Project Summary/Abstract The brain comprises two distinct hemispheres mainly connected to each other by the corpus callosum. Despite the proven role of callosal connections in sensorimotor behaviors involving both sides of the body, the nature, area and cell-type specificity, and the function of interhemispheric interactions in sensory perception are far from understood. The proposed project will investigate those issues in the context of active bilateral vibrissa-mediated somatosensation in the mouse, focusing on primary (S1) and secondary (S2) somatosensory cortices and their associated callosal projections. The work will combine laminar extracellular recordings in S1 and S2, optogenetic identification of callosal neurons, and chemogenetic modulation of callosal inputs with decoding and signal detection analytic approaches to relate neuronal activity to stimulus encoding and perception while the mouse actively whisks to contact static poles located on each side of the face. The first aim of the work is to investigate the existence and nature of bilateral tactile signal interactions in S1 and S2 and their relation to sensory-evoked callosal activity, as well as to establish whether bilateral features of tactile stimuli can be decoded from S1 and S2 activity. The second aim of the work is to reveal the contribution of homologous callosal neurons of S1 and S2 to the discrimination of bilateral tactile stimuli, and to determine whether S1 and S2 activity encodes behaviorally relevant bilateral stimulus properties predictive of stimulus perception. Significance: The proposed work will provide unprecedented information about the functional role of specific populations of neurons constituting the corpus callosum. It will allow to reconcile investigations about the locus and the nature of interhemispheric interactions conducted in reduced preparations with studies indirectly probing their behavioral relevance. Furthermore, this work will provide a more complete understanding of somatosensation, identifying area and cell types critical for bilateral tactile perception. It will also establish a novel sensory coding framework, encompassing tactile signals arising from both sides of the body. Broad Impact: This project lays the groundwork for future investigations on the role of interhemispheric interactions in the coordination of motor behaviors and in cognitive processes implicating the left and right cerebral hemispheres. Additionally, it will enable targeted functional investigations at the cellular and network level of several mental disorders characterized by abnormal anatomical and functional interhemispheric connectivity, such as ADHD, autism and schizophrenia. Separately, knowledge about cerebral cross-areal communication and its detailed computations will also be beneficial to neuroengineering applications, particularly those regarding movement coordination and natural integration of sensory feedback for bilateral neuroprostheses.