Mushroom body memoir: from maps to models

Key Points

  • Since their discovery, the mushroom bodies of the insect brain have been assumed to be involved in cognitive processing. Genetic intervention in the fly Drosophila melanogaster has provided strong evidence that they are the seat of a memory trace for odours.

  • This localization of the 'engram' to a single layer of synapses allows us to design a simple circuit model of odour memory based on the functional anatomy of the olfactory system. In the model, complex odour mixtures are assumed to be represented by neuronal activity in sets of intrinsic mushroom body neurons (Kenyon cells). Conditioning renders an extrinsic mushroom-body output neuron (CR neuron) specifically responsive to such a set (and hence to the respective odour).

  • The localization of the memory trace for odours is based on the assumption that associative olfactory learning is mediated by synpatic plasticity. Evidence that the memory trace is represented by the output synapses of Kenyon cells relies on three findings. First, the mushroom bodies are necessary for olfactory learning. Second, in many animals (molluscs, mammals), cyclic AMP signalling is crucial for synaptic plasticity. In the fly, this has been confirmed for the larval neuromuscular junction. Third, in Drosophila several genes involved in cAMP regulation are required for olfactory learning and memory. They are all preferentially expressed in the mushroom bodies, some of them specifically in the mushroom body lobes (output region). One of them, rutabaga, has been shown to be required for olfactory learning exclusively in a set of about 700 Kenyon cells. Another one, amnesiac, reveals that cAMP regulation is required for olfactory learning only during the learning experiment (rather than during development of the mushroom bodies). The output of the Kenyon cell synapses can be blocked while they are modulated, and the memory can still be retrieved later.

  • Mushroom bodies have other functions that are less understood. They seem to be involved in 'decision making', they regulate the perseverence of behaviour and they protect visual memories against context changes. A future circuit model that also addresses these functions might throw light on the basic operating principles of the brain.

Abstract

Genetic intervention in the fly Drosophila melanogaster has provided strong evidence that the mushroom bodies of the insect brain act as the seat of a memory trace for odours. This localization gives the mushroom bodies a place in a network model of olfactory memory that is based on the functional anatomy of the olfactory system. In the model, complex odour mixtures are assumed to be represented by activated sets of intrinsic mushroom body neurons. Conditioning renders an extrinsic mushroom-body output neuron specifically responsive to such a set. Mushroom bodies have a second, less understood function in the organization of the motor output. The development of a circuit model that also addresses this function might allow the mushroom bodies to throw light on the basic operating principles of the brain.

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Figure 1: Drosophila brain shown in the head capsule.
Figure 2: Olfactory pathway.
Figure 3: Circuit model of odour memory.
Figure 4: Presynaptic modulation of transmission at Kenyon cell-to-output neuron synapses is thought to underlie short- and middle-term memory of odours in flies.
Figure 5: Memory phases after electric-shock conditioning.

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Acknowledgements

I am indebted to B. Gerber for a discussion of the manuscript, to N. Strausfeld and T. Préat for sharing unpublished data, and to the German Science Foundation and the Human Frontiers Science Program for financial support.

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CONCENTRATION INVARIANCE

Consistency in response to odourant molecules across different concentrations.

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Heisenberg, M. Mushroom body memoir: from maps to models. Nat Rev Neurosci 4, 266–275 (2003). https://doi.org/10.1038/nrn1074

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