Synapses, neurons and brains
Idan Segev
Lesson #2
The Materialistic Brain: Your Brain Ingredients
1. The Neuron
2. The axon
3. Dendrites/Dendritic
spines
4. Neuron types
5. Synapses
6. Electrical signals
1. the spike (action potential)
2. the synaptic potential (PSP)
7. Neuron as I/O device
Historical perspective for “brain ingredients”
Key players
1665 – First use of simple microscope to view living cells (Robert Hooke)
1839 – “Cell theory” (Theodor Schwann) – but is it true for the brain?
1870 – Camilo Golgi develops his silver-based method, for randomly
staining nerve cells
1887 – S. Ramon Y. Cajal uses Golgi technique – proposes the “neuron
doctrine”
1891 – Hienrich Waldeyer – coined the word “Neuron”
1897 - Charles Sherrington coined the word “synapse”
Sigmund Freud drawing crayfish neurons, 1882
Our “meat machine” what does it consists of?
Parietal Lob
Frontal Lobe
Occipital Lobe
Temporal Lobe
Zooming into cortical networks
Courtesy of the Blue Brain Team, EPFL
tical (2-photons) imaging of cortical circuit (anatomy & activity)
Courtesy of Adi Mizrahi, Hebrew University
Optical (2-photons) imaging of Hippocampal circuit
Courtesy of Adi Mizrahi, Hebrew University
Adi_Green.jpg
Layer 5 neocortical pyramidal cells
The Nobel Prize in Physiology or Medicine 1906
in recognition of their work on the structure of the nervous system
Camillo Golgi Santiago Ramón y Cajal
(1843-1926) (1852-1934)
S. Ramon Y Cajal
Possible direction of current flow and pattern of axo-dendritic connection
The “Neuron Doctrine” and the“Theory of dynamic polarization”
dendrites axon
Dendrites are receptive (input) devices
Axon are the sending (output) devices
The neocortical (pyramidal) cell
Axonal tree + varicosities
Dendritic tree
Courtesy of Kevan Martin, Univ.
Zurich)
The neuron as an input-output electrical device
(conceptual, details will follow)
INPUT
OUTPUT
excitatory
Excitatory
inhibitory
Inhbitory
spikes
Axon
Soma
Dendrites
Inhibitory post synaptic
Excitatory post-synaptic potential (IPSPs)
potential (EPSPs)
Spiking activity of a neuron
Axons “fire” spikes (carrying the brain code)
Axonal tree sending output - Spikes
Typical morphology of a neuron
axon
dendrites Axon terminals
Inter-node (pre-synaptic site)
nodes of
Ranvier myelin
soma
axon initial segment
(AIS)
“HOT” region
generating “spikes” no myelin
Poliak & Peles
Nature Reviews Neuroscience 4, 968-980 (December 2003)
The myelin of axons
0.3 - 4mm
Myelinating glial cells, oligodendrocytes in the central nervous system (CNS) or
Schwann cells in the peripheral nervous system (PNS), form the myelin sheath
by enwrapping their membrane several times around the axon.
Poliak & Peles
Nature Reviews Neuroscience 4, 968-980 (December 2003)
The node of Ranvier in axons
Hot (excitable) region
Helen C. Lai and Lily Y. Jan
Nature Reviews Neuroscience 7, 548-562 (July 2006)
A typical axon in the central nervous system (CNS
summary
1. A single, highly branched, thin (mm) process emerging from the
soma. Branched locally but may extend far (many centimeters
and even meters) away from the soma
2. At the “hot” axon initial segment (AIS) the spike (“action
potential”) is initiated and then propagates along the axon
3. Covered with myelin (isolating) lipid sheath, with intermittent
small gaps – the nodes of Ranvier (where “hot” – excitable ion
channels reside)
4. Decorated with frequent swellings (axonal boutons) – where the
neurotransmitter “hides” (the pre-synaptic site)
The axon is the output electrical device of neurons,
It generates and carries electrical signals called spikes
Dendrites
Purkinje cell (cerebellum) Starburst amacrine cell (retina) CA1 Pyramidal cell (hippocampus)
(Courtesy of M. Hausser) (Courtesy of W. Denk) (Courtesy of D. Johnston)
An example: The layer 5 cortical pyramidal cell
(the “psychic” cell by Cajal)
Dendrites with spines
Spiny neurons
Dendritic spines
Typical numbers
Total dendritic area – 20,000 mm2
Number of dendritic spines/cell – 8,000
Spine area – ~1 mm2
Number of converging inputs (synapses/cell) – 10,000
Intracellular injection of Lucifer
Yellow in fixed cortical tissue
Human pyramidal
neuron from the
neocortex
1 mm
spines
Layer II
20 mm
Spines
Courtesy of Javier DeFelipe, University Madrid
Layer V
Neuron types
• Classification by anatomical features (“the face” of dendrites and axons)
• Classification – functional (e.g., Excitatory (principal) vs. Inhibitory (inter)
neurons)
• Classification using electrical/spiking activity pattern
• Classification using chemical characteristics
• Classification using gene expression
Microcircuit of the Neocortex
Principal neurons
(excitatory) - axon projects
to other brain regions
Interneurons (inhibitory) –
local axonal projection
Z. J. Huang, G. Di Cristo & F. Ango
Nature Reviews Neuroscience 8, 673-686 (September 2007)
Morphometric-based classification of (inhibitory) interneurons
DeFelipe et al., Nature Review neuroscience, 2013
Electrically-based neuron classification
(based of spiking patterns)
Courtesy of the Blue Brain
data-base
The Chemical Synapse
A (chemical/electrical) device that connects
axon of neuron A to dendrites of neuron B
Dendrites of
neuron B
Axon of
neuron A
(note varicosities)
A chemical synapse
formed between axons and dendrites
Axonal terminal
Synapse (pre-synaptic)
(with gap)
Dendritic spine
(post-synaptic)
The chemical synapse
SPIKE at axon (digital - “all or none)
Spiny dendrite
Axon cell A
(small vesicles)
Spine: cell “B”
axon
excitatory
synapse
Excitatory synaptic potential
(analog/graded)
The Chemical Synapse
Axon of Cell A Dendrite of Cell B
Cell A
When two cells fire together
Vesicles containing Receptors binding
neurotransmitter molecules neurotransmitter
the synapse between them strengthens
Chemical synapse
E. Lisman, Sridhar Raghavachari & Richard W. Tsien
Nature Reviews Neuroscience 8, 597-609 (August 2007)
Vesicle quantal release
E. Lisman, Sridhar Raghavachari & Richard W. Tsien
Nature Reviews Neuroscience 8, 597-609 (August 2007)
Vesicle quantal release
E. Lisman, Sridhar Raghavachari & Richard W. Tsien
Nature Reviews Neuroscience 8, 597-609 (August 2007)
Vesicle quantal release
E. Lisman, Sridhar Raghavachari & Richard W. Tsien
Nature Reviews Neuroscience 8, 597-609 (August 2007)
What neurons “see” when embedded in the
(cortical) circuit
L4 Spiny Stellate Cell
covered with (excitatory and inhibotory synapses)
The neuron as an input-output electrical device
(SUMMARY after you’ve been learning)
INPUT
OUTPUT
excitatory
Excitatory
inhibitory
Inhbitory
spikes
Axon
Soma
Dendrites
Inhibitory post synaptic
Excitatory post-synaptic potential (IPSPs)
potential (EPSPs)
NEXT LESSON #3
Electrifying brains –passive electrical signals
Courtesy of Kevan Martin, Univ. Zurich)
