PSYC 310 Lecture Notes - Lecture 22: Putamen, Headword, Reuptake
7 May 2018
School
Department
Course
Professor
PSYC 318
Behavioural Neuroscience II
January 24th, 2018
Lecture 6/24: Reflexive vs. reflective decisions
• Monday’s paper:
o Dopamine dependency for acquisition and performance of Pavlovian conditioned
response
▪ The word Pavlovian means the animal has no control over his
environment at all, is just a recipient to what happens, but as he learns
things his behavior will change through experience
▪ Behavior is the ‘conditioned response’ and the task is a mouse in a cage,
every minute pellet of food drops into food port, then he can go over to
eat it
▪ Every time food drops, instinctual response: when good things happen in
your environment there’s an instinctual response to approach them
• Volitional decision-making involved
o There is learning of many different types
▪ 10 seconds before food comes, lever sticks out into cage for 10 seconds,
food drops then it retracts
▪ Mouse learns over time that the lever comes out 10 s before food
delivery, and it can lead to anticipation of food delivery – amount of value
food represents starts to be signaled when lever comes out
▪ Dopamine release invigorates behavior – lever considered something
positive, so there’s instinctual response to approach it
o Introduced two kinds of mice:
▪ Dopamine KO mouse: wanted to reduce dopamine throughout the brain,
first attempt didn’t really work
• Created conditional dopamine KO mouse by locking in LoxP sites
on either side of gene of enzyme that makes dopamine
• Crossed with dopamine transporter cre mouse: it was thought that
all dopamine neurons have a dopamine reuptake transporter
• Put cre under control of gene promoter, all dopamine neurons
have cre, lose ability to make dopamine
▪ Reduced dopamine dramatically in this mouse but there was still 5% left
of normal dopamine levels
▪ True dopamine KO mouse: The zero dopamine mice (DD mice)
• Stop signal flanked by LoxP sites between gene promoter
encoding enzyme to make dopamine: no cells can ever make
enzyme needed to make dopamine unless they have cre (tyrosine
hydroxylase)
• Require daily injection of L-Dopa to keep them alive
• Pavlovian learning protocol
o For 5 days, 25x a day, food is dropped in food port, preceded by presentation of
a lever
o Measuring head entries from mouse into food hopper during cue presentation,
indicating that the mouse has learned cue-reward association
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o A demonstration of learning is the mouse sticking head into food hopper when
lever is out for 10 seconds, do it more during this time than any other time
▪ Mice tend to check food port on average once every 10 seconds, but
when lever is out they check every other second – dramatic increase in
rate of checking food port
▪ This is the conditioned approach behavior = (head entries during cue
period) – (head entries during intertrial interval)
▪ Following training, wild-type mice with no manipulations 4x as likely to
check food port when lever is out than they are otherwise
o Pavlovian learning with 5% of dopamine
▪ 5% dopamine mice do not exhibit Pavlovian conditioned approach
behavior
• Over 5 days of training, conditioned approach (head entries per
minute when lever is out – when it is not out)
• 0 on y-axis is that the animal is not checking food port more often
when the lever is out
• For 5% dopamine animals after 5 days, they are basically no more
likely to stick head into port when lever is out than not: whereas
wild-type mice show increase over 5 training days with a higher
conditioned approach score
▪ 5% dopamine mice are always checking food port every 10s and are
eating all the food, they just do not use lever to guide their behavior at all
▪ You need more than 5% of dopamine to recognize that the lever is
predicting food availability
▪ One critique of this experiment:
• 5% dopamine mice are not running over to food hopper as soon
as lever comes out because they’re obsessed with sign tracking:
seen in some other animals (pigeons, rats)
• You need to measure if lever excites/motivates them
• Manifesting their learning in a different kind of behavior?
o Video recording mice to see what exactly they do when the
lever comes out:
o Wild type mice check food hopper whenever lever comes
out, dopamine knockout mice don’t respond at all to the
lever
o Dopamine knockout animals don’t exhibit sign-tracking
either: all mice are either going to food hopper or do
nothing
▪ Another critique: mice are slow, maybe they are not motivated enough
when lever comes out to approach it (not running like the other mice)
• Restore dopamine by giving L-DOPA injection
• Give one injection of L-DOPA to cause slow mice to become
hyperactive for 2 hours, they should start acting like control mice
• After 10 days, with restored dopamine release just before
eterig age, doest help their perforae at all (the
dopamine knockout mice)
o KO ie dot respod a differetl to leer: ot just
slow but really have not learned
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• BUT if you give KO mice injection of L-DOPA everyday before they
eter the task thell lear it at sae rate as ild-type mice
o Restoring dopamine learning
o Dopamine seems to be necessary to learn that a lever can
be used to predict food availability
o If dopaie is ot preset eforehad the ot lear it
o But if restored for 5 days before they have the capability
to learn this
• There should be a burst of dopamine release initially before food
osuptio: KO ie dot hae eough dopaie to hae this
urst
• Eer tie food oes, aial goes oer to eat it ut doest
osider it a reard eause dopaie sigal ist oeig this
(in KO mice)
o In WT animal, food comes and strengthens synaptic
connections of whatever was recently active: what
happened in seconds preceding food delivery (aka reward)
which was the lever coming out
o After 3 days of training, lever information has strong
synaptic strength and enters basal ganglia as an important,
valuable piece of information that should cause an
instinctive motivated approach
o When you restore dopamine, it strengthens neural circuits
recently active before food delivery
• Is dopamine needed to maintain behavioral response to the
lever?
• So:
o Daily injections of L-dopa from the beginning largely
restores learning ability
o The first day L-dopa injections are stopped, but mice still
perform just fine
o It appears that the learned cue-reward association soon
extinguishes without L-dopa, despite the mice still getting
food
• Stimulus-reward learning performance
o In KO animals, as soon as you removed dopamine again
the ehiited ehaiors as if the eret gettig reard
despite still receiving the food and eating it
▪ 5% of normal dopamine levels in the striatum is enough to provide some
ability for mice to move and eat, but this amount of dopamine is not
sufficient to learn simple cue-reward associations
• If mice first learn a cue-reward association then their dopamine
levels are brought down to 5% of normal, these mice will initially
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Document Summary
Is dopamine needed to maintain behavioral response to the lever: so, daily injections of l-dopa from the beginning largely restores learning ability, the first day l-dopa injections are stopped, but mice still perform just fine. It appears that the learned cue-reward association soon extinguishes without l-dopa, despite the mice still getting food: stimulus-reward learning performance. Imagine you wake up each morning and go for half hour run throughout. Montreal: at each corner you choose if you want to go left or right. Differences in predictions (incorporating current real value) causes error signal that is presumably used to update previous predictions. If you find yourself in a new kind of situation, these values may not be that helpful. However now he is thirsty, and water is right. Initially he will probably go left and encounter cheese, but not want it. There is also time of day, presence of specific cues, et(cid:272).
