TOPO_HOX

Mapping the face in the somatosensory brainstem: genetic and activity-dependent mechanisms

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'Somatosensory information from the physical world is accurately relayed from body surface receptors to brain cortex through topographic connectivity maps enabling to spatially locate and distinguish stimuli such as touch, temperature, proprioception (body position), and nociception (pain). This organization provides a somatosensory body-map representation in the brain exemplified by the concept of sensory homunculus. In mammals, the cortical representation of face receptors has a prominent role in fine tactile discrimination, taking-up more cortical space than other body parts. This is more striking in the cortical representation of the rodent whisker pad through the trigeminal circuit. Inputs from single whiskers cluster into discrete anatomical and functional cortical units, the barrels, which faithfully reproduce the whisker spatial arrangement on the rodent face. Whisker-related neuronal aggregates are also observed in brainstem and thalamic subcortical stations relaying the input to the cortex, maintaining a somatotopic point-to-point representation throughout the entire pathway. However, the molecular mechanisms of whisker-to-barrel topographic map formation, especially at subcortical level, remain poorly understood. This proposal focuses on the development of whisker-related circuitry and ascending pathways in the brainstem trigeminal sensitive column. I will investigate intrinsic (genetic) and extrinsic (sensory activity-dependent) mechanisms establishing whisker maps in the Principal (PrV) and Spinal (SpV) nuclei, the brainstem relay stations where whisker-related neuronal modules, or barrelettes, are firstly formed. Using ad hoc genetic tools, virus-based transynaptic circuit tracing techniques, and functional analysis of relevant homeobox transcription factors and neurotrasmitter receptors, I will investigate rostrocaudal specification of PrV vs. SpV barrelette neurons, as well as the establishment and refinement of their input-output connectivity.'