metabolism
  6. altered axonal transport
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
74
Q

what are two specific treatments for ALS

A
  1. Na+ channel blocker
    - limits Glu release and excitotoxicity
  2. antioxidant
    - has some reduction in symptoms
75
Q

do basal ganglia have direct connections to the spinal cord

A

no

76
Q

do deficits in basal ganglia lead to paralysis

A

no, but can lead to involuntary movements or immobility without paralysis

77
Q

what are the effects of movement from the basal ganglia in Parkinson disease and Huntington disease

A

Parkinson: diminished movement
Huntington: excessive movement

78
Q

besides movement, what other deficits are basal ganglia involved in

A

cognitive/behavioral

79
Q

what are the motor areas of the basal ganglia

A

striatum: caudate and putamen

pallidum: globus pallidus, substantia nigra pars reticulata

subthalamic nucleus

80
Q

what comprises the ventral striatum

A

nucleus accumbens
(non motor area)

81
Q

how many non motor circuits does the basal ganglia have

A

2

82
Q

what is the main cell of the striatum

A

medium spiny neurons

83
Q

what is the main modulator of cortical input to the striatum

A

dopaminergic input from substantia nigra pars compacta and VTA onto medium spiny neurons

84
Q

what kind of output do medium spiny neurons have on globus pallidum and substantia nigra pars reticulata

A

GABAergic

85
Q

what would happen if a synapse that was originally on a dendritic shaft was moved to the end of a dendritic spine

A

the influence on the neuronal signal would be lessened

86
Q

what kind of output does the thalamus have on the motor cortex

A

glutamatergic output to motor cortex which then has excitatory input on cerebellum and other motor pathways

87
Q

how does the direct pathway inhibit the thalamus

A

caudate/putamen is low activity
globus pallidus is high activity and secretes GABA which inhibits the thalamus

88
Q

what neurotransmitter facilitates the expression of movement

A

dopamine

89
Q

what does dopamines ability to increase or decrease excitability depend on

A

the receptor type

90
Q

what is the difference between D1 and D2 receptors

A

D1 increase cAMP levels
D2 decrease cAMP levels
(both GPCRs)

91
Q

what is focused selection in relation to basal ganglia

A

suppression of competing motor programs that could interfere with the expression of sensory-driven or goal-directed behaviors

92
Q

what does dopamine do to the direct and indirect pathways

A

dopamine activates the direct pathway through D1 receptors and inhibits the indirect pathways through D2 receptors

93
Q

what is parkinsons disease

A

loss of dopamine input to striatum due to degeneration of dopaminergic neurons

94
Q

how does the loss of dopamine in parkinsons affect the basal ganglia and movement

A

D2 receptors will not inhibit indirect pathway so there is a overactivity (less movement)

D1 receptors will not enhance direct pathway (less movement)

  • leads to sluggish movement, failure to initiate movement, and lack of control of the size of movements
95
Q

what are some motor symptoms of parkinsons disease

A

rigidity, bradykinesia, balance/coordination problems,, resting tremors

(symptoms usually affect one side more than others)

96
Q

what are non motor symptoms of parkinsons disease

A

changes in executive function, depression, anxiety, dementia, altered behavior, impaired sense of smell

97
Q

what is neuromelanin

A

polymer pigment found primarily in the dopaminergic neurons of human substantia nigra
-increase with age

98
Q

what kind of proteins does neuromelanin contain

A

proteins that bind metals like zinc and iron that scavenge reactive metals and other toxins

99
Q

what are lewi bodies

A

formed by accumulation of alpha-synuclein that eventually fill cell body

100
Q

what is the function of alpha-syniclein

A

modulates the SNARE complex that is important for synaptic vesicle release
- normally binds to synaptobrevin and regulates availability of synaptic vesicles for release

101
Q

what is the role of Parkin and PINK1

A

proteins that recognize and destroy damaged mitochondria but after mutation they are unable to remove faulty mitochondria which continue to produce ROS

102
Q

what happens when alpha-synuclein is mutated or aggregated

A

it cannot function and vesicles cannot be released from synaptic terminal

103
Q

what is the structure of alpha-synuclein

A

in membranes, alpha helicies but overexpression, abnormal phosphorylation, or modifications of ROS result in the protein assuming a beta pleated structure

104
Q

what system has a reduced function in lewi bodies

A

proteasome-ubiquitin system

105
Q

how do dopaminergic neurons in substantia nigra pars compacta have a high rate of tonic firing

A

changes in calcium levels

106
Q

what is a prion

A

misfolded protein

107
Q

what does a prion-like mechanism refer to

A

the fact that prions can interact with normal proteins and cause them to misfold
- autophagosomes get overwhelmed with too many misfolded proteins and start to aggregate which causes the flow around axons and microtubules to be blocked

108
Q

what are four treatments for parkinsons disease

A

L-DOPA: converted to dopamine in neurons
dopamine agonists
dopamine reuptake inhibitors
deep brain stimulation: near thalamus

109
Q

what are 4 of the protein mutations that cause parkinsons

A

alpha-synuclein
LRRK2
Parkin
PINK1

110
Q

what is an animal model treatment for PD

A

MPTP is a lipid soluble toxin that crosses the BBB and glia convert it into a form that is transported into neurons by dopamine transporters

it inhibits ETC and mitochondria eventually die

111
Q

what is huntingtons disease

A

autosomal dominant disorder that leads to progressive degeneration of striatum

112
Q

what are early motor symptoms of huntingtons

A

chorea (spastic, abnormal involuntary movement)
athetosis (writhing in distal extremities)

113
Q

what are early non motor symptoms of huntingtons

A

mood swings, depression, learning and memory problems, decision making problems, change in personality and suspiciousness

114
Q

what are some late symptoms of huntingtons

A

concentration problems, trouble eating and swallowing

115
Q

what is the gene involved in huntingtons

A

htt gene on chromosome 4 codes for HTT (protein)

116
Q

what change in repeats in mutated htt leads to huntingtons disease

A

increased number of CAG repeats (coding for glutamine) in mutated htt (mhtt)

117
Q

what happens to successive generations with huntingtons disease

A

due to the DNA pol not being able to move smoothly over the stretch containing CAG repeats, it adds extra CAGs with each replication cycle causing successive generations to get huntingtons symptoms earlier

118
Q

what in the basal ganglia is changed with huntingtons

A

there is degeneration of D2 containing medium spiny neurons which results in:
- less inhibition of caudate/putamen
- less inhibition of globus pallidus external
- more inhibition of subthalamic nucleus
- less excitation of globus pallidus internal
- less GABA release on thalamus
- disinhibition of thalamus leads to increased unwanted movement

119
Q

what are some of the functions of huntintins protein at the synapse and synaptic transport

A

regulates axonal and dendritic transport
regulates endocytosis and exocytosis (quantity and rate of NT release)
regulates synaptic receptor stabilization at the post synaptic neuron

120
Q

what are some of the results of a huntintins protein mutation at the presynaptic terminal

A

less endocytosis
fewer synaptic vesicles
less release of NT

121
Q

what are some of the results of a huntintins protein mutation at the postsynaptic terminal

A

fewer receptors at post synaptic density
fewer signaling molecules
disrupted receptor clustering
disrupted receptor localization

122
Q

does the striatum produce BDNF

A

no it depends on BDNF delivered by cortico-striatal afferences

123
Q

how does HTT (protein) regulate BDNF delivery to striatum

A
  1. transcription regulation
  2. regulates transport of BDNF down cortico-striatal axons
  3. BDNF released at the synapse binds TrkB receptors and HTT stimulates endocytosis of BDNF at striatal synapse
  4. retrogradely transports BDNF to soma of striatal neuron
124
Q

how does HTT regulate transcription of BDNF

A

REST represses transcription of the BDNF gene by binding to a silencer region in DNA

HTT normally binds REST (repressor) and sequesters it in the cytosol so BDNF is transcribed

mHTT cannot bind REST as well and BDNF is not transcribed

125
Q

what are inclusion bodies

A

found in huntingtons disease and contain aggregates of mutant huntingtin (mHTT) and other precipitated proteins

126
Q

what are 3 cellular pathologies in huntingtons

A

inclusion bodies
excitotoxicity
impaired BDNF

127
Q

where are inclusion bodies found in HD

A

only in neurons

128
Q

what cells die in HD and what are spared

A

medium spiny neurons dies
glia are spared

129
Q

what happens when there is expression of mHTT in astrocytes

A

decreased expression of EAAT2
- more synaptic glutamate that overflows from the synapse
- neuronal cell death due to excitotoxicity

130
Q

what does continued depolarization of a neuron lead to

A

increased intracellular calcium

131
Q

what is the only approved drug for HD

A

VMAT2 inhibitor
(inhibits the loading of dopamine into synaptic vesicles)

132
Q

what is the mouse model for HD

A

mice expressing mHTT clasp their hind feet and have striatal atrophy, motor impairments, and inclusion bodies containing mHTT protein

also show signs of depression and spatial memory loss

depletion of htt gene is embryonically

133
Q

what is declarative memory

A

memories that can be brought to consciousness and expressed as remembered events
(daily events, words and meanings, history)

134
Q

which type of memory involves the hippocampus

A

declarative

135
Q

what is nondeclarative memory

A

procedural or implicit
memory that is acquired and retrieved unconsciously
(motor skills, associations, priming cues)

136
Q

what brain areas support declarative memory formation

A

hippocampus and its subcortical connections to mammillary bodies and dorsal thalamus

137
Q

where are declarative memories stored

A

distributed throughout cortical - medio-temporal lobe network

138
Q

how are declarative memories retrieved

A

via the entorhinal cortex and processed by hippocampal formation

139
Q

what is the hippocampal circuit affected by

A

inputs from amygdala, adding emotional aspect to memory

140
Q

what kind of amnesia will occur with damage to the hippocampus or entorhinal cortex

A

anterograde
(inability to form new memories but old memories remain intact)

141
Q

what brain areas are involved in nondeclarative memories

A

basal ganglia
prefrontal cortex
amygdala
sensory association corticies
cerebellum

NOT medial temporal lobe or midline diencephalon

142
Q

what kind of memories are likely stored in the basal ganglia

A

motor related memories and learning

143
Q

what is the morris water maze

A

tub of water with a platform underwater so mouse cannot see it

mice with normal hippocampus learn where platform is

mice with lesioned hippocampus do not learn where platform is

144
Q

what are four different kinds of dementia

A

alzheimers
vascular
lewy body
frontotemporal

145
Q

what is vascular dementia

A

sudden onset with variable symptoms from a stroke

146
Q

what is frontotemporal dementia

A

primarily affects frontal lobe (atrophy of frontal lobe) so more cognitive symptoms

group of neurologic disorders associated with changes in personality, behavior, language, movement

gene pathology involves C9orf72 gene

147
Q

what is lewi body dementia

A

progressive disease that causes hallucinations, decline in mental abilities, rigid muscles, slow movements, tremors

no hippocampal atrophy

148
Q

what is the preclinical phase of alzheimers

A

minimal behavioral symptoms but pathological changes are occurring in cells

149
Q

what is the mild cognitive impairment phase of alzheimers

A

neurological symptoms become apparent

low levels of Abeta and high levels of tau in CSF

plaques apparent but not correlated with degree of impairement

150
Q

what is the dementia stage of alzheimers

A

profound neurological symptoms and rapid decline

neurofibrillary tangles become apparent

symptoms not associated with increase in plaque burden

151
Q

what are two proteins involved in alzheimers pathology

A

phosphorylated tau form neurofibrillary tangles inside the cell

amyloid beta forms plaques outside the cells

152
Q

where is phosphorylated tau and amyloid beta detected

A

both detected in CSF

phosphorylated tau can be detected in blood as well

153
Q

where is the most prominent structural change in alzheimers

A

atrophy in temporal lobe
vascular changes
breaches of BBB
plaques, tangles, neuronal death, gliosis

154
Q

what is amyloid precursor protein (APP)

A

transmembrane glycoprotein found in many different cell types

155
Q

how is APP degraded

A

enzymes called secretases

156
Q

what happens to APP in the non-pathogenic pathway

A

APP is cleaved by alpha and gamma secretases and the resulting fragments are soluble and can be cleared easily

157
Q

what happens to APP in the pathogenic pathway

A

APP is cleaved by beta (not alpha) and gamma secretases resulting in a fragment called amyloid beta that has a tendency to aggregate and cause extracellular plaques

158
Q

what are presenilins

A

subunits of gamma secretases

159
Q

what is beta secretase also called

A

beta-site amyloid precursor protein cleaving enzyme 1 (BACE1) because it initiated production of the toxic amyloid beta that plays a part in early alzheimers disease

160
Q

what are two mutations that are sufficient to cause AD

A

amyloid precursor protein (APP) mutation

pre-senilin-1 and pre-senilin-2 mutation account for most cases of familial early onset AD

161
Q

what is notch signaling

A

cleaved by gamma secretase and is important in adult nervous system for learning and memory

162
Q

what are Abeta plaques surrounded with

A

Abeta oligomers that are in equilibrium with the plaques
- act as storage sites for Abeta oligomers

163
Q

what can Abeta plaques do

A

disrupt synaptic activity
activated microglia and trigger inflammation
deposit on blood vessels increasing the risk of hemorrhage

164
Q

what are neurofibrillary tangles

A

tau is hyper-phosphorylated and polymerizes forming twisted strands called neurofibrillary tangles

165
Q

what do neurofibrillary tangles cause

A

they no longer bind to tubulin so they disrupt all intracellular transport including transport along axons and dendrites

166
Q

what is the location difference between tangles and plaques

A

tangles: intracellular
plaques: extracellular

167
Q

what are tauopathies

A

class of neurodegenerative disorders characterized by neuronal and/or glial tau-positive inclusions
(FTD, AD, parkinsons)

some are a result of mutations in the tau gene

168
Q

how do microglia interact with plaques

A

microglia surround plaques forming a protective barrier and clear away Abeta deposits by secreting substances that breakdown plaques

169
Q

what glia can amyloid deposits activate

A

astrocytes and microglia

  • microglia are initially beneficial because they mop up excess amyloid but as the disease progresses they become harmful as they release ROS that can activate neuronal apoptosis
170
Q

what do plaques do to blood flow

A

reduce blood flow

compromise integrity of blood vessels and affect BBB

increased levels of Abeta seen in other organs (heart, muscles) as well

171
Q

what is a specific mutation that increases AD risk

A

APOE 4
associated with increased risk and lower onset of AD

(APO 2 reduces risk)

172
Q

what is the cholinergic hypothesis for AD

A

ACh is reduced at synapses in amygdala, hippocampus, and cortex of AD brains so cholinergic failure thought to underly AD symptoms

projections to cortex of presynaptic cholinergic neurons in NBM undergo profound degeneration in late AD

173
Q

what are 4 drugs that are used as treatment for AD

A
  1. drugs that increase cholinergic activity
  2. NMDA receptor blocker
  3. antidepressants/psychotropic drugs reduce delusions and psychosis
  4. monoclonal antibodies against Abeta to remove plaques
174
Q

what is a way that there can be early detection of amyloid plaques

A

retinal scans

175
Q

what are antisense oligonucleotides (ASO)

A

DNA oligos with sequence complimentary to mRNA of a protein
- makes a mRNA-DNA hybrid
- mRNA destroyed by RNAse
- no protein synthesis

ASO spans splice sites to allow inclusion or exclusion of an exon that would have not normally been included

176
Q

what are two types of inhibitory RNAs

A

siRNA
microRNA

177
Q

what are the phases of a clinical trial

A

preclinical validation in animal models

phase 0: pilot studies
phase 1: studies of drug safety in patients or volunteers
phase 2: studies of drug efficacy
phase 3: studies of broader applicability of effect

drug/device approval

phase 4: postmarketing analysis for interaction with other drugs and long term effects

178
Q

what are the inputs of the basal ganglia

A

inputs to striatum (caudate/putamen) is from entire cortex but caudate has more multimodal inputs than putamen

substantia nigra pars compacta

179
Q

what are the outputs of the basal ganglia

A

from substantia nigra and globus pallidus

globus pallidus –> thalamus –> motor cortex

180
Q

what is the main function of the indirect pathway

A

reduce unwanted movements (reduces firing of neurons that are not part of the direct pathway)

181
Q

what is the primary problem in huntintons disease

A

degeneration of the neurons in the striatum and release less GABA

direct pathway is unaffected

182
Q

what is the pathway for saccadic eye movement

A
  1. D1 receptors activate the caudate/putamen
  2. Caudate releases more GABA so more inhibition on the substantia nigra
  3. Since the substantia nigra is tonically firing, the inhibition from the caudate will cause the substantia nigra to release less GABA on the superior colliculus, activating the superior colliculus
  4. The superior colliculus has an excitatory effect on the gaze centers and eye movement, causing eye movement to occur
183
Q

what is the pathway for movement through the direct pathway

A
  1. Cerebral cortex or the D1 receptors have excitatory input on the caudate/putamen
  2. Caudate/putamen releases GABA onto the globus pallidus internal inhibiting it
  3. Since the globus pallidus is tonically active, inhibition of it causes there to be less GABA released onto the thalamus
  4. Less GABA onto the thalamus causes it to be disinhibited, which activated the frontal cortex, causing movement
184
Q

what does D2 receptor activation do to the indirect pathway

A

causes more movement
1. D2 receptors are activated which inhibit the caudate/putamen
2. Inhibition of the caudate causes less GABA to be released on the globus pallidus external
3. Less inhibition of the globus pallidus external causes there to be more GABA released onto the subthalamic nucleus since it is tonically firing
4. More inhibition of the subthalamic nucleus causes there to be less excitation of the globus pallidus internal
5. Less excitation of the globus pallidus internal means there is less inhibition of the thalamus
6. Disinhibition of thalamus leads to movement

Clinical Neuroscience (4 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions