Tanner 1st third Flashcards
four CNS types
astrocytes
ependymal
microglial
oligodendrocytes
PNS types
satellite cells
schwann cells
ependymal cells
line ventricles produce CSF form blood-CSF barrier neural stem cells precursors of neurons and astrocytes
myelin
lipid rich wrapping of glial membrane around axons to provide insulation and conduction
PNS: schwann cells
CNS: oligodendrocytes
PNS myelin
one schwann cell one axon
axons are sheathed by many schwanns
CNS myelin
one oligodendrocyte, multiple axons
axons may be sheathed by many oligodendrocytes
microglia
smallest star shaped few processes mesoderm derived (not ecto) scavenger function/ macrophages dormant
microglia respond to injury by
mitosis retract processes product signal molecules migrate to injury destroy dying cells
astrocytes
many processes
end feet
ectoderm derived (neural origin)
CNS
astrocyte function
3D framework for CNS; guide neuronal migration along radial glia
repair damaged neural tissue
maintain BBB with end feet
metabolic support for neurons (break glucose down give lactate)
control ionic environment; aquaporins
uptake of NT
astrocyte synaptic functions
uptake GABA and Glu
express glutamate receptors, calcium entry alters shape
promote synapse formation w synaptogenic factors (tear down synapse, stabilize synapse)
envelop and isolate individual synapses
BBB
keeps out: pathogens, immune cells
allows to pass: O2,CO2,lipids passively; glucose, AA, hormones actively
compromise is bad
how do astrocytes bridge synaptic activity to blood flow??
neuronal activity locally incrases cerebral blood flow via vasodilation and increasing delivery of O2 and nutrients to neurons
glutamate reuptake by mGluR on astrocyte: signal for vasodilation
growth cone filopodia
test environment and attracted to some chemicals and repelled by others
signals transduced in cytoplasm of GC into motility and directional changes
depends on cyto calcium levels
axon guidance
elongation mediated by actin in filopodia and myosin
neurite MT backbone elongates w polymerization of tubulin and membrane is added to both sides via exocytosis
slit
dec cell motility
Ca - depoly - endocytosis - retraction
ROBO
netrin
inc motility
Ca - poly - exocytosis - elongation
intracellular Ca2+ regulates
Rho-GTPase effectors
protein pohsphatases (calcineurin)
protein kinases **poly, survival, not death, mitosis
types of cues
long range: soluble, secreted
short range: membrane bound, contact mediated
all act with gradient dependence
adhesion molecule interactions
CAM-CAM homophilic
Integrin-laminin heterophilic
axon crossing in spinal cord
first express netrin receptors and attract netrin in center
cross over; on robo receptor and repelled from midline
synapse formation
formation of selective contacts
differentiation of growth cone
elaboration of postsynaptic apparatus
synapse formation
axon guidance: cadherin and neuroligin
cell cell adhesion: homophilic with N-cadherins
synapse formation:heterophilic neurexin and neuroligin
cadherins
link to catenins; catenins link cyto domain of cadherins to actin cytoskeleton
NRX
neurexin interacts w presynaptic scaffold proteins
neuroligin NLG
post synaptic density scaffold proteins
what forms points for contact enabling recruitment of cytoplasmic scaffold proteins>
binding of neurexin to neuroligin
NMJ
large synapse
larger than average euk soma
nAChr
patch clamping
suck hole draw it up
activators
acetylcholine carbachol nictoine varenicline glycopyrronium bromide muscarine
inhibitors
hexamethonium
tubocurarine
succinylcholine
nAChr structure
2 binding sites, 5 subunits
bind on alpha
electroplax
noncontracting muscle cells innervated by motor neuron
resting potential dominated by K+
nAChr on one side only
Ek = 90; ENa=60
5k rows in a series each with of 150mV
nAChR desensitization
with time, closed desensitized slowly
Reversal potential
point at which current charge switches
Reversal potential stuff
PNa + PK = 1
PNa(60) + PK(-90) = 0
PNa = 0.6
quantal hypothesis
NT is released from nerve terminals in discrete packets called quanta
EPP
end plate potential postsynaptically
muscle EPSP
result of nAChR binding to NT; EPP followed by muscle AP
EPP drives AP
mEPP
spontaneous, 1 vesicle
evidence for QH
(m)EPP amp decreases with inc. distance from NMJ; mEPPs originate at NMJ synapse
mEPPs disappear upon motor axon removal; mEPPs arise from motor axon; EPPs from stimulation
(m) EPPs disappear upon application of ACh inhibitor; ACh NT action causes minis
(m) EPPs are mimicked by spritzing several thousand ACh to NMJ; mEPPs represent spontaneous release of discrete packets of ACh (quanta)
Stimulated EPPs have an mEPP shape and timecourse; synaptic potentials arise from simultaneous release of many quanta of NT
Q
quantal size = amplitude of post synaptic response of ONE QUANTUM of NT ==== MINI
M
quantal content/number
average number of presynaptic quanta released by one presynaptic AP
vesicle hypothesis
axon terminals are filled w spherical vesicles
omega figures are evident in nerve terminal ms after electrical stimulation
vesicle depletion apparent after heavy stimulation
biochemical analysis has shown that vesicles are filled with NT
vesicles contain transporters that can be specific for the type of NT released from associated neuron
vesicle hypothesis equation
c = dielectic constant*area / distance between surfaces
c = capacitance
C increases with AP because vesicle fusion increases SA
vesicle fluoresence
fill vesicles w fluorescent NT - flash seen when vesicle fuses with membrane
dense core vesicles
electron dense; peptide NT; more stimulation, further from active site
stimulation (AP) only causes EPP in presence of
calcium to release NT
one vesicle represents
1 quantum
small clear core vesicles
small NT
active zone
lower stimulation
why does TTX increase K0 and cause vesicular release
changing Ek for more positive
leak channels dominate
depolarization
ca2+ in
release
excitation secretion
AP down axon
depolarization opens VGCCs
Ca2+ in
Ca2+ vinds synaptotagmin
detection of Ca triggers fusion and NT release
postsynaptic current =
k[Ca2+]i^4
SNARE Hypothesis
SNARE proteins on vesicle surface interact w snares on plasma membrane internal face
vsnare
on vesicle
SNAP
soluble NSF attachment protein
NSF
n-ethykmaleimide sensitive factor
Snare hypothesis experiment
N-ethylmaleimide binds in column
to purify NSF:
load sample, add NSF and it binds; wash
use of purified NSF
sequence and use it to learn about SNAP
use of purified SNAP
learn about it and learn snares
Snare hypothesis stages of exocytosis
trafficking: movement of vesicles
tethering: restraint of vesicles
docking: binding of vesicles to membrane
priming: tight molecular interactions via SNARES
fusion: merging of membranes, release and inversion; ca2+ is signal REQUIRES ATP
docking
SNAP25 and syntaxin on presynaptic plasma membrane
interacts with synaptobrevin on outside of vesicle membrane
priming
SNARE complexes form to pull membranes together
ATP dependent
Ca2+ sensing
entering Ca2+ binds to synaptotagmin
sensor: force trans to cis
rapid; 0.2ms – pore formation and vesicle fusion
steps that are ATP dependent
priming
disengagement of SNARE complex
after fusion
SNAPs bind NSF
bind SNARES and disengage
endocytosis
translocation of fused membrane
clustering of vesicle proteins
clathrin coating - forms on intracellular side; guided by receptors
fission - invagination; pinching off from dynamin
recycling and refilling; decoating; merging of vesicle with endosome; retethering/filling
buffers
control calcium and vesicular release
what matters with calcium concentratioN?
distance and time
facilitation
a temporary increase in synaptic strength
