Insights into a Mini-Brain

Jour Fixe talk by Andreas Thum on July 17, 2014

Understanding how a brain functions is quite difficult as it consists of a highly complex network of innumerable neurons. However the fly brain of Drosophila melanogaster consists of only about 200.000 neurons and is accessible on the neuronal, molecular and behavioral level due to a well-established set of genetic tools. And even simpler - the larval brain of Drosophila melanogaster consists of only about 10.000 neurons (about 5% of the adult brain). For that numerical reason Andreas Thum ´s research is focused on the brain of Drosophila larvae which he presented in his talk on “Cognitive architecture of a mini-brain: developmental, neuronal and physiological fundamentals of learning and memory”.

Neuroscientist Eric R. Kandel stated in his Nobel Lecture on December 8, 2000: “Instead of studying the most complex cases, we needed to study the simplest instances of memory storage, and to study them in the elementary reflex behavior of those animals that were most experimentally tractable.” “Although Eric R. Kandel may never have thought about the Drosophila larva, he exactly lists all advantages that this model organism offers to analyze how a brain organizes behavioral outputs” Andreas Thum points out.

To study associative learning processes in Drosophila larvae the biologist and his collaborators conduct olfactory as well as visual tests by stimulating the larvae with sugar reward or salt or electric shock punishment. Thereby, a comprehensive set of behavioral experiments was established that can be now used to identify the parts of the brain that are important for reward and punishment learning.

But before doing so, detailed knowledge about the larval brain anatomy is necessary. Therefore, in collaboration with the lab of Albert Cardona from the Howard Hughes Medical Institute Janelia Farm (USA) and 18 additional labs world-wide, Andreas Thum joined a community approach to reconstruct every single neuron of the brain with its entire synaptic connectivity. Once established a unique instrumentation will be available to identify the neuronal circuits of the larval brain including the ones required for reward and punishment learning.

But already today some information on the neuronal circuits underlying larval learning is available.
Among other neurons, the mushroom body, which is formed mainly by Kenyon cells (third order olfactory neurons) was identified as the memory center necessary for odor-reward and odor-punishment learning. “Thus, we have identified an elementary circuit necessary to establish odor-sugar memories.”

The group of Andreas Thum could also show that associative olfactory salt punishment learning can be recalled up to four hours after training. They found out that this type of memory is resistant to cold-shock treatment and is established independently of the molecular machinery involved short term and long term memory. “We have gained insights into a molecular machinery necessary to establish odor-salt memories – that is exclusively ARM – an anesthesia resistant type of memory. Interestingly, although also present in flies and other animals this type of memory was so far often neglected”, concluded Andreas Thum.

At the end he gave a short outlook to his future research plans that will also address how sensory information is actually sensed and signaled “upstream” of the brain and how changes in the brain will also activate different types of motor neurons that ultimately trigger an appropriate behavioral output in a given situation.