Lecture 19 – NS V -- Synapses Flashcards
LO1: how are messages transmitted form one neuron to another?
electrical synapse and chemical synapse
LO1: how are messages transmitted form one neuron to another?
electrical synapse (explain, advantages, disadvantages):
adjacent cells joined by gap junctions
ions diffuse directly from 1 cell to next
advantage: much faster
disadvantage: can’t integrate info
LO1: how are messages transmitted form one neuron to another?
chemical synapse (explain, advantages, disadvantages):
gap b/n 2 neurons
info passes chemically in form of neurotransmitters
advantage:
NTs can be both excitatory and inhibitory
quantity can vary –> allows integration of info
LO2: what kind of molecules are neurotransmitters?
“classical” neurotransmitters are ___
small molecules
LO2: what kind of molecules are neurotransmitters?
___ neurotransmitters are small molecules
“classical”
LO2: what kind of molecules are neurotransmitters?
list out different types of “classical” NTs:
amino acids
monoamines
acetylcholine
ATP and its derivatives (adenosine)
LO2: what kind of molecules are neurotransmitters?
“classical” NTs:
(amino acids, monoamines, acetylcholine, ATP & derivatives)
peptides
some “unconventional” NTs (modulators)
LO2: what kind of molecules are neurotransmitters?
examples of amino acid NTs:
glutamate – excitatory
GABA – inhibitory
glycine – inhibitory
LO2: what kind of molecules are neurotransmitters?
examples of monoamine NTs:
catecholamines:
(dopamine
norepinephrine
epinephrine)
serotonin
histamine
LO2: what kind of molecules are neurotransmitters?
what are peptides?
short protein chains of 2-40 amino acids
LO2: what kind of molecules are neurotransmitters?
examples of peptide NTs:
B-endorphin
substance P
LO2: what kind of molecules are neurotransmitters?
examples of “unconventional” NTs (modulators):
gases like nitric (NO) and carbon monoxide (CO)
LO3: which steps are involved in the synthesis and release of “classical” NTs?
1) enzymes that synthesize the NTs are made in rough ER
2) enzymes sent to Golgi apparatus
3) enzymes are modified in Golgi apparatus
4) enzymes are transported along axon to nerve terminal by anterograde axonal transport
5) precursor needed for synthesis of NTs is taken up into the presynaptic nerve terminal mb –> NT is synthesized in presynaptic nerve terminal
6) NT is taken out of cytoplasm and into small vesicles by Vesicular MonoAmine Transporter (VMAT)
7) NT is released by exocytosis when appropriate stimulus comes
LO4: Describe the steps (including enzymes) in the biosynthesis of catecholamines. Which are the 2 major enzymes responsible for their catabolism.
what are all catecholamines derived from?
tyrosine
LO4: Describe the steps (including enzymes) in the biosynthesis of catecholamines. Which are the 2 major enzymes responsible for their catabolism.
what is the rate-limiting step in the biosynthesis of catecholamines?
tyrosine hydroxylase
LO4: Describe the steps (including enzymes) in the biosynthesis of catecholamines. Which are the 2 major enzymes responsible for their catabolism.
describe the steps:
tyrosine –> DOPA –> dopamine –> norepinephrine –> adrenaline
LO4: Describe the steps (including enzymes) in the biosynthesis of catecholamines. Which are the 2 major enzymes responsible for their catabolism.
what are the 2 major enzymes responsible for catecholamine catabolism in the brain:
catechol-O-methyltransferase (COMT)
monoamine oxidase A (MAOa)
LO4: Describe the steps (including enzymes) in the biosynthesis of catecholamines. Which are the 2 major enzymes responsible for their catabolism.
how is epinephrine (adrenaline) synthesized?
epinephrine is synthesized from norepinephrine w/in the adrenal medulla, which are small glands associated w/ the kidneys
LO5: how does norepinephrine (NE) work in the synapse?
1) tyrosine is transported into the noradrenergic nerve terminal
2) dopamine (DA) is transported from cytoplasm into vesicle by vesicular mono amine transporter (VMAT)
3) DA is converted to NE in vesicle
4) AP causes influx of Ca2+ ions –> causes vesicles to fuse to mb surface and expel NE
involves SNAPS and VAMPS
5) NE released into nerve terminal can act on G protein-couple receptors (adrenoceptors)
6) NE can diffuse out of cleft or go back into nerve terminal by NE transporter (NET)
LO6: what type of receptors do NTs bind to?
2 types of receptors:
ionotropic receptors
metabotropic receptors
LO6: what type of receptors do NTs bind to?
ionotropic receptors are…
ligand-gated ion channel receptors
LO6: what type of receptors do NTs bind to?
metabotropic receptors are…
G-protein coupled receptors
require intermediate molecules called G-proteins to activate second messenger molecules
LO7: how does synaptic transmission finish?
3 ways:
diffusion and absorption
degradation
reuptake
LO8: what does the monoamine hypothesis of depression suggest?
depression was associated with a deficiency of ___, such as ___ and ___
monoamines
serotonin
noradrenaline
LO9: how does serotonin work in the synapse?
1) synthesis – serotonin is synthesized
2) storage – VMAT2 transports serotonin into storage vesicles
3) release – vesicles release serotonin into synaptic cleft
4) activation – serotonin binds to receptor and initiates a signal to cell body of postsynaptic neuron
5) clearing – receptor clears
6) some leftover serotonin is taken up by SERT (serotonin transporter) back into the presynaptic membrane
7) metabolism – monoamine oxidase (MAO) breaks down serotonin
L10: which NT is associated w/ Parkinson’s disease (PD) and how?
neurons of substantia nigra and basal ganglia produce nigrostriatal dopamine pathway –> voluntary motor coordination
when neurons of substantia nigra degenerate –> less dopamine –> leads to Parkinson’s
LO11: what does the dopamine theory of schizophrenia state?
positive symptoms
examples: hallucinations, delusions
receptor: D2
activity: hyper-
brain region: nucleus accumbens in limbic system
LO11: what does the dopamine theory of schizophrenia state?
negative cognitive symptoms
examples: lack of motivation, cognitive impairment
receptor: D1
activity: hypo-
brain region: prefrontal cortex
LO12: describe the 4 dopaminergic pathways in the brain and indicate their associated disorders:
1)
D1 –> Schizophrenia –> mesocortical –> prefrontal cortex
cognition and executive function (planning)
emotions and affect
decrease D1 == negative cognitive symptoms (e.g. apathy)
LO12: describe the 4 dopaminergic pathways in the brain and indicate their associated disorders:
2)
D1 –> Schizophrenia –> nucleus accumbens in limbic system
motivation and reward
increase D2 == positive symptoms in schizophrenia (e.g. hallucinations)
LO12: describe the 4 dopaminergic pathways in the brain and indicate their associated disorders:
3)
nigrostriatal –> dopamine in substantia nigra and basal ganglia –> Parkinson’s
motor movement
disorders: hypokinetic (e.g. Parkinson’s symptoms) and hyperkinetic movement disorders
LO12: describe the 4 dopaminergic pathways in the brain and indicate their associated disorders:
4)
tuberoinfundibular –> dopamine in arcuate nucleus –> tuberal region of hypothalamus
inhibition prolactin release
decrease dopamine == hyperprolactinemia
affects motor movement
LO13: which inhibitory NT is associated w/ epilepsy?
GABA
gamma-aminobutyric acid –> inhibitory –> amino acid NT –> ionotropic NT
GABA (inhibition) needs to offset glutamate (excitatory)
LO14: describe how GABA exerts its inhibitory effects thru the GABAa receptor:
GABA binds to ion channel subunits –> causes conformational changes that open chloride ion channels –> lead to neuronal membrane hyperpolarization
LO15: what does the cholinergic hypothesis of Alzheimer’s postulate?
ACh acts on target neurons in the hippocampus and the cerebral cortex, strengthening the neural circuits that are involved in memory formation
ACh disorder == loss of limbic and neocortical cholinergic innervation
LO16: define synaptic plasticity:
neuroplsticity (define)
the ability of the brain to change, or rewire, throughout a person’s life
LO16: define synaptic plasticity:
synaptic plasticity (define)
process of neuroplasticity occurring at the single-cell level (individual synapse)
basis of learning and brain repair after injuries
LO17: differentiate the types of neuroplastic changes (temporary vs. long-lasting)
temporary (short-term memory)
sec to hrs
neurons can temporarily enhance their connections by:
chemical/synaptic changes
- release more NT
- activate a new receptor
- modify an existing receptor
LO17: differentiate the types of neuroplastic changes (temporary vs. long-lasting)
long-lasting (long-term memory)
lifetime
requires strong or sustained actives
structural and functional changes
- structural changes in dendrite and synapses
- changes in cortical area
- functional changes
LO18: what are the 2 forms of long-term memory?
what are the 2 places important for long-term memory and what do they do?
hippocampus – forms memories
cerebral cortex – stores memories
LO18: what are the 2 forms of long-term memory?
2 forms of long-term memory
explicit/declarative – conscious recollection of facts
implicit – procedural or unconscious (ex. riding a bike)
LO18: what are the 2 forms of long-term memory?
what are the 2 forms of explicit/declarative long-term memory?
semantic – facts and general knowledge (ex. capital of Spain)
episodic – personally experienced events (ex. what you did on 10th birthday)
LO19: differentiate long-term potentiation and depression:
depression – weakening of synaptic connection – lose memory
potentiation – strengthening of synaptic connection – improve memory
LO19: differentiate long-term potentiation and depression:
how is long term potentiation caused?
high frequency (strong experience)
repeated stimulation (studying, revising)
LO19: differentiate long-term potentiation and depression:
how is the strength of a synapse measured?
measured by the excitability or responsiveness of the post-synaptic neuron in response to a stimulus
L20: what is the role of glutamate in memory and Alzheimer’s disease?
glutamate is main excitatory NT in CNS
main glutamate receptors are AMPA and NMDA receptors –> ligand-gated ion channels
–> major role in synaptic plasticity
L20: what is the role of glutamate in memory and Alzheimer’s disease?
what happens when Ca2+ passes thru postsynaptic NMDA channels?
can have 2 different forms of synaptic plasticity – LTP or LTD
too much Ca2+ results in excitotoxicity
LO20: what is the role of glutamate in memory and Alzheimer’s disease?
what is a result of too much NMDA activity?
too much Ca2+ flows thru NMDA channels –> causes excitotoxicity and promotes cell death –> leads to neurodegeneration and Alzheimer’s
LO21: how do AMPA and NMDA receptors induce LTP?
4 steps:
1) glutamate release activates AMPA
2) AP allows Ca2+ to flow thru NMDA
3) more AMPA receptors gets inserted in plasma mb
4) postsynaptic cell is now more sensitive to glutamate – has more AMPA receptors, dendritic spines grow, more membrane is depolarized more efficiently
LO22: what is the proposed mechanism of LTD at the glutamatergic synapse?
1) low firing rate of presynaptic neuron
2) few glutamate molecules
3) calcium that flows thru NMDA does different cellular cascade (phosphatase)
4) endocytosis of AMPA receptors
5) postsynaptic neurons are now less responsive to glutamate bc there are less receptors available
