Final Flashcards
Is acetylcholine (ACh) excitatory or inhibitory?
excitatory
What is the function of ACh in the PNS?
activates skeletal muscles via ionotropic
inhibits muscles via metabotropic
helps w/autonomic NS (release adrenaline etc)
WHat is the function of the ACh in the CNS?
invoved w/synapses in short term memory
What is AChE inhibitors?
enhance ACh levels, used in elderly patients w/memory issues
What enzyme synthesizes ACh?
choline acetyltransferase (CAT)
What does CAT use to make ACh?
choline and acetate (from acetyl CoA)
How is choline transported back to presynaptic?
Na+ depedent choline co-transporter (ChT)
What breaksdown ACh?
acetylcholinesterase (AChE)
What is Sarin? How does it work??
nerve gas
inhibits AChE, causes muscle spasms + neuromuscular paralysis
What is atropine?
works as antidote to nerve gas (Sarin, insecticides)
blocks ACh muscarinic receptors
What are the two types of ACh receptors?
nicotinic (ionotropic) and muscarinic (metabotropic)
What inhibits nicotinic ACh receptors?
curare
Where are nicotonic receptors found?
neuromuscular junctions of skeletal muscles
Where are muscarinic receptors found?
neuromuscular junctions of smooth and cardiac muslce, glands
Is nicotonic receptors selective?
no, non selective channels
Where does ACh bind on nicotonic receptors?
on both of the alpha subunits
need both
What does black widow venom do?
stimulates release of ACh, causes muslce spasms and cramps
What does alpha-bungarotoxin do?
irreversibly binds to nAChR
What is the structure of nicotine similar to?
ACh
What does nicotine cause changes in?
number of cholinergic receptos and sensitivity of these receptors
How does nicotine trigger reward?
stimulates release of dopamine, directly and indirectly
What is myasthenia gravis?
autoimmune disease that disrupts nerve muscle signal transmission
attacks acetylcholine receptors
Myasthenia gravis most often affects?
women under 40 and men over 60
What are the symptoms of myasthenia gravis?
weakness and rapid fatigue in muscles that control the eye/eyelid, facial expressions, chewing, talking, swallowing, breathing, neck/limb movement
What gland is abnormal 75% of the time in myasthenia gravis patients?
thymus gland
What damage is seen in cells of person w/myathenia gravis?
lymphocyte aggregates, widening of synaptic cleft
What can cause myasthenia gravis?
some drugs, some viruses/infections
How can you diagnose myasthenia gravis?
blood tests, edrophonium test, nerve conduction studies
What are the treatments for myasthenia gravis?
AChE inhibitors, immunosuppresants, plasmaphersis, thymectomy
What is the main inhibitory neurotransmitter in brain?
GABA
Are GABAergic synapses or glutamergic synapses formed first?
gaba-ergic
Early in development GABA is?
main excitatory NT
In immature neurons the intracellular concentration of chloride is?
relatively high
The activation of GABA receptors in mature neurons generates?
an influx of chloride
in immature its oppossite
NKCC1 is?
Na/K/Cl co transporter
in immature neurons
KCC2 is?
K/Cl co-transpoer
in mature neurons
What is GABA synthesized from?
from glutamate
What syntehsizes GABA?
glutamic acid decarboxylase (GAD)
What is GAD’s cofactor?
pyridoxal phosphate
form of B6 vitamnin
What types of GABA receptors are ionotropic?
GABAa and GABAc
What GABA receptor is metabotropic?
GABAb
GABA receptors are found where on neuron?
soma
Glutamate receptors are found where on neuron?
on denrdrites
Where do benzodiazepines bind?
outside the pore (GABA)
What do benzodiazepines do?
increase GABA binding, reduces anxiety
Where do barbituates bind?
inside the pore (GABA)
What are barbituates used for?
anaesthesia, treatment for epilepsy
What does alcohol do? (GABA)
increases the effects of the inhibitory GABA ligand
WHat is GHP?
date rape drug
naturally produced in CNS in small amounts, GABA derivitive, acts on GABAb
What is GHP used to treat?
insomnia, clinical depression, narcolepsy, alcoholism
How is glycine synthesized?
from serine by transhyrdroxy-methylase
What is major inhibitory neurotransmitter in CNS?
glycine
What is hyperglycinemia xaused by?
mutation in glycine reuptake transporter
What are symptoms of hyperrglycinemia?
lethargy, seizures, mental retardation
Can glutamate cross thee BBB?
no
How is glutamate syntehsized?
in neurons from glutamine, also could be from glucose
by glutaminase
What are the ionotropic gluatmate receptors?
AMPA, NMDA, kainate
What pushes Mg2+ out of NMDA receptors?
depolarization
NMDA receptors open when?
glutamate binds, and strong depolarization of postsynaptic membrane
Where are metabotropic glutamate receptors found?
hippocampus, cerebellum, cerebral cortex
What is serotonin synthesized from?
tryptophan
What is SERT?
serotonin reuptake transporter
Serotonin receptors are all?
metabotropic receptors
What does raphe nucleu regulate?
mood, sleep, emotions, body temp, appetite, mempry processing
What is the biosynthetic pathway of catecholamines?
tyrosine -> L-DOPA -> Dopamine -> Norepinephrine -> Epinephrine
What is tyrosine made from?
phenylalanine
What enyme makes l-dopa?
tyrosine hydroxylase
What produces norepinehprine?
locus coeruleus
What is the fight or flight hormone?
epinephrine
Where does epinephrine go in the brain?
medulla, hypothalamus, thalamus
All epinephrine and norepinerhine receptors are?
metabotropic
Both NE and E affect ______ nerves?
sympathetic
Whatt converts L-dopa to dopamine?
dopa decarboxylase
What does the substantia nigra project to?
striatum
What does the ventral tegmental area project to?
prefrontal cortex and the basal forebrain including the nucleus accumbens
What is the role of dopamine?
coordination of body movements, pleasure and motivation, reward, moods, emotions
What does MAO do?
breakdown dopamine
What does cocaine do in the body?
inhibits DAT, increases dopamine in synaptic cleft
What does amphetamine do in the body?
forces dopamine out of their storage vesicles, increase DA concentration
What does D1 do?
binds Gs protein, activates adenylyl cyclase, cAMP levels is increased
What does D2 do?
binds Gi protein, inhibits adenylyl cyclase, cAMP levels is decreased
What is included in basal ganglia?
caudate & putamen (striatum), globus pallidus, substantia nigra, subthalamic nucleus
What damage is first seen in parkinsons?
damage to dopaminergic neurons in substantia nigra pars compactaW
What damage is first seen in huntingtons?
degeneration of striatum, starts w/GABA and dopamine neurons
Tyrosine hydroxylasse levels are lower in?
parkinsons patients
What genetic defect is seen in huntingtons?
37+ CAG repeats in huntingtin gene
The number of repeats in huntingtin gene decides?
if they develop disease and how old they will be
more repeats, younger onset
Addiction is characterized by?
compulsive behaviour, reinforcing behaviour, loss of control
Drug addiction can be considered drug-induced ____ ______?
neural plasticity
Repeated exposure to drug alters?
gene expression in specific brain regions, behavioural abnormalities
What are the 3 major structures in the reward pathway?
VTA, nucleus accumbens, prefrontal cortex
What are the 4 general categories of drugs?
narcotics, stimulants, hallucinogens, sedative-hypnotics
What are some examples of narcotics?
opium, morphine, heroin, codeine
What do narcotics do?
euphoria, pain relief, depresses CNS
What are examples of stimulants?
cocaine, amphetamines
What do stimulants do?
DA reuptake inhibitors, heightened activity, excitability, manic behaviour, cardiovascular failrue
What are examples of hallucinogens?
LSD, shrooms
What do hallucinogens do?
usually serotonin agonists, hallucinations
What are examples of sedative-hypnotics?
alcohol, barbiturates, benzodiazepines
What do sedative-hypnotics do?
act on GABAa receptors, relaxation, impair motor control, impaired judgement, respiraotry depression
What are the functions of serotonin pathways?
mood, memory processing, sleep, cognition
Where does cocaine concentrate in the brain?
caudate, VTA, nucleus accumbens
The icnreased activation of dopamine receptors causes?
increase cAMP production, abnormal firing patterns, continuous activation of reward pathawy
How does prolonged use of cocaine change feelings about reward?
loss of pleasurable feelings of natural rewards (food, sex, etc)
What three neurons participate in opiate action?
dopamine terminal, gabaergic neuron, cell w/dopamine receptors
Inhibiting GABA neurons allows dopamine to?
fire mroe
How does fentanyl increase dopamine levels?
blocks GABA release in VTA, causes less inhibition in nucleus accumbens, therefore more DA
What is anandamide?
endogenous cannabinoid neurotransmitter in the brain
What is THC?
active component of marijuana
What does THC cause?
induces cell death w/shrinkage of neurons, dna fragmentation in the hippocampus
Where does marijuana concentrate in the brain?
VTA, nucleus accumbens, caudate nucleus, hippocampus, cerebellum
How can nicotine directly trigger reward?
through interaction with the nACh receptors on the VTA dopaminergic
neurons which project to the NAc
How does nicotine indirectly trigger reward?
by stimulating the nACh receptors on the glutamatergic nerve terminals
What does ΔFosB trigger?
a series of transcription events that produce an
addictive state
also it has a long half life
What does chronic exposure to cociane, amphetamines, morphine do?
upregulates the
cAMP pathway and CREB in the NAc
Chronic exposure to drugs of abuse has
been shown to decrease?
new neurons in adult hippocampus
WHat are the treatments for addiction?
withdrawal therpay, psychological therapy, long term pharmacological treatment
What are positive symptoms in schizophrenia?
behaviours not seen in normal people
hallucinations, delusions, movement disorders
What are negative symptoms in schizophrenia?
absence of normal behaviour
social withdrawal, flat affect, lack of pleasure, not speaking
What are the cognitive symptoms of schizophrenia?
poor executive function, trouble focusing, problems w/working memory
Who is more frequently and severly affected in schizophrenia?
males
What is the genetic inheritance like in schizophrenia?
non-mendelian, polygenic (~20 genes)
What are environmental risks for schizophrenia?
urban residence in upbringing, labour complications, retroviral activation, maternal infection during pregnancy
How is eye movement different in schizophrenics?
40-80% have abnormal smooth pursuit eye movements
What do PET and MRI show in schizophrenic patientss?
frontal lobe hypometabolism
increased vetnricle volume, decfreased volume of hippocampus, prefrontal cortex, and thalamus`
What is the two hit hypothesis?
1st: developmental defects in neuron formation and/or migration/synapse formation
2nd: stress during adolescence
What are silent synapses?
synapses w/no ampa receptors only nmda
WHat is the major difference between early and late LTP?
early LTP does not have new proteins being synthesized
Phosphates causes _______ to AMPA?
internalization of the postsynaptic ampa
LTD causes _______ sensitivity?
decreased sensititivtiy to glutamate from Schaffer collaterla terminas
NO is a ________?
retrograde messanger
released by postsynaptic
How is the neurotransmitter nitric oxide produced?
nitric oxide synthase
converts arginine and citrulline to NO
What is hebb’s hypothesis?
synpases are strengthened when pre/post synaptic terminals are stimulated at same time
WWhat is procedural memroy?
skills, habits, procedures, how to knowledge
What is asssociative learning?
classical conditioning
What is non-associative learning?
habituation and sensitization
What is episodic memory?
memroy of events
What is semantic memory?
memory of facts
Where is long term storage of non declarative memory?
cerebellum, basal ganglia, premotor cortex
Where is short term storage of declarative memory?
hippocampus and related structures
Where is long term storage of declarative memroy?
medial temporal lobe, wernickes area, + a variety of cortical areas
What is a MCI assessment?
mild cognitive impairment assessment
What is karyotyping?
evaluates the number and
structure of a person’s chromosomes in order to detect abnormalities
What is FISH?
Fluorescence in situ hybridization
detect and map specific genes or gene sequences
What can look at entire genome?
microarray analysis
How is the cerebral cortex different in autism?
medial prefrontal region is less active
How is the amygdala different in autism?
decreased volume/cell size, less active
How is the hippocampus different in autism?
decreased volume/cell size
How is the cerebellum different in autism
decreased size/number of purkinje cells
How is brain growth different in people w/autism?
early brain overgrowth at beginning of life, possible decline/degen later in life
What are possible reasons for brain overgrowth in autism?
disruption of early neurodevelopment, premature myelination, excess neurons, reduced pruning, excess glia
When is the critical period of development for autism?
embryonic stage
What are 5 factors related to autism risk?
maternal rubella infection, ethanol, thalidomide, valproic acid, misoprostol
Mifepristone and misoprostol work together to?
terminate prgnancy
Misoprostol is structurally similar to?
prostaglandin E2 (PGE2)
Schaffer collaterals are the axons of?
pyramidal cells in the hippocampus
Tetanus is referred to as?
high-frequency bursts of presynaptic action potential
CA1 and CA3 are two major regions of the?
hippocampus
Hyperphosphorylate tau protein forms tangles _______ neurons?
within
Where do beta-amyloid plaques first appear in brain?
neocortex
Do calcium ions flow through AMPA receptors?
no
People w/down sydrome who develop alzheimers develop it by what age?
40 ish
What 3 envrionmental factors correlate with alzherimers?
poor early education, serious head injury, aluminum in drinking water
First signs of alzheimers?
slight memory loss, change in personality
What is tau protein important for?
axon and
dendrite remodeling involved
in forming and storing memories
stablizies microtubules
Where do neurofibrillary tangles form?
in soma
What makes tau go bad?
when its hyperphosphorylated
What do normal beta amyloid precursor proteins do?
protect against glutamate toxciity
What is the bad form of beta amyloid?
AB42
42aa beta amyloid aggregattion causes?
disruption in calcium homeostasis, mitochondrial damage, inflammatory response, impaired energy metabolism, loss of neuronal function
Tau pathology first appears in the?
entorhinal cortex
Tau and B-amyloid 42 form __________?
indenpendently
What parts of the brain does alxheimers affect in order?
entorhinal cortex, limbic system, neocrotex
What is anti-acetylcholinesterase?
slows down progression of AD, conserves ACh as they get destroyed
What do iron and copper chelators do?
reduces iron/copper which contributes to peroxide formation caused by β-amyloid
42aa aggregation
What are some treatments for alzheimers?
anti-acetylcholinesterases, iron/copper chelators, target gamma and beta secretases, beta amyloid vaccine
