An overview of University of Southampton semester 1 year 2 neuroscience lectures. Covers molecular neuroscience, synaptic integration and plasticity, and motor systems.
+
signals are operated on micro millisecond timescale -
• The brain is a non vital-
organ
-
can be brain dead.
t survive
Investigating
DNA studies mutants , disease
promoter identifying
° -
,
mouse
in humans
forming mutations
ORNACDNAS PCR ,
t in-situ hybridisation gene profiling
,
leg microarrays
RNAseg.to
.
,
Proteins antibody (
.
staining western blotting or
immunity to chemistry
nun m wide
synaptic cleft
i. earlier aeons have shorter
length
constants IN
A membrane resistance th
Promoters
controlling nerve function
Glutamate -
natural amino acid .
excitatory Glutamate decarboxylase synthesises GABA
the
decarboxylation of glutamate produces GABA ( via glutamate decarbotylase)
GABA synthesised
-
, inhibitory What is the GAD gene?
GAD
gene is
recognised by transcription factors to ensure it's
selectively -codes for glutamate decarboxylase (involved in
expressed in GABA neurons GABA production)
variation in -recognised by transcription factors to ensure it is
morphology expressed in GABA
°
Aton is the presynaptic nerve terminal , Dendrite is
postsynaptic -
neurons
their basic
retain shape but are
highly dynamic
•
The
cytoskeleton is the important molecular component :
micro tubes 25mm diameter vllimeric structure consists of dB
-
-
-
dinners , tend ( where dimes added ) and -
end ( where
cytoskeleton contains microtubules, actin filaments
and intermediate filaments
dinners are removed) -
dynamic
-
actin filaments -7mm diameter consist of G- actin monomers which make
What are intermediate filaments?
,
an F- actin filament
-the intermediate component of neutrons
intermediate filaments Ionm diameter dimers of individual fibrous subunits
-dimers of neurofilaments
-
-
.
leg .
neuro filaments ) build tubular structures
-build tubular structures
o
Organisation the major cytoskeleton components -stabilise the axon
Post-synaptic terminal
Dendrite
/ cell
body
•
presynaptic
terminal
A + on
opt
actin
cytoskeleton often ,
associated in a cortical
to
/ f
network enriched in
terminal
regions microtubules orientated neurofilament stabilises
Unidirectional ly in the
[
axons
Atm compartment but
bidirectionally in the
dendrite mane tracks
-
for transport
, Transport mechanisms : kinesin
paradigm
0
Kinesin around
What’s kinesin and how does it work?
moves
things
-motor protein
0 Binds to or protein that needs to be transported
cargo -binds to microtubules/cargo/proteins
Binds to microtubules
-uses ATP to move proteins to where signalling
0
o uses ATP
activity happens
Walk the microtubule
0
along
0 Move protein to extremities of the processes where the major
Kinesin moves proteins to where signalling happens
signalling happens
Neuron excitation
Nat /Kt ATPase 2kt into
pumps 3 Nat
0
out + neurons
•
more sodium outside than inside + more potassium inside than outside
outside than inside minor positive cart
0
Major negative Ct is higher ,
is low outside
very
• Processes with Caton dendrite) close to each other
polarity + come
-
.
there's potential communicate -
use chemical + electrical communication
voltage gated channels
What is the threshold for activation and inactivation
0 Sodium consist of 1 protein sequence that contains 4 domains each
of Na+?
-
-
has a
voltage sensor and V4 of pore -activation- -50mV
threshold for activation is -50mV, inactivation 0mV
-inactivation- 0mV
-
v is ~
Potassium contains 4 domains has
What is the threshold for activation and inactivation
0 .
consist of 1 protein sequence that -
a
voltage sensor t V4 of the pore ,
come together in a tetramer
of K+?
to make a functional channel -activation- 0mV
-
threshold for activation is ~ 0mV inactivation
,
is ~ +50mV
-inactivation- +50mV
Bridging the synaptic gap How can the synaptic gap be bridged electrically?
Electrical there is direct electrical flow between 2 cells tonne ✗ 0ns with
-direct flow between 2 cells
-
-
pores to allow electrical signal through gap -connexons with pores allow electrical signals
chemical -
electrical
signal
→
chemical signal → electrical signal through the gap
0
Stimulated channels those that allow
neuron opens ion
including
"
Ca
connexons- direct electrical flow between 2 cells
to enter
"
ca is sensed recognised by protein lsynoiptotaymin ) binds
o
a
-
,
ca
"
+
changes its conformation Synaptotagmin binds to Ca2+
0
Conformational change allows SNARE proteins to promote fusion
SNARE proteins promote vesicle/
via a vesicle /plasmamembrane protein complex
plasma membrane fusion
0
Vesicle fuses with membrane -
NT →
synaptic cleft leeocytosed)
0 ion channels with
receptors bind Nts →
opens channel ,
allows
ion flow
0
Signal is terminated by diffusion
away / reuptake from cleft Gephyr in -
encodes neuronal assembly protein that
anchors GABA
Excitatory -
de polarise membrane ,
+ ve
signal
to
postsynaptic cytoskeleton
Inhibitory -
hyperpolarise membrane ,
we
signal
synapses Features of major excitatory synapses
Major excitatory -
located on dendrites ,
use glutamate as transmitter, -found in dendrites
Often asymmetric ,
vesicle 1pm glutamate transporters ,
-asymmetric with thick organiser proteins and
thick specilisah.vn organiser proteins cytoskeleton, 4 subunits in ion channel
+
cytoskeleton ,
i on channel has 4 subunits Nat / cant excite
Features of major inhibitory synapses
-
brain cord
µ µ spinal
minor located GABA /glycine 0th
inhibitory on cell
body + use
-found in cell body
-
,
symmetric , inhibitory AA vesicle transporter /glycine -symmetric with thin organisers proteins and
PM
transporter ,
thin specialisation organiser proteins cytoskeleton, 5 subunits in ion channel
+
cytoskeleton ,
ion channel has 5 subunits - Ct
inhibition
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