The assessment of working memory in rodents Dr
- Slides: 38
The assessment of working memory in rodents Dr. Paul Dudchenko University of Stirling United Kingdom
outline • how is working memory defined? • how is working memory measured in the rodent? • neural substrates of working memory
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 (1980 s; Fuster, Kubota 1970 s): 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)
Neanderthals had a limited capacity to hold and manipulate information. Working memory may underlie ability to imagine future events. “On the basis of brain-imaging studies and other research, [Daniel] Schacter and Donna Rose Addis of the University of Aukland have concluded that the same neural networks Are implicated in both remembering the past and imagining the future and that both processes probably involve something like Baddeley’s proposed episodic buffer. “Working memory is criticially important for constructing simulations of future events, ” Shacter says. ” Michael Balter (2010) Did working memory spark creative culture? Science
outline • what is working memory? • how is working memory measured in the rodent? • neural substrates of working memory
• 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
How long after the determining stimulus can an animal wait and still react correctly? (pg. 2) 1913
Hunter observed delaydependent memory. Rats could remember which light had been illuminated after a delay of up to 10 s. 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)
“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 can’t be bridged by a behavioral response.
A simple way of testing short-term memory is the delayed alternation task on a T-maze. sample Start arm delay choice Start arm
number of correct responses Performance on the T-maze is delay-dependent 6 5 4 chance 3 2 0 s 1 min 2 min memory delay 5 min 10 min
Average number correct Working memory on the radial arm maze Olton and Samuelson (1976) 4 3 2 1 chance 5 min 20 min 60 min 120 min 240 min Memory delay Bolhuis et al (1996) From: Neuroscience exploring the brain, Bear, Connors, Pardiso (2001)
outline • what is working memory? • how is working memory measured in the rodent? • neural substrates of working memory
Brain circuits implicated in neurocognitive deficits in schizophrenia Prefrontal Cortex Amygdala Temporal Cortex Striatum VP BFCS Midbrain DA neurons Raphe 5 HT neurons slide from Dr. Holly Moore
14 10 chance 6 control hippocampus lesion 2 1 2 3 Session block 4 100 90 80 70 60 50 40 percent correct Number correct 18 control chance 10 s 30 s medial prefrontal cortex 1 min memory delay Aggleton et al. (1995) J. Neuroscience
A spatial span memory task
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).
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 (Mc. Gaughy et al. , 2005). • Mice without α 7 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 β-amyloid (Young et al. 2009).
Neurons in the hippocampus fire with respect to the rat’s future destination. no reward Ainge et al. (2007) Journal of Neuroscience
goal 2 goal 1 goal 3 goal 4
food if food is found on every maze arm (so no memory is required)… food …place cells no longer encode different maze arms Stevenson et al. (2010) SFN abstracts
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 Baddeley’s human working memory model
Differential activity was also seen before the second choice point
A) B) first run start box goal box second run Dennis (1939) food Delay box food Ladieu (1944)
Average Number Correct Cue No cue 6 5 4 3 chance 2 0 s 10 s 1 min 2 min 5 min 10 min Memory Delay
sample choice Ennaceur & Delacour (1988)
sample 100 delay (0 -6 sec) 80 Percent correct choice 90 70 60 50 40 0 1 3 memory delay (seconds) 6
Control Hippocampus lesion
An olfactory “span” memory task
Distribution of correct choices on the odor span task with 12 odors 100 All animals chance % correct 80 60 40 20 0 0 1 2 3 4 5 6 7 8 9 10 11 number of odors to remember (span)
left-turn trials right-turn trials * * *
Modified T-maze spatial alternation task Do place cells that fire on the central stem of the T-maze differentiate between leftturn and right-turn trials? left-turn trial right turn trial Wood, Dudchenko, Robitsek Eichenbaum (2000) Neuron, 27: 623 -633
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