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