Petersen is head of the Laboratory
of Sensory Processing at L’ecole
Polytechnique Fédérale de Lausanne (EPFL). He will deliver the European Dana
Alliance for the Brain (EDAB) / Max Cowan Special Lecture at the 10th
FENS Forum of Neuroscience in
Copenhagen on Monday.
are the main aims of the work going on in your lab?
CP: Our main goal is to understand the “bird’s eye view” of sensory
perception—how sensory information enters the brain, how it’s processed, and
how we learn to use it. Ultimately, we’d like to understand this at the
neurons communicate sensory information, how that
information gets processed and transformed.
When we look at the world around us,
sensory information comes into the brain, but the only way we know how to make
sense of it is through learning and experience. That’s how you know a chair is
a chair, even though there are many types of chairs that can look very
different from one another. Somehow, we know how to put that sensory
information into the idea of a chair.
This tells us that perception is an active
process where learned features of sensory information can generate internal
representations or useful concepts. There are “feed forward”
pathways, say from the eye to the brain, but there’s also what’s called “top-down
control” of how sensory information is processed and distributed throughout
kind of experiments you do?
CP: We work on the mouse whisker system, a very important sensory
organ through which mice can sense the shape and texture of objects. To keep
things simple, we work with one particular whisker, and trim all the others
away, so our animals only have this one whisker to learn about their
environment. We teach the animals to learn very simple tasks. We stimulate the
whisker, and teach them to lick one particular waterspout in response, for
example, so it learns to associate the stimulation with a reward, but only if
it does something. This involves learning how to act upon sensory information.
We also do recordings from cells
in the barrel cortex and other parts of the brain, to track where the
information goes, and now we’re using optical imaging methods to monitor
activity on the surface of the animals’ brains while they’re performing our
More recently we’re turning our attention
to the learning mechanism. Presumably, reward signals are a key aspect of
learning, so we’ve also been looking at a brain region called the striatum,
because it receives dopamine. When there’s an unexpected reward, there’s a
brief burst of dopamine in the striatum, so we’ve started looking at this in
the context of whisker stimulation.
makes the mouse whisker system so amenable to this type of experiment?
In the mouse brain there’s a large region
called the “barrel
cortex” which is set aside for processing sensory information from the
whiskers, and what’s really nice about it is that you can actually see the
representation of each whisker individually. These anatomical representations
functionally link up very nicely to the whisker system. You can look at the
mouse brain and literally see the whiskers represented as single units: Each is
represented by a column of tissue, about 250 micrometers (billionths of a
meter) in diameter, which can be recognised anatomically inside the mouse brain.
The pattern of columns resembles the pattern of whiskers on the animal’s snout
very closely, so we have this very precise “topographic” map—we can simply look
at the brain and know exactly where we are, and we can pinpoint the small patch
of tissue devoted to this one whisker.
are some of your key findings so far?
We see early sensory responses in the
barrel cortex, and then we see activity spreading to many other brain regions.
Everything’s very fast in the signaling pathway, but 15 milliseconds or so
after we stimulate the whisker, we see differences between naïve animals and those
that have learnt the task. In the animals that learned, additional brain areas
are being recruited, and we see responses all over the surface of the brain.
We had assumed that sensory processing is
relatively simple, and that information has to be sent from the barrel cortex
to the motor cortex [which executes movements]. Surprisingly, though, we see
that the barrel cortex also communicates with another region called the
secondary somatosensory cortex, and it looks like it’s these signals that
change during learning, while signals to the motor cortex are supressed. We’re
imagining a longer pathway, where the barrel cortex talks to the secondary
somatosensory cortex, which in turn probably talks to various regions of the
frontal cortex, which might evaluate the situation and place values on things,
then decide on the appropriate action. We think signaling between the barrel
cortex and secondary somatosensory cortex is the next stage, or at least one of
the critical next stages, of the transformation from a sensory stimulus to a
We know that the barrel cortex sends
massive inputs to the striatum, so this is the first place where
information from the whiskers meets dopamine reward signals. We think that
dopamine is involved in generating synaptic plasticity during learning, perhaps
by changing circuits in the striatum to determine reward. In this way, learning
reward-based signals could cause plasticity at a specific set of synapses in
There are two major signals going out of
the striatum—the so-called “direct” and “indirect” pathways. We’ve made
recordings from both, and we find that cells in the
direct pathway have a very large whisker-related sensory response that
seems to be missing in the indirect pathway. This is consistent with the idea
that dopamine strengthens the signals onto these direct pathway neurons, and
this might encourage the animal to lick. That is, it acts as a “Go” signal that
promotes certain actions.
experiments are you planning to do in the near future?
Although there appears to be a lot of
activity across many different brain structures during the learning process,
some of this might not that actually be contributing to the behavior, and we
need to figure out which activity patterns are critical, and which ones are
just correlations. We hope within the next 5 to 10 years we’ll understand how sensory
information flows through the brain for the animal to perform a task. We’ll
be able to track the information and what changes need to take place inside the
brain for the animal to learn to do specific things.
Also, context is critical in sensory perception,
so we want to see if we can get the animal to do different things by changing
the context of whisker stimulation, and combining it with auditory and visual
stimulation. Can we, for example, teach the mice to lick the one spout in
response to a particular sound followed by whisker stimulation, and another in
response to stimulation alone? Or can they to learn to perform certain tasks in
response to specific sequences of different sensory stimuli in order for it to
obtain a reward?
your findings have any clinical relevance?
In patients with Parkinson’s disease,
dopamine depletion is thought to affect neurons in the direct pathway. That’s
what affects movement—they don’t have that Go signal—and we think that’s
potentially interesting. It’s likely to be far more complicated than that, but
now the story’s beginning to emerge, we can probe whether or not these
mechanisms actually do drive certain behaviors.
We’d also like to look at mouse models of
schizophrenia. There’s a phenomenon called pre-pulse inhibition, where you give
first a weak sound and then a strong sound. Most people exhibit a startle
reflex in response to a loud sound, but if it’s preceded by a weaker sound, you’ve
got this context dependence and you’re warned that a louder sound is coming.
Healthy people will have a smaller startle reflex, but patients with
schizophrenia do not. The preceding sound fails to act as a warning, because
they apparently don’t have this top-down control.
just a hypothesis, but I think this aspect of schizophrenia might relate to an
absence of top-down control and the contextual processing of sensory
information. There appear to be deficits like this in other mental illnesses
too, but schizophrenia is particularly interesting, because it often involves hallucinations
and other unusual percepts.