Neuronal mechanisms of cortico-subcortical communication via cortical giant synapses in the mammalian brain.

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Research on the mammalian cortex over the past decades has substantially advanced our knowledge about cortical networks in brain function. The cerebral cortex is viewed as the cognitive headquarter of the brain, accommodating specific cortical circuits for decision making, conscious perception and coordination of behavior. But how does the cortex communicate with the rest of the brain to fulfill these functions? In order to execute appropriate responses to the sensory environment, the cortex must delegate to subcortical areas of the nervous system which directly control behavior. The cortex coordinates responses to the environment by modulating the activity of diverse subcortical target areas such as the thalamus, basal ganglia and brainstem via cortical output pathways. While cortico-subcortical signaling is essential for the interaction between the brain and the environment, we are only at the beginning to investigate the neuronal basis of cortico-subcortical mechanisms with modern anatomical and functional techniques. The proposed project investigates the structure and the functional mechanisms underlying the interplay between the cortex and subcortical target networks by leveraging a combination of in vivo deep-brain electrophysiology, optogenetics, and cell-type-specific approaches in the mouse model system. We will first map the subcortical targets of the somatosensory cortex and characterize the structural organization of these connections in a cell-type specific manner. Based on this anatomical map, we will characterize the synaptic physiology of these connections in vitro and subsequently study the signaling between the cortex and individual target nuclei in vivo, during sensory processing and behavior. The particular focus of this project will be the cortical output via pyramidal neurons in layer 5, as these neurons connect the cortex with numerous subcortical target nuclei with putative giant synapses. Giant synapses transfer neuronal signals with exceptionally high efficiency. We are specifically interested in layer 5 cortical interactions with the superior colliculus, a premotor center which controls movements, as well as the anterior pretectum, which putatively gates sensory information in the thalamus by strong inhibition. While these two cortical target networks will be our starting point, the long-term goal is the comprehensive characterization of cortico-subcortical interactions which will also be relevant for brain diseases such as chronic pain. The results of this project will contribute to a mechanistic understanding of the processes underlying the transformation of sensory signals into behavior.