Neuro Brainstem Modulation Of Arousal, Cognition, Emotion Ssom Forster

Front 1

Monoamines
Catecholamines
(name)

Back 1

Dopamine
Norepinephrine
(Epinephrine)

Front 2

Monoamines
Indolamines
(name)

Back 2

serotonin

Front 3

Monoamines
(name)

Back 3

Catecholamines:
-Dopamine, NE, E
Indolamines:
-Serotonin

Front 4

Catecholamines synthesized from _

Back 4

tyrosine

Front 5

Rate-limiting enzyme in catecholamine synthesis

Back 5

tyrosine hydroxylase (TH)

Front 6

Synthesis of Catecholamines
Entire pathway and enzymes

Back 6

Tyrosine to DOPA: tyrosine hydroxylase
DOPA to Dopamine: AADC (dopa decarboxylase)
Dopamine to NE: Dopamine beta-hydroxylase (DBH)
((NE to E: PNMT))

Front 7

Dopamine broken down by?

Back 7

MAO-B

Front 8

NE broken down by?

Back 8

MAO-A

Front 9

Dopamine reuptake into presyn neurons by?

Back 9

dopamine transporter (DAT)

Front 10

NE reuptaken into presyn neurons by?

Back 10

NE transporter (NET)

Front 11

Serotonin
Synthesis pathway

Back 11

Tryptophan to 5-hydroxytryptophan: TPH
5-hydroxytryptophan to 5-HT: AADC

Front 12

Serotonin broken down by?

Back 12

MAO-A

Front 13

Rate-limit enzyme in 5-HT synthesis?

Back 13

Tryptophan hydroxylase (TPH)

Front 14

Serotonin
reuptaken by?

Back 14

serotonin transporter
aka SERT or 5-HTT

Front 15

Dopamine neuronal cell bodies
(location)

Back 15

substantia nigra (SN)
ventral tegmental tract (VTT)
both located in lower midbrain/ upper pons

Front 16

Dopamine systems arising from brainstem
(name)

Back 16

Nigrostriatal system
Mesocortical system
Mesoaccumbal system
Mesolimbic system

Front 17

Nigrostriatal system

Back 17

SN to striatum (motor)

Front 18

Mesocortical system

Back 18

VTA to cortex (planning, attention, working memory)

Front 19

Mesoaccumbal system

Back 19

VTA to nucleus accumbens (NAc) - reward and reinforcement

Front 20

Mesolimbic system

Back 20

VTA to limbic system

Front 21

Reward

Back 21

positive emotion that could be interpreted as pleasure (hedonia)

Front 22

Reinforcement

Back 22

the increased probability that behaviors paired or associated with reward will be repeated

Front 23

Drug Addiction

Back 23

compulsive drug use despite negative consequences (ex. loss of income, family support, health)
characterized by dependence, tolerance, and sensitization

Front 24

Tolerance

Back 24

diminished effect of the drug after repeated administration
tolerance to the rewarding and therapeutic effects of drugs of abuse normally develops

Front 25

Sensitization

Back 25

enhanced effect of the drug after repeated administration
sensitization to the motivational and reinforcement effects of drugs of abuse normally develops

Front 26

Withdrawal symptoms

Back 26

physical (autonomic symptoms and seizures) and psychological (anxiety, craving, depression, irritability, poor attention, insomnia, anhedonia) that occur in the absence of the drug

Front 27

Dopamine and Addiction
Drugs with addictive properties and natural rewards all increase Dopamine release in the _ by
_ or
_

Back 27

nucleus accumbens
increasing firing rates of dopamine neurons in the VTA (eg. nicotine activates excitatory nicotinic receptors on dopamine neurons)
acting on dopamine synapses in the nucleus accumbens to block reuptake of dopamine (eg. cocaine blocks DAT, causing an accumulation of dopamine in synapses)

Front 28

Addictive drugs cause large activation of _ system, but the system then undergoes short term depression due to:
_ _ _

Back 28

mesoaccumbal dopamine system
depletion of dopamine
short-term molecular events that desensitize dopamine receptors
short-term molecular events that reduce VTA neuron firing

Front 29

Opponent-process model of addiction
(repeated activation of what system, adaptive changes in _ _, reduced _, _ to rewarding effects, enhanced motivation to _)

Back 29

repeated drug taking results in repeated activation of mesoaccumbal dopamine system
results in adaptive changes in VTA dopamine neurons and dopamine receptors in accumbens to restore homeostasis
reduced sensitivity of mesoaccumbal system to compensate for excessive activation
tolerance to rewarding effects of drug
enhanced motivation to administer drug (sensitization)

Front 30

In the absence of the drug, mesoaccumbal dopamine neurons are at point lower than homeostasis due to reduction in activity of the system which results in _ _ _

Back 30

ahedonia
low motivation
craving

Front 31

Major cause of drug relapse that facilitates cycle of addiction

Back 31

negative withdrawal symptoms

Front 32

Psychosis
can be caused by drugs of _
definition

Back 32

drugs of abuse
a **state** in which an individual appears to have lost touch with reality, and shows little ability to understand the external world

Front 33

Psychotic symptoms

Back 33

Hallucinations
Delusions
Illusions
Formal thought disorder

Front 34

Hallucinations

Back 34

perceptions not connected to reality, such as hearing voices (mostly olfactory)

Front 35

Delusions

Back 35

fixed, false beliefs that are not based on reality
such as believing one's teeth are radio transmitters

Front 36

Illusions

Back 36

severely distorted perceptions,
such as the perception that fixed objects are pulsing

Front 37

Formal thought disorder

Back 37

disruption of the logical flow of ideas

Front 38

Psychosis is _ rather than _

Back 38

is a mental state
not a disorder

Front 39

Psychosis associated with range of conditions with altered state of consciousness such as:
_ _ _ _

Back 39

delirium
drug effects
Alzheimer's disease
Schizophrenia

Front 40

Symptoms of Schizophrenia
Positive symptoms refer to

Back 40

new mental phenomena
such as hallucinations and delusions (psychosis)

Front 41

Symptoms of Schizophrenia
Negative symptoms refer to

Back 41

loss of motivation
flat affect
social withdrawal

Front 42

Symptoms of Schizophrenia
Other symptoms

Back 42

cognitive disruption
poor attention
socially inappropriate behaviors
disorganized speech
catatonia (motoric immobility)
peculiar voluntary mvment - such as prominent gestures, stereotyped mvments, prominent grimacing
paranoia

Front 43

Schizophrenia
Risk factors

Back 43

combined genetic and enviro
enviro risks:
malnutrition or viral infection in utero
stress during dev't
drug use

Front 44

Neuroanatomical correlates of Schizophrenia

Back 44

reduced brain volume, enlarged ventricles
reduced gray matter volume, particularly temporal lobes
decreased blood flow in prefrontal cortex
reduced neural activity in frontal cortex during working memory tasks

Front 45

Dopamine traditionally implicated in Schizophrenia b/c

Back 45

drugs that increase dopamine (amphetamines) can cause schizo-like symptoms
schizo patients show greater sensitivity to drugs of abuse (ex. greater amphetamine-induced dopamine release in NAc
typical antipsychotics (haloperidol) block dopamine D2 receptors
alterations to dopamine metabolites have been observed in CSF of schizo patients
alterations to dopamine receptor levels and distribution have been noted in post mortem studies of schizo patients

Front 46

Dopamine hypothesis:
dysfunction of _ neurons is thought to partially underlie schizophrenia
_ of mesoaccumbal system
_ of mesocortical system

Back 46

dysfunction of VTA dopamine neurons
hyperfunction of mesoaccumbal system (greater sensitivity to drugs of abuse, psychosis)
hypofunction of mesocortical system (symptoms of perseveration, working memory deficits)

Front 47

Schizophrenia
more recently, alterations to other neurotransmitter systems have been indicated
atypical antipsychotics (clozapine) act to block _ receptors

Back 47

serotonin

Front 48

Serotonin neuronal cell bodies
(location)

Back 48

midline raphe nuclei:
dorsal and median raphe nuclei
(provide serotonin to limbic system and cortex)

Front 49

NE neuronal cell bodies
(location)

Back 49

locus ceruleus (LC)
of the rostral to mid-pons provides NE to limbic system and cortex

Front 50

Autoreceptors
(aka)

Back 50

presynaptic receptors

Front 51

Autoreceptors for NE
(locations, receptor type)

Back 51

neuronal cell bodies/dendrites
presynaptic terminals
both alpha2

Front 52

Autoreceptors for Serotonin
(location, receptor type)

Back 52

neuronal cell bodies/dendrites = 5HT-1A
presynaptic terminals - 5HT-1D

Front 53

Autoreceptors are _ receptors

Back 53

inhibitory
designed to reduce neuronal activity when excessive NT release occurs

Front 54

Autoreceptor activation can result in:
_ _

Back 54

reduction of neuronal activity (open K+ channels)
activation of a cascade of events that inhibits activity of rate-limit enzyme involved in synthesis of NT (eg. TH or TPH)

Front 55

Projections from _ and _ to _ _ _ are involved in mediating arousal and emotion

Back 55

raphe and LC to
limbic system, hypothalamus, cortex

Front 56

Dysfunction of _ and _ plays a role in affective disorder b/c of their role in coordinating emotional responses

Back 56

raphe and LC

Front 57

Phenelzine
(antidepressant class, actions to increase monoamines, monoamine affected)

Back 57

MAOIs
Inhibition of MAO-A
NE and 5-HT

Front 58

Amitriptyline
(antidepressant class, actions to increase monoamines, monoamine affected)

Back 58

tricyclic
inhib SERT and NET
NE and 5-HT

Front 59

Desipramine
(antidepressant class, actions to increase monoamines, monoamine affected)

Back 59

tricyclic
inhib NET
NE

Front 60

Fluoxetine
(antidepressant class, actions to increase monoamines, monoamine affected)

Back 60

SSRIs
Inhib SERT
5-HT

Front 61

Why do antidepressants take weeks to become clinically effective?

Back 61

Autoreceptor Desensitization Hypothesis

Front 62

Why not just target 5-HT1A receptors directly for antidepressant and anxiolytic effects?

Back 62

have been trialed
not as effective as SSRIs probably b/c rapid half-life
combo or extended slow release in current studies

Front 63

ACh
synthesized from _ by enzyme _ and metabolized by _

Back 63

from choline by
choline acetyltransferase (ChAT)
metab by AChE

Front 64

ACh is not re-uptaken into presyn terminals. What happens?

Back 64

choline re-uptaken (formed by AChE breakdown of ACh)

Front 65

ACh
(two receptors, and type)

Back 65

nicotinic receptors (excit ionotropic, Na+ ion channel)
muscarinic receptors (metabo, can be excit or inhib)

Front 66

ACh neuronal cell bodies
(location)

Back 66

Pedunculopontine tegmental nucleus (PPT) and
laterodorsal tegmental nucleus (LDT) in the upper pons

Front 67

PPT and LDT
major ascending targets

Back 67

thalamus
medial septum
superior colliculus
substantia nigra/ventral tegmental area

Front 68

Cholinergic neurons highly active during _ sleep

Back 68

REM
are REM-on cells

Front 69

cholinergic neurons of PPT/LDT are responsible for onset of REM sleep, and also produce physical char of REM sleep:
mechanism

Back 69

descend chol projections from PPT/LDT excite neurons of medullary reticular formation which then inhib spinal cord motor neurons to produce muscle atonia, while sparing the diaphragm
projections to CN nuclei involved in eye mvmnt to produce rapid eye mvmnt

Front 70

Chronic REM Sleep Behavior Disorder (RBD)

Back 70

REM sleep w/o muscle atonia
0.5 % population
leads to motoric expression of dreams (acting out dreams)
associated with injury and nocturnal violence and falls
often associated with neurodegen diseases like:
-Parkinson's disease
-Dementia with Lewy Bodies
-Multiple System Atrophy
loss of cholinergic neuron thought to underlie
Tx:
Clonazepam (benzodiazepine) to decrease REM sleep
Donepezil (AChE inhib) to increase ACh induced muscle atonia

Front 71

In addition to being highly active during REM sleep, cholinergic neurons of PPT/LDT highly active during _

Back 71

arousal

Front 72

Arousal and Attention:
Ascending cholinergic neurons projections thought to: _ and _
Called

Back 72

promote allocation of sensory-motor resources during states of arousal
underlie attention and appropriate cognitive functioning
Termed the ascending reticular activating system (ARAS)

Front 73

Arousal and Attention:
PPT/LDT projections to the superior colliculus activate neurons involved in _

Back 73

visual orienting

Front 74

Arousal and Attention:
PPT/LDT projections to the thalamus activate neurons involved in _

Back 74

cortical arousal

Front 75

Arousal and Attention:
PPT/LDT projections to the LGN of the thalamus activate neurons involved in _

Back 75

visual salience

Front 76

Arousal and Attention:
PPT/LDT projections to the VTA/SN activate neurons involved in _

Back 76

reward salience

Front 77

Arousal and Attention:
PPT/LDT projections to the cholinergic basal forebrain (medial septum) activate neurons involved in _

Back 77

learning/ memory processes

Front 78

Anesthetics appear to have effects on _

Back 78

PPT/LDT

Front 79

Patients suffering from _ show the most severe loss of chol neurons in PPT/LDT and exhibit greater _

Back 79

Dementia with Lewy Bodies
exhibit greater attention deficits compared to other neurodegen diseases

Front 80

MRI studies of patients with brainstem lesions as result of stroke:
non-recovery coma patients = ?

Back 80

large or bilat lesions of upper pons

Front 81

MRI studies of patients with brainstem lesions as result of stroke:
patients with transient coma = ?

Back 81

small unilat lesions of upper pons

Front 82

MRI studies of patients with brainstem lesions as result of stroke:
patients w/o coma

Back 82

lesions outside the upper pons (lower pons, midbrain, medulla)

Front 83

MRI studies of patients with brainstem lesions as result of stroke:
Note that _ or _ also produce coma

Back 83

Note that extensive bilat lesions of cerebral cortex or bilateral lesions of thalamus also produce coma

Front 84

L-Dopa
(can cross _, converted to _ by _, must give _ with it because)

Back 84

can cross BBB
by-passes TH step to be converted to
dopamine by AADC
carbidopa (AADC inhib) given with it to prevent conversion peripherally (carbidopa can't cross BBB)
Sinemet has L-Dopa + carbidopa

Front 85

Increased Dopamine in NAc = ? = ?

Back 85

hedonia = reinforcement (increase prob of repeating behavior)

Front 86

working memory in _ cortex believed to depend on _

Back 86

prefrontal cortex
dopamine innervation

Front 87

Autoreceptor Desensitization Hypothesis

Back 87

1) increasing synaptic levels of NE and serotonin cause greater autoreceptor inhibition of LC and raphe neurons via autorec activation (could have worse symptoms in first week)
2) compensatory mech occur over time to allow for chronic elevations in NE and serotonin = decrease in autorec sensitivity
3) decrease in autorec activity = clinical efficacy

Front 88

REM associated _ is activated by cholinergic input from the PPT/LDT to the thalamus

Back 88

cortical asynchrony

Front 89

Brainstem cholinergic control of REM sleep
(3 projections)

Back 89

cranial nerve motor nuclei: eye mvmnt
Thalamus: cortical asynchrony (EEG)
activate Medullary Reticular Formation which inhib SC: muscle atonia