Nervous system, synapses and

neurotransmitters

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Nervous system, synapses and neurotransmitters

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Camillo Golgi Santiago Ramon y Cajal

• Golgi Stain 1873

• Nerve Reticulum vs Neuron Doctrine

Nobel Prize in Physiology or Medicine 1906

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Nervous system, synapses and neurotransmitters
Two types of synapses:
- Chemical synapse
- Electrical synapse

Spines

Three dimensional reconstruction of

part of a dendrite

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 Nervous system, synapses and neurotransmitters

Chemical synapses

Charles Sherrington 1897: Used the term synapse to describe the structure that
mediates transmission of nerve impulse from one cell to another.

Nobel prize, 1932

Faculty.washington.edu

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Figure 55-12 Kandel 4 edition, p1100
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Nervous system, synapses and neurotransmitters
Chemical synapses

 A presynaptic element consisting of a swelling of the axon :

Varicosity (along the axon) or Bouton (tip of the axon)
Contained neurotransmitter molecule packaged in synaptic vesicles

 A postsynaptic element , often on dendrites and dendritic spines,

Contained receptors for bindings of the neurotransmitters.

 A synaptic cleft (or gap) = A space of 20-40nm between two cells

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Nervous system, synapses and neurotransmitters
Chemical synapses, synaptic transmission

Active zone

v
Unidirectional

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Nervous system, synapses and neurotransmitters

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Nervous system, synapses and neurotransmitters
Chemical synapses
Some essential proteins at the vesicles :
v-SNARE (associated with Vesicle, Synaptobrevin)
t-SNARE (Target, associated with the membrane at the presynaptic site,
SNAP-25, Syntaxin is a Q-SNARE)
Synaptotagmin: Calcium sensor at the vesicle.

“the entire process from arrival of an action potential at

the presynaptic bouton to the generation of a
postsynaptic potential : 1 ms
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Nervous system, synapses and neurotransmitters
Chemical synapses

Some neurons receive thousands of synaptic contacts

In this photo:
• Soma and dendrites are stained blue
• Axon terminals are stained white

J. Dorn//www.sharpbrains.com

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Nervous system, synapses and neurotransmitters
Chemical synapses

What is inside the vesicles ?

The Neurotransmitters: Amino-acid transmitters
 Excitatory or inhibitory Biogenic Amines
Excitatory
- Acetylcholine (principal NT at the neuromuscular junction)
- Glutamate
- Catecholamines : Dopamine / norepinephrine (Noradrenaline)/ epinephrine (adrenaline)
- Serotonin (or 5-hydroxytryptamine)
- Histamine
- ATP/adenosine
- Neuropeptides

Inhibitory
- GABA
- Glycine

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Neuropeptides….

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v

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Nervous system, synapses and neurotransmitters
Chemical synapses,
Receptors at the postsynaptic terminal

1. Neurotransmitters binds to extracellular part of a receptor

2. Activation of the receptor induces conformational changes in an associated ion-channel

protein, leading to opening or closing of this channel

Ionotropic vs Metabotropic receptors

Ionotropic : Receptor domain is part of the ion channel

Example: - NMDA (N-methyl D-aspartate) receptor for glutamate
- α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPA) also binds
glutamate
Metabotropic : Receptor is at some distance of the ion channel, need a second messenger
Example: - mGluR (metabotropic Receptor)
- Adrenergic receptors for Norepinephrine

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Nervous system, synapses and neurotransmitters

Direct Gating Indirect Gating

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Nervous system, synapses and neurotransmitters
Example: the Nicotinic acetylcholine receptor

First neurotransmitter receptor

whose molecular structure was
elucidated

The receptor can be activated by

Acetylcholine and by the plant
alkaloid Nicotine.
Opposed to Muscarinic
acetylcholine receptors (activated
by Ach and muscarine)

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Nervous system, synapses and neurotransmitters

Excitatory post-synaptic
potential EPSP
Inhibitory post-synaptic
potential IPSP

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 Nervous system, synapses and neurotransmitters
Electrical synapses

- Interneural signaling by electrotonic

transmission (or electrical)
- Gap Junction : Channel that connect the
two cells; Connexins in vertebrates and
innexins in invertebrates

2-directional current flow

Very fast transmission
Passage of cytoplasmic contents
Pores open/close

Figure 2.15 chap 2

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Nervous system, synapses and neurotransmitters

Environment  Sensory organs  Central Nervous System

Transduction

 Sensory modality :
hair cells of the cochlea in the auditory system transduce mechanical energy
Rods and cones, in the visual system, transduce light energy

These cells are : Receptor cells

 Transduction leads to a change in membrane voltage of the receptor cell = Receptor
potential (or generator potential). It is graded.
 Amplification of the energy from the stimulus

 Frequency coding : The graded receptor potential  series of impulse

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Nervous system, synapses and neurotransmitters
Frequency coding in sensory neurons

• The stronger the stimulus, the higher frequency the Action

potentials

Figure 2.16 chap 2 19

Nervous system, synapses and neurotransmitters

Neurons are excitable cells

How can we measure electrical activity or

membrane potentials of a cell ?

 Voltage – sensitive fluorescent dyes

 Electrophysiology

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Nervous system, synapses and neurotransmitters

Voltage – sensitive fluorescent dyes

Change their spectral properties in response to voltage changes

• Excellent spatial and temporal

resolution
• In vivo brain imaging
• Large population of neurons

• Difficult to know the origin of the

signal
• Excitatory or inhibitory or both ?

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 Nervous system, synapses and neurotransmitters
Electrophysiology

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Julien Gibon, Barker Lab UBCO
Nervous system, synapses and neurotransmitters
The Patch-Clamp Technique

Leica

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Nervous system, synapses and neurotransmitters

Depolarization

hyperpolarization

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Nervous system, synapses and neurotransmitters
The Resting membrane potential

Potential difference between the extracellular fluid and the intracellular electrode
around -60 to -80mV at rest.
The neuron is polarized and this value is called the Resting Membrane Potential (RMP)

• Differential distribution of ions across the

plasma membrane
• Potassium K+
• Sodium Na+
• Chloride Cl-

Intracellular Extracellular
(mM) (mM)
Na+ 14 140
K+ 160 3
Ca2+ 0.0001 1
Cl- 14 150

Example of intra/extra [c]

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 Nervous system, synapses and neurotransmitters
The Resting membrane potential

Maintenance of the potassium gradient :

the sodium/potassium pump

Intra Extra
(mM) (mM)

Na+ 14 140
K+ 160 3
Ca2+ 0.0001 1
Cl- 14 150

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 Nervous system, synapses and neurotransmitters
The Resting membrane potential

The membrane potential at which the equilibrium is reached = Equilibrium potential

Can be calculated for each ion, depends on its concentration intra and extracellular

Nernst equation : Eion= Ln

Eion = log z= number of

charge

Eion in mV
Intracellular Extracellular
(mM) (mM)
Na+ 14 140
K+ 160 3 What is the equilibrium
Ca2+ 0.0001 1 potential of these ions ?
Cl- 14 150

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 Nervous system, synapses and neurotransmitters
The Resting membrane potential

Intracellular (mM) Extracellular (mM) Eion

Na+ 14 140 +58 mV

K+ 160 3 -100 mV
Ca2+ 0.0001 1 +116mV
Cl- 14 150 - 60mV

Why is it important, it tells us:

Opening of potassium channel , efflux of potassium Hyperpolarization
Opening of Sodium or Calcium , influx of Calcium Depolarization
The RMP depends mainly on K, Na and Cl, and on the permeability of each of these ions

The Goldman-Hodgkin-Katz equation :

At rest in a Neuron
pK : pNa : pCl =1.0 : 0.04 : 0.45
Vm = -68mV
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Nervous system, synapses and neurotransmitters
Generation of action potentials

For small current pulses : graded potential

Ohm’s Law: V=R*I
R = Membrane resistance (Ω Ohms)
I = Current (A Amperes)
V = Voltage (V volts)

But at a certain threshold, the potential increased not linearly 

Action potential = not graded, all-or-nothing property

What is happening before, during and after an action potential ?

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Nervous system, synapses and neurotransmitters

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Nervous system, synapses and neurotransmitters

1) Channel is deactivated
2) Activated and open
3) Inactivated & closed
4) Back to deactivated

Very high density of Voltage-gated Na+ channels at the node of Ranvier

“Saltatory conduction”
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 Nervous system, synapses and neurotransmitters
α-subunit of the channel

Voltage-gated sodium channels

Channels with three states:
Activated by a depolarizing stimulus
Inactivated , also unavailable to reopen
Deactivated , closed but can be activated again

• Note there are 4 domains with 6

segments each
• S4 segments have ++ charges 
voltage sensor
• An ion selectivity filter is formed
by loops in the channel pore
• An intracellular loop forms an
inactivation gate : the IFM motif

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Nervous system, synapses and neurotransmitters The simpsons

The puffer fish

Produces Tetrodotoxin (TTX), a very potent Voltage-gated sodium channels blocker

Food poisoning often fatal (respiratory distress)

Muthukrishnan Renganathan, Theodore R. Cummins, Stephen

G. Waxman
Journal of Neurophysiology Published 1 August 2001 Vol. 86 no.
2, 629-640 DOI: 33
What did we learn Today ?

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