Report

Teaser, summary, work performed and final results

Periodic Reporting for period 2 - ACoolTouch (Neural mechanisms of multisensory perceptual binding)

Teaser

How we sense the world around us has fascinated philosophers and scientists for a thousand years. We know that sensory perception is a major function of the brain and one that goes wrong during psychiatric diseases such a schizophrenia or autism. What we do not know is exactly...

Summary

How we sense the world around us has fascinated philosophers and scientists for a thousand years. We know that sensory perception is a major function of the brain and one that goes wrong during psychiatric diseases such a schizophrenia or autism. What we do not know is exactly how the brain manages this computational feat.

A fundamental aspect of sensory perception is the combination or “binding” of different modalities of sensory input. For example, when we grab a milk bottle from the fridge, how do we put together the sensation of cold with that of smooth to generate a single percept of a cold bottle? Sensory binding is a central function of the neocortex, the large folded sheet of neurons on the outside of our brain, but how the cortex achieves this is unclear. The main objective of this project is to uncover neuronal mechanisms of sensory binding in the mammalian brain.

We use the mouse forepaw thermo-tactile pathway as a model system to investigate this question because it is a relevant sensory pathway similar to the human hand, mice naturally perform thermo-tactile binding in their home environment and there are techniques available that allow both the recording and manipulation of activity of genetically identified single neurons while mice perform sensory binding tasks.

Work performed

Very little was known about what temperature and touch stimuli a mouse can perceive. We therefore have developed a behavioral test whereby a mouse reports a touch or a temperature change to the forepaw skin. This has shown that mice are incredibly sensitive to both touch and temperature stimuli in a range similar to that of humans. Moreover they report the stimuli robustly and rapidly. We have gone on to train different strains of mouse with specific ion channels knocked out of neurons that innervate the skin to examine which are responsible for detecting temperature changes of the skin.

Even less was known about which parts of the brain are responsible for processing non-painful temperature information in the brain. We have used electrical and optical recordings at different spatial scales to map different areas of the thalamus and cortex to identify the pathways responsible for processing temperature and touch.

To examine cellular mechanisms of sensory processing in the cortex, we have examined neurons in living mice that are monosynaptically connected. Paradoxically, we have shown that single action potentials from cortical excitatory neurons can evoke inhibition of surrounding neurons. This type of inhibition is important for the processing of touch and temperature information in the neocortex.

Final results

The areas of the brain responsible for processing non-painful temperature information were previously unknown. In this project we have identified key pathways that are required for temperature processing.

Transmission of sensory information between nerve cells occurs via synapses but very little is known about the properties of synaptic transmission or connected neurons in vivo. We developed a new approach to be able to identify and examine monosynaptic connections between identified neurons in living mice. Paradoxically, we have shown that single action potentials from cortical excitatory neurons evokes inhibition of surrounding neurons. This type of inhibition is important for the processing of touch and temperature information in the neocortex.

By the end of the project we expect to (i) identify the sensory pathways used in non-painful thermal sensation (ii) understand neural processing rules and mechanisms of thermo-tactile integration (iii) develop novel thermo-tactile perception tasks for mice