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LEARNING AND MEMORY
- Cellular and molecular mechanisms
Øyvind Høydal
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What is learning and memory?
Learning can be defined as acquisition of new
knowledge or skills and/or changes in behaviour as
a result of experience.
Memory refers to the storage and retrieval of
learned knowledge, skills or behaviours.
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Information and skills are stored within the networks
of neurons in the brain.
When we learn, changes take place that alters the way
neurons communicate with eachother.
Can you guess what changes take place?
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Cellular plasticity in learning
and memory
The efficacy of signalling between neurons are altered.
New synapses form
New neurons?
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Aplysia californica as a model system for
cellular learning and memory
Studying cellular mechanisms for learning and memory in the mammalian
brain is a formidable challenge due to the enormous number of neurons and
the complexity of synaptic connections.
Aplysia californica is an advantagous model organism because:
- Neurons are quite few (20 000) and can be identified in the circuit.
- Neurons are rather big, making them readily accessable
for in vivo intracellular recordings
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The gill-siphon reflex in aplysia offers a great
opportunity to link changes in neurons and
synapses with a behavioral output.
When a mechanical stimulus
is applied to the siphon, the
slug responds by withdrawing
its gill.
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Gill-siphon-withdrawal reflex
S
M
Tactile
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The synapse and some common forms of short-
term synaptic plasticity
Synaptic facilitation: rapid increase in synaptic strength when two APs arrive at the axon terminal
within a short interval of time. Increased Ca+ -influx causes more transmitter substance to be
released.
Synaptic depression: neurotransmitter release decline with sustained stimulation. A possible
mechanism might be depletion of neurotransmitter-containing vesicles in the presynaptic neuron.
Augementation (acts over seconds) and potentation (post-tetanic, acts over minutes) are other forms
of short-term plasticity that enhance transmitter release due to prolonged and increased Ca+ levels.
NMDA
AMPA
AMPA
Na+
AP
Ca+ Ca+ Ca
+
Na+
Na+
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Habituation in Aplysia
Habituation: reduced response to a stimulus that is neither harmful nor
beneficial.
In Aplysia: if the siphon is touched repeatedly, the snail will eventually stop
withdrawing its gill.
The response in the sensory neuron is mostly unchanged, so the habituating
effect on behaviour is likely to be mediated by a.
NTNU, May 2009 ntnu.nocbm 1 LEARNING AND MEMORY .docx
1. NTNU, May 2009 ntnu.no/cb
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LEARNING AND MEMORY
- Cellular and molecular mechanisms
Øyvind Høydal
NTNU, May 2009 ntnu.no/cb
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What is learning and memory?
knowledge or skills and/or changes in behaviour as
a result of experience.
learned knowledge, skills or behaviours.
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mation and skills are stored within the networks
of neurons in the brain.
neurons communicate with eachother.
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3. Cellular plasticity in learning
and memory
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Aplysia californica as a model system for
cellular learning and memory
mammalian
brain is a formidable challenge due to the enormous number of
neurons and
the complexity of synaptic connections.
because:
- Neurons are quite few (20 000) and can be identified in the
circuit.
- Neurons are rather big, making them readily accessable
4. for in vivo intracellular recordings
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The gill-siphon reflex in aplysia offers a great
opportunity to link changes in neurons and
synapses with a behavioral output.
is applied to the siphon, the
slug responds by withdrawing
its gill.
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Gill-siphon-withdrawal reflex
5. S
M
Tactile
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The synapse and some common forms of short-
term synaptic plasticity
two APs arrive at the axon terminal
within a short interval of time. Increased Ca+ -influx causes
more transmitter substance to be
released.
sustained stimulation. A possible
mechanism might be depletion of neurotransmitter-containing
vesicles in the presynaptic neuron.
-
6. tetanic, acts over minutes) are other forms
of short-term plasticity that enhance transmitter release due to
prolonged and increased Ca+ levels.
NMDA
AMPA
AMPA
Na+
AP
Ca+ Ca+ Ca
+
Na+
Na+
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Habituation in Aplysia
harmful nor
7. beneficial.
is touched repeatedly, the snail will
eventually stop
withdrawing its gill.
the habituating
effect on behaviour is likely to be mediated by a change in the
efficacy of the
synapse between the sensory neuron and the motoneuron.
Motor neurons
Sensory neurons
Gill withdrawal
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Habituation in Aplysia
A possible mechanism for the short-term habituating effect is
that presynaptic
Ca2+ channels become less sensitive with repeated stimulation.
Long-term habituation involves a decrease in the number of
8. synaptic contacts
between the sensory neurons and the motoneurons.
Control sensory neuron
Habituated sensory neuron
S
S
Long-term habituation
m
m
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S
M
S
I
Current
Tactile
9. Sensitization: Increased response to harmful stimulus and
stimuli concurrent to the harmful
stimulus.
In Aplysia: touching the siphon while applying electric shock to
the tail, causes enhanced
response to subsequent siphon stimulation.
Sensitization in Aplysia
Gill reflex
Stimulus
One single tail shock gives short term
(minutes) while repeting shock gives a
lasting sensitization (weeks).
Before sensitization After sensitization
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G
R AdC
11. channel
Ca 2+
Potassium
channel
Potassium
channel
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1. Tail shock: facilitating interneurons active.
2. Facilitating interneurons release 5-HT
onto the presynaptic terminal of the
sensory neuron
3. 5-HT binds to G-protein coupled
receptors to activate adenylate cyclase.
5. cAMP activates PKA which
phosphorylates K+ channels. This
12. causes K+ channels to close. Now:
a) cells stay depolarised longer
b) and release more neurotransmitter
6. The synapses are more efficient in
transmitting information
4. Adenylate cyclase makes cAMP from
ATP
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Long-term sensitization
tivity for several
minutes.
activity (and thus the behavioural response), can be
strengthened for several days.
-term response requires protein synthesis.
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R
G
AdC
ATP
cAMP
PKA PKA
MAPK
PKA
CREB1
CREB2
CRE
K+
K+
Interneuron
14. Sensory
neuron
Motor
neuron
Protein
synthesis
Mechanisms for long-term sensitization
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Molecular mechanisms for long-term sensitization
Release of serotonin from interneuron which binds to G-protein
coupled receptors on
sensory neuron.
G-protein activates adenylate cyclase
Adenylate cyclase transforms ATP to cAMP
cAMP activates PKA
PKA recruites MAPK
15. PKA activates CREB1
MAPK deactivates CREB2, wich when active inhibits CREB1.
CREB1 bindes to CRE wich induce transcription of genes
involved in synaptic growth and
development.
S S
Normal neuron Sensitized neuron
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Structural changes in long-term habituation and
long-term sensitization
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-to-motor pathway in Aplysia serves as a
prime example of how changes in synapses can lead to
a changed (learned) behavior.
16. humans? Can these also be explained by changes in
synaptic transmission?
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Molecular mechanisms for LTP
channels
18. currents, but the pore is blocked by
Mg2+ unless the cell is depolarised.
requirements to act as coincidence
detectors.
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LTP induction (early phase)
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LTP induction (late phase)
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Structural changes associated with LTP
P causes existing spines to split or enlarge.
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Ca2+ to
activate kinases (phosphorylating enzymes). These kinases
cause
higher activity in AMPA receptors, more AMPA receptors to be
included in the membrane, and synthesis of proteins involved
with
making new spines etc.
efficient at
activating the postsynaptic cell.
at some
point LTP would reach its limits.
strength, is
termed long term depression (LTD).
so depend on the NMDA receptor.
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LTD
of Ca2+ that enters the cell.
arrives, alot of Ca2+ will enter to activate kinases.
This results in LTP.
activates phosphatases (enzymes that dephosphorylates
proteins). This causes reduction of AMPA receptor
activity and density and, in the long term, a decrease in
number of dendritic spines. The result is thus a long term
depression (LTD) of the synapse.
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Spike timing dependent plasticity (STDP)
ore the postsynaptic cell fires an action potential, it is
highly
depolarised. This relieves the Mg2+ block from the NMDAR.
Thus, if the signal
from the presynaptic cell arrives just before the postsynaptic
cell fires, large
amounts of Ca2+ will enter the postsynaptic cells, and the result
will be LTP.
potential, it is
hyperpolarised. If the signal from the presynaptic cell arrives at
this point, little
Ca2+ will enter the postsynaptic cell, and the result will be
LTD.
presynaptic spiking
activity relative to the postsynaptic activity, this phenomena has
been termed
spike timing dependent plasticity.
connections between neurons that are active
simultaneously will
be strengthened. The connections between asynchronized
neurons will be
weakened.
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LTP has several features that makes it an
attractive candidate as a cellular mechanism for
learning and memory
-lasting
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Questions to be answered if we want to know if
LTP really is a cellular mechanism for learning
-
induction, will it also affect learning and memory?
24. LTP?
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Effects of manipulating LTP
studied using the Morris water-maze
task.
-knockout mice show impaired
LTP and deficits in spatial learning
Tsien et al., 1996
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Effects of manipulating LTP
LTP.
the drug ZIP erases both LTP and
memory.
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Does LTP accompany learning?
hippocampus
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Effects of saturating LTP prior to learning
spatial learning.
memory.
Moser et al., 1998
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Does learning occlude subsequent LTP
in vivo
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From LTP/LTD to memory
plasticity, and seemingly it is very much involved with
learning and memory.
formation of complex memories?
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Hebbian learning theory
repeatedly or
persistently takes part in firing it, some growth process or
30. metabolic change
takes place in one or both cells so that A’s efficiency as one of
the cells firing
B is increased».
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Hebbian learning theory
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= ”Cirkel”
External
stimulus
Cell assembly
31. Activation in cell
assembly
Reverberating
Activity in
Cell assembly
Hebbian
modification
Hebbian learning Memory / Engram
Partly activating
of network gives
Activation in whole
Bear 2008
reciprocal connections
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2006 2007
Leutgeb & Moser, Neuron, 2007
David Marr:
Pattern
separation
(1969)
Different memories are stored as different
patterns
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Emotions and memories
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Good luck on your exam!!!!
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Running Head: Planning for Retirement
Planning for Retirement
5
Planning for Retirement
AB 104- Personal Financial Management
Kaplan University
34. Parvin Hasanova Oskouie
Instructor: Gita Srinivasan
November 12, 2013
1. Have you been successful in setting up your plan?
Enchanting regulator of the savings and assembly strategy to
accomplish our objectives are the principal steps near grasping
the monetary preparation procedure. A healthy monetary
preparation guarantees a maintainable and tenable monetary
life. However captivating the first ladders to plan our savings
himself is a decent fright, the subsequent tips would safeguard
that we gain supreme welfares from the entire monetary
preparation procedure (Elmerraji, 2009).
1. Stopover escapes first: Accurate your previous financial
blunders2. Recognize that each financial judgment has an
influence on other features of your monetary life3. Know that
goal setting is a tradeoff: Prioritize realistically4. Go for a
credible expert5. Don't sit on your monetary strategy, device
directly: Budgets of postponement are enormous.
2. Has there been a change in your financial outlook for the
future?
The first thing you have to do is make a mindset shift. You have
to accept the fact that living in debt is actually an abnormal
thing to do. It’s like a house of cards that can fall at any time.
It’s like building your entire financial future on sand. There has
to be something rock-solid under your finances in order to make
sure that you have enough for the future. People have to realize
that it’s up to the individual to take care of themselves. The
only way that you can make certain that you have plenty of
money to take care of yourself in the future is to save it. To
change your own mindset about saving money, sit down and
35. make a list of what you want your future to look like. Then,
figure out how much money it will take for you to be able to
achieve your vision of the future. By doing the necessary
calculations now, you’ll be able to figure out how much you
need to be saving on a monthly or even yearly basis in order to
make that happen. You have to decide whether or not you want
a future that is fraught with danger and uncertainty, or do you
want a future that is peaceful and stable.
3. Have you found areas of your spending or saving which does
not work for you or is not beneficial to your financial success?
There are few ways to control and track your money according
to your budget. There are many areas which are not beneficial
for your spending or savings.
1) In waiting an everyday guardian of the earnings and archives.
2) Circumvent disbursing for luxurious planning packages.
3) Pathway every expenditure.
4) Program an interval for greatest care.
5) Observe your expenses, plot your forthcoming and make
alterations
4. Tell me about this experience and how it has helped you to
think more about your current and future money habits.
1. Not Placing Sufficient in Your Alternative Investments.
If you are about to leaving your occupation or be fired up
tomorrow, consuming sufficient money in your investments to
withstand you would be significant. In rational about your
present investments account, how extended would that currency
last you in the occasion that you were finished.
2. Not Following The Money You Occupy.
In deliberating evil money habits, monetary organizer Wendy
Weaver notes that not meaningful where your currency's
profitable will impede you from assembly your expenditure and
36. exchangeable boxes. For this purpose, it is serious that you
salary consideration to your cash flow while actuality aware of
the procurements you make. If you are not comfortable to
following the cash you spend, there are numerous ways to
assistance you flinch (Yahoo Finance, 2013).
3. Consuming a Ton of Credit Cards
Consuming a lot of credit cards is a wicked money custom for
numerous reasons, counting the detail that it types it
problematic for you to save pathway of anywhere all your
currency is going. Oftentimes expenditure a few bucks here and
insufficient dollars there involves misperception and prevention
at the conclusion of the month when you understand you be
indebted more than you supposed (Forbes, 2013).
5. Explain any other information which has helped you
understand the process better than you had known.
There are few things which need to understand in a better way
to develop your personal finance plan in a better way.
Following things will develop better understanding with more
depth.
1- How credit works. Credit is a contractual agreement in which
a borrower receives something of value now and agrees to repay
the lender later. It often materializes in the form of credit cards,
or loans for a car, home, or education.
2- How to check your credit report. Maintain good credit health
by verifying the accuracy of your credit report regularly.
Request an annual free copy of your report and ensure all the
information listed is accurate.
3- How to attack debt. View getting out of debt as a long-term
goal, but set smaller milestone goals that you can celebrate
achieving, such as paying off each individual creditor.
4- How to retire comfortably. Calculate how much money you’ll
need to live comfortably and learn which financial resources
37. can help you get there. Options range from basic savings
accounts and certificates of deposit, to 401(k) and pension
plans, mutual funds, stocks, bonds, and more. Boost your
knowledge about these products and seek help from a certified
financial planner when necessary.References
Elmerraji, J. 2009. Retirement Planning: Introduction. USA:
Cengage Learning.
Forbes. 2013. Personal Finance Information and Personal
Finance News. [online] Available at:
http://www.forbes.com/finance/ [Accessed: 12 Nov 2013].
Telegraph.co.uk. 2013. Personal finance news, how to make
money, how to save money - Telegraph. [online] Available at:
http://www.telegraph.co.uk/finance/personalfinance/ [Accessed:
12 Nov 2013].
Yahoo Finance. 2013. Personal Finance - Yahoo Finance.
[online] Available at: http://finance.yahoo.com/personal-
finance/ [Accessed: 12 Nov 2013].