Transcript A nerve cell

What is the brain made of,
how does it work and
how can we maintain it?
Nord Pool’s market forum 2007
Garmisch-Partenkirchen May 14
Jon Storm-Mathisen
Linda Hildegard Bergersen
Anatomy, Institute of Basic Medical Sciences &
Centre for Molecular Biology and Neuroscience
University of Oslo
ISBN 978-82-995010-3-3
What’s the brain made of?
•
•
•
•
78% water, 10% lipid, 8% protein, 1% carbohydrate, 3% other
All animals have a nervous system
All mammalian brains are built in the same way
The human brain is more complex than other brains (“the most
complex structure in the universe”)
"From the brain and the brain alone arise our pleasures, joys,
laughter and jests, as well as our sorrows, pains and griefs"
Hippocrates (‘Father of Medicine’, b ca 460 BC, island of Cos, Greece)
The brain and spinal cord (central nervous system,
CNS) form from the outer layer (“skin”) of the embryo
The CNS forms as a tube
at the end of the third
week after conception
The cavity of the tube
becomes the ventricular
system of the brain and
spinal cord
Langman’s Medical Embryology 6th edition
The CNS
floats in the
cerebrospinal
fluid,
formed inside
the ventricles
The living
brain can be
“seen” by
magnetic
resonance
imaging (MRI)
Brodal: Sentralnervesystemet 2nd edition
1.4 Kg
4.8 Kg
The brain is
alone….fanthastic
The brain contains ~100 billion
(1011) nerve cells
Each nerve cell connects to
~10000 others
The total number of connections
in the brain is ~1015 – rivalling
the total number of leaves in
the Amazonas rain forrest
We loose nerve cells all the time
~1/sec, 31million/year
It amounts to ~2% in a lifetime
What is a neuron?
What is a synapse?
A nerve cell is called a neuron –
after the Greek word for fibre, sinew
– because they form long fibre-like
processes, both in the brain and
spinal cord (CNS) and in the
peripheral nervous system (PNS)
A synapse is a contact point
between neurons
Nerve cell = Neuron
Nerve fibre = Axon
Receiving part = Dendrite
Nerurons are independent cells that form networks
Contact points = Synapses
In the cerebral cortex,
pyramidal cells (green)
project axons to local
and distant sites,
interneurons (red)
project locally
Synaptic transmitters
Pyramidal cells:
glutamate (excitatory)
Interneurons:
GABA (inhibitory)
Glia
Neurons are the ’main
cells’ of the brain
Glial cells comprise
’supporting’ cells of
several kinds – named
after Greek glia = ’glue’
Glia are many times as
numerous as neurons
Dendrites
Dendrites (of Greek
dendron = ’tree’) are
branched like a tree.
They receive information
from other neurons
Many neurons have spines
on their dendrites (Latin
spina = ‘thorn’), receiving
excitatory synapses
Axon
Axon (after Greek axon = axle) is
like a long cable. Many axons are
insulated by a myelin sheath
(myelin)
The axon carries the nerve signal
(electric impulse) to the nerve
ending (nerve terminal), several
thousand per nerve cell.
The nerve terminal releases the
transmitter into the synaptic cleft.
nerve terminals
Synapse
When the nerve impulse
(electrical signal) enters the
nerve ending, it opens
voltage sensitive calcium
(Ca2+) channels. Calcium
entering the nerve ending
triggers the fusion of synaptic
vesicles with the nerve
terminal membrane, to
release neurotransmitter
from the vesicle to the
synaptic cleft. The transmitter
activates receptors on the
surface of the dendrite of the
next neuron
Ca2+
How does the brain work?
Glutamate
Indeed a useful
substance
• Glutamate (gluten + amino + -ate)
[gluten: akin to clay, Old High
German kliwa bran, Latin gluten
glue, Middle Greek glia]
• Most abundant amino acid
• Protein constituent
• Metabolite
• Nutrient
• Umami taste (Japanese ‘savoury’)
[savor: from Anglo-French savur,
from Latin sapor, from sapere to
taste; be wise sage; sapiens]
• Signalling functions
Nervous tissue
Network of independent cells
Web between cell bodies = Neuropil
Approximate size
of a red blood cell
NC Danbolt
The glutamatergic synapse
VGLUT1
VGLUT2
VGLUT3
PAG
SAT1, SAT2
Farrukh A
Chaudhry
SN1
GS
EAAC1
Niels Christian Danbolt
GLT
GLAST
Storm-Mathisen får medisinpris
24.aug 2006 13:55
Jon Storm-Mathisen tildeles Anders Jahres store medisinske pris for 2006. Han
får prisen for banebrytende forskning på signalstoffer i hjernen.
Does glia release glutamate?
?
synaptiske vesikler
nerveende
?
glutamat
synapse
dendritt
glutamatresepto
r
glutamat
astrocytt
V Gundersen
Glial cells can act as servomotors
enhancing the performance of synapses
Nature Neurosci 10:331-9
http://www.cmbn.no/news.html
Publication in Nature Neuroscience on the function of glial glutamate release
[Announced 27 February 2007]
CMBN researchers Linda H Bergersen and Vidar Gundersen publish in Nature
Neuroscience on the function of glial glutamate release. Synaptic activation of
granule cells by the perforant path (the main input to the hippocampus) is
enhanced by glutamate exocytosed from astrocytes onto presynaptic NR2B
containing receptors. The mechanism is triggered by neuronal activity dependent
stimulation of P2Y1 purine receptors on the astrocytes.
Jourdain P1, Bergersen LH1, Bhaukaurally K1, Bezzi P, Santello M, Domercq M,
Matute C, Tonello F, Gundersen V2, Volterra A2 (2007)
Glutamate exocytosis from astrocytes controls synaptic strength
Nat Neurosci, 10, 331-339
1contributed equally; 2corresponding authors
See also News and Views.
Linda H Bergersen
Vidar Gundersen
The nerve impulse (= action potential)
K,Na ATPase
-makes ion gradients
that drive other tramsmembrane events
-consumes most of
the energy produced
in the brain
Voltage dependet
Na-channel makes
(first part of) the
action potential
Synapses on spines are candidates for
plastic changes
A
B
P
|||||||||||||||||||||||||||||||||||||||||||||||
PSD95
s
s
C
d
s = spine
d = dendrite
= postsynaptic density
Per Andersen 2004
AMPA receptors are inserted on demand
Activity can potentiate (LTP) or
depress (LTD) synapses
Simplified model of the intracellular pathways involved in LTD and LTP. LTD is
triggered by a modest rise in calcium that activates protein phosphatase 2B
(calcineurin) and protein phosphatase 1. This leads to the endocytosis of
synaptic AMPA receptors as well as to their dephosphorylation. LTP is
triggered by a large rise in calcium that activates CaMKII. This causes the
delivery (exocytosis) of intracellular AMPA receptors to the synapse. CaMKII
may also phosphorylate AMPA receptors directly, although this may not be
required for their synaptic delivery.
Malenka (2003) NY Acad Sci
Glutamate neurotransmission and
DNA damage and repair
Centre of Molecular Biology and Neuroscience (CMBN)
Ole Petter
Ottersen
The nerve impulse travels
at high speed – 120 m/sec
Det er helt avgjørende at
farten til elektriske
nerve impulser er rask
De raskeste
nerveimpusene har en
fart på 120 m/sek
(=432km/h). Raskere
enn en Formel 1 bil.
For at de elektriske
impulsene skal være
raske må aksonet
(nervefiberen ) være
isolert med myelin
(fettlag)
Myelin
Hvis du brenner deg på fingrene er
det svart viktig at du trekker til
deg hånden raskt.
Nerveceller sender sine signaler
raskt via nervefiberutløperen og
er dekket av et hvitt fettlag som
vi kaller myelin. Myelinet virker
som isolasjon rundt en elektrisk
ledning og får nervesignalene til
å gå 20 ganger raskere enn om
myelinet ikke var der.
I multippel sklerose ødelegges
gradvis myelinet slik at
nervecellene ikke kan sende
elektriske impulser effektivt
mellom hjernen og kroppen.
The combined length of myelinated nerve
fibres in the brain is 180000km – half the
distance from the earth to the moon
NMDA receptors are expressed in
oligodendrocytesand activated in ischaemia
Káradóttir, Cavelier, Bergersen, Attwell (2005) Nature
First paragraph | Full text | PDF | Supplementary information
See also:
Editor's summary
Article in UNIFORUM
News from Science's STKE
The myelinating processes of oligodendrocytes (needed by nerve fibres to conduct at high
speed) are shown to have a class of glutamate receptors previously thought to be confined
to neurons: NMDA receptors make cells 'learn' but can kill them if getting out of control.
EM Localization
Post-embedding immunohistochemistry reveals NMDA receptors in the myelinating processes of
oligodendrocytes. (a) EM of cerebellar cortex showing immuno-gold (arrowheads) over the
myelin. No labelling was seen with primary antibody omitted. (b) Gold particle density over
myelin was comparable to that at mossy fibre post-synaptic density (psd), and much higher than
at parallel fibre fibre psd or over axons or mitochondria in mossy fibre terminals. Scale 0.5mm
Linda H Bergersen
The brain hemispheres into four “lobes”
The lobi share the work
Parietal lobe: Body
sensation, localization
of touch, pain, etc
Frontal lobe: Start of
movements, speaking,
decision making
Occipital lobe: Vision
Temporal lobe:
Memory, sense of
place, language,
hearing, olfaction,
initiative, spontaneity
Cerebellum:
Coordination of
movement, balance
http://en.wikipedia.org/wiki/Image:Brain-anatomy.jpg
Brain stem: Connection between the
brain and the rest of the body. Centres
for control of respiration, cardiovascular
function, etc
Most brain functions are served by several brain
regions. These are interconnected by bundles of
myelinated axons.
Therefore, localized brain damage usually does
not completely destroy function, and function can
be regained through training.
Brain activity tunes brain blood flow, which can be recorded through
imaging techniques
Vision (flicker-board)
Atle Bjørnerud, Rikshospitalet
Brodal: Sentralnervesystemet 2nd edition
Brodal: Sentralnervesystemet 2nd edition
Finger-tapping
Atle Bjørnerud, Rikshospitalet
SENSASJON: En liten brikke gjør
det mulig for Matthew Nagle å styre
TV-apparatet ved hjelp av tankene.
Foto: MICHAEL EDWARDS
VG 04.04.2005
Neuronal ensemble control of prosthetic devices by a
human with tetraplegia Hochberg et al. 2006 Nature
Speach
Broca's centre
Wernicke's
centre
Atle Bjørnerud, Rikshospitalet
Pathways for sensory coding & analysis
Adapting to novel situations: Basic characteristics of events are stored as
generalized classes. Abstracted beyond specific details of sensory inputs and
motor outputs, they can be easily generalized and adapted to new circumstances.
interact
steer
store
Miller et al. (2003) Curr Opin Neurobiol 13: 198-203 / Per Andersen
How can we maintain the brain?
Use it – or loose it!
The more you put into the brain,
the more room there is
And – physical exercise is good for the brain
Physical training strengthens
the brain
(several reasons to be physically active)
Though not everyone acts accordingly, most people know
that physical activity counteracts the deterioration of the
body during aging and protects against cardiovascular
disease
Now it turns out that physical exercise protects the brain
against early aging and degenerative disease such as
Alzheimer’s and Parkinson’s
Physical exercise even enhances the performance of the
healthy brain
Didn’t we know?
Marcus Tullius Cicero ~65 BC: “It is exercise alone that supports
the spirits, and keeps the mind in vigor”
John Adams, the second president of the United States, mid-1760s:
“Exercise invigorates, and enlivens all the faculties of body and
of mind . . . It spreads a gladness and satisfaction over our
minds and qualifies us for every sort of business, and every
sort of pleasure”
Henry Ford (1863-1947) was of a different opinion (he sold T-Fords):
“Exercise is bunk. If you are healthy, you don’t need it, and if
you are sick, you shouldn’t take it”.
Motion is natural……
was necessary to survive
Hunters, gatherers, farmers, workers – human beings
always had to be in motion to find their food, to earn
their living
Only during the recent 50 years our life style has
changed to sedentary – we sit – in the car, in the truck,
in front of the PC, in front of the TV, …
Walking, jogging, running often enhance clear thinking
Research in animals and humans
show the brain works better in
physically active than in inactive
individuals
Trening og hjernehelse
Linda Hildegard Bergersen & Jon Storm-Mathisen
Tidsskr Nor Lægeforen 2006; 126: 3253
http://www.tidsskriftet.no/pls/lts/pa_lt.visSeksjon?vp_SEKS_ID=1465573
Hippocampus (on the inner/lower side of the
temporal lobe) is a part of the cerebral cortex
involved in memory
http://en.wikipedia.org/wiki/Hippocampus
New neurons are formed
continuously in certain parts of the
mature brain
Recently it was discovered that even in mature individuals new nerve cells
are continuously being formed in certain parts of the brain, notably in
hippocampus, a brain region needed for memory
If the hippocampus is destroyed, you can read the same newspaper at
breakfast every morning – you will remember neither what you read, nor
what you ate
Physical exercise enhances the formation of new nerve cells in the
hippocampus – and imporves memory and the ability to learn
What happens in the brain during
physical exercise?
Physical activity increases hippocampus dependent memory in adult
rats, and leads to increased formation of new granule cells in the
dentate gyrus, while the dendrites grow and get more spines, ie
more synapses (Eadie et al. 2005 J Comp Neurol)
New neurons continue to be formed in the dentate gyrus of
hippocampus in mammals including man. The newly formed
neurons are particularly sensitive to ’long term potentiation’ (LTP),
ie enhanced efficiency, of active synapses. They may provide
encoding of time into new memories (Aimone et al. 2006 Nat
Neurosci; Kee et al. 2007 Nat Neurosci)
Physical activity enhance by several fold the formation of new
neurons, whereas ’enriched environment’ increases the survival
rate of the new cells (Olson et al. 2006 Hippocampus)
Exercise induces new cells, growth
factors, and excitatory synaptic receptors
Growth factor: BDNF
NMDA type glutamate receptor: subunit NR2B
AMPA type glutamate receptor: subunit GluR5
Internal control (‘house-keeping gene’): HPRT
Green: neurons (NeuN)
Blue: glial cells (S100b)
Red: newly formed cells
(BrdU)
Farmer et al. (2004) Neuroscience
Physical exercise can be used as a
’mood enhancer’
Depressive disorder may be caused
reduced new formation of neurons in the
dentate gyrus
Antidepressive therapy (drugs or electroconvulsive shock) enhance this proliferation
of neurons, which may explain the latency
of the therapeutic effects
Physical activity is antidepressant, partly
through the same mechanisms, and has
addional, faster mood enhancing effects
(Ernst et al. 2006 J Psychiatry Neurosci)
Antidepressive therapy enhances the
production of endorphins (morphin-like
hormones), which enhance the
production of nerve growth factors,
which then cause new neurons to form
Physical exercise seem to work through
the same mechanisms as conventional
antidepressive therapy
In addition physical activity has other,
faster positive effects on mood – and
probably no untoward side effects
How much do you need to exercise?
A little is much better than nothing. But you must feel
the heart beat!
The more the better, up to moderate doses. The curve
levels off.
The levels of nerve growth factors continue to increase
during regularly repeated exercise for several months.
For nerve growth factors optimal effect is attained by
training only every second day, but the perspective is
lifelong, training works at all ages.
Regardless of outset – physical condition, body weight,
handicap – everyone can find a form of training to
benefit from.
Even if you have been prevented from training during a
period, you still have benefit from earlier training –
provided you continue (as is the case for the muscles).
KR Norum
Joy!
Paul Smaglik
Naturejobs editor
ISBN 978-82-995010-3-3