Neural circuits mediating aversive olfactory conditioning in Drosophila

For all animals it is highly advantageous to associate an
environmental sensory stimulus with a reinforcing experience.
During associative learning, the neural representation of the
sensory stimulus (conditioned stimulus; CS) converges in time and
location with that of the reinforcer (unconditioned stimulus; US).
The CS is then affiliated with a predictive value, altering the
animal’s response towards it in following exposures. In my PhD
thesis I made use of olfactory aversive conditioning in Drosophila
to ask where these two different stimuli are represented and how
they are processed in the nervous system to allow association. In
the first part of my thesis, I investigated the presentation of the
odor stimulus (CS) and its underlying neuronal pathway. CS-US
association is possible even when the US is presented after the
physical sensory stimulus is gone ('trace conditioning'). I
compared such association of temporally non-overlapping stimuli to
learning of overlapping stimuli ('delay conditioning'). I found
that flies associate an odor trace with electric shock
reinforcement even when they were separated with a 15 s gap.
Memories after trace and delay conditioning have striking
similarities: both reached the same asymptotic learning level,
although at different rates, and both memories have similar decay
kinetics and highly correlated generalization profiles across
odors. Altogether, these results point at a common odor percept
which is probably kept in the nervous system throughout and
following odor presentation. In search of the physiological
correlate of the odor trace, we used in vivo calcium imaging to
characterize the odor-evoked activity of the olfactory receptor
neurons (ORNs) in the antennal lobe (in collaboration with Alja
Luedke, Konstanz University). After the offset of odor
presentation, ORNs showed odor-specific response patterns that
lasted for a few seconds and were fundamentally different from the
response patterns during odor stimulation. Weak correlation between
the behavioral odor generalization profile in trace conditioning
and the physiological odor similarity profiles in the antennal lobe
suggest that the odor trace used for associative learning may be
encoded downstream of the ORNs. In the second part of the thesis I
investigated the presentation of different aversive stimuli (USs)
and their underlying neuronal pathways. I established an
odor-temperature conditioning assay, comparable to the commonly
used odor-shock conditioning, and compared the neural pathways
mediating both memory types. I described a specific sensory pathway
for increased temperature as an aversive reinforcement: the thermal
sensors AC neurons, expressing dTrpA1 receptors. Despite the
separate sensory pathways for odor-temperature and odor-shock
conditioning, both converge to one central pathway: the dopamine
neurons, generally signaling reinforcement in the fly brain.
Although a common population of dopamine neurons mediates both
reinforcement types, the population mediating temperature
reinforcement is smaller, and probably included within the
population of dopamine neurons mediating shock reinforcement. I
conclude that dopamine neurons integrate different noxious signals
into a general aversive reinforcement pathway. Altogether, my
results contribute to our understanding of aversive olfactory
conditioning, demonstrating previously undescribed behavioral
abilities of flies and their neuronal representations.