Functional Diversity of Corticothalamic Pathways Underlying Visual Processing

The cerebral cortex and the thalamus are in constant communication with one another, and their interactions are thought to underlie fundamental brain functions such as perception, attention, sleep, cognitive flexibility, and even consciousness. Still, a multitude of questions remains as to how corticothalamic interactions subserve these functions. This dissertation explores one major aspect of these interactions - how the cortex communicates with the thalamus, using the mouse visual system as model. This is an area in which considerable groundwork has been laid by decades of research into the underlying anatomy and physiology of these connections, which have led to influential hypotheses about how those attributes may relate to function. Yet, many of these hypotheses have been left untested, due to challenges and technical limitations in selectively perturbing different corticothalamic pathways and assessing their in vivo functions in an awake animal. In this dissertation, modern advances in mouse transgenics, extracellular electrophysiology, and circuit manipulation are harnessed to directly assess how distinct populations of corticothalamic neurons contribute to visual thalamic processing in vivo. Chapter 1 explores the role that a unique population of corticothalamic neurons in layer 6 of the mouse primary visual cortex play in the dorsolateral geniculate nucleus and the pulvinar, which represent two distinct classes of visual thalamic nuclei. By using optogenetics to selectively stimulate these neurons, we find that they act similarly upon both classes of thalamic nuclei, yet their influence in both is highly dynamic and dependent upon the context of their activation. In Chapter 2, the endogenous function of these layer 6 corticothalamic neurons is further examined with optogenetic inactivation and contrasted with that of an additional corticothalamic population in cortical layer 5 that exclusively projects to the pulvinar. We find novel evidence in support of longstanding hypotheses that layer 5 corticothalamic projections “drive” visual responses in the pulvinar, whereas the layer 6 projections play a fundamentally “modulatory” role. Altogether, this dissertation reveals how functionally distinct corticothalamic pathways influence the visual thalamus and suggests fundamental principles in how corticothalamic communication is organized for sensory processing in the awake, behaving animal