Neurotransmission
Structure of a neuron
Dendrites - recieves info from other neurons
Soma - cell body, processing, integrates information
Axon - carries information
Terminal boutons - communication point with other neurons, location of synaps
Neuronal membrane
the neuron's 'skin'
lipid bilayer (5nM thick)
membrane is hydrophilic on the outside layer, and hydrophobic on inside
throughout membrane, there are protien structures: receptors - detect substances outside the cell
ion channels - some gated, either electric or chemical
Cytoskeletal structures also
Resting Membrane potential (RMP)
electrical charge across the membrane
difference between total charge outside and inside
65-70 mv difference between inside and out
because the inside has more negative charge, it is -65-70mv (relative to outside)
Positive Ions move across membrane due to concentration gradient
as charge changes (become more negative as positive ions leave) this attracts positive ions from the outside
eventually equilibrium potential is found
Force of Electrostatic pressure
particles of same charge (++ or --) repel
particles of opposite charge attract (+- or -+)
Cations - positive
Anions - negative
Force of diffusion
high concentration to low concentration (concentration gradient)
More sodium (Na+) outside neuron
More Potassium (K+) inside neuron
More Chloride (Cl-) outside neuron
ATP Sodium/Potassium pumps
3 sodium out
2 potassium in
At rest more K+ channels are open than Na+ channels
(leak or resting channels)
More potassium leaks out than sodium can come in
Sodium potassium pump
breaks down ATP, releases energy
forces ions to move against concentration gradient
Moves sodium back out and potassium back in
Action Potential
nerve impulse
communication within the neuron along the axon
generated at the axon hillock
generated by summation of converging inputs from dendrites
(or experimentally through electrical stimulation)
Hyperpolarisation
membrane potential more -ve than RMP
Inject negative current
Cations move out (e.g. K+) - less positive/more negatives
Anions move in (e.g. Cl-)
Depolarisation
membrane potential more +ve than RMP
Inject positive current
Cations move in (e.g. Na+)
As membrane depolarises it moves
from -65 to -70 mv it becomes less negative
moves towards zero
then above into +ve charge (more positive inside cell than outisde)
Conductance
rate of ion travel through channels
potassium is slow, sodium is fast
a small positive stiumulation doesn't travel far along neuron
a small depolarisation
this is called decremental conductance
If the stimulation is large and causes more than -50 mV potential (threshold) Action potential is fired
all or nothing response
Voltage gated channels
open when cell becomes depolarised (positive)
Once high depolarisation happens, Na+ channels become inactive
voltage clamp
inject a current into membrane to create steady MP
Sodium (Na+) channels
at -70mV these are closed
as depoloarisation happens, Na+ channels open
at a high point of depolarisation, they inactivate
This is refractory period
resting, activation gate closed (inactication gate open)
depolarisation, activation gate opens (inactication gate open)
at large depolarisation but inactivation gate closes (activation gate stays open)
Potsssium (K+) channels
at -70mV these are closed
at high level of depolarisation K+ channels open
much higher level needed than Na+ to open
Stay open even during refractory of Na+
Process:
RMP most channels are closed
small depolarisation Na+ channels open
Na+ cmes in leading to further depolarisation
depolarisation continues (past -50mV) more Na+ channels open
more Na+ comes in
again leading to further depolarisation
Some K+ channels open allowing K+ to go out.
at very depolarised point, NA+ channels become inactive (refractory)
K+ channels still open.
K+ leave due to diffusion + electrostatic (inside neuron is now positive)
repolarisation and then hyperpolarisation
K+ channels close
difficult to make a new AP during this period
Finally sodium/potassium ATP pumps engage to restore equilibrium
Myelination
Myelin sheath - fatty tube placed around axon
Schwann cell in PNS (whole Schwann cell)
Oligodendrocite in CNS
Gaps between myelinated portions of axon
called Nodes of Ranvier
Un-myelinated axons still transmit AP
in myelinated axons, APs only happen at nodes of Ranvier
#
inside myelinated areas, depolarisation decays
built up again at next node of ranvier
Returning to RMP requires energy (ATP + pumps) and time
myelination means that less energy is required
In multiple sclerosis (MS) myelin sheaths become damaged
loss of sensitivity, muscle weakness, balance & coordination problems
Tetrodotoxin (puffer fish)
blocks voltage gated Na+ channels
Paralysis
(AP doesn't start)
alpha-dendrotoxin (green mamba snake)
Blocks voltage gated K+ channels
convulsions
(AP doesn't stop)
The Synapse
Electrical synapse very rare in adult mammals
Chemical synapse common in mammals
Mostly axodentritic - axon to dendrite
Pre-synaptic neuron - terminal boutons
post-synaptic neuron - dendritic spine
Some axosomatic - axon to soma direct (GABA neurons)
some axoaxonic - axon to other axon
Location of synapse
the closer the synapse is to the soma, the more infulence
(decremental decay) #
the soma takes all dendrite signals and sums them
enough excitation produces AP
Overview
- AP travels down the axon
- at synapse, depolarisation opens Ca2+ chanels
- influx of Ca2+ triggers neurotransmitter release
- neurotransmitters bind to and activate receptors at post-synaptic dendrite
- depolarisation or hyperpolarisation at post-synaptic dendrite
- spreads to post-synaptic soma - summation
- enough excitation generates AP at axon hillock
Neurotransmitters
- chemically synthesised presynaptically
- electrical stiumlation leads to release
- chemical produces physiological effect
- Terminate activity (it has to stop)
Dales's law says that if neurotrasmitter found at one synapse, it will at all synapses for that neuron
Note dendrites can recieve many neurotransmitters
Stored in vesicles
Neurotransmitter release
- vesicles dock at synaptic membrane
- depolarisation in presynaptic neuron opens Ca2+ channels
- vesicles fuse with membrane and release neurotransmitter into synapse
- vesicles detatch from docking zone
post-synaptic cell
Neurotransmitter binds to receptors on post-synaptic cell
Ionotropic receptors open ion channels
metabotropic receptors 2nd messenger
Ionotropic receptors
very fast
ion movement effects changes in cell rapidly
Excitatory fast transmission
Ion channel allows cations in (Na+)
(e.g. glutamate receptors)
Depolarisation
Excitatory Post Synaptic Potential (EPSP)
Inhibitory fast transmission
Ion channel allows anions in (Cl-)
(e.g. GABAa receptors)
Hyperpolarisation
Inhibitory post synaptic potential (IPSP)
Metabotropic receptors
G-protien coupled receptor
slow but bigger effect
- neurotransmitter binds & activates G-protien
(exchange GDP for GTP) - G-protien splitsand activates enzymes
- breakdown of GTP turns off G-protein activity
- chemical reactions amplify signal - 2nd messenger
Neurotransmitter deactivation
reuptake
(vacuum cleaner)
deactivating enzymes
neurotransmitter broken down
Classes of Neurotransmitter
Classic: Amino acids, monoamines & acetylcholine
synthesised in presynaptic terminal
stored in synaptic vesicles
released in response to local to Ca2+ increase
Neruopeptides
synthesised in soma & transported to terminal
stored in secretory granules
released in response to local to Ca2+ increase
Soluable gasses
Acetylcholine
Monoamines
Neuropeptide
Amino acids
Glutamate
Aspartate
Glycine
GABA
Catecholamines
Dopamine
Epinephrine (adrenaline)
norepinephrine (noradrenaline)
Indolamines
Serotonin
Nitric Oxide
carbon monoxide
Acetylcholine
Endorphines
Glutamate
Major fast excitatory in CNS
very widespread
both ionic and metabotropic
activates:
mGluR
NMDA
AMPA
Kainate
Mostly acts on AMPA (ionotropic)
- presynaptic release
- postsynaptic AMPA receptor activation
- influx of Na+
- Depolarisation (EPSP) #
learning & memory
Integration
EPSPs are summed
spacially - e.g. 3 butons on one dendrite
temporally - e.g. rapid AP
GABA
major fast inhibitory
does not pass brain-blood barrier
ionotropic activation
opens chloride channel Cl-
hyperpolarisation (IPSP) #
drugs/hormones which enhance
ethanol
neurosteroids
benzodiazepine
barbiturates
autoreceptors
located on presynaptic terminal (bouton)
respond to neurotransmitter in cleft
generally G-protein coupled (metabotropic)
do not cause ion channel opening
do not cause depolarisation
negative feedback mechanism
not the same as reuptake sites