The assessment of working memory

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The assessment of working memory in rodents
Dr. Paul Dudchenko University of Stirling United
Kingdom
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outline

• how is working memory defined?

• how is working memory measured in the rodent?

• neural substrates of working memory

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How is working memory defined?
Baddeley and Hitch (1974) Working memory is
comprised of a visual-spatial sketchpad, an
episodic buffer, a phonological loop, all of
which are controlled by a central executive.
(humans)
Honig (1978) Working memory is a representation
of a cue over a delay period in which the cue is
not present, to be subsequently used to respond.
(pigeons)
Olton, Becker, and Handelman (1979) Spatial
working memory, but not reference memory,
depends on the hippocampus. (rats)
Goldman-Rakic (1980s Fuster, Kubota 1970s)
Working memory operationalised as the on-line
representation of a stimulus over a delay period
in the pre-frontal cortex. (monkeys)
Dudchenko (2004) Working memory is a short term
memory for an object, stimulus, or location that
is used within a testing session, but not
typically between sessions. (rats)
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outline

• what is working memory?

• how is working memory measured in the rodent?

• neural substrates of working memory

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• all spatial working memory tasks

• all depend on the hippocampus/medial temporal
  cortex

From Hagan and Jones (2005) Predicting drug
efficacy for cognitive deficits in
schizophrenia Schizophrenia Bulletin, 31(4)
830-853
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How long after the determining stimulus can an
animal wait and still react correctly? (pg. 2)
1913
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Hunter observed delay-dependent memory.
Rats could remember which light had been
illuminated after a delay of up to 10s.
Hunter (1913)
However The rat, when put into the release box
during the delayed reaction, oriented immediately
to the light with its entire body, and began a
series of attacks on that side of the box in
an effort to get out. (pg. 41)
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Mediating behaviours during the delay between
the to-be-remembered stimulus and the response
has also been observed in operant delayed
non-matching to position tasks (Dudchenko
Sarter (1992) Chudasama Muir (1997)).
sample
delay
choice

• So, one of the intrinsic challenges in
  developing valid rodent
• memory tasks is ensuring that delays cant be
  bridged by a
• behavioral response.

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A simple way of testing short-term memory is the
delayed alternation task on a T-maze.
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Performance on the T-maze is delay-dependent
number of correct responses
chance
memory delay
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Working memory on the radial arm maze Olton and
Samuelson (1976)
Bolhuis et al (1996)
From Neuroscience exploring the brain, Bear,
Connors, Pardiso (2001)
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outline

• what is working memory?

• how is working memory measured in the rodent?

• neural substrates of working memory

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Brain circuits implicated in neurocognitive
deficits in schizophrenia
Prefrontal Cortex
Amygdala
Striatum? VP
Temporal Cortex
BFCS
Midbrain DA neurons
Raphe 5HT neurons
slide from Dr. Holly Moore
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A spatial span memory task
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Odor span memory in rodents is excellent, but
may not require the hippocampus.

• The hippocampus is required for remembering the
  order in which odors are presented
• (Fortin et al. 2002).

• Humans with hippocampus damage are impaired on
  an odor span task (Levy et al.
• 2006).

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Odor span neural substrates

• Removal of basal forebrain cholinergic neurons
  impairs performance on this task (Turchi
• and Sarter, 2000).

• Removal of cholinergic inputs to the entorhinal
  cortex does not impair memory for familiar
• odors, but does impair memory for new ones
  (McGaughy et al. , 2005).

• Mice without a7 nicotinic acetylcholine receptor
  are impaired on the odor span task
• (Young et al. 2007).

• Nicotine improves odor span memory scopolamine
  and mecamylamine impair it
• (Young et al. 2006 Rushforth et al. , 2010).

• Odor span also impaired in mice that
  over-express ß-amyloid (Young et al. 2009).

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Neurons in the hippocampus fire with respect to
the rats future destination.
no reward
reward
no reward
reward
Ainge et al. (2007) Journal of Neuroscience
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goal 2
goal 3
goal 4
goal 1
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if food is found on every maze arm (so no memory
is required)
place cells no longer encode different maze arms
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summary

• notions of working memory have developed
  independently
• in the human and non-human literatures

• in rodents, working memory has been
  operationalized a
• delay-dependent, short-term memory for a
  location, object,
• or stimulus

• in rodents, spatial working memory requires the
  temporal
• cortex and hippocampus, and neurons in the
  hippocampus fire
• with respect to future goal locations

• as such, rodent spatial working memory tasks may
  reflect
• the episodic buffer portion of Baddeleys
  human working memory
• model

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Differential activity was also seen before the
second choice point
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B)
A)
first run
start box
goal box
second run
Dennis (1939)
Ladieu (1944)
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Cue
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No cue
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Average Number Correct
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chance
3
2
0 s
10 s
1 min
2 min
5 min
10 min
Memory Delay
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sample
choice
Ennaceur Delacour (1988)
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sample
delay (0-6 sec)
choice
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Control
Hippocampus lesion
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An olfactory span memory task
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Distribution of correct choices on the odor span
task with 12 odors
100
80
60
correct
40
20
0
0
1
2
3
4
5
6
7
8
9
10
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number of odors to remember (span)
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Modified T-maze spatial alternation task
Do place cells that fire on the central stem of
the T-maze differentiate between left-turn and
right-turn trials?
Wood, Dudchenko, Robitsek, Eichenbaum
(2000) Neuron, 27 623-633