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Pavlov's Maggots: Dr Liria Masuda-Nakagowa

Circuit mechanisms of odour discrimination learning in the higher brain

Smell is evocative of various memories - memories of experiences, places, events in the past. These memories can have positive or negative values, such as being attractive or repulsive. The problem of smell recognition is universal; animals in the wild are dependent on their sense of smell to find prey and therefore responding to attractive cues, or to avoid poison and therefore being repulsed. Therefore the brain must have mechanisms to discriminate smell in order to form and retrieve relevant memories.

The mushroom bodies (MBs) of insect brains are higher brain centers essential for associative olfactory learning. The relatively simple Drosophila larval mushroom body calyx, the dendritic input region, has a relatively simple organisation that makes it easy to see how specific neurons fit in. We previously found stereotypic innervation of the calyx glomeruli by neurons that bring sensory input, but apparently random innervation by mushroom body neurons that integrate and process these inputs, by a combinatorial mechanism that can discriminate a large number of odours or other inputs.

However, the specificity and stringency of sensory representations in the calyx is of central importance in ensuring good discrimination of stimuli, and likely involves additional neurons. We have identified a number of genetic lines that label novel neurons that innervate the calyx. One neuron labels all detectable termini that bring inhibitory input, and this input appears to come from the mushroom body output region. Imaging neuronal activity in live larval brains shows that this neuron responds to odours; and genetically blocking synaptic output from mushroom body neurons decreases its activity. It therefore appears to function as a feedback neuron connecting mushroom body output to its input in the calyx – and indeed the only neuron in the system that does this.

Our current goal is to understand how this and other neurons fit in the context of the global calyx circuitry, to determine the mechanisms that regulate the sensitivity and stringency of sensory discrimination.

Presented at Churchill College, 6th November 2014.

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