The nature of sensory gating – probing the function of a corticofugal loop.

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The brain is assumed to contain many predictive systems spanning the enormous functional range from simple sensorimotor interactions to conscious planning. It is a challenge to delineate predictive systems, as they are related to highly plastic brain structures that co-evolved and tend to be highly interconnected (e.g. neocortex vs. cerebellum). The challenge, however, is worth to be tackled, as dysfunction of one predictive system, could in principle alleviated by furthering another one with overlapping function. The classical description of sensory gating (SG) has been that planning and execution of body movement leads to modulation of peripheral sensory signal flow. This description already assumes a role for feedback signals sent from central to peripheral processing stations, and it points to a possible role of SG as a predictive system. The goal of the present proposal is three-pronged. We firstly want to demonstrate the separation of SG from other predictive systems. Second, we attempt to explain its elusive behavioral function. Third we plan to elucidate its neuronal mechanisms, involving a corticobulbar loop, with which peripheral sensory signals are brought under top-down control. In preliminary work we have shown that SG is different from state estimation (SE, the classical concept of reafference principle), two systems that so far always have been studied in the context of body movement. To begin to test novel functions of SG we will study it in non-movement behavioral elements introduced to a paw reach-out-return paradigm in head-fixed mice, as well as with a reward expectation task devoid of any movement. We further aim to demonstrate SG’s independence from cerebellum using optogenetic interference. Both aims, if supported, will delineate SG from SE and point to possible novel functions to SG. With respect to the neuronal substrate we will study the corticobulbar projection from neocortex to the cuneate nucleus using projection-specific optogenetic stimulation of cortical projection origins, as well as interfering with local cuneate inhibitory interneurons. To affirm that we deal with comparable neuronal mechanisms in situations with and without contribution of the motor system, we will test whether they all identically involve functions of corticobulbar loop and intrinsic cuneate neurons.