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New research published in Nature, led by researchers Dr Zeynep Okray, Dr Pedro Jacob and Professor Scott Waddell at the Centre for Neural Circuits and Behaviour, has discovered a detailed neural circuit mechanism that explains how multisensory learning improves memory performance.

© Images based on FlyEM / Hemibrain project data from the Janelia Research Campus
3-Dimensional reconstructions of neurons in one hemisphere of the fly’s mushroom bodies: Kenyon cells receiving visual input (left), Kenyon cells receiving olfactory input (middle), and a large serotonergic neuron that spans the mushroom body and connects the two sensory streams (right).

It is widely appreciated, from observational studies of children in the classroom and controlled experiments in animals, that using multiple senses aids learning and improves later memory. While it was known that cross-talk between the brain’s various sensory cortices likely supports this phenomenon, there was no mechanistic explanation for how such an interaction could occur and how memory could be enhanced by such a process.

To identify these neural mechanisms, Dr Zeynep Okray and Dr Pedro Jacob developed a novel multisensory learning paradigm where fruit flies learn to associate an odour, a colour, or a combination of the two, with a reward or punishment. They found that learning and later memory retrieval were improved when multiple senses were engaged.

The researchers studied the fly’s neuronal responses using cutting-edge optical recording techniques and found that training with odours and colours together altered subsequent responses to these sensory cues in learning-relevant neurons. Surprisingly, visual-selective cells became activatable by the learned odour, whereas odour-selective cells became responsive to the learned colours. These changes in neural responsiveness in effect permit the flies to conjure a mental representation of the whole memory from only partial information.

Furthermore, the team discovered that broadly projecting serotonin-releasing neurons provide a bridge after multisensory learning that connects the activity of the colour and odour sensory streams. Cutting-edge neural connectomics analyses revealed that the large serotonergic neurons are composed of many microcircuits that can be independently regulated by learning. Dr Zeynep Okray said: “We found that multisensory learning opens specific microcircuit bridges within this big neuron so that an odour-specific stream can also activate the colour neurons, and vice versa. These bridges bind the learned sensory cues so that the animal can recall the complete memory using either sensory cue alone.”

The team also found that the bridges between the sensory streams rely on signalling through a particular type of serotonin receptor called 5-HT2A. Dr Pedro Jacob said: “The 5-HT2A receptor allows the visually-responsive neurons to receive excitatory information from the odour neurons via the serotonergic neurons. This is a particularly interesting receptor because it is known to be a target for hallucinogens, antipsychotics, and some antidepressants. Moreover, multisensory learning can be defective in human disorders such as schizophrenia or autism, and difficulties in processing multisensory information have been associated with dysregulation of serotonin and the 5-HT2A receptor. So, we now have ideas how and why multisensory processing might be aberrant in these human conditions."

The full paper “Multisensory learning binds neurons into a cross-modal memory engram” is available to read in Nature.