Nervous System: composed of neurons and glia

- Sensory input, Integration and motor output

o Sensory receptors detect stimuli  integration (nervous system processes
input, decides what to do about it)  motor output (response from nervous
system activating certain parts of body)
- Organisation of central and peripheral systems
o Central NS: brain + spinal cord (main control centre, gives orders to motors)
o Peripheral NS (PNS): All the nerves branching off from brain and spine that
allows CNS to communicate with rest of the body
 Sensory division (afferent): picks up sensory stimuli
 Motor division (efferent): sends directions from brain to muscles and
glands
 Somatic NS (voluntary): rules skeletal muscle movement
 Autonomic NS (involuntary): keeps heart beating, lungs
breathing and stomach churning
o Sympathetic division: mobilises body into action
o Parasympathetic division: relaxes body
- Glial cells: provide support (covering axons to increase transmission speed of action
potentials), nutrition (transferring nutrients from blood to neurons), insulation, and
help with signal transmission (regulation of neuron-neuron communication) and the
removal of pathogens (and their cell bodies) from the brain in the nervous system.
Outnumber neurons by roughly 10:1.
o In CNS:
 Astrocytes: Anchor neurons to blood supply; exchange of materials
between neurons and capillaries (most abundant and versatile glial
cells)
 Microglial cells: Immune defence against invading microorganisms in
brain and spinal cord
 Ependymal cells: Create, secrete and circulate cerebrospinal fluid
 Oligodendrocytes: produce an insulating barrier (myelin sheath)
o In PNS:
 Satellite cells: surround and support neuron cell bodies (do what
astrocytes do in CNS)
 Schwann cells: produce insulating barrier (myelin sheath) – like
oligodendrocytes in CNS
- Role, anatomy and function of neuron types
o Background:
 Neurons are some of the longest-lived cells in the body
 Neurons are irreplaceable; mostly amitotic (so once they take on
highly specialised roles in NS, lose ability to divide)
 Neurons have a very high metabolic rate – need abundant supply of
oxygen and glucose.
 Our brain contains many billions of neurons
- Structure and Function of Neurons
 o Soma (Cell body) – has all the basic cell stuff (nucleus, mitochondria,
ribosomes etc)
o Dendrites – branch-like projections out of soma: receive input from other
neurons and convey to cell body
o Axons: transmit output in the form of electrical impulses / action potential
away from cell body to other neurons (*longest in body is 1m)
o How to differentiate nerve cells: How many processes (projecting part of
organic structure) extend out from cell body
 Most are multipolar neurons with at least 3 processes sticking out
from soma (dendrites, axon)
 Bipolar neurons have 2 (axon, dendrite) – rare in sensory receptors
like retina of eye
 Unipolar neurons (mostly in sensory receptors) have 1
o Function: Which way an impulse travels through a neuron in relation to brain
and spine
 Sensory (afferent) neurons: transmit impulses from sensory receptors
toward CNS; mostly unipolar
 Motor (efferent) neurons: impulse moves from CNS to rest of body;
mostly multipolar
 Interneurons (association neurons): live in CNS; impulse moves
between sensory and motor neurons; mostly multipolar
- Neuron-Neuron Communication: Neurons communicate with each other using
synapses (chemical signals are sent from presynaptic cell to postsynaptic cell)

o Synaptic transmission: one-way communication from axon of presynaptic

neuron (releases neurotransmitters) to dendrite of postsynaptic neuron (detects
neurotransmitter)
 o Dendritic spines: small protrusions that occur in the middle of synaptic
complex

Action Potential

- Our body as a whole is electrically neutral, but some parts are more
positively/negatively charged than others; membranes keep these charges separate
(build potential) till ready to use the force they create.
- Voltage (V) : difference in electrical potential energy (generated by separate charges)
between two points per unit electric charge; in body measured in millivolts
o In a cell: difference in charge is the membrane potential
 Hence the greater the difference in charges, the higher the voltage
and the greater the potential
- Current (I): flow of electric charge from one point to another
o I=V/R
o Currents indicate flow of positively/negatively charged ions across the
resistance of cells’ membranes; membranes separate the charges – hence are
what provide the potential to convert electricity into something useful
- Resistance: Measure of difficulty to pass current through a material
- Conductance (G): inverse of resistance (G = 1/R)
- Membrane of a neuron: made of phospholipid bilayer (with water trapped inside and
outside); protein molecules also imbedded in this phospholipid bilayer to connect
exterior to interior of cell
- Equilibrium / Nernst potential: membrane potential at which net flow of ions is zero
(equilibrium), given a specific intra- and extra-cellular concentration of an ion.
It is the membrane potential that leads to zero ionic current (equilibrium) given
certain ionic concentrations.
o [K+] higher inside cell, charges both in and outside balanced. K+ ion channel
opens, K+ ions flow out of the cell down the concentration gradient. Now
inside is more negatively charged.
 o Since inside is now more negatively charged, K+ ions would be drawn back in
through electrical force.
o Equilibrium potential for a specific ion: where opposing forces (concentration
gradient and electrical force) equal to each other, net flow of ions is zero, ie.
For every K+ ion that exits the cell, a K+ ion enters the cell.
o Equilibrium potential of a specific ion changes depending on concentrations
of the ion.
o Nernst potentials of different ions are different because both concentration
and charge differences determine the different reversal potentials for
different ions.
- Resting neuron: intracellular more negative than extracellular space around it
o Resting membrane potential (difference in charges): ~ -70mV
 Outside cell has lots of positively charged Na+ ions
 Inside cell has lots of positively charged K+ ions mingled with
negatively charged protein
 But Na+ outside > K+ inside, hence cells’ interior has overall negative
charge; negative membrane potential: polarised
 At rest, only K+ channels are open – K+ enters cell (electrical
gradient), membrane potential is close to reversal (Nernst) potential
of K+ (~ -70mV); Na+ channels are closed (Na+ would enter if channel
were open)
 Resting membrane potential: when membrane is not undergoing
action potential. It is primarily dominated by K+ conductance, hence it
is close to the K+ Nernst potential (not exactly equal as there are
other small conductance eg. from Na+ and Ca2+ that move potential
towards more positive values)
 Hence resting membrane potential depends on the reversal
potential of ions and their conductances
o Sodium-potassium pump: embedded in the neuron’s membrane; lots of them
along the axon  for every 2 K+ ions pumped into cell, pumps out 3 Na+ ions
 concentration of ions and difference in charges make exterior more
positively charged
 Electrochemical gradient (difference in overall charge due to
concentration and charges)
o Membrane also has ion channels (proteins): can let ions pass through when
gates are open – this movement of ions is key to all electrical events in
neurons
 Voltage-gated channels: ion channel that opens in response to an
increase of membrane potential (depolarisation) as long as this
increase crosses a certain threshold. Open and close in response to
changes in membrane potential (at certain levels) eg. Na gated
channels open ~ -55mV
 To send long signals along an axon, need a big enough change
in voltage to trigger voltage-gated channels to open (action
potential)
  Depolarise resting neuron  causes big enough change in
membrane potential  triggers voltage-gated channels to
open
 Many more Na channels than K channels hence when they
open, membrane potential gets closer to reversal potential of
Na (+60 mV – but voltage does not reach this as K+ channels
still open to drive voltage down; K reversal potential close to -
80 mV)
 Ligand-gated channels: open when a neurotransmitter latches onto its
receptor (eg. serotonin, hormone)
 Mechanically-gated channels: open in response to physically
stretching membrane

1. Neuron in resting state; all ion channels closed; membrane potential: -70mV
a. At rest, K+ has higher conductance than Na+ hence membrane potential is
closer to Nernst potential of K+
2. Sensory stimulus  Na channels open, increasing charge in membrane
3. Stimulus and resulting change have to be strong enough and cross threshold of
-55mV for action potential to kick in, otherwise neuron returns to resting state
4. Action potential: above threshold, voltage-gated Na channels open, a lot of Na+ ions
enter neurons  massively depolarise such that it even becomes positive (~ +40mV)
a. Action potential: temporary reversal of membrane potential; brief
depolarisation caused by change in currents
5. Electrical signal sent down axon
6. Repolarisation: voltage-gated K channels open, K+ ions leave through channel to
balance charges
7. Hyperpolarisation: Process goes too far at first (membrane potential drops below
-70mV), before all gates close and Na-K pump takes over, bring back to resting state

- Refractory period: part of the axon is involved in this process, ion channels are open
 cannot respond to any other stimulus; there to prevent signals from travelling in
both directions down axon at once.
- A weak stimulus tends to trigger less frequent action potentials (less demanding
tasks  lower frequency; more demanding tasks  high frequency – telling muscles
to contract harder/faster…
- Action potentials vary by speed (conduction velocity)
o Most affected by whether there’s myelin sheath on axon.
 Saltatory conduction: Axons coated in insulated myelin conduct
impulses faster – instead of triggering one channel at a time in a chain
reaction, can leap from one myelin (nodes of Ranvier) to the next

Nernst = Reversal = Equilibrium potential

2 forces that define movement of ions across membranes:
- Chemical / concentration gradient
- Electrical gradient (charges)

Equal concentrations intra- and extra-cellular  Nernst potential is 0

Qn: If only one specific ion (charged particle) could freely cross a membrane, what would be
the voltage of this membrane?

Na diffuses from left to right down a concentration (chemical) gradient, but diffuses from
right to left due to electrical gradient. Nernst potential: both forces equal so remains in
equilibrium
*[Cl-] does not affect concentration gradient of Na+; only think about specific ions at a time.

Nerve impulse / action impulse travels down axon from soma to external terminal
 o From 1 to 2: neuron starts depolarising slowly due to synaptic input (gradual
increase in potential)
o 2: Neuron depolarises fast due to opening of voltage-gated Na+ channels
o 3: Neuron repolarises fast due to opening of voltage gated K+ channels and
the (inactivation) closure of voltage-gated Na+ channels

With regards to movement of ions:

- Ions move in a specific direction if a force is applied to them
- If forces are applied in opposite directions, then the ion will move in the direction
dictated by the strongest force
- Hence if the electrical and chemical gradients exert forces in opposite directions, the
strongest force will dictate the actual movement of the ions.

To determine whether Nernst potential of an ion is positive or negative

- It’s in reference to the inside of the cell
- Eg. For ion X+: if [X+] inside neuron > [X+] outside neuron, then chemical gradient
will cause X+ to diffuse out of neuron  positive charges flow out, inside neuron left
with unbalanced negative charge

Is it true that Glutamate is an excitatory neurotransmitter and GABA is an inhibitory

neurotransmitter?
 No. The specific effect of a neurotransmitter will depend on the specific ion channels
opened by the neurotransmitter and the specific ionic balance of the neuron.
 Glutamate can excite (commonly) or inhibit (rarely) neurons.
 GABA can excite (rarely) or inhibit (commonly) neurons.
 But they’re referred to as excitatory and inhibitory neurotransmitters respectively due to
their most common effects.
- Glutamate and GABA act as the primary excitatory and inhibitory neurotransmitters
in the CNS respectively.