Bilateral Integration in the Mouse Whisker System

Abstract

To generate a coherent percept of the external world, the brain needs to combine and integrate sensory signals processed in the left and right hemispheres. In humans, bilateral integration is an essential and ubiquitous process. Common tasks such as tying shoelaces or typing on a keyboard, require one hand to be aware of what the other is doing, or rather, the brain to be aware of what both hands are doing. Although an essential exercise since the origin of separate cerebral hemispheres 500 million years ago, little is known about the neuronal mechanisms underlying bilateral integration. The primary aim of my PhD project is to elucidate the underlying circuitry involved in the transfer of information across hemispheres and its integration in cortical neurons of the primary somatosensory cortex. By designing a behavioural paradigm which requires bilateral integration, I was able to observe the transformation of sensory signals between the two vS1 hemispheres and propose a basic mechanism for the comparison of sensory stimuli between cortical sides. Here, I investigated bilateral integration of somatosensory inputs in mouse primary vibrissal (vS1) cortex under urethane anaesthesia, awake and passively receiving stimuli and during an active sensory integration task. For the behavioural task, the mice were trained to compare the stimuli between the two whisker pads during head-fixation. In Experiment 1 (Go/No-Go), mice were trained to respond to uni-lateral (Go) but not to bilateral stimulation (No-Go) of whiskers. In Experiment 2 (2-Alternative-Forced-Choice), mice were trained to choose one of two reward spouts that corresponded to the stronger stimulus. Mice learned to perform the task in both behavioural paradigms. In the case of the Go/ No: Go paradigm, mice were required to make comparisons that were more complex than simple associations. Here mice were required to respond to left or right stimulus presentations, but to withhold responses when the left and right were presented simultaneously. This is a complex task, akin to an Exclusive/Or operation in logic, and similar to negative patterning paradigms in learning theory. Surprisingly, mice were capable of solving this task albeit after extensive training. During the behaviour, I visualised vS1 neuronal activity by using NeuroNexus and Neuropixels probes. Under anaesthesia, vS1 neurons were predominantly responsive to contralateral whisker stimulation with no detectable modulation by the ipsi-lateral stimulation. When mice were awake and passively receiving whisker stimuli, the neuronal profile was as expected, with predominantly contralateral and bilateral stimulus responsive neurons, and some responsive to the ipsilateral stimulus presentation. This response profile changed significantly during the Go/No-Go paradigm, where responses to ipsilateral (Go) stimuli became more pronounced and the response to bilateral (No-Go) stimuli was distinct from contralateral (Go) stimuli. The proportion of stimulus responsive neurons also shifted after training, with a distinct population only responsive to the No-Go stimuli. Our results thus showed that neuronal activity in the primary sensory cortex can be functionally reshaped to reflect the ecological relevance of the incoming bilateral stimuli. Future experiments could investigate how interactions with other cortical areas, such as the secondary somatosensory cortex or the medial posterior complex, could underlie this finding. In summary, this thesis presents a novel behavioural paradigm which can be successfully implemented in head-fixed mice, allowing for the investigation of bilateral integration in vS1. The paradigm itself also lends the ability to study complex logical operations in mice. The neuronal findings implicate the involvement of the primary somatosensory cortices in bilateral integration, and support the literature regarding task-relevant plasticity in the barrel cortex. Show more