Download What is the role of acetylcholine in mediating the interaction

What is the role of acetylcholine in mediating the interaction between
visual attention and perceptual learning?
Proposed by: Matthew Chalk
Speaker: Alex Thiele
Perceptual learning, where performance in a simple sensory task improves with practice, has usually been thought to occur only when attention is focussed on the stimuli that is to be learned [1].
However, recent psychophysical experiments have suggested not only that learning can occur as a result of exposure to a subliminal stimulus [2], but that there is a complicated interaction between the
processes of perceptual learning and attention [3]. While there are indications that the neuromodulator acetylcholine (ACh) plays an important role in both attention and perceptual learning, the
molecular basis for the interaction between these two cognitive processes is not understood. Here,
I propose to investigate this in experiments where macaque monkeys perform perceptual learning
tasks involving motion discrimination of a random-dot image, with and without local blockade of
ACh receptors in visual area MT. Training will take place under different states of task-specific
attention to the stimulus that is to be learned, using psychophysical paradigms developed by Seitz
et. al [2, 3]. Finally, by applying direct stimulation during training to areas of the brain that send
cholinergic projections to the visual cortex, I propose to investigate whether these projections are
responsible for mediating the interaction between task-specific attention and perceptual learning.
Introduction
Perceptual learning is the process whereby practice of simple sensory tasks leads to an increase in performance. Such
improvements have been shown to be very specific to the
trained task: for example, in tasks where participants have
to discriminate between small changes in the direction of motion between two stimuli, improvements in performance occur
only for the direction of motion for which the training took
place [4]. This learning specificity has lead to the assumption
that perceptual learning takes place in the early sensory areas
where neurons have such specificity, and indeed, electrophysiological studies in the visual cortex have shown changes in
the stimulus response properties of neurons in V1, MT and
V4 following various different perceptual learning tasks [5–7].
Interestingly, a recent study by Li et. al. [8] found that following training on several different object recognition tasks,
the response properties of V1 neurons changed in a way that
depended on the perceptual task that was being performed,
suggesting that changes in the neural response of early sensory
areas during perceptual learning are dependent not only on
bottom-up signals relating to the sensory input, but also on
top-down influences which relate to the behavioural context
and attentional state of the animal.
In a series of psychophysical experiments, Seitz and
Wanatabe investigated how task-specific attention interacts
with and modulates perceptual learning. In one experiment, subjects were required to perform recognition of letters
flashed in front of them while in the background a motion
signal was displayed, with low coherence so subjects were unaware of the direction of motion. When susequently tested in
a motion discrimination task, subjects exhibited an increase in
performance in the task only for the direction of motion corresponding to the below threshold stimulus which they had been
exposed to previously, suggesting that attention to the stimulus that is being learned is not required for perceptual learning
to occur [2]. In a later experiment, where the direction of the
background motion signal was allowed to change randomly as
each letter was presented, they observed direction specific improvements in motion discrimination only when the ‘target’
letters for the recognition task were consistently paired with
one particular direction of motion. To explain this result,
the authors proposed that presenting a task-relevant stimulus can give rise to an internal reinforcement signal and lead
to learning of the subliminal paired stimulus [3].
One hypothesis is that this reinforcement signal is mediated
by neuromodulators such as acetylcholine (ACh) dopamine
and noradrenaline, released from sub-cortical brain areas in a
task-specific manner, facilitating synaptic plasticity. Indeed,
ACh has been implicated to play an important role in both
attention [9–11] and perceptual learning [12–14], making it a
tempting candidate molecule for such a mechanism. In accordance with this hypothesis, in vitro studies have shown that
ACh is capable of enhancing synaptic modification [15] as well
as acting to reduce the influence of feedback and intracortical connections relative to afferent feed-forward connections,
while in vivo studies have shown that ACh serves to facilitate neuronal responses, alter the orientation tuning curves
and increase the synchronization of neurons in visual area V1
during exposure to a visual stimuli [16–18], in a manner that is
similair to the affects that are observed with visual attention.
Scientific Aims
Here, I propose to investigate the role of ACh in mediating
the interaction between task-specific attention and perceptual
learning. Specifically, by combining tasks based on the psychophysical experiments used by Wanatabe et. al. on human
subjects, with localized application of cholinergic antagonists
to macaque area MT (which has been shown to be associated with perceptual learning of the direction of motion of
a random dot stimulus [5, 19]), it should be possible to test
the hypothesis stated above; that ACh released during behavioural states of heightened arousal (as a result of attention
to a distractor task) is responsible for perceptual learning of
a subthreshold stimuli.
The proposed study will be divided into four parts which
seek to analyze the role of ACh in perceptual learning during various different states of task-specific attention. In each
experiment the effects on learning of local pharmacalogical
blockade of muscarinic acetylcholine receptors (mAChR) in
macaque visual area MT will be assessed.
The first experiment will investigate the effects of ACh on
perceptual learning in the case where attention is directed towards the relevant stimulus during training, while the second
experiment will look at the case where the monkeys are unaware of the training stimulus (presented as a subthreshold
background ‘noise’ during a distractor task). In the third ex-
2
periment the role of ACh in the psychophysical task of Seitz
et. al. [3] will be investigated, where pairing of task-relevant
target objects in the distractor task with a particular motion
direction of the subthreshold stimulus results in perceptual
learning for this direction only. In the fourth experiment
I propose to try and replicate the hypothesized attentiondependent conditioning signal artificially, by pairing stimulation of brain regions which send cholinergic projections to
the visual cortex with particular directions of motion for the
subthreshold motion stimulus.
Experimental Procedure
Initial training: Monkeys will be trained on a task where
they have to decide whether two sequentially presented motion stimuli are moving in the same or different directions.
Each stimuli consists of a small number of coherently moving
(signal) dots, and a larger number of randomly moving (noise)
dots. The second stimuli will be moving in the same direction
for half the trials, and varied by ±3◦ for the rest. Initial training will be at a high (20%) coherence with the angle of the
first motion signal randomized over trials, and will proceed
until asymptotically stable performance is achieved. It should
be noted that it has been reported that even when monkeys
achieve asymptotic performance in this task over many weeks
of training, perceptual learning is still possible over short periods of time, as some improvement in performance will occur
during the first 500 trials of one session taken alone [5].
Experiment 1: What is the affect of ACh on the
perceptual learning of a visual stimulus? At the beginning of a session, task performance (fraction of correct answers) will be tested and plotted as a function of the initial
stimulus angle for a on-threshold stimulus and a subthreshold stimulus, with coherence levels c1 and c2 respectively (c1
and c2 will be initialized beforehand). Monkeys will then be
trained on the task for a session of around 2000 trials, with
a constant direction of motion for the first stimuli and a coherence level equal to c1 . After training, task performance
will be tested again and plotted as a function of the initial
stimulus angle for both c1 and c2 . For later sessions, mAChR
antagonist scopolamine will be infused into visual areas MT
during training (using the method of [9]), and performance
changes before and after training at different coherence levels
and angles of motion will be assessed.
Experiment 2: What is the affect of ACh on perceptual learning when the training stimulus is subliminal? Initial performance will be tested as in exp 1. Instead
of a training period, there will be an ‘exposure’ period where
monkeys perform a task while different objects are flashed in
front of them and they have to pull a lever every time a specified ‘target’ object appears. During this task, monkeys will be
exposed to a background motion stimulus at below-threshold
coherence of c2 moving at a constant angle throughout. Performance changes following the exposure period will be assessed as in exp 1, for both the control situation and the case
where scopolamine is infused into MT during the exposure
period.
Experiment 3: How does ACh affect perceptual
learning of a subliminal stimulus as a result of pairing it with a task-relevant stimulus? Initial performance
will be tested as in exp 1. The exposure period will proceed
similairly to exp 2, except that the direction of the subliminal
motion stimulus will be allowed to change randomly for each
trial. Subsequent performance changes will be assessed in this
case, and in the case when the target objects for recognition
are consistently paired with a particular direction of background motion direction during the exposure period. Again,
scopolamine will be infused into MT during the exposure period, and its affect on performance changes assessed.
Experiment 4: Can this pairing affect be explained
by cholinergic projections from the basal forebrain to
the visual system? The initial testing and exposure period
will be similair to exp 3, except that instead of pairing of
target objects with particular subliminal stimulus directions
during the exposure period, a particular direction of the background motion stimulus will be paired with electrical stimulation to the mesencephalic reticular formation (MRF), which
projects to the visual cortex via cholinergic projections from
the basal forebrain (BF). Performance changes following the
exposure period will be assessed as before, and in the case
where scopolamine is infused into MT during the exposure
period.
Predicted Results
Experiment 1: Before the training period, performance
at coherence levels c1 and c2 should be around 75% and 50%
respectively for all stimulus angles. From [4], after training,
performance at c1 should be improved for the angle corresponding to the angle of motion of the training stimulus only,
while it should not have improved for the sub-threshold stimulus c2 . If ACh plays an important role in perceptual learning,
then the angle-dependent improvements in performance at c1
should be reduced when ACh blocker is infused into MT.
Experiment 2: From [2], after the exposure period, performance at c1 should be improved for the angle corresponding to the angle of motion of the subliminal stimulus, while
it should not improve for the sub-threshold stimulus c2 . If
ACh is important for mediating perceptual learning even in
the absence of attention directed towards the task that is
being learned, then there should be a reduction in any performance improvements when mAChR blocker is infused into
MT, while if ACh only affects perceptual learning through
its role in controlling task-specific attention, mAChR blocker
should not affect perceptual learning of a subliminal stimulus. A third alternative is that ACh is released as a result of
attention being payed to the distractor task which facilitates
learning of the subliminal stimulus, in which case mAChR
blockade would also result in a reduction in perceptual learning of the sub-threshold stimulus.
Experiment 3: From [3], improvements in performance
should only occur at c1 when a specific direction of the target
stimulus is paired to target objects during the exposure period. If ACh release is related to the conditioning signal which
links attention to target objects to perceptual learning of the
corresponding motion direction, then such learning should be
reduced on infusion of mAChR blockade.
Experiment 4: MRF stimulation has been shown to result in activation of cholinergic projections coming from the
BF to the visual cortex [17]. If this cholinergic activation is
responsible for providing the conditioning signal that results
in learning of subthreshold motion directions paired to taskrelevant stimuli in the distractor task, then by paring direct
MRF stimulation with specific motion directions of a subthreshold stimuli, it should be possible to induce perceptual
learning for the corresponding motion direction. Conversely,
blocking of mAChR in MT by scopolamine should reduce this
affect.
3
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