1
Q
steps of memory storage in brain
A
- release of neurotransmitter
- activation of postsynaptic receptors
- trafficking of receptors to PSD
- local translation of new proteins
- altered gene expression
2
Q
sodium potassium pump pumps
A
3 Na out and 2 K in
3
Q
calcium homeostasis
A
pumping Ca out of cell, and intracellular calcium-binding proteins and organelles: mitochondria and endoplasmic reticulum
4
Q
influx of +ve ions
A
depolarised, excites the neurons EPSP
5
Q
influx of -ve ions
A
hyperpolarized, inhibits the neurons IPSP
6
Q
membrane potential changes during an action potential
A
- stimulus moves membrane potential to threshold
- opens voltage-gated Na channel, Na flows in
- Na channels close and voltage-gated K channels open
- K flows out until K equilibrium potential reached
- Na/K pumps return membrane to resting potential
7
Q
spatial summation
A
multiple input neurons (EPSP) generate simultaneously at many different synapses on a dendrite
8
Q
temporal summation
A
one input neuron strongly activated
9
Q
chemical synapse
A
transmission via the release of a neurotransmitter
10
Q
electrical synapse
A
transmission via electrical currents flowing from one neuron to the next at gap junctions
11
Q
presynaptic events
A
- action potential reaches axon terminal and depolarises membrane
- voltage-gated Ca channels open and Ca flows in
- Ca influx triggers synaptic vesicles to release neurotransmitters
- neurotransmitter binds to receptors on target cell
12
Q
visualising communication between neurons
A
through micro-periscope, in vivo. view calcium activity in subfield CA1 in excitatory neurons
13
Q
small synaptic vesicles
A
50nm diameter, clear, membrane bound, most abundant within CNS, contain glutamate, GABA and glycine
14
Q
small synaptic vesicles at readily releasable pool
A
docked at the active zone
15
Q
small synaptic vesicles at reserve pool
A
distal to active zone, associated with cytoskeleton
16
Q
small synaptic vesicles at recycling pool
A
diffusing
17
Q
vesicle cycle
A
formed in golgi apparatus —– transport along microtubules to axons —> filled with neurotransmitter at never terminal —> release transmitter then ercycle via endocytosis to endosomes or reserve pool and refilled with transporters
18
Q
large dense core vesicles structure
A
100nm diameter, electron dense/dark, membrane bound, contain catecholamine neuropeptides, neurotrophines, nor/adrenaline
19
Q
large dense core vesicles function
A
local diffusion to active synaptic partners, act on g-protein-couple receptors, may contribute to presynaptic modulation in addition to postsynaptic effects, comprise of 1-2% of vesicles
20
Q
synthesis pathway
A
- synthesis and modification of neuropeptides (RER and golgi apparatus)
- packaging pro-peptide and modifying enzymes
- axonal transport
- cleavage of pro-peptide (will dock on membrane to release contents)
- release
21
Q
why prolonged stimulation of LDCV
A
not pre-docked, requires more widespread increase in Ca including activation of CaMKII via calcium - induced calcium release from ER.
22
Q
primary locations of LDCV
A
neurosecretory and neuroendocrine cells as well as sympathetic neurons of PNS, neurohypophysis, hypothalamus
23
Q
neurosecretory cells (location of LDCV)
A
neurons that secrete their products into pituitary portal vessels at the median eminence
24
Q
neuroendocrine cells (location of LDCV)
A
cells which receive neuronal input and release hormones into the blood stream - chromaffin cells
25
chromaffin cells
neurendocrine cells: medulla of adrenal glands, enriched with LDCVs
26
chromaffin cells role
contain and release many substances into circulatory system: catecholamines, peptides, proteins, microRNa, neuromodulations, stress transducers
27
what are the snares involved with
exocytosis
28
v-snare
synaptopbrevin (from synaptic vesicle)
29
t-snare from cytosol
SNAP25
30
t-snare from embedded in plasma membrane
syntaxin
31
binding of snares
synaptobrevin binds to alpha primed end of SNAP25 while syntaxin binds to alpha helix terminal at end of SNAP25
32
what drives the dissociation of the SNARE complex
ATPase N-ethylmaleimide-sensitive fusion (NSF)
33
Rab proteins
small GTP binding proteins
34
rab protein function
involved in vesicle guiding and docking at membrane. GTP is hydrolysed which results in fusion of vesicle and release of neurotransmitter
35
what results in the fusion of vesicles and release of neurotransmitter
GTP hydrolysis
36
exocytosis
synaptic vesicle protein, calcium sensor, docking, vesicle fusion+release, ca influx
37
clathrin-mediated endocytosis
the process by which vesicular membrane is retrieved back into the cytoplasm
38
clathrin
assists in the formation of a coated pit on the inner surface of the plasma membrane of the cell which buds into cell to form a coated vesicle
39
clathrin structure
subunits comprise 3 large and 3 small polypeptide chains that form a triskelion and assemble into basket-like frameworks.
40
dynamin
a GTPase, binding to form a bud on membrane. forms a helical collar around the neck of the bud
41
what do dynamin spirals undergo
a length-wise extension which pinches or pops the vesicle from the parent membrane
42
synaptic vesicle cycle exocytosis
Rabs, v-SNARE, t-SNARE, synaptotagmin
43
synaptic vesicle cycle endocytosis
clathrin, dynamin
44
botulinum toxin
blocks release of acetylcholine at the NMJ resulting in muscle paralysis lasting 3 months
45
one of the most poisonous biological substances
botulinum toxin (produced by clostridium botulinum)
46
heavy chain toxin binds to what
binds selectively and irreversibly to presynaptic receptors on cholinergic neurons
47
behaviour of heavy chain - preventing muscle contraction
binded with cholinergic neurons, it is endocytosed during which the light chain is cleaved and released from heavy chain to bind to SNAP25. this prevents exocytosis.fusion of vesicles so no acetylcholine is release and muscles cannot contract
48
tetanus toxin
cleaves synaptic vesicles associated proteins synaptabrevin in cytosol. meaning glycine or gaba cannot be secreted nor acetylcholine so no muscle contraction will be halted resulting in spastic paralysis
49
what does botulinum toxin cause
muscle paralysis
50
what does tetanus toxin cause
spastic paralysis
51
tetanus toxin pathway
binds to presynaptic membrane of NMJ, then transports back to CNS by axon to bind to inhibitory neurons by endocytosis, then leaves vesicle and goes into cytosol to cleave
52
alpha latrotoxin
derived from widow spiders - causes release of small synaptic vesicles, via forming a calcium channel - causes spasms?
53
synapsin
a phosphoprotein controlling synaptic vesicle mobility and post-docking steps of exocytosis
- maintain the SSV reserve pool and contribute to synaptic plasticity
54
most abundant isoform of synapsin
SYN1
55
ca activation of CaMKii / protein kinase results in what
phosphorylation of synapsin
56
what does the phosphorylation of synapsin result in
reduction of synapsin binding to the actin cytoskeleton. this makes vesicles now available for exocytosis
57
what happens in the absence of synapsin
binding disperses the distal cluster of SV's, while docked SV's remain intact. synaptic depression is hastened following peptide injection
58
cellular changes from excitatory synapses
synapsin deletion reduces size of reserve pool of synaptic vesicles. this impairs the glutamate release and delayed recovery from synaptic transmission with relatively normal basal transmission
59
cellular changes from inhibitory synapses
knockout of synapsins inhibitory neurons result in a loss of synaptic vesicles from both the readily releasable and the reserve pool (excitatory is just reserve pool only)
60
knockout phenotype
deletion of SYN gene produces epileptic phenotype
61
synapsin in terms of autism
those autistic have many mutations in genes which encode synaptic proteins
62
knockout mouse results of synapsin 2 deletion mouse
displayed deficits in short-term social recognition and increased repetitive self-grooming behaviour
63
knockout mouse results of synapsin 1 and 3 deletion
displayed an impaired social transmission of food preference
64
knockout mouse results of synapsin 1 and 2 deletion
displayed a decreased environmental interest
65
four classes of neurotransmitters
1. amino acids (glutamate excit, GABA inhib)
2. amines and purines (actyl, nor/adren, serotonin)
3. neuropeptides (opioids, substance P, neuropeptide Y)
4. gases (NO, CO)
66
where amines and purines found
small synaptic vesicles
67
where neuropeptides found
large dense core vesicles
68
dopamine
a catecholamine - involved in regulation of movement, attention, mood, cognition, addiction, reward
69
parkinsons prevalence
age of onset 55 to 65 years
1 in 100 people >60 years of age
70
arvid carlsson
discovered that circuits that control movements dont work properly when dopamine levels are decreased
71
parkinsons is a loss of what
dopamine and substantia nigra
72
tyrosine to epinephrine process
tyrosine -> L-Dopa -> dopamine -> norepinephrine -> epinephrine
73
synaptosomes
are a synaptic terminal isolated from a neuron, involved in reuptake
74
bromocriptine
an agonist approved to treat parkinson's disease, hyperprolactinemia and related conditions
75
haloperidol
an antagonist that is used in treating schizophrenia, bipolar disorder and stimulant-induced psychosis
76
L-Dopa treatment for Parkinson's disease
L-dopa treatment does not stop neurodegeneration but might enhance the activity of the neurons remaining
77
what side effects does prolonged L-DOPa treatment result in
L-DOPA-induced dyskinesia and psychosis
78
NO - what its not
not stored in lipid vesicles, not released by exocytosis, not bind to receptors, not metabolized by hydrolytic enzymes
79
NO
a gas derived from arginine, synthesized on demand, an important retrograde messenger involved in the long-term potentiation model for memory
80
fast acting receptors
ligand-gated ion channels (glutamate receptors)
milliseconds
excitatory or inhibitory, depending on ion involved and its direction of movement
81
slow acting receptors
1. g-protein coupled receptors
2. D1 - like receptors (D1 and D5)
3. D2 - like receptors (D2, D2, and D4)
82
g-protein coupled receptors
metabotropic receptors
7-transmembrane domains
directly regulates ion channels
generate second messengers
83
D1 like receptors
stimulation of adenylate cyclase, coupled to Gs, mediate excitatory neurotransmission
84
D1 like receptors
stimulation of adenylate cyclase, coupled to Gs, mediate excitatory neurotransmission
85
D2 like receptors
inhibition of adenylate cyclase, couple to Gi/Go, mediate inhibitory neurotransmission
86
dopamine sites of actions
substantia nigra to striatum circuit
ventral tegemental area to cortex
limbic system
dopamine can be in SSV and LDCV
87
ventral tegemental area dopamine system
projects to the nucleus accumbens
is a reward system which reinforces desirable behaviours - opiates and nicotine stimulate VTA neurons
88
what do opiates and nicotine stimulate
VTA neurons
89
cocaine and amphetamines do what
block reuptake which increases dopamine at synapses
90
what does prolonged activity of VTA result in
down-regulation, drug tolerance, and with any removal - withdrawal
91
ATP a neurotransmitter
acts on purinergic receptors it is co-stored and co-released with classical neurotransmitters, are both ion channel and G-protein coupled
92
brain derived neurotropic factor
high levels found in hippocampus, has a role in neuronal plasticity
93
proBDNF
BDNF is synthesized as the precursor proBDNF but proBDNF is not an inactive precursor, it is a signalling protein in its own right
94
proBDNF
BDNF is synthesized as the precursor proBDNF but proBDNF is not an inactive precursor, it is a signalling protein in its own right
95
BDNF action
undergoes Ca influx-dependent release from pre and post synaptic sites, act on ligand-gated ion channels, voltage-gated ion channels, second-messenger pathways
96
what activates CB1 receptors which are coupled to G-protein
endocannabinoids
97
how many transmembrane domains does each unit of an enzyme-linked receptor usually have?
one
98
GABA-A receptors
ionotropic
98
GABA-A receptors
ionotropic
99
GABA-B receptors
metabotropic
100
what is GABA
an amino acid, not found in proteins, is synthesized in GABA'ergic neurons by glutamatic acid decarboxylases
101
GABA-A distribution
widespread CNS, PNS, limbic system, eye, amygdala, nuerons, oligodendrocytes, NMJ
102
activation of GABA gated ion channels cause a
IPSP via opening chloride ion channels and resulting influx of Cl.
103
substances that enhance the natural effect of GABA
benzodiazepines and ethanol enahnce the natural effect of GABA
104
phasic inhibition
GABA is released from presynaptic terminals and binds to postsynaptic GABA-A R's
105
tonic inhibition
ambient extracellular GABA binds to extrasynaptic GABA-A r's and modulates resting membrane potentials and cell excitability
106
drugs that enhance GABA action are what
anxiolytic - they reduce anxiety or panic
107
GABA - B distribution
both pre and post synaptically
108
GABA-B receptor associated with
epilepsy, spasticity, schizophrenia, anxiety, depression, cognitive deficits, and addiction
109
acetylcholine receptor distribution
transmitter at NMJ, autonomic ganglia, postganglionic parasympathetic synapses
110
acetylcholine synthesization
AcH is synthesized by choline acetyltransferase and transported into vesicles. following synaptic release, AcH degraded by acetylcholinesterase
111
muscarinic AchR
metabotropic - sensitive to muscarine, G-protein couples, found in: glia, heart muscle, salivary glands
112
nicotinic AchR
ion channels - sensitive to nicotine, ligand-gated channel, mediate fast synaptic transmission, occur in high density at neuromuscular junction, sensitive to alpha-bungarotoxin
113
ligand-gated ion channels
results in depolarisation of muscle cell, opening of voltage-gated sodium channels; action potential and muscle contraction
114
in vitro
molecular and cellular events: cells in culture, acute brain slices, organotypic brain slices
115
in vivo
simple invertebrate models, vertebrate rodent models
115
in vivo
simple invertebrate models, vertebrate rodent models
115
in vivo
simple invertebrate models, vertebrate rodent models
115
in vivo
simple invertebrate models, vertebrate rodent models
115
in vivo
simple invertebrate models, vertebrate rodent models
115
in vivo
simple invertebrate models, vertebrate rodent models
116
nonassociative learning: behavioural responses
habituation and sensitization
117
aplysia california models learning and memory with example of what reflex
siphon-gill-withdrawal refex, undergoes either habituation or sensitization when a stimulus is applied
118
presynaptic facilitation (gill-withdrawal response)
stimuli activate interneuron L29. this enhances neurotransmitter release from the sensory neuron presynaptic terminal and alters gene expression
119
single tailed shock
L29 releases serotonin activates its receptors on presynaptic nerve terminals as well as stimulates formation of cAMP, which activates protein kinase A and the release of neurotransmitter
120
PKA increases what
phosphorylation of Ca and K+ channels
121
multiple tailed shock
same as single except PKA moves to nucleus, alters gene expression and new proteins stimulate synapse growth
122
drosophila melanogaster
small genome and nervous system, rapid life cycle, easy to identify circuits
123
aplysia california
small nervous system, large neurons, easy to identify individual neurons and circuits
124
AMPA receptors
ligand-gated, mediate fast depolarisation, na channel
125
NMDA receptor subtypes
ligand and ion-gated, slightly slower response, ca and na channel
126
long term potentiation summary
ca influx into dendritic spine activates protein kinases such as Ca calmodulin-dependent protein kinase II. it phosphorylates the AMPA receptor to increase conduction.
AMPA receptors get trafficked to the membrane, and long term changes are made to gene expression
127
long term depression summary
repetitive low frequency stimulation results in a low level Ca influx through NMDARs
low levels of Ca activate protein phosphatases, removing phosphates from AMPA receptor and other targets, results in long-term changes to gene expression
128
AMPAR subunit GluA1-GluA4
assemble as dimers-of-dimers to form hetero-tetrameric or homomeric receptors (GluA1)
129
GluaA2 permeability
impermeable when containing AMPAR, permeable without
130
what would create more long term significant change
homomeric receptors (AMPA)
131
what would create more short lasting changes
properties of phosphorylation
132
polyribosomes
found in spines, translocate from dendritic shafts to spines in response to activity
133
mRNA
found in dendrites, translated in response to activity
134
immediate early genes
are fast responding genes that are altered in response to activity. they are transcription factors and will also mediate target genes. these target genes will mediate significant changes
135
secondary response genes
receptors and many others, new and larger synapses, re-structured synapses
136
amyloid beta causing an initial hyperexcitability of neurons leads to what
excessive levels of glutamate in the extra-synaptic space, leading to overstimulation of NMDA receptors and subsequently synaptic loss and cell death
137
what does AB-induced endocytosis of the AMPA-type glutamate receptors lead to?
long-term depression
138
what does disruption to actin dynamics from AB cause
impairments in the trafficking of AMPA, NMDA
139
memantine
antagonist of the NMDA receptor subtype of glutamate receptor. it is used to slow neurotoxicity
140
what did researchers at Genetech find?
a small molecule that enhances GluN2A function to boost synaptic NMDAR signalling. found that abnormal low-frequency oscillations and epileptiform bursts were reduced and morris water maze performance impoved
141
sAPPalpha
enhances plasticity, protein synthesis, GluA1 synthesis
142
hypothalamus
a hypophysis that secretes many hormones and regulates the function of other hormone-secreting glands
143
lateral and medial zones of the hypothalamus
project to brain stem and telencephalon
144
periventricular zone of the hypothalamus
multiple functions including regulation of the pituitary
145
magnocellular
release neurohormones, oxytocin and antiduretic hormone into the capillary bed
146
oxytocin involved in
uterine contraction and milk ejection
147
antidiuretic hormone
regulates extracellular fluid volume and acts on kidney to increase water retention and constricts blood vessels
148
magnocellular neurons project to where
posterior lobe of pituitary
149
what neurons regulate the anterior lobe of the pituitary
parvocellular neurons
150
parvocellular neurons
secrete hypophysiotropic hormones into the hypothalamic pituitary portal circulation
151
follicle stimulating hormone (FSH)
stimulates estrogen secretion, egg production, sperm production
152
luteinizing hormones (LH)
triggers ovulation, progestin production (females), androgen production (males).
153
LH and FSH collectively known as
gonadotrophins
154
thyroid stimulating hormone (TSH)
triggers thyroid hormone release called thyroxine
155
adrenocorticotropic hormone (ACTH)
stimulates glucocorticoid release from the adrenal gland
156
growth hormone (GH)
stimulates growth via somatomedins released from liver
157
prolactin
stimulates mammary gland development and milk secretoin
158
gonadotropin-releasing hormone (GnRH)
is released by hypothalamus and travels to anterior pituitary where it causes the release of LH/FDH and travels to target tissues testes/ovaries to produce estrogen/androgen
159
absence of gonadotrophins in females
means ovaries are inactive (e.g. childhood)
160
estrogen distribution
distributed in CNS, concentrated in pituitary and hypothalamus and also in cortex, midbrain and cerebellum
161
estrogen
alters the intrinsic excitability of neurons via modulating the flow of potassium ions, depolarisation and more potentials. fast action
162
estrogen role
development and regulation of female reproductive system as well as physiological roles in males
163
estrogen receptors
intracellular
164
reverse transcription-polymerase chain reaction (4)
1. isolate (purify) RNA
2. convert RNA to DNA by process of reverse transcription
3. amplify target DNA (PCR)
4. analyse products
