Neurophysiology: Neural Signals

Warning:
 Sheila (UK)
Sheila fell in her English garden, cutting her leg. She was taken to local ER
where the wound was cleaned and stitched. But she was forced to seek
further help 3 days later when her face began to ache and she had difficulty
opening her mouth.

She looked unwell and complained of diffuse pain. Her condition worsened; 24
hours later she developed jaw stiffness, and severe back and limb spasms.
She was transferred to ICU.
My diagnosis of Sheila is

A. Excessive glycine activity

B. Impaired serotonin activity
C. Dopamine deficiency
D. I have no idea what she has

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20

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The Big Picture
 Ionic Forces Underlie Electrical Signaling

Key: semipermeable membrane

(a screen door)

Diffusion causes ions to flow from areas

of high to low concentration, along
their concentration gradient

Electrostatic pressure causes ions to

flow towards oppositely charged areas
(electrical gradient)
 The Resting Potential
Neurons are just batteries – they store charge to use when needed

Resting
Potential
Cell membrane is a lipid bilayer

Ion channels are proteins that span the

membrane and allow ions to pass in and
out
Gated channels – open and close in
response to
• voltage changes
• chemicals
• mechanical action

The neuronal cell membrane repels water; this

property necessitates ion channels. Ions are
surrounded by water, therefore they can enter
the cell only through a channel
 Origin of the resting membrane (equilibrium) potential
Neuronal membranes are not
permeable to big negatively
charged proteins (anions)

Neurons are selectively permeable

to K+ – it can enter or leave the cell
freely
At rest, K+ ions move into the
negative interior of the cell
because of electrostatic pressure
As K+ ions build up inside the cell,
they also diffuse out along the
concentration gradient K+ reaches equilibrium when ion movement
out is balanced by ion movement in
 Resting Membrane Potential
The membrane is slightly permeable to sodium ions (Na+) so they
slowly leak in

Sodium-potassium pump pumps

Na+ out and K+ in, to maintain the
resting potential
Distribution of Ions Inside and Outside a Neuron
 Beware cheap Japanese restaurants
Tetrodotoxin blocks nerve action by binding to / blocking pores of voltage-gated,
sodium channels in neuron membranes

Fugu 河豚

A 32-year-old man ate three bites of fugu, and

then noticed tingling in his tongue and right
side of his mouth followed by a "light feeling,"
anxiety, and "thoughts of dying." He felt weak
and then collapsed.
 How is this stored charge used?

Graded Potentials The Action Potential

 Graded potentials - occur in dendrites
As graded potentials spread across membrane, they diminish - ”ripples in a pond”

If membrane reaches threshold it triggers an

action potential; inside of the cell becomes
briefly positive
 All-or-none property of the action potential
Neuron fires at full amplitude or
not at all – thus cannot reflect
increased stimulus strength
analogy: rifle firing

Action potentials increase in

frequency with increased
stimulus strength
 Summary

Axon hillock

Graded potentials start here

Action potential starts here

 Before the synapse
presynaptic action

How is an action potential sent down the axon?

 Ionic basis of action potential – step by step

1) Voltage-gated Na+ channels

open in response to initial
depolarization 3

2) More voltage-gated channels

open and more Na+ ions enter 2

until membrane potential

reaches +40 mV 1

3) Voltage-gated Na+ channels

close
 Resting potential is restored
At peak, concentration gradient pushing Na+ ions
in equals positive charge driving them out

4) As inside of cell becomes

more positive, voltage-gated
K+ channels open 4

5) K+ moves out and the resting

potential is restored
5
 Refractory periods
Absolute refractory phase (AR)
no more action potentials can be
produced AR RR

Relative refractory phase (RR)

only strong stimulation can produce
an action potential
 Refractory periods
Na+ channel

the inactivation gate acts just like the deadbolt on your apartment front door

At rest During AP Absolute refractory

period
 Action potentials are regenerated along the axon

Action potentials travel in one direction because of the refractory state of the
membrane after a depolarization
Conduction Speed
– myelin vs. unmyelinated
axons
 Ion channels are selective filters

K+ ions pass through this filter more easily

than Na+
Recall: each ion has its own channel

Channelopathy – genetic abnormality of ion

channels:
epilepsy, migraine, weakness
At the Synapse
 Sequence of Transmission at Chemical Synapses

1. Action potential travels down

axon to the axon terminal

2. Voltage-gated calcium channels

open and Ca2+ enters

3. Synaptic vesicles fuse with

membrane and release
transmitter into the cleft
 Sequence of Transmission at Chemical Synapses

4. Transmitter binds to postsynaptic receptor – causes EPSP or IPSP

Excitatory postsynaptic potential (EPSP) – small local

depolarization, pushing cell closer to threshold
 EPSPs result from Na+ ions entering the cell,
making inside more positive

Inhibitory postsynaptic potential (IPSP) – small local

hyperpolarization, pushing cell away from threshold
 IPSPs result from Cl- ions entering cell, making
inside more negative
EPSPs and IPSPs are integrated by the axon hillock
‘dendrites vote, and the axon hillock decides’

Cell body

axon hillock
Axon hillock
 Sequence of Transmission at Chemical Synapses

5. Transmitter may bind to presynaptic

autoreceptors, decreasing release

6. After binding, neurotransmitter is

inactivated by: degradation or reuptake
 Neurotransmitter reuptake
all good things must end

Reuptake:
 Neurotransmitter degradation
breakdown/inactivation of
transmitter by an enzyme

Example: acetylcholinesterase
(AChE) breaks down acetylcholine
(Ach)

AchE inhibition (Raid)

 Electrical synapses

Ions flow directly through large

channels into adjacent neurons,
with no time delay

Benefit: faster, allows

neurons to synchronize,
saves energy

Golgi was right after all

 Review

1. Transmitter release from

presynaptic neuron
2. Opens ion channels (e.g., Na+) in
postsynaptic membrane
3. Creating depolarizing current (EPSP)
4. Which passively flows down to axon
hillock to
5. Trigger action potential that is
6. Conducted down the axon to
presynaptic terminal
7. And the cycle continues, from toe to
brain (or brain to toe)
 Ligands
Ligands fit receptors to activate or block them: lock-and-key
• Endogenous ligands – neurotransmitters and hormones
• Exogenous ligands – drugs and toxins from outside the body
 ligand

Acetylcholine
Receptor
 Number of receptors in a neuron varies over time
Receptor number changes rapidly – esp. during development, with drug use,
learning

Up-regulation is an increase in Down-regulation is a decrease

number of receptors ex.: benzodiazepines (Valium, etc.)
ex.: nicotine receptors down-regulate their receptors
when you start smoking - tolerance
- sensitization
Is there a point to all these neuron facts?

Na+ channel stays

open too long
Electoencephalogram (EEG) is a recording of brain potentials: A functional test

Normal EEG
 Seizure Disorders
whole-body convulsion
Generalized convulsions –
abnormal activity throughout
the brain

Characteristic movements are

tonic and clonic contractions

Seizure is followed by
confusion and sleep
 Seizure Disorders

Absence seizure – brain waves

show generalized rhythmic activity
for a few seconds, but hundreds of
times a day

No unusual muscle activity, except

for stopping and staring

Events during seizure are not

remembered
 Partial seizures

Do not involve entire brain

Start in one area
May have jerking of one side
_________
Simple Partial Seizure – normal
awareness
Complex Partial Seizure – impaired
awareness

Abnormal EEG
 Seizure Disorders
Myoclonic Seizures
rapid, brief contractions of bodily muscles, which usually occur
at the same time on both sides of the body
 Categories of seizures - summary

Partial onset
• simple partial seizures (normal awareness)
• complex partial seizures (awareness impaired)

Generalized onset
• absence seizures (petit-mal)
• myoclonic seizures
• generalized tonic-clonic seizures (grand-mal)