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Fabrizio Gardoni 9 Marzo 2010
Il cervello come funziona 1: neuroni
Neurons
Types of Neurons
Sensory Motor Interneurons
From sensory organs to the brain and spinal
cord
From the brain and spinal cord to the
muscles and glands
Carry information between other neurons
Principali componenti di un neurone
7
The cell body
Round, centrally located structure
Contains DNA
Controls protein manufacturing
Directs metabolism
No role in neural signaling
Contains the cell’s Nucleus
8
9
1
0
Dendrites
Information collectors
Receive inputs from neighboring neurons
Inputs may number in thousands
If enough inputs the cell’s AXON may generate an output
1
1
Axon
The cell’s output structure
One axon per cell,
Tube-like structure branches at end that connect to dendrites of other cells
Diversi tipi di neuroni nel Sistema Nervoso Centrale: classificazione in base alla morfologia
1
5
How neurons communicate
Neurons communicate by means of an electrical signal called the Action Potential
Action Potentials are based on movements of ions between the outside and inside of the cell
When an Action Potential occurs a molecular message is sent to neighboring neurons
Concentrazioni degli ioni
Cell Membrane in resting state
K+
Na+ Cl-K+A-
Outside of Cell
Inside of Cell
Na+ Cl-
Le caratteristiche più salienti del potenziale d’azione sono:
- Una forma particolare (spike) che presenta un’inversione transitoria della polarità della membrana
- Propagazione senza decremento per l’intera lunghezza della fibra
- Ruolo attivo dei canali di membrana del Na+ e del K+ voltaggio-dipendenti.
Condizione necessaria e sufficiente affinché un potenziale d’azione possa innescarsi è che
la depolarizzazione della membrana cellulare, opportunamente stimolata, raggiunga un
livello di potenziale soglia (threshold)
Potenziale d’azione
Synapse
What does a synapse (and a neuron) look like?
MicroscopyFluorescent Proteins
Post Synaptic Density Electron microscopy
What does a synapse look like?
Wild-type
Fragile X syndrome
Alteration of dendritic spine morphology in Fragile X Syndrome
Comery et al., 1997
Dendritic spine alterations in Alzheimer’s Disease
Rocher et al, 2008
Control
Alzheimer’s Disease
Model of Excitatory Central Synapse Formation
Goda et al., 2004
1
2
3
4
The mechanisms that govern synapse formation and elimination are fundamentalto our understanding of neuronal development and synaptic plasticity.
How do thin spines learn to be mushroom spines that remember?
Synaptic activity leads to a “maturation” of thin spines into mushroom spines.
Determining the mechanisms that regulate spine morphology is essential for understanding the
molecular and cellular changes that underlie learning and memory.
The mechanisms that regulate spine morphology is essential for both neurodevelopmental and
neurodegenerative disorders.
modified by Bourne and Harris, 2007
Mushroom spines have larger postsynaptic densities, which anchor more AMPA glutamate receptors and make these synapses functionally stronger
How do thin spines learn to be mushroom spines that remember?
Sugiura et al., 2009
Regulation of dendritic spine maturation and plasticity by N-Cadherin
Regulation of dendritic spine maturation and plasticity by N-Cadherin/ADAM10 pathway
Mysore et al., 2008
NMDA receptors
MAGUKs
aCaMKII
AMPA receptors
a-actinin
actin
mGlu receptors
homershank
GKAP
N-Cadherin
Catenina
b
nNOS
RASSynGap
actin
mGlu receptors
ab
Major Neurotransmitters in the Body
Neurotransmitter Role in the Body
Acetylcholine A neurotransmitter used by the spinal cord neurons to control muscles and
by many neurons in the brain to regulate memory. In most instances,
acetylcholine is excitatory.
Dopamine The neurotransmitter that produces feelings of pleasure when released by
the brain reward system. Dopamine has multiple functions depending on
where in the brain it acts. It is usually inhibitory.
GABA
(gamma-aminobutyric acid)
The major inhibitory neurotransmitter in the brain.
Glutamate The most common excitatory neurotransmitter in the brain.
Glycine A neurotransmitter used mainly by neurons in the spinal cord. It probably
always acts as an inhibitory neurotransmitter.
Norepinephrine Norepinephrine acts as a neurotransmitter and a hormone. In the
peripheral nervous system, it is part of the flight-or-flight response. In the
brain, it acts as a neurotransmitter regulating normal brain processes.
Norepinephrine is usually excitatory, but is inhibitory in a few brain areas.
Serotonin A neurotransmitter involved in many functions including mood, appetite,
and sensory perception. In the spinal cord, serotonin is inhibitory in pain
pathways.
NIH Publication No. 00-4871
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