Periodic Reporting for period 5 - ACoolTouch (Neural mechanisms of multisensory perceptual binding)
Reporting period: 2022-03-01 to 2023-02-28
How we sense the world around us is one of the major current questions for biological research. We know that sensory perception is a key function of the brain and one that goes wrong during psychiatric diseases, but we do not know 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? The main objective of this project is to uncover neuronal mechanisms of sensory binding in the mammalian brain. We use the mouse forepaw thermotactile system as a model because it is a relevant sensory pathway similar to the human hand, and mice naturally perform thermotactile tasks in their home environment. Moreover, there are techniques available that allow both the recording and manipulation of the activity of genetically identified single neurons while mice perform sensory binding tasks. Overall, our project took a system approach and identified key encoding schemes of thermotactile information at different stages of the sensory pathway and established the mouse thermotactile system as a new model to understand brain function and dysfunction.
Little was known about neural mechanisms of thermotactile perception. In this project we pinpointed representation of temperature in the central and peripheral nervous system and went on to uncover the cellular encoding schemes. In particular, we have shown that the primary thermal cortex is located in a posterior region of the insular cortex. Despite being at different end of the same sensory axis, we were surprised to find that warm and cool are processed in very different ways in the brain and appear to resemble sub-modalities of the somatosensory system. This is also reflected in perception, where mice, like humans, have different sensory thresholds and response latencies. Our work with mice with knock outs of different sensory ion channels highlighted which thermally sensitive ion channels are involved in thermal perception. We went on to examine the perception and neural encoding features of thermotactile integration and observed an enhancement of perception during multisensory stimulation and have characterized key cortical encoding schemes underlying thermo-tactile integration. Finally, to examine cellular mechanisms of cortical processing, 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. Our work has been published in peer reviewed journals and presented at national and international conferences and public science days. Overall, we hope that our work has made fundamental step to an understanding of sensory perception and established the mouse thermotactile system as a good model to understand brain function and dysfunction.
How the brain generates a percept of temperature was unclear. In this project, we identified key pathways and cellular encoding schemes that underlie thermotactile perception. We took a systemic approach to identify the primary cortical, thalamic and sensory afferent representations of temperature in the mammalian brain. 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 that could underly sensory integration properties in the cortex. We identified sensory pathways used in non-painful thermal sensation, temporal cellular encoding schemes and established the mouse thermotactile system as a novel sensory system to understand mechanisms of sensory processing and perception.