Understanding the consequences
THOMAS J. CAREW
Thomas J. Carew
is in the Department of Neurobiology and Behavior, 2205 McGaugh
Hall, and the Center for the Neurobiology of Learning and Memory,
University of California at Irvine, California 92697-4550, USA.
in several ways, one of which involves forming an association between
an action and its consequence. Studies of a marine mollusc shed
light on how this creature forms a connection between biting and
to assess the consequences of one's actions is fundamental to survival:
an animal must learn an effective hunting strategy if it is to eat,
and to elude predators if it is to live to see another day. Writing
in Science, Brembs, Lorenzetti and colleagues1
describe their studies of the neural basis of this type of learning
in the marine mollusc Aplysia, which could serve as a useful
model for understanding more complicated organisms.
class of learning is known in the trade as 'operant' or 'instrumental'
conditioning2. It was first brought
into the laboratory over a century ago by Thorndike3,
who studied the ability of cats to learn to escape from a 'puzzle
box'. At about the same time, another form of learning was discovered
by Pavlov4, who described how animals
form an association between a neutral (also termed a 'conditioned')
stimulus, such as a ringing tone, and an 'unconditioned' stimulus
that has inherent meaning, such as food. This is known as classical
or pavlovian conditioning. Together these two types of learning
provide most of the tools that all animals need to negotiate their
environment successfully, enabling them to associate their behaviour
with its consequences and to learn predictive relationships about
In modern neuroscience,
the analysis of learning mechanisms is a thriving enterprise. But
although classical and operant conditioning are both important,
the mechanisms of classical conditioning have received far more
attention. Why should this be? The reason lies, at least in part,
in how researchers approach the problem. The basic goal of a neurobiological
analysis of associative learning is twofold: first, to identify
the site of the association in the brain; and second, to characterize
the neural mechanisms involved in forming the association. For classical
conditioning, this strategy is relatively straightforward. One would
first identify the pathways of neurons that respond to the conditioned
and unconditioned stimuli. The points at which the two pathways
converge would be good candidates for the sites at which an association
between the stimuli is formed.
are potentially more complicated in the case of operant conditioning.
Here, an association is made not between two stimuli but between
an action and its consequence, such as a benefit (or 'reward', in
learning parlance) or punishment. So the site of association is
not intuitively obvious. For example, it could occur where information
about the reward converges with the brain region that initiates
the behaviour, which could be more difficult to locate than the
regions that respond to conditioned and unconditioned stimuli.
al.1 have overcome these difficulties
by studying the operant conditioning of feeding in Aplysia
(Fig. 1). The authors attacked the problem at several levels,
from the behaviour of the whole animal down to the electrophysiological
properties of single neurons. They focused on feeding in Aplysia
because this is known to be capable of operant conditioning5
and, more importantly, because the neural circuitry underlying feeding
has been well characterized.
1 Learning model — the marine mollusc Aplysia. The new paper
by Brembs et al.1 gets to grips with how Aplysia learns to associate
biting with a food reward, a type of 'operant' conditioning.
resolution image (47k)
et al. looked at the electrical activity of the oesophageal
nerve in whole animals, and found that it increased when the animals
ingested food. Presumably, this activity signals the presence of
a reward — food. Next, Brembs et al. 'trained' the
animals to associate spontaneous biting (whether or not food was
ingested) with a reward by stimulating the oesophageal nerve, mimicking
the usual reward signal, during biting. The result was that the
molluscs made significantly more spontaneous bites than controls,
both immediately and 24 hours after training. In other words, the
operant response (biting) can be reinforced by a food-related reward
signal (stimulation of the oesophageal nerve); moreover, the memory
of the association between biting and reward can persist for at
least 24 hours.
then turned their attention to where this memory might be stored.
Here, the previous detailed characterization of the neural circuitry
underlying feeding behaviour was a big help. In the central nervous
system, a particular group of neurons — the buccal ganglia
— controls biting, and the authors studied one of these, called
B51, because it is essential in generating the correct programme
of neuronal activity. By recording the electrical activity of B51
neurons in buccal ganglia that had been surgically isolated from
Aplysia, Brembs et al. showed that the burst threshold
was lower and the input resistance higher in neurons from trained
animals than in controls. The changes in these properties together
increase the likelihood that B51 will become active, and hence improve
its ability to generate ingestion-related neural programmes.
So it seems
that operant conditioning can alter certain properties of the B51
neuron. But it was not clear whether B51 is a genuine site of convergence
between bite behaviour and reward — that is, if it is where
the association is formed and stored — or whether it is simply
affected by that site. To find out, Brembs and colleagues isolated
and cultured B51 neurons and examined whether similar changes in
properties could be induced by mimicking the operant conditioning
procedure at the single-neuron level. They paired the activation
of B51 (that would generate a bite) with brief pulses of dopamine,
a neuromodulator that probably serves as the reward signal in this
system6 and many others7.
They found a significant reduction in burst threshold and increase
in input resistance in B51. This did not occur when dopamine application
and B51 activation were unpaired.
How do these
observations relate to the learned association between biting and
reward? The idea is this. B51 activity is required for an animal
to attempt to take a bite of food. If that attempt is successful
— if food ends up in the mouth — the oesophageal nerve
is stimulated. This causes the release of dopamine in the buccal
ganglia, increasing the excitability of B51. Given that direct activation
of B51 can elicit ingestion-related activity in isolated ganglia8,
one can envisage that a direct consequence of enhancing B51 excitability
would be a greater likelihood of further biting.
the data show that B51 is directly affected by operant conditioning,
implying that it is at least one important site of memory storage.
Moreover, an exciting aspect of the study is that it provides a
neuronal mechanism for operant conditioning that can explain not
only its associative features, but also how that associative component
might control future biting behaviour.
But the significance
of the paper extends further. Now that an associative site for operant
conditioning has been found, it will be possible to examine the
underlying cellular and molecular mechanisms in detail — though
this is no easy chore, to be sure. Moreover, Aplysia shows
classical conditioning9, and much is
known about the molecular and cellular mechanisms underlying this
form of learning10-12. So it might
be possible to compare classical and operant conditioning in Aplysia
in mechanistic terms. If they have features in common, an exciting
principle might emerge: evolution may have come up with a neural
'associative cassette' that can be used in either type of conditioning,
depending on the neural circuit in which it is embedded. Of course,
this is pure speculation, but the work by Brembs and colleagues
will be instrumental in exploring this intriguing possibility.
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© Macmillan Publishers Ltd 2002 Registered No. 785998 England.