Brainscape's Knowledge GenomeTM

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


See full index

Clinical Neuroscience > module 2 > Flashcards

module 2 Flashcards

1
Q

what is the difference between emotion and mood

A

emotion: intense feeling that is short-term and typically directed at a source

mood: state of mind that tends to be less intense than an emotion and does not necessarily need a contextual stimulus

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

what are the three components of emotion

A

behavior
physiology
feeling

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

what are the 6 basic emotions

A

anger
sadness
happiness
fear
disgust
surprise

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

what part of the brain was needed to produce sham rage (not directed at a target) in cats

A

caudal hypothalamus

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

where are basic circuits for emotion concluded to be found

A

in the diencephalon

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

where is the site of associative learning of fear

A

amygdala

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

what was significant about patient S.M

A

bilateral destruction of amygdala
- showed all emotions except fear

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

what areas are seen as important for emotion

A

orbital and medial prefrontal cortex
amygdala
thalamus
hypothalamus
stratum

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

what areas of the brain are no longer considered important neural centers for processing emotion

A

hippocampus
mammillary bodies of the hypothalamus

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

what are the three catecholamines

A

dopamine
epinephrine
norephinephrine

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

what are the four monoamines

A

dopamine
epinephrine
norepinephrine
serotonin

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

what AA are catecholamines produced from

A

tyrosine

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

what AA is serotonin produced from

A

tryptophan

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

where are NE neurons located

A

locus coeruleus

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

where do NE project

A

all over the brain

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

where are epi neurons located

A

medullary epinephrine neurons

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

where do epi neurons project

A

not as widely spread throughout brain

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

what gland synthesizes NE and epi

A

adrenal gland

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

what is the pathway from tyrosine to NE/epi

A

tyrosine - (tyrosine hydroxylase) -> DOPA –> dopamine –> NE/epi

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

how does NE, epi, dopamine, serotonin get into vesicles

A

VMAT (vesicular monoamine transporter)

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

what does the NET do

A

norepinephrine transporter
- removed NE from synaptic cleft and back into presynaptic cell (GPCRs)

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

what receptors are on the postsynaptic neuron that bind NE and epi

A

postsynaptic adrenergic receptors
alpha 1, alpha 2, beta

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

what enzymes are present on mitochondria that metabolize NE, epi, and dopamine

A

COMT - catecholamine methyl transferase
MAO - monoamine oxidase

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

what two drugs block dopamine reuptake

A

cocaine
amphetamines

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

where are serotonin neuron cell bodies

A

raphe nuclei

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

where do serotonin neurons project to

A

extensively branched

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

what is the pathway from tryptophan to serotonin

A

tryptophan - (tryptophan-5-hydroxylase) -> 5-hydroxytryptophan -> serotonin (5HT)

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

what transporter brings 5HT back into the presynaptic terminal

A

5HTT

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

are serotonin receptors on the post synaptic neuron metabotropic or ionotropic

A

both

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

what is the serotonin presynaptic receptor called

A

presynaptic serotoninergic receptor

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

what enzymes are on the mitochondria that break down serotonin

A

MAO - monoamine oxidase

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

what is the relationship between serotonin and the enteric NS

A

serotonin inhibits peristalsis

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

what is responsible for the variation in serotonin transcriptional efficiency

A

polymorphic gene promotor
- long and short polymorphism both produce the same protein but the quantity of protein synthesized is different

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

what is difference between the long and short serotonin allele

A

long: higher levels of transporter protein (less serotonin in synaptic cleft)
short: lower levels of transporter protein

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

is the long or short serotonin allele more likely to result in depression

A

long because there is more serotonin being transported out of the synaptic cleft

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

where are dopamine cell bodies located in the brain

A

substantia nigra and ventral tegmental area

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

where do dopamine neurons project to

A

all over the brain

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
38
Q

what is the pathway to make dopamine from tyrosine

A

tyrosine - (tyrosine hydroxylase) -> DOPA -> dopamine

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

what transporter takes dopamine back into the presynaptic neurons

A

DAT - dopamine transporter

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

what are the dopamine receptors on the postsynaptic terminal

A

D1 and D5: excitatory
D2, D3, D4: inhibitory
all GPCRs

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

what is the most important way to remove monoamines from the synaptic cleft

A

reuptake
DAT
NET
SERT

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

where are enzymes to break down catecholamine located

A

both neurons and glial cells

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

what is MAO and where is it found

A

2 forms of monoamine oxidase are located on the presynaptic mitochondria (A and B)

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

what is COMT and where is it found

A

catechol-O-methyl transferase
in pre and post synaptic cells
- only for catecholamines (not serotonin)

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

what was the milner and olds experiment

A

implanted an electrode in the pleasure center (DA secreting neurons) and the rat pressed a lever to receive stimulation
- rat would keel pressing lever to the point of extreme exhaustion

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

what is the primary reward circuit

A

VTA-NAc
dopaminergic projections from the VTA to the NAc
- NAc releases DA in response to reward related stimuli

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

what is the lateral habenula

A

important part of the reward circuit that provides negative value signals to dopaminergic and serotonergic systems

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

how are LHb (lateral habenula) neurons excited

A

when reward is less than expected
activity is reduced when a go response is elicited

excited by unexpected non-rewarding or unpleasant events

inhibited by unexpected rewarding events

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

what is reward prediction error

A

positive RPE - reward is greater than predicted and the action associated with the reward is facilitated

negative RPE - actual reward is smaller so the action is suppressed

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

what does the hypothalamus control

A

homeostasis
- outputs to the autonomic nervous system and pituitary gland (HPA axis)

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

what is essential for circadian rhythms

A

suprachiasmatic nucleus (SCN)

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

how do releasing factors travel from the hypothalamus to the anterior pituitary

A

dedicated portal system

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

what do releasing factors do

A

stimulate release of stimulating hormones

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

what do stimulating hormones do

A

enter blood stream and travel to various areas leading to secretion of hormones

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

what is the HPA axis

A

hypothalamus: CRH
pituitary: ACTH
adrenal gland: cortisol

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

what can increased cortisol lead to

A

loss of synapses and decreased synaptic complexity in prefrontal cortex
reduced BDNF
altered glucocorticoid receptors

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

what do antidepressants try to reverse

A

the symptoms associated with increased cortisol levels

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

what is bipolar I

A

at least one episode of mania and episodes of major depression

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

what is bipolar II

A

at least one episode of hypomania and one depressive episode

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

what is cyclothymia

A

cycling mood
- does not meet the criteria of major depression and hypomania

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

what is the mean age of onset for bipolar disorder

A

~20

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

what are two drugs that can induce manic episodes

A

cocaine
amphetamine

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

what drug can lead to early onset of bipolar disorder

A

THC

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

how many regions of genes are identified as contributing to bipolar disorder

A

18 regions (not genes)

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

what are three environmental factors that can contribute to bipolar disorder

A

early trauma
substance use
stressful events

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
66
Q

what is the most effective drug for bipolar depression

A

lithium

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

what are the 4 categories of drugs used to treat bipolar disorder

A

mood stabilizers: lithium and valproate (anticonvulsant)

antipsychotics: thorazine, quetiapine, risperidone (common schizophrenia drugs)

antidepressants

anxiolytics (antianxiety): GABA agonists

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

what are symptoms of major depressive disorder

A

sad mood, anhedonia, recurrent suicidal ideation

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

what is disruptive mood dysregulation disorder (DMDD)

A

seen in children and adolescents with frequent anger outbursts and irritability out of proportion to the situation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
70
Q

what is persistent depressive disorder (PDD) or dysthymia

A

depressed mood that is not severe enough to meet the criteria for a major depression disorder

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
71
Q

what is premenstrual dysphoric disorder (PMDD)

A

characterized by irritability, anxiety, depression, and emotional lability occurring a week before the onset of menses followed by resolution of symptoms after onset

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
72
Q

what is postpartum depression

A

MDD after giving birth

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

what is seasonal affective disorder (SAD)

A

MDD with a seasonal pattern

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
74
Q

what is an example of learned helplessness in mice

A

unpredictable, uncontrollable stress like a foot shock

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
75
Q

what is chronic social defeat stress (CSDS) in mice

A

mild-mannered mice paired with aggressive mice for several weeks and eventually the docile animals exhibit anxious and withdrawn behavior

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
76
Q

what is an example of helpless entrapment in mice

A

forced swim test in water without way to escape

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
77
Q

what is the concordance of a disorder

A

the degree to which it is inherited

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
78
Q

what does polygenic mean

A

no single gene can be linked to a cause of all the symptoms

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
79
Q

what are two genes that are hypothesized to be associated with depression

A

calcium channels
glutamate receptors

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
80
Q

what are two genes that are known to be associated with depression

A

polymorphism in the promotor and in second intron (VNTR) of the 5HTT gene

epigenetic regulation of BDNF gene

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
81
Q

what does BDNF signaling modulate

A

LTP (long term potentiation)
- BDNF enhances LTP by both modulating presynaptic release of NT and postsynaptic growth of spines

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
82
Q

what is mTOR

A

mechanistic target of rapamycin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
83
Q

what does mTOR do

A

coordinates cell growth and metabolism with environmental inputs (nutrients and growth factors)

serine/threonine protein kinase

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
84
Q

how is BDNF stored and released

A

stored in vesicles and released in an activity dependent manner

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
85
Q

what receptors bind BDNF

A

both presynaptic and postsynaptic TrkB receptors

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
86
Q

how does BDNF affect proteins

A

global effect on translation of proteins

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
87
Q

what is the relationship between stress and dendrites

A

stress causes atrophy of dendrites and decreased number and size of dendritic spines

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
88
Q

what are epigenetics

A

regulation of gene expression
- no changes in DNA sequence

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
89
Q

what are the three steps of epigenetics

A
  1. methylation
  2. acetylation
  3. RNA based modulation
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
90
Q

what is the role of the methylation step in epigenetics

A

methylation of cytosine nucleotides of DNA silences RNA transcription

methylation inhibits transcription

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
91
Q

what is the role of the acetylation step in epigenetics

A

acetylation of histone proteins interferes with DNA-histone interactions and exposes DNA segments so they are accessible to transcription machinery

acetylation increases transcription

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
92
Q

what is the role of RNA based modulation in epigenetics

A

RNAs can increase or decrease transcription of a gene by interacting with DNA and histones

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
93
Q

what are six things that decrease or are reduced in depression (structural changes)

A
  1. reduced medial prefrontal cortex
  2. reduced hippocampus
  3. reduced size of pyramidal neurons
  4. loss of GABAergic neurons
  5. reduced glia in hippocampus
  6. decreased number of spines in hippocampus
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
94
Q

what increases in depression (structural changes)

A

increased size of amygdala and more complex dendritic tree

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
95
Q

what happens to inflammation during depression

A

increased levels of proinflammatory factors such as cytokines (interleukins and tumor necrosis factor)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
96
Q

what does ketamine block

A

NDMA receptors on interneurons (more than other neurons) which inhibits GABA release

(less inhibition because less GABA release)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
97
Q

where are neuroblasts found (where neurogenesis is seen in adults)

A

in the subgranular zone (SGZ) of dentate gyrus and subventricular zone of the lateral ventricles

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
98
Q

what happens to BDNF and its receptors in depression

A

they are reduced

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
99
Q

what does reducing BDNF lead to

A

anxiety

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
100
Q

what do mood stabilizing drugs promote

A

neurogenesis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
101
Q

what drug restores changes in dendritic morphology resulting from depression

A

lithium

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
102
Q

what are the three subtypes of antidepressants

A

tricyclic
MAOI
SSRI/SNRI

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
103
Q

what is esketamine

A

ketamine nasal spray used for treatment resistant depression
- has to be administered in a clinical setting

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
104
Q

what is bupropion

A

norepinephrine and dopamine reuptake inhibitor

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
105
Q

what drug has been used for postpartum depression

A

derivative of progesterone
positively modulating GABAA receptors

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
106
Q

what is schizophrenia

A

disorder of cognitive abnormality and abnormality of sequential thought
(causes people to interpret reality abnormally)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
107
Q

what is psychosis

A

refers to a collection of symptoms that affect the mind - some loss of contact with reality

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
108
Q

what are hallucinations

A

perceptions with no external stimuli
-auditory or visual

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
109
Q

what are illusions

A

severely distorted perceptions

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
110
Q

what are delusions

A

unrealistic beliefs that can’t compare with reality

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
111
Q

what are the three classes of symptoms for psychosis

A

positive (addition)
negative (removal)
cognitive

112
Q

when does schizophrenia usually develop

A

late adolescence and early adulthood

113
Q

what innervation increases dramatically during late adolescence and early adulthood

A

dopamine innervation of prefrontal cortex

114
Q

what are three ways circuits are refined during early adulthood

A

pruning of asymmetric (excitatory) synapses
proliferation of inhibitory circuits
continued elaboration of pyramidal dendrites as targets of inhibitory input

115
Q

what part of maturation is compromised with schizophrenia

A

final burst of maturation of the cortex

116
Q

where does the mesocortical pathway project to

A

prefrontal cortex

117
Q

where does the mesolimbic pathway project to

A

hippocampus
cingulate
amygdala
olfactory bulb

118
Q

what is the dopamine hypothesis

A

increased dopamine levels result in schizophrenia

119
Q

what is haloperidol

A

D2 antagonist that reduced psychotic symptoms
(lead to dopamine being considered the underlying cause)

120
Q

what was the mechanism of haloperidol

A

increased synthesis and release of dopamine
no change in D2 receptors
no change in dopamine transporters

121
Q

what are some structural white matter changes in schizophrenia

A

overall reduction in white matter volume
reduced myelination (oligodendrocytes decrease)
fornix and cingulum reduced

122
Q

what structure enlarges in schizophrenia

A

ventricles

123
Q

where is there enhanced activity (1) and decreased activity (2) in the brain with schizophrenia

A

enhanced activity in the DLPFC

decreased activity in the amygdala and hippocampus

124
Q

what are some of the GABAergic deficits seen in schizophrenia

A

reduction in GABAA receptors
reduced number of interneurons
50%reduction in GABAergic synapses

125
Q

what are some glutamatergic deficits in schizophrenia

A

smaller pyramidal cells
reduced NMDA receptors
increased levels of glutamate in untreated patients and decrease after treatment

126
Q

what are some dopaminergic deficits in schizophrenia

A

decreased dopaminergic innervation of PFC
increased dopamine receptors

127
Q

what are the two kinds of GABAergic cells

A

chandelier: inhibit initial segment of axon
basket: inhibit cell body

128
Q

what are gamma oscillation a result of

A

rhythmic depolarizing glutamatergic activity and hyperpolarizing GABAergic activity of pyramidal cells

129
Q

what is the amplitude of gamma waves increased by

A

working memory load

130
Q

what are mutations in the major histocompatibility complex (MHC) genes associated with

A

schizophrenia

131
Q

how are synapses pruned in schizophrenia

A

in an activity-dependent fashion
- C4 complement protein tag synapses to be removed
- microglia surrounding the synapse recognize the tag and remove the synapse
(more synapses are removed in schizophrenia)

132
Q

what is the mechanism of overactive pruning in schizophrenia

A

microglial dysfunction and mutation of C4 gene

133
Q

what happens to the spine density in the DLPFC in schizophrenia

A

it decreases

134
Q

what happens to the connectivity of the brain in schizophrenia

A

atypical connectivity rather than overall reduction in connections

135
Q

what is the glutamate hypothesis

A

schizophrenia is due to hypofunction of NMDA receptors

136
Q

what do PCP and ketamine (NMDAR antagonists) mimic

A

psychosis

137
Q

normally, how is dopamine release inhibited

A

glutamate inhibits dopamine release via activation of GABAergic neurons

138
Q

how can over pruning of spines during development cause enhanced dopamine release

A

increased glutamate causes increased GABA inhibition on dopamine neurons which reduces dopamine release

139
Q

what is the startle response

A

person is startled by an unexpected loud noise
-controls show habituation and second stimulus does not lead to startle response
-schizophrenic patients do not show habituation

140
Q

what is pre pulse inhibition (PPI)

A

EEG measures response to a click/sound
control subjects show a lower response to the second stimulus but not schizophrenic patients

141
Q

why does PPI contribute to the cholinergic hypothesis for schizophrenia

A

PPI is enhanced by acetylcholine receptor agonists

142
Q

what ACh receptors are reduced in schizophrenia

A

alpha7nAChR

143
Q

what is the function of neuregulin

A

secreted from presynaptic terminals and binds to ErbB4 receptors

required for synapse maintenance

144
Q

what is the function of PSD 95

A

part of postsynaptic complex that keeps glutamate receptors in place

145
Q

what is the function of DISC1

A

involved in formation of synapses

146
Q

what is the function of Karilin-7

A

needed for synapse stabilization

147
Q

what does deletion of 22q11.2 cause

A

deletion of two microRNAs that regulate proteins involved in spine development as well as COMT

148
Q

what are typical anti-psychotics (older drugs) that treated schizophrenia

A

D1 antagonists

149
Q

what do D2 antagonist drugs do for schizophrenic patients

A

treat positive symptoms but not good for negative symptoms or cognitive defects
- good to treat first psychotic episode
- lots of side effects

150
Q

what are atypical anti-psychotics (newer drugs)

A

weaker D2 antagonists and more activity on other receptors especially 5HT

151
Q

what is the mechanism of atypical antipsychotics

A

exert clinical effects over weeks

152
Q

where was a lesion made in an animal model to reduce schizophrenic symptoms

A

ventral hippocampus lesion postnatal day 7

153
Q

where are alpha 7 nAChRs found

A

presynaptic terminals

154
Q

where in the brain has been found to be modulated by alpha 7 nAChRs

A

VTA, subthalamic nucleus, nucleus accumbens
(dopaminergic, glutamatergic, GABAergic neurons)

155
Q

what kind of agonists can enhance cognition and are used in disorders like alzheimers

A

nicotine and cholinergic agonists

156
Q

what do pre and post synaptic alpha 7 nAChRs do

A

pre: increase release of NT
post: depolarize neurons acting like AMPA receptors

157
Q

how are NMDA receptors activated

A

via activation of mGlu receptors on pyramidal cells and interneurons
or
via activation of mACh receptors on GABA interneurons

158
Q

how are NMDA receptors modulated

A

D-serine and glycine are both agonists at a co-agonist site on NMDARs

158
Q

how is NMDA receptor modulation affected with schizophrenia

A

people with schizophrenia have lower levels of D-serine and glycine
- glycine can be increased by blocking reuptake into astrocytes with glycine transporter inhibitors

159
Q

what is glutathione (GSH)

A

nutritional supplement that mops up ROS in cells (does not cross BBB but the precursor does and enhances the effects of anti-psychotics)

  • schizophrenics have lower levels of GSH
160
Q

what are stem cells

A

cells that can form any other cell

161
Q

what is a embryonic stem cell (ES cells)

A

can divide indefinitely (once start differentiating, will stop dividing)
pluripotent: can give rise to all cell types

162
Q

what are induced pluripotent cells (iPS cells)

A

cells that are introduced to 4 transcription factors to convert the somatic cell into a stem cell

163
Q

what are the two layers of an ES cell in the two-layer stage

A

epiblast layer
hypoblast layer

164
Q

what happens to the cell when the cells migrate to begin forming 3 layers

A

the epiblasts start migrating between the two layers to create 3 layers of cells and the hypoblasts go away

165
Q

what happens after the 3 layers of the cells are formed

A

the body axis develops

166
Q

in response to signals from the mesoderm/notochord, what do ectoderm cells divide to form

A

a thick neural plate

167
Q

what eventually gives rise to the CNS

A

the neural plate

168
Q

what do cells at the edges of the neuronal plate divide to form

A

neural crest cells

169
Q

what forms the neural tube

A

the neural plate folds

170
Q

what eventually gives rise to the PNS

A

the neural crest

171
Q

what eventually gives rise to sensory and autonomic ganglia

A

neural crest cells

172
Q

which part of the neural tube closes first

A

middle first, then the top/head side

173
Q

what do cells of the neural tube give rise to

A

neurons
astrocytes
oligodendrocytes

174
Q

what are two examples of unique markers for neural stem cells

A

Sox2
bHLH

175
Q

what is spina bifida

A

incomplete closing of the neural tube that leaves a section of spinal cord and nerves exposed
- vertebra fail to develop properly and skin may fail to develop

176
Q

what kind of deficiency leads to spina bifida

A

folic acid (vitamin B) deficiency

177
Q

what determines what kind of cell the cells of the neural tube become

A

the position of cells within the tube
transcription factors
diffusible factors

178
Q

what is neuron restrictive silencing factor (NRSF) aka REST

A

binds to neuron specific genes to repress them and is highest expression in areas where stem cells for non-neuronal cells are found and lowest in neuron-specific areas

(neural tube little REST - liver cells lot of REST)

179
Q

what are hox genes

A

genes that contain highly conserved homeobox domains and express helix-loop-helix transcription factors

180
Q

what does a HoxD 13 mutation cause

A

synpolydactyly
fusion of digits and extra digits

181
Q

what does a HoxA 13 mutation cause

A

hand-foot-genital syndrome
- skeletal and urogenital defects

182
Q

in general, are Hox gene mutations embryonic lethal

A

yes

183
Q

what signals determine neuron identity

A

transcription factors
ligands and receptors
their relative concentrations (gradients)

184
Q

what are the two axes of neural tube unduction

A

rostral to caudal
dorsal to ventral

185
Q

what structures produce signals that induce cells to differentiate

A

roofplate
floor plate
surrounding cells

186
Q

what three signals have a gradient on the rostro-caudal axis

A

retinoic acid
FGF
Hox genes

187
Q

what three signals have a gradient on the dorso-ventral axis

A

BMPs secreted by ventral cells
Noggin secreted by dorsal cells
Sonic hedgehog (Shh) in dorso-ventral axis

188
Q

what does retinoic acid cause

A

rostro-caudal axis

high concentrations form spinal cord
low concentrations form cortex

binds to nuclear retinoid receptors and acts as a transcription factor

189
Q

what does a deficiency of retinoic acid cause

A

craniofacial abnormalities like microcephaly or cleft palate

190
Q

what does BMPs cause

A

bone morphogenic protein - secreted by ventral cells

cause ectodermal cells to develop into skin by activation of kinases and transcription factors

191
Q

what are chordin and noggin

A

proteins expressed by dorsal cells that bind and inhibit BMPs

192
Q

where are the concentrations of BMP, chordin/noggin high

A

BMP high concentration in skin (ventral)
noggin/chordin high concentration in nervous system (dorsal)

default mode is to develop into nervous system so BMP can only inhibit/modify it

193
Q

what is sonic hedgehog involved in

A

peptide that is involved in
closing of neural tube
dorso-ventral patterning
differentiation of different types of neurons
limb formation

194
Q

where is there low, mid, and high concentrations of Shh in the spinal cord

A

low in dorsal - sensory
mid in interneurons
high in ventral - motor

195
Q

what is holoprosencephaly

A

single lobed brain
(caused by Shh mutation)

196
Q

what mutation causes basal cell carcinoma

A

Shh mutation

197
Q

what is a meduloblastoma

A

lack of Shh signaling leads to uncontrolled growth in cerebellum

198
Q

what side of the body does the floor plate and roof plate develop into

A

floor plate - ventral side of body
roof plate - dorsal side of body

199
Q

what are the 6 steps of development of the CNS in order

A

neurulation
neuronal proliferation
neural migration
apoptosis
synaptogenesis
myelination

200
Q

when does neurogenesis begin

A

after dorsal/ventral and rostral/caudal patterning is complete

201
Q

what are 3 things that control migration

A

cell adhesion molecules (CAMs)
extracellular matrix (ECMs)
secreted diffusible signals modifies the actin cytoskeleton to make the cell move in desired direction

202
Q

what do neuronal precursor cells migrate along

A

radical glia processes that span across neural tube touching both surfaces

203
Q

how are layers of the cortex formed

A

inside out fashion
layer VI is formed first (oldest cells)
layer I is formed last (youngest cells)

204
Q

what is reelin

A

glycoprotein that is expressed in high levels during development
- signal for neurons to jump off radical glia
- modulates synaptic plasticity
- stimulates dendrite/dendritic spine development
- regulates migration of neuroblasts in adult

205
Q

what do reelin mutations cause

A

less white matter
enlarged ventricles
disrupted sulci and gyri
(associated with schizophrenia, bipolar, autism, alzheimers, epilepsy)

206
Q

what is lissencephaly and what is it caused by

A

smooth brain
caused by total absence of reelin
- thick cortex and cell lamination is abnormal (cells in wrong place)

207
Q

what is the order of birth for astrocytes, oligodendrocytes, and neurons

A

neurons
oligodendrocytes
astrocytes

208
Q

once cells stop migrating, how do they define their polarity

A

by reorientation of the cytoskeleton

209
Q

what proteins specify the axonal end of the neuronal processes

A

partitioning defective proteins (PAR)
- PAR mutations cause polarity to not be specified and all processes express the axonal marker tau
- mutations identified in schizophrenia

210
Q

what guides the cell to the target neuronal

A

axonal growth cone

211
Q

what are the parts of the axonal growth cone

A

lamellipodium - tip of the axon that is specialized to form a flat extension of microtubules
filopodia - finger-like projections containing actin fibers that protrude out and sense chemo-attractants

212
Q

what influences the movement of filopodia

A

rapid changes in intracellular calcium that flows in through voltage gated calcium channels and TRP channels

  • moves forward by actin filaments assembling and disassembling at the leading edge of the cone
213
Q

what are the two main things influencing axonal growth

A

CAMs
diffusible factors with specific receptors

214
Q

what is the difference between a tropic factor and a trophic factor

A

tropic: the guiding factors (chemoattractants or chemorepulsants)
trophic: support factors supporting neuronal survival

215
Q

what are semaphorins

A

membrane-bound proteins that are cleaved to be diffusible
chemorepulsive
bind to receptors, plexin

216
Q

what are slits

A

chemorepulsive that binds to receptor robo

217
Q

what are netrins

A

chemoattractants

218
Q

are sonic hedgehog and wnts chemotropic

A

yes

219
Q

where do proprioceptive neurons send collaterals

A

to the ventral horn because they are not repulsed until the concentration of semaphorin is high

220
Q

where to touch-receptive neurons send collaterals

A

they turn as soon as they enter the spinal cord to ascend in the dorsal horn because they are repulsed at the intermediate concentrations of semaphorins

221
Q

where do temp and pain receptive neurons send their collaterals

A

stop growing at dorsal horn and later form synapse with spinothalamic neuron that crosses midline because they are very sensitive to low concentrations of semaphorins

222
Q

how is the axon guided across the midline

A

the floorplate secretes netrin that attracts the axon

slit expression on the contralateral side prevents axon from turning back (has slit receptors called robo)

semaphorin gradient repels the growth cone and maintains its path

223
Q

what are 4 examples are non diffusible signals for axon guidance

A
  1. ECM extracellular matrix that interact with cell-membrane bound integrins
  2. calcium independent cell adhesion molecules (CAMs)
  3. calcium dependent cell adhesion molecules (cadherins)
  4. ephrins and eph receptors (tyrosine kinases)
224
Q

what is the difference between semaphorin in axons and semaphorin in dendrites

A

axons: chemo repulsive
dendrites: becomes chemo attractive due to soluble guanyl cyclase (sGC) conversion

225
Q

what molecule is associated with dendritic and axonal tiling

A

DSCAM
down syndrome cell adhesion molecule

226
Q

what does homophilic binding between DSCAMs lead to

A

repulsion of processes and prevention of synapses between axons and dendrites on the same neuron

227
Q

what are the steps in synaptogenesis

A
  1. synaptic adhesion molecules stabilize the initial contact causing recruitment of synaptic proteins and retrograde signaling to the soma
  2. increased synthesis of neurotrophic factors
  3. presynaptic axon and cell survive if trophic factors are released
  4. stable synapse is maintained by synaptic activity
228
Q

what are three trophic factors that are involved in synaptogenesis

A

NGF
BDNF
neurotrophins

229
Q

what leads to differentiation of pre and post synaptic sites

A

signaling between inductive factors

neurexin-neuroligin interactions are essential for stable synapse formation

230
Q

what are neurexins

A

presynaptic
localize synaptic vesicles and docking proteins

231
Q

what are neuroligins

A

postsynaptic
affect clustering of AMPA and NMDA receptors
(can confer specificity of synapses)

232
Q

what do polymorphisms in inductive factors lead to

A

links to autism and schizophrenia

233
Q

what are three things that are necessary for formation of a synapse

A

contact-dependent interactions
secreted factors
signaling factors from astrocytes

234
Q

what is hebbs postulate

A

neurons that fire together wire together
- synapses will be lost if they are not used

235
Q

what is the definition of an intellectual developmental disability

A

intellectual disability as well as problems with adaptive behaviors

236
Q

what is trisomy chromosome 21

A

down syndrome

237
Q

what does the severity of down syndrome symptoms depend on

A

the amount of duplicated DNA
(not all of the chromosome needs to be present for trisomy)

238
Q

what is trisomy 21 the result of

A

non-disjunction of chromosomes or chromatids during meiosis

  • some of the expressed genes are transcription factors resulting in altered genome-wide expression
  • altered methylation patterns also seen
239
Q

what happens to GABA in down syndrome

A

increased GABAergic inhibition

240
Q

what is the increased GABAergic inhibition due to in down syndrome

A
  1. changes in synapse structure in the hippocampus (synapses are larger and on shaft of axon which increases inhibitory effect)
  2. olig1 and olig2 transcription factors are overexpressed and drive overgrowth of GABAergic interneurons
  3. fewer glutamatergic synapses and they have smaller dendritic spines leading to lower activation
  4. overexpression of inwardly rectifying potassium channels (GIRKs)
241
Q

how does overexpression of GIRKs lead to increased inhibition

A

gene for GIRK expressed on chromosome 21 so over expressed in down syndrome

  1. activation of GABA B receptors by GABA activates G proteins
  2. subunits of G proteins dissociate and activate potassium channels called GIRKs
  3. activation of the potassium channels hyperpolarizes neurons making it harder to fire action potentials - increasing the inhibition
242
Q

what could be the reason for the memory and cognitive deficits in down syndrome

A

reduced LTP
enhances LTD

243
Q

what disrupts synaptic vesicle recycling

A

overexpression of some genes
- will further impact LTP

244
Q

what developmental pathways are disrupted in down syndrome

A

DOPEY2: cortical cell density - overexpression may lead to abnormal cortical lamination

SIM2: regulates sonic hedgehog expression

TPRD: growth of neurites

245
Q

why is the neuron glia interaction impaired in down syndrome

A

S100beta
calcium binding protein secreted by glia
overexpression can lead to changes in dendritic spine density and impaired spatial learning

246
Q

in mouse models, what treatments have helped to reverse symptoms of down syndrome

A

blocking GABA A receptors
blocking inward rectifiers
reducing copy number of olig 1 and olig 2 to restore hippocampal function

247
Q

why does fragile X syndrome disproportionally affect males

A

it is on a X chromosome

248
Q

what is fragile X syndrome caused by

A

deficiency or absence of fragile X messenger ribonucleoprotein 1 (FMRP)
- caused by expansion of CGG in the promoter region of FMR1 gene on X chromosome

249
Q

what does the expansion of the CGG on the FMR1 gene lead to

A

methylation and repression of FMR1 gene transcription and FMR protein is not synthesized

250
Q

what does the increased methylation of promoter due to extra repeats cause in fragile X syndrome

A

reduced or absent transcription
(more repeats –> more methylation –> less transcription/translation –> less protein)

251
Q

what are three effects that FMRP has on brain development and function

A

effects every aspect

  1. inhibits transcription/translation of too many proteins
  2. alters epigenetic regulation/chromatin modification
  3. directly interactions with ion channels and regulates their function
252
Q

what are early development consequences of FMRP deficiency

A

altered proliferation and differentiation of progenitor cells - increased proliferation and preferentially develop into glia

  • altered development of astrocytes
  • deficiencies in myelination and white matter
  • synaptogenesis reduced
253
Q

what are the dendrites like in fragile X syndrome

A

long, thin dendritic spines
smaller spine heads
increased spine density

254
Q

what is the mechanism of mGluR dependent LTD

A

activation of mGlu receptors
Gq g proteins are activated
phospholipase c activated
mTOR and ERKs increase translation of mRNAs in dendrites

FMRPs inhibit translation
OR
endocytosis of AMPA receptors leading to reduced post synaptic activity (LTD)

255
Q

what is the mechanism that causes an FMRP deficiency to increase LTD

A

there is no FMRP so there is more endocytosis of AMPA receptors leading to more reduction of post synaptic activity (LTD)

256
Q

what are treatments for fragile X syndrome

A

reduce mGlu receptor expression or mGlu antagonist

GABA agonists to reduce the release of glutamate

lithium

257
Q

what is rhett syndrome

A

x linked disorder - almost always affects girls

development normal at first then regression
loss of cognitive functions
handwringing movements

258
Q

what is the cause of rhett syndrome

A

de novo mutation of MeCP2

259
Q

what is MeCP2

A

nuclear protein that modulates transcription
modifies transcription of BDNF

260
Q

where does the methyl binding domain of MeCP2 bind

A

to methylated CpG sites on DNA

261
Q

what causes the genes in the region of DNA that MeCP2 binds to not be expressed

A

transcription repression domain (TRD) recruits corepressor proteins which results in deacetylation and condensation of chromatin which makes it not accessible to transcription machinery

262
Q

in rhett syndrome, what does a lack of functional MeCP2 impair

A

activity-dependent release of BDNF

263
Q

normally, how is BDNF synthesized

A

neuronal activity –> Ca influx –> activation of CamK II which phosphorylates MeCP2 –> MeCP2 dissociates and transcription activates

264
Q

what are structural changes associated with MeCP2 deficiency

A

decreased brain volume
simpler dendrites

265
Q

what functional changes are associated with MeCP2 deficiency

A

reduction in glutamatergic synapses
reduced LTP
reduction in NT and their functions

266
Q

what are some synaptic changes in rhett syndrome

A

decrease in number and size of dendritic spines
decreased LTP
decreased GABAergic transmission

267
Q

if the MeCP2 mutation is reversed in rhett syndrome, can the symptoms be reversed

A

yes

268
Q

what are the changes in glia in rhett syndrome

A

impaired activity of microglia
thinner myelin
decreased microtubule stability
decreased expression of EAAT2

269
Q

what are treatment options for rhett syndrome

A

replacement of bone marrow cells with cells containing normal MeCP2
restoring BDNF in brain
symptomatic treatment

270
Q

what are some characteristics of autism spectrum disorder (ASD)

A

difficulties in social communication
restricted/repetitive behaviors and interests
hyper/hyposensitivity
language difficulties

271
Q

what is different about the connectivity in ASD

A

hyperconnectivity between neurons of the same region
hypoconnectivity between various areas of the brain

272
Q

what are many of the autism genes involved in

A

synapse development and maintenance

273
Q

what are the changes in synaptic genes that are seen in ASD

A

mutations in neurexins and neuroligins
mutations in SHANK protein making post synaptic scaffold
ubiquitin ligase mutations

274
Q

what are NT changes in ASD

A

glutamate and serotonin are increased
GABA is decreased

275
Q
A

Clinical Neuroscience (4 decks)

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