Download MOLECULES and BEHAVIOR

MOLECULES and BEHAVIOR
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Motivation
Reward
Depression
Anxiety
Stress
Schizophrenia
TOC-Compulsive Disorder
ADHD-Attention Deficit Hyperactivity Disorder
Aggressivity
Mood Disorders
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MOLECULES and BEHAVIOR
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Motivation
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b.
c.
d.
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Generalities: the Brain - the Neuron - Neurotransmitters
Brain and Behavior
Motivation Theories - Self-motivation - Motivation and Learning
Types of Learning - Motivation and Memory
Reward
Depression
Anxiety
Stress
Schizophrenia
TOC-Compulsive Disorder
ADHD-Attention Deficit Hyperactivity Disorder
Aggressivity
Mood Disorders
The Brain
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The Brain
The Brain
• Cerebral Cortex –
thought, language,
reasoning,
movement, sensation
• Corpus Callosum –
connects the right
and left hemispheres
• Cerebellum –
movement, balance
• Brainstem –
breathing, heart rate
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Lobes of the Brain
hippocampus
PLAN
ACTION
LEARN
MEMORY
GOAL
DIRECTED
BEHAVIOR
OPTIMAL
STIMULI
RESPONSE
AFFECT
amygdala
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The Neuron
• The brain’s most basic functional unit
The Neuron
Soma
Dendrites
Myelin
Sheath
Axon
Axon
Terminals
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The Neuron
• Soma (cell body) – contains nucleus,
cytoplasm, organelles
• Dendrites – receive info
• Axon – transmits info
• Myelin sheath – covers the axon to
increase transmission speed (cause of
sensory and motor disturbances in
multiple sclerosis)
Action Potentials
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Action Potentials
•
•
•
•
•
•
•
How neurons transfer info
Changes neuron’s membrane potential
Rising phase – membrane depolarizes
Overshoot
Falling phase – membrane repolarizes
Undershoot
Restoration of resting potential
The Synapse
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The Synapse
• Axon terminal releases
neurotransmitters
• Neurotransmitters cross
the synapse and bind to
receptors on another
neuron
• Neurotransmitters
released, taken up
again by first neuron
Neurotransmitters
• Acetylcholine – movement (respiratory paralysis)
• Serotonin – mood, sleep, appetite, anxiety
(depression, obsessive-compulsive disorder, panic
disorder)
• Dopamine – motivation, pleasure (schizophrenia,
Parkinson’s)
• Epinephrine and Norepinephrine – attention, anxiety,
stress (epilepsy, mania in bipolar disorder)
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neurotransmitter criteria
According to classical definitions, what criteria must be met in order to claim that
a substance serves as a neurotransmitter?
1) Substance is present in nerve cell, specifically at the terminal
2) Cell can synthesize or accumulate the substance
3) Substance is released from nerve terminal in activity- and Ca2+-dependent fashion
4) Substance mimics functional activity seen following nerve cell stimulation (in magnitude
and quality).
5) Drugs that simulate/antagonize effects of nerve cell activation have identical effects on
exogenously applied substance.
6) Active mechanism for terminating action of the substance (e.g. enzymatic degradation,
uptake)
Main Neurotransmitters
⇒ Biogenic amines (classical
neurotransmitters)
catecholamines (dopamine,
norepinephrine and epinephrine)
serotonin (5-HT)
histamine
⇒ Acetylcholine
⇒ Purinergic transmitters
(ATP, UTP, adenosine)
⇒ Amino acid transmitters
Glutamate (aspartate)
GABA, glycine
⇒ Peptide neurotransmitters
(a huge and growing list)
⇒ Unconventional transmitters
(nitric oxide, carbon monoxide)
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types of receptors
ionotropic receptors
the receptor itself incorporates an
ionophore (ion channel), the gating
of which is allosterically regulated
by agonist binding to the receptor
metabotropic receptors
the receptor signals via intracellular
intermediates to effect a change in ion
channel gating, cell excitability,
metabolic state or gene expression
catalog of receptors
ionotropic receptors
metabotropic receptors
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why are there so many flavors of
transmitter and receptor?
1) Chemical coding of inputs
can be used to distinguish among
different afferents
2) Differential release depending
on presynaptic activity pattern
alter qualitatively the postsynaptic
response as a function of presynaptic
activity pattern
why are there so many flavors of
transmitter and receptor?
3) Allow summation of effects from different afferents
4) Allow effects in different time domains
fast ionotropic effects
slower metabotropic effects
5) Allow effects in different spatial domains
e.g. peptides can diffuse away from release sites and interact with very
high affinity receptors
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Precursor
Synthesis
Storage
= vesicle
= neurotransmitters
= receptor
Degradation
Reuptake
Release
Synaptic
Cleft
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dopamine
transporters
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Neuropharmacology
Reuptake Inhibitors
• Prevent reuptake of neurotransmitters
from the synapse
• Selective serotonin reuptake inhibitors
• Example: Prozac<
– Treats depression, OCD, panic disorder
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Brain and Behavior
Brain and Behavior
• Unlikely to be a center in the brain causing a
single behavior (eg. bulimia, anorexia)
• Behavior combination of multiple “traits”
• Gene differences can alter temperament “traits”
and brain chemistry
• How do we figure out what is a trait?
– Do they occur before someone develops a certain
pathological behavior ?
– Do they persist after recovery from pathology?
– Do they run in families?
• How does temperament become an illness?
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DOES THE BRAIN CODE
BEHAVIOR?
• OLD: Syndromes – collection of symptoms
– anorexia, bulimia, depression, anxiety
• NEW: Behavioral Economics
– Assess stimuli
– Compare to past memories
– Choose appropriate response, consider short and
long term consequences
– Action
– Assess effect of action
– Learn from experience
What Is Motivation?
Direction
Intensity
Prentice Hall, 2001
Persistence
Chapter 6
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What Is Motivation?
I was saying
"I'm the greatest”
long before
I believed it.
Intensity
What Is Motivation?
Direction
Intensity
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What Is Motivation?
Direction
Intensity
It's not that I'm so
smart, it's just that I
stay with problems
longer.
Persistence
Theories of Motivation
Needs theories
• Maslow’s
hierarchy of needs
• Herzberg’s two
factor theory
Process theories
• Expectancy Theory
• Goal Setting Theory
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Needs Theories
Needs theories
• Maslow’s
hierarchy of needs
• Herzberg’s two
factor theory
Maslow
Herzberg
Self-Actualisation
Motivators
Esteem
Social
Safety
Hygiene
Factors
Physiological
Contrasting Views of Satisfaction
and Dissatisfaction
Traditional view
Satisfaction
Dissatisfaction
Herzberg's view
Motivators
Motivators
Satisfaction
Herzberg
No satisfaction
Hygiene Factors
No dissatisfaction
Dissatisfaction
Hygiene
Factors
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Expectancy Model of
Motivation
Effort
Effort
Performance
Perceived effort performance
probability
Perceived
performance reward probability
Perceived
value of reward
“What rewards
will I get when
the job is well done?”
“What rewards
do I value?”
“If I work hard,
will I get the job
done?”
Reward
Expectancy Model of
Motivation
Individual
Effort
1
Individual
Performance
2
Organisational
Rewards
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1. Effort-Performance relationship = Expectancy
2. Performance-Rewards relationship = Instrumentality
Personal
Goals
3. Rewards-Personal goals relationship = Valence
Prentice Hall, 2001
Chapter 6
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Expectancy Model of
Motivation
How Expectancy Theory Works
Your tutor offers you £1 million if you memorise the textbook by tomorrow morning.
Expectancy
Instrumentality
Effort - Performance Link
Performance - Rewards Link
No matter how much effort
you put in, probably not possible
Valence
Your tutor does not look
Rewards - Personal Goals Link
There are a lot of wonderful things
like someone who has £1 million
you could do with £1 million
I=0
V=1
to memorise the text in 24 hours
E=0
Conclusion: Though you value the reward, you will not be motivated to do this task.
Goal Setting
Goals
Specific
Difficult
Accepted
Effects on Person
Directs attention
Energises
Encourages persistency
New strategies developed
Performance
Feedback
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Self-Motivation
• Self-fulfilment and satisfaction
• Difficult goals lead to higher performance
• Motivation to act depends on the attractiveness of
the outcome
Goals
Specific
Difficult
Accepted
Effects on Person
Directs attention
Energises
Encourages persistency
New strategies developed
Performance
Feedback
Motivation
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How can satisfaction and its linkage with performance
help tie together insights of the motivation theories
into an integrated motivational model?
Work
effort
needed
Organizational
support
Amount &
schedule of
contingent
extrinsic
rewards
Equity
comparison
Net
amount of
valent
intrinsic
rewards
Satisfaction
Motivation
Individual
attributes
Performance
An Integrated Model of Individual Motivation to Work
Experience is based on Reward
•a positive experience induces reinforcemement
• and leads to habit
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a REWARD
induces Positive Emotional Response
acts as a REINFORCER or GOAL
prevents EXTINCTION of a habit
EFFORTFUL Response
arises through Learning
WHAT is
REWARD
ENVIRONMENT
INSTINCT
PROCESSING
IMAGERY
PERCEPTION
MEMORY
ANTICIPATION of PLEASURE
AROUSAL
MOTIVATION
COMPLEX BEHAVIOR
(feeding, HABITS
sex, learning, etc)
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Natural Rewards Elevate Dopamine Levels
% of Basal DA Output
NAc shell
150
100
50
Empty
Box Feeding
SEX
200
150
100
15
10
5
0
0
0
60
120
Time (min)
Di Chiara et al., Neuroscience, 1999.
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Copulation Frequency
DA Concentration (% Baseline)
FOOD
200
Female Present
Sample
Number
1
2
3
4
5
6
7
8
Mounts
Intromissions
Ejaculations
Fiorino and Phillips, J. Neuroscience, 1997.
Increase in DA in nucleus accumbens induced
by food and by amphetamines as assessed by
microdialysis in rodents
Volkow and Wise 2005
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Brain Reward Center - Dopamine D2 Receptors
are Lower in Addiction Volkow et al
DA
DA
DA
DA DA
DADA
DA D2 Receptor Availability
Cocaine
Alcohol
Heroin
DA
DA
DA DA
DA
Reward Circuits
Non-Drug Abuser
DA
DA
DA
DA
DA
DA
Reward Circuits
control
addicted
Drug Abuser
The Reward Pathway
Sustains life
through pleasure
Activated by pleasurable
experience
Food - sex - learning - etc
Dopaminergic
Major Anatomical Structure
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• DA neurons are activated to perform certain behavior
–motivational stimuli
–motivational learning
–reward prediction
Activity in a DA neuron during a task
DA Neuron are activated immediately before delivery of a
reward,
whether a movement is required or not,
but are not activated in unrewarded trials
1. DA neurons respond to unpredictable
rewards and produce a global
reinforcement signal
2. Some neurons also react to the
expectation & detection of
reward.
3. Other neurons show reward-related
activities related to the
preparation,
initiation
execution
of movement.
Learning Theories
How do we know what we know? - What do we mean by “learning”?
we say that we have learnt something, if our experiences result
in a change of our behaviour or our capabilities.
“We learn by association. Our minds naturally connect events
that occur in sequence.”
This process of learning associations = “Conditioning”
classical conditioning
instrumental learning or operant conditioning
Observational Learning
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Learning Theories
• Nonassociative Learning
– Habituation
– Sensitization
• Classical Conditioning
• Instrumental Learning
• Observational Learning
Reinforcement theories
how are they linked to motivation?
 Reinforcement.
– The administration of a consequence as a
result of a behavior.
– Proper management of reinforcement can
change the direction, level, and persistence
of an individual’s behavior.
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Reinforcement theories
how are they linked to motivation?
 Classical conditioning.
– A form of learning through association that
involves the manipulation of stimuli to
influence behavior.
– Involves an initial stimulus (unconditioned
stimulus) and a conditioned stimulus in the
learning of behavior.
Reinforcement theories
how are they linked to motivation?
 The classical conditioning process.
– Behavior is caused by an unconditioned
stimulus.
– A conditioned stimulus is paired with the
unconditioned stimulus.
– The conditioned stimulus is able to evoke
the behavior.
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•Tone comes to produce same response as food.
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Classical conditioning
Discrimination Learning
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

Discriminative Schedule – present 2 distinct stimulis CS+
8,000 Hz tone (reinforced) CS- (not)
Stimulus Generalization – tendency to respond to similar
stimuli
Discrimination training increases weights between CS+ & CR,
increases inhibition between CS- and CR
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Reinforcement theories
how are they linked to motivation?
 Operant conditioning.
– The process of controlling behavior by
manipulating its consequences.
– Focuses on the interplay of antecedents,
behavior, and consequences.
Reinforcement theories
how are they linked to motivation?
 Antecedents
– The condition leading up to or cueing behavior
 Behavior
– The action taken by the person
 Consequences
– The outcome received by the person
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Operant Conditioning
How animals learn to solve Problems (Thorndike, 1898)
Example : place a hungry animal in a cage, which opens by pressing a lever.
Outside the cage there is food. On successive trials the animal became quicker
at opening the cage door (= instrumental learning or operant conditioning)
the animals behaviour is instrumental for bringing about a certain outcome.
Skinner’s experiments (Skinner box)
Chamber with metal flooring and a
lever connected to a food dispenser.
The metal floor enables the
administration of an electric shock,
whereas pressing the lever releases a
food pellet.
if a lever press resulted in the release
of a food pellet, the rats’ “response”
would soon increase in frequency.
Thus the lever pressing was reinforced.
If the press of the lever is punished
with the delivery of an electric shock, the
animals’ response frequency would
soon decrease.
Operant Conditioning
Instrumental Learning




Instrumental Learning
Reinforcement
Operant Behaviors
Skinner Box
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Mixtures of Classical and
Instrumental Conditioning
• Both Occur Simultaneously
• Instrumental (operant) conditioning ResponseReward contingency
– but, Stimulus-Reward contingency is also being
tracked
• Autoshaping
– suggests, stim-reinforcer relations inevitably present
when response-reinforcer relations present
Observational Learning
How do we learn how to write, drive a car read,…?
Classical and Operant conditioning would be tedious ways of learning such
complex behaviours. It is easier to observe someone and then imitate what
they did = observational learning
Especially humans are extremely efficient at this type of learning
because we are able to use language in addition.
Similar to Classical and Operant conditioning it has important adaptive
functions.
4 components:
Attention
Retention = Remember what you want to imitate.
Reproduction = Imitation of behaviour.
Motivation = Incentive for imitating behaviour
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Learning and Memory
Learning = Acquisition of knowledge or
skills through experience and / or
instruction.
Memory = The storage of acquired
knowledge for later recall.
The basis for learning and memory is achieved through:
• changing the effectiveness of a synapse
• developing new synapses.
Learning and Memory
Types of learning
1. Habituation – a decrease in response
occurring from repeated stimulation
2. Sensitization – an increase in response
after experience of an unpleasant
stimulus
3. Classical conditioning – an association of
two stimuli, expecting one with the other
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Learning and Memory
MEMORY : the Hippocampus
We have two types of memory: Short Term and Long Term
Important for formation of
short term memory
Important for transferring
short term memory to long
term memory
Types of Memory
“primary”
short-term
working memory
episodic memory
[declarative, explicit]
“secondary”
long-term
semantic memory
procedural memory
[non declarative, implicit]
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Discriminative Learning
Role of the Accumbens
Stages of conditioned taste aversion learning (CTA)
1.
2.
3.
4.
Consistently with its evolutionary significance of avoiding harmful foods, CTA takes place in
relation to the consequences of the digestion and absorption of food contents.
To allow sufficient time for these processes to be completed, a short-term memory trace of
the salient gustatory stimulus has to be formed and stored to be later associated with the
outcome of feeding.
Blockade of D1 DA receptors impairs consolidation of the gustatory trace. Thus, the
gustatory trace is weakened and eventually lost before an association between the
representation of the gustatory stimulus and the aversive visceral state is made.
By this mechanism, the whole associative learning process is impaired.
Hypothesis on the Neural
Substrate of Memory
genomic level
changes in genes associated with plasticity
cellular level
changes in the connections between
neurons [synaptic plasticity]
neural ensemble level
behavioral level
changes in the dynamics of neuronal
groups [metaplasticity, maps]
behavioral changes associated with
learning and memory
Do causal links exist between the different levels?
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Short Term Memory
Short Term Memory involves changing the effectiveness of
a synapse. (Strengthening or Weakening of synapses)
In a simplistic way this means that either less or more
neurotransmitter is released from a synapses or synapses
following a repeated stimulus.
It all requires CALCIUM IONS
•Habituation
(decreased neurotransmitter release)
•Sensitization
•Long Term Potentiation
(increased neurotransmitter release)
Long Term Memory
Involves protein synthesis
Formation of new dendritic ‘spines’ (increased surface area)
Formation of new synapses
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Long Term Memory
Dendrites
Dendritic Spines
Long Term Memory
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Basal Ganglia
The medial caudate and nucleus
accumbens receive their input from
frontal cortex and limbic areas
The caudate and putamen are
reciprocally interconnected with the
substantia nigra (SNr-SNc)
The caudate and the putament send
most of their output to the globus
pallidus (Gpe-Gpi)
The globus pallidus can also be divided
into two parts: the globus pallidus
externa (GPe) and the globus pallidus
interna (GPi). Both receive input from
the caudate and putamen, and both are
in communication with the subthalamic
nucleus (STN).
Basal Ganglia
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GABA and Glutamate Role in Motivation
Basolateral
Amygdala
Nucleus
Accumbens
Prefrontal
Cortex
Ventral
Pallidum
Dopamine
Ventral Tegmental
Area
Mediodorsal
Thalamus
Motor
Nuclei
GABA
Glutamate
Adapted from Kalivas and Nakamura, Curr. Opin. Neurobiol., 1999.
Reading
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