Bo

Neuron is basis cell type of the nervous

6
system.

&
O
It has 4 main parts:
Dendrites
⑧ D - Receive signals either from receptors

Zo
↳
--

or from other neurons

- These receptors can be for:

-
- Chemicals (e.g. smell)
- Force (e.g. touch, but also internal

-⑧ 1blood pressure) E
- Pain (can be chemical or⑳ force here)

D
- Heat

-h
Soma/Cell body
- Typical cell functions like energy
production and protein production;

D
- But also conducts and sums signals
from dendrites and therefore involved
in signal intergration
E
 D -EED
-

I
-
↳

dendwites
-

↓
always
receive

informato
-
Axon
electrical
Long distance/high speed transmission
Can
-
be myelinated or unmyelinated signe
Ze -h
Axon terminal/synapses
=>
↳
Transmission
-
to effector cell.
Effector cells can be another neuron, a muscle cell (contraction), a gland
-
(hormone release).
Neurons have 100’s of dendrites but only one axon.

Integrate all these inputs decide whether to “fire” or not.

Firing is producing an action potential.

Action potential is an electrical impulse that travels down the axon.

Action potential are all-or-nothing.

A neuron fires or it does not.
How does a neuron “fire”?
It changes its membrane potential.

Membrane potential
Difference in electric potential between
the interior and the exterior of a biological
cell.

All living cells have a membrane potential.

If an cell is “excitable” this means it can

actively change its membrane potential.

Muscle and neurons are excitable cells.

 opositie
↓ ~
W
↳
resting
membrane
potential
in e e
Depolarization – less negative
Hyperpolarization – more negative
 I
mute
.
nichs
↑

I
-
K T
-(

I
KC
*
HP03
↑
Consider you have a container with a membrane.
The membrane lets only cations through.

You have pure water on the other side.

Your anion will flow out to the other compartment because of the concentration gradient.
 fers -

pro
au
.
8 0
-
-

kt

ariors
/
v
-

-
-

-
-
⑧
Not au

cation
-

⑳ mall
S
⑱

050
-me ⑧
As the cation flows out, an electrival gradient will be created such that the left hand side is
negatively charged and the right hand side positive.

This electrical gradient will eventually stop the flow of cations, even if the concentration
-

gradient is not resolved yet.

This is a membrane potential.

The balance between the chemical and electrical gradient created by a semi permeable
membrane/
If *
⑰

Iposite
 T

0
t t
t

I 7 - t
->
chemica
t
gradient
t
e
t

-
electrical
gradient
In cells, proteins are generally negatively charged and too large to pass over the
membrane.

Small cations can therefore leach out.

So generally, cells have a negative membrane potential

Membrane potential can be calculated by balancing these forces

A
↓ ⑧ Fick's
# Ms
⑧
M

lay

-
Fick’s law.

I
[C] is concentration of ion. &

↳
l ⑧
!"
& i
&

Ms Xi0
=

1 %
Calculates flux (Vab) due to electrical field
!s is electrical mobility ↑
*
Zq is charge of ion
v is electrical potential
⑧

=0
Nernst Einstein relation

-
!! $% "! &" '
"! = !! =
&" ' $%

F is faraday.
R is ideal gas constant
T is temperature
e

Total flux is sum of both

~tot ↓
Fra
00
*+! "! &" ' *-
(! = −"! − +
*, $% ! *,
At equilibrium flux is zero,
-
%&! $! (" ) %,
E-! = 0 0 = −$! -
%'
−
*+
&!
%'
/

%&! $! (" ) %,
0 = −$! − &!
%' *+ %'

D I
%&! (" ) %,
=− &!
%' *+ %'

- !"
!#
= −
$% !("
&! '(" !# Nernst Equation

.or %) = %* − %+ =
$%
&! '
&'
(",$
(",%
 3M
R 377273
8

=
For a neuron
+ =

T
[K+]o = 5 mM
B =

[K+]i = 140 mM
-

z
=
+

96700
Vm=-89,1 mV at body temperature I
=

t
This is the Nernst potential for K+
 -
↓quak
Early 1900’s, Bernstein proposed K+ permeability
controls membrane potential. -

Later realized that it is several ions ↓

ampach

-O
↳
Na+
K+
Cl-
Major role in
membrane
potential
Ca2+
Mg2+
Low
concentration so
no major effect
ref
kl

we
,

At
wat
Natat
 Nat

:fr
-
->

-Nat

I -> kt
-
 Last

meroree
A

1
a
Cells are not permeable to all ions at all times. -
for
S
mische
They have ion channels that open/close.
Eete
As they increase permeability to an ion, the membrane potential moves towards the
Nernst potential of that ion
Depolarise (EK+)= -89 mV
Hyperpolarise (Ena+)=67 mV
Depolarise (Ecl-)= - 89 mV
Ion channels are specific – can only let one ion through.

A
Permeability – depends on no. of channels for an ion and
ease of the ion through the channels

Membrane generally 100x more pereable to K+ than Na+

Equivalent to circuits
!
O Nat
"
Nat
a Nat
->
as Nat
d
If Vm is constant than Im = 0
Im = IK++ INa++ ICl-
Is = MszsF
Zs is the charge on the ion
F is faraday’s constant

And from before

>
!*, ), ,- - !"
(, = −), − *,
!+ ./ !+
0 = MK+zK+F + MCa2+zCa2+F + MCl-zCl-F

0 = MK+ + MNa+ - MCl-

!*./ )./ - !"

−)./ − *./
!+ ./ !+
!*01/ )01/ - !"
+ −)01/ − *01/
!+ ./ !+
!*234 )234 - !"
− −)234 − *234 =0
!+ ./ !+
 !"
Solving for
!#

!"
!+
./ )./ !*./
= 2−
- )./ *5/ + )01/ *01/ − )234 *234 !+
)01/ !*01/
−
)./ *5/ + )01/ *01/ − )234 *234 !+
)234 !*234
+ 3
)./ *5/ + )01/ *01/ − )234 *234 !+
 Integrating from outside the cell to inside
the cells

./ [5 / ]+ 7./ + [89 / ]+ 701/ + [:& 4 ]* 7234

%) = "* − "+ =
- [5 / ]* 7./ + [89 / ]* 701/ + [:& 4 ]+ 7234

Ps is permeabilty of solute

This is Goldman Equation

 ......
- -

->70

-
-
-I
- -
k
- -

-90
But even if membrane less permeable
to Na+ than K+

Eventually Vm=0

If cell is permeable to only one ion,

membrane potential can be
maintained without metabolic energy
 een

wat I wi n
lowe

⑧
.

⑰
 If not, as channels
open/close eventually
would go to zero

>h
Neurons have Na+/K+ pumps
 -
Na+/K+ pumps is electrogenic, it produces a net flux
-

- Introduces 2 K+ ions to cell for every 3 Na+ ions that it expels.

Therefore, it tends to hyperpolarize cell

 de
auts ,

k k

-
-

-
-
insie
-> WIN Nä
ATP
Notar
* Pi
Na ADP +

-
reie

-Le -

inside
Every exchange (2 K+ for 3 Na+ ) uses one ATP molecule.
- -

Na+/ K+ pumps account for 1/3 of resting energy

expenditure

- These pums are present in all cells.

What about Cl-

- Most membranes highly permeable to Cl-

- Freely diffuses in/out and does not actively affect resting

potential

- More appropriate to say resting membrane potential controls

Cl- concentration in/out cell.

%) =
$%
'
-
&'
[23]%
[23]$
%
>° [:&]*
[:&]+
= ;+<
%) -
./
Review Question
1) Explain what gives rise to a membrane potential.

2) Describe the chemical and electrical gradients in a

neuron, using K+, Na+ and Cl-.

3) Explain why the membrane potential doesn’t

eventually disappear.
Ion channels are either

>
1. Always open (leak channels)
-
-
mechanical
Chemical
2. Gated (open close in response to stimuli) -

voltage
-
.

For gated channels, transition from close to open state:

1. Creates wider lumen
2. Shifts relatively more polar amino acids to the surface
that lines the pore.
-
Three types of gating
1. Voltage gated
2. Ligand gated (also called chemically gated)
3. Mechanically gated

Cystic fibrosis and some cardiac arrythmias are

malfunctions of ion channels

Some anaesthetics (lidocaine) block ion channel function.

Opening of ligand and mechanically gated channels cause
small regional depolarizations.
to
Called graded potential. -> proportional
imput stimuli

Graded because
e the more open, the more depolarization
you have.
- -

-
Ife
two or more local
- stimuli are received essentially at the
same time, then these stimuli will be additive (called
summation)
E
i -> e -

ad
E
↳I

Al
&
A m
-
-

--
E

.
x·Il
-

Een2
+

-
III Il
↳o
IX

Zo
~

- -

graded potential
-
.

-
-
-

1
dendrites
I
to
-

proportional
the amount
of
Stimuli
=

channels -> 4 Hes

+ 4 open
more depotaizal zi
=45

D
..
------

m
We
I -
-

adding
graded potentials
up= -
If sum of graded potentials reach excitation threshold

→ An action potential is produced.

Steps in an action potential

1. Local gated channels (mechanically or chemically gated)

open and depolarize membrane

2. Once excitation threshold is reached (usually 10-15 mV

Ee
above resting), this opens voltage-gated Na+ channels.

- permeability of Na+ ⇪
- lots of gates open
-
-

-
-

I
At this point, both chemical and electrical gradients
favour the influx of Na+ -
 90
Ekt

-
-
=

50

↑
ENot =
+

98
Eci
-

Permability
=

Nat
-

3 increases
massively ~
 Vm (resting membrane
potential) changes from being
closer to Nernst potential from
e
K+ (-89) to being closer to that of
Na+ (+67 mV)
-

Called sodium activation

3. K+ voltage gated channels open once membrane potential
is positive.

→ K+ ions start flowing out

Electrical gradient that was opposing flow of K+ ions is

now inverted.

Flow of K+ ions causes repolarization.

Dips a little further than it should

*
→ Hyperpolarization
↳
This returns everything to normal resting potential.
All channels closed.
>°
ois I
ee
 electrical

I
outsideMoch conc
-

mate
k I
->
0
I ->

wi +I I -
O

④ ⑤ Cl
OtI O E
high
insch
-
Action potential are « all of nothing »
mechanisms

If threshold is reached, the channel will fire.

Around 0.5 ms after local membrane is

depolarized, it starts to repolarise.
08

But local current inside the cell depolarizes the

adjacent region.
→ it reaches excitation threshold ⑧
→ action potential starts at
neighbouring location ↳

So action potentials run down the length of the

neuron, and self-renew
->-o
-Lo

↳
bb he b
-
same the whole
Wa}
Normal conductance in a wire

Because action potentials self renew

Depolarization/repolarization occurs locally, so it is not very
much K+/Na+

Most of cell does not change concentration/charge

Localized to 1 micron from cell membrane
⑱

S
Do not need to wait for Na+/K+, normal concentrations can
be restored by diffusion

⑰
·
Action potential is followed by a refractory period.

Made of:

Absolute refractory period

- Based on the closing of Na+ voltage channels

- Conformational change prevents reopening for a period of

time
- Caused by part of channel separate from the pore.
 Relative refractory period
- Cause by the fact that membrane hyperpolarizes after
membrane potential

donde
vo
hold
poriThres
sme Trou
ro

- Bigger=-threshold for firing is present

- But, if enough graded potential arrive, it can fire.
->
-45

-
-
--

-
-
2
e

-
e

=
Refractory period controls firing rate.

Intensity of a signal is conveyed by changes in frequency of

action potential and not changes in amplitude or shape.

An action potential is an action potential.. They all look the

same.
→ All or nothing
→ An intense signal refire immediately after absolute
refractory period.

Refractory period also makes action potentials unidirectional.

Previous segment cannot refire right away.
-
IIIIII IIIII
u
- 11 I1 11 I
Conduction velocity

I
Conduction velocity is an inherent property of a neuron.

Proportional to fibre diameter

**
! = !#$%$&'()# = 8
0
+'
Where ri = axoplasmic resistivity
a = radius#of axon
or I d small
->

Rit

①ann)
N

axom
- -
.

-
In
R T
,
 -adipose/fet
O
- -

Myelination can increase

conduction velocity

Oligodendrocytes
(brain/spinal cord) or
Schwann cells (rest of
body) wrap around
neurons to myelinate
them.

Myelin electrically isolates neurons so action potential do not

fire at every step
-
dendr -

cytes

⑨
E /5
-
⑳ì
⑳
-
-

⑧
modes of
Ramen
Rest of ↓ 7
body D
schwan call
WEW
Action potential moves by passive conductance until next
break in myelin sheath where it self renews
assie is

diffusionaster
- -
Recht
ther
constantly
D
8

⑳
forming
↑
&amaterial
action
-
Breaks in myelin sheath every 1-2 mm, called Nodes of
Ranvier
⑧
white matter ->
mun
Called saltatory conductance (saltatory – to leap/jump)

Baby-steps

Leaping over
puddles
Not all neurons are myelinated.
Not all neurons can form action potentials
− some interneurons passively transduce graded potentials
− interneurons are a type of non-myelinated neuron in the
brain.

Conduction velocities therefore from a few cm/s for

unmyelinated to around 120 m/s for myelinated.
 if sum
high

I
enough
↓ ->

-
-
AP
No
- --

- -R aon
- - arow Herme

dendrites body
some
a ->

&
sum up
->
e along
· boc
graded
poterte e
-
Review Question
1) Explain what a graded potential is and what
summation is. absolute
Lact
Open

2) Explain the steps in an action potential.

~
I
ee
3) What refectory periods exist and why do they arise?
radius ar
"

4) I
a. What two factors affects conduction velocity? - met
2
-

b. Explain saltatory conductance. *

.

#X
-

↳i
-voltage gated
chauds
-It Ope

·
~ voltage positie
· (0-r)

closing of

overstart
->

↑ I channels
too
Nat
-

voltage I
gated
chaavel
e

D
⑳
- -> -
->
Za

Herma

I1 :
receiver
all
-
-
-
synapse

- -

axon

de e el
ind
Synaptic transmission
-

Signals come in on the dendrites

They travel by action potential down the

axon

When the reach the axon terminals, they

need to transmit their signal to the next
cell

Next cell can be another neuron

(neuronal synapse), a muscle or a gland
(neuroeffector synapse).
SGe
->
sowe alls Lardiomzoufje
to
allom change directly from one

next

- But most neurons don't use

this
-> instead use chemical signals .
Synapse

ìï
Synapse is Greek for junction

Synapse are sites of ligand-based transmission of signal

- >

murdtransmitte

- -

afon
permind
Use of chemical synapses
allows other chemical signals
to affect excitability of synapse
C
·
so -
(hormones, drugs, etc.)
 W
-

-
-
-
-
-
-
-

↑
al
chem s

mechanical
-
-

*
=D
-

-
M
Chemicallychannel
dendate
.

gated an
-
-
type
Steps in signal transmission

1. Action potential arrives at

synaptic knob and
depolarizes it.
⑧
2. Depolarization causes
opening of-ma
voltage-gated
calcium channels. -
-

3. Calcium rushes in, causing

the fusion of synaptic
vesicles to the presynaptic
=

membrane.
-

-I
This releases neurotranmittor
into the cleft.
I
Nat
Mart
kt et

Cir
Me

-
- too low a

membrane concentrete
potentie to matte
-
-

for membran

potential -
gat a
typo
&

4. NeurotransmittorA

diffuses over synaptic

cleft and binds ligand
gated channels.

5. Removal of unbound
neurotransmittor occurs
Ob of -
by either
-
diffusion,
enzymatic degradataion
⑫
or by reuptake from

graded P
otential in
Epresynaptic knob (most
common)
next call
Two common antidepressants ⑥
inhibitis
-

essation
- SSRIs – selective serotonnin reuptake inhibitors L
Met e
-

of signal
C

- MAOIs – monoamine oxidase inhibitors

=
 I

11
~
-

-
& o
⑧
⑳

-d ⑤ ⑳

return
pumps
neuwstransmitter er

He vesicles for pre-use

M
Two common antidepressants

n
- SSRIs – selective serotonnin reuptake inhibitors
- MAOIs – monoamine oxidase inhibitors

O
Synaptic fatigue – if a synapse fire faster (and for too long) than
- -

neurotransmittor can be synthesized/replenished,

- the synapse will
-

eventually stop functioning until the neurotransmittor is replenished.

-
-

↳ habitration
-
 Common neurotransmitters don't
memorie
to

⑳
-
noch
nections
-

-
Acetylcholine – AcetylCoA + Choline → Ach
Ach is degraded in cleft and choline is re-uptaken

Biogenic⑧
amines – Dopamine
Norepinephrine (also called noradrenaline)
Serotonin

Tyrosine + O2 → L-DOPA → CO2 + dopamine

Tryptophan → 5HTP → serotonin

-
Amino acid (derived) – GABA
Glutamine
Glycine

glutamate → GABA + CO2

 Every neuron uses
just one neurotransmitter
-
.

A single neuron uses the same neurotransmittor at all of its synapses

- so you have noradrenergic, GABAergic or cholinergic neurons

Some neurodegenerative disease cause loss of a specific type of neuron

--
-

Huntington’s disease – loss of certain

GABAergic neurons
-
Parkinson’s disease – destruction of
dopaminergic neurons in the basal
-
-

ganglions

E
Alzheimer’s disease – shortage of
acetylcholine and structural changes in
-
the brain.
⑭
Neurotransmitters are either inhibitory or excitatory

ώ
Dopamine
*Glycine Usually inhibitory E -
D
-GABBA
N
z⑰
-

Glutamate ↑

⑧Acetylcholine
Norepinephrine ⑧
Usually excitatory
either
to
close
threshold
E Cexcetato -y)
WatI or Fathe
Lumkulatorg
So neurons (and therefore also synapses) are either excitatory or inhibitory.
Chantall alearen
ligand 13
ated
I

-
E
-
0

1
I

->

↓
soc
- -
tre-
res
-60
If Nat Haus-depolanen
·
-
to 30
close Ewat
+

- > =

excetate

Ek+= -

90
if E claws -hyperpolaes
Eci- =
90
Why inhibitory signals?

• Muscles usually come

in pairs
(flexors/extensor)
• Does not make sense to
activate at same time
(would do nothing)
• So one inhibits the
other
⑱
Excitatory synapse
- Depolarize post-synaptic membrane in a graded fashion
- Creates an &
EPSP (exctitatory
E post synaptic potential)
- - -

-is
EPSP open channels for cations (both K+ and Na+ such that each
A
-

flows down their own concentration gradient)

IK+ dampens the Na+ signal

-
-

Occurs through one channel, so not

sequential
- so one has

preferent
 [
Nat chem
Nat
- nigh
-> low

At low chen -

high

= t Eleat E-

INat
only
↑ steep rise
-

2
Nat/kt
ony
- gradual rise
⑬
Inhibitory synapse
- Hyperpolarizes post-synaptic membrane away from excitation
threshold.
- Increases membrane conductance as well (essentially creating
a mini short circuit)
- Creates an IPSP (inhibitory post synaptic potential)

IPSPs open ligand gated K+ and Cl- channels.

Membrane potential goes

closer to Nersnt
Al for K
+
 -

Signal integration by neurons

- Most of the dendrites/soma must be depolarized to about -
40mV to reach excitation threshold.
- A region near the# start of the axon has a lower threshold
(about -55 mV)

it -wort
- Used to be called axon hillock, now realize that the initiation
region is larger and less specific.

lote
or

tuinstold
aborm ↑
EPSP and IPSP are created in dendrites, travel passively towards
axon as a graded potential.

The IPSP and EPSP add and subtract each other to decide if
threshold is reached.
Integration of all signals from all synapses (often 10K
synapses per neuron.

One excitatory
> synapse firing give about 200M
uV change
Need 10-15 mV change to reach excitation threshold.

&
Adding signals called summation
You have bothof
spatial and temporal summation.
--

2on
-

-
-
->

-
- & D her
Sum
-
-
-

en
Spatial Summation
multiple
sigmals in

comme
auch R
7
meltp
a

on
dendric
Temporal Summation

-> one Location activated

repeatedly
 synapse
.

For a neuron, position is everything.

-
-

A signal travels from dendrites by

litude
electrotonic
>
--
- conduction. -> loses am

I
diffusion El widers

0
-
--

Dendrites and soma are unmyelinated

so signal attenuates and widens as it
travels.

Signals can be given more importance by placing them closer

to trigger zone.

IPSP weaker than EPSP so always located closer to trigger.

Less powertal
A

D
-
⑳

-
-

-
B

-
distence
distanc
- - >

the more

distance the move a

signal
dampers-
.
A
↳ -
-

~ -> -
flows
to
apon
miloch

samal

In
B - - -

klef m ->
~
* lows
H
AH
Learning

Learning and memory occur because the nervous

-
system is endowed with plasticity.

Plasticity – changes in a network of neurons as

results of experiences.

No neurons are formed.

- Pattern of connection and location of synapses
changes.
 -> with harming
neuron
-
-- ⑧

-
-

E
-

en

↳mor likels
to
make thes
one
fina .
Mechanisms underlying plasticity

1) Location of synapse
serd
in
2) Changes in quantity of neurotransmitter released
->

3) Changes in how cell responds to neurotransmitter.

&
F

L M
wette
each
is
wel
↓
werel 5f
L
Mis pub
-
me

/Nators te
e
Central Nervous System

Composed of:
1) Brain
• 2 cerebral hemispheres -
(cerebrum)
e I
• Diencephalon >
• Brain stem
• Cerebellum
2) Spinal Cord

3) refina
-
n
 ric/ste
⑮
Protective Structures
- Located between skull and brain.
- Called>mmeninges.
- Three meninges:
1) Dura mater (hard mother)
2) Arachnoid mater
3) Pia mater (soft mother).

- Cushions skull brain I

- Cerebrospinal fluid I
between pia mater and
arachnoid mater
Extends all the way down spinal column.

- Not attached to bone in spinal cord, creates

epidural space.
Cerebrospinal Fluid
- This is the liquid your brain floats in.
- Produced from blood plasma in the choroid plexus.
- Returned to blood plasma when finished circulating.
- Essentially composed of blood plasma minus proteins.
 Produced in ventricles.
- Ventricles are large
3

>
-spi n al
cavities in the brain.

Owaterblod
& do

·
Flows down central canal.

Te
er Flow up side of spinal cord
(in arachnoid space).
-

Flow up around exterior of

brain. ~

I
--
Reabsorbed in arachnoid
villus.
Cerebrum
-

Consists of> -
grey matter and white
-
matter.

Gray matter
-
- Consists of cell bodies and dendrites.
- Location of synaptic transmission and signal
integration.
- Unmyelinated.
I
White matter
- Myelinated axons for transmission within sections of
brain.
-

·je
- e
corte
 ·

ze atteeen

i
met -
niet
In the brain, gray matter on outside.
- plus a few spots inside the brain called basal nuclei.
In the spinal cord, gray matter on the inside.
Spinal Cord

Motor neurons are located ventrally

Sensory neurons are dorsal.
In white matter, neurons organized in bundles or
tracts bran
↑to -
-

-
-
Ascending tracts: to brain, sensory info.
-

Descending tracts: to periphery, motor info.

Atobran <

in
D
Sensory

S
wom
,
White matter organized into bundles of axons.
1)Projection fibers – connect cortex with lower levels of brain
or spinal cord
2)Association fibers – connect one area of cortex to another.
3)Commissural fibers – connect one side of brain to other.
Most commissural fibers located in corpus
callosum.
Spinal cord has two functions:
1) Conduct nerve impulses to/from brain
2) Serve as center for spinal reflexes.

4
↳zat
0- ge
-

=>

rel lex
R
Ee
Brain not needed for
reflexes.

hindbran
ind
->
sp
⑧ -
-

fast
Reflex -> I

few neurors
-> very

(minimum two
neurdre
L
-> neurors
5-6
max .