The lateral posterior nucleus of the thalamus (LP), which is the mouse analog of the primate pulvinar, is a higher-order visual thalamic nucleus that is thought to play an important role in visual attention. A key difference between LP/pulvinar and the first-order visual thalamic nucleus LGN is that LP/pulvinar receives two distinct cortical inputs: one from layer 6 that it shares with LGN, and one from layer 5 that avoids LGN. Prior studies of the morphological and physiological characteristics of these inputs have suggested that the two corticothalamic (CT) populations may have very different effects on activity in LP/pulvinar. In particular, it has been hypothesized that the layer 5 CT group, which has large synaptic terminals in LP/pulvinar that resemble retinal ganglion cell terminals in LGN, provide the primary ?driving? input to LP/pulvinar and shape its visual response properties. Meanwhile, the layer 6 CT population, which has more numerous but smaller terminals in LP/pulvinar, may contribute ?modulatory? input. While this ?driver/modulator? framework has been very influential in generating hypotheses about LP/pulvinar's interactions with cortex, whether layer 5 and layer 6 CT cells are functional drivers and modulators, respectively, of LP/pulvinar has never been directly tested. This is due to the lack of tools for selectively targeting each of these CT populations in primates, in which the pulvinar has been much more extensively studied than LP in rodents. However, transgenic and viral tools enabling cell-type specificity as well as a recently improved understanding of the mouse visual system now make this a tractable question in mice. To test this longstanding hypothesis, the layer 5 CT population will be selectively targeted for optogenetic manipulations by injecting a retrograde viral vector carrying Cre recombinase to superior colliculus (which is another projection target of layer 5 CT neurons in addition to LP), and layer 6 CT neurons will be specifically targeted with the Ntsr1-Cre transgenic mouse line. Multi-shank neural probes with high-density microelectrode arrays will be used to record extracellular single-unit activity in LP of awake mice while optogenetically manipulating CT neurons. This will make it possible to measure each CT subpopulation's effect on visual and spontaneous activity in LP and determine if they are functional ?drivers? or ?modulators?. Layer 5 and layer 6 CT neurons originating from primary versus higher visual cortex will also be separately targeted in order to more precisely evaluate how different visual cortical areas communicate with LP. This will also address the question of whether either of the CT subpopulations relay the visual preferences of their source cortical area to LP as would be hypothesized of a functional ?driver? but not a ?modulator?. Together, the proposed set of experiments will have significant implications for understanding LP/pulvinar's role in visual processing through its interactions with visual cortex.
My proposed research will investigate the contributions of distinct visual cortical inputs to activity in a higher- order visual thalamic nucleus, LP/pulvinar. Results of this work will elucidate the function of LP/pulvinar in visual processing through its interactions with visual cortex. Given the proposed role of LP/pulvinar in coordinating between visual cortical areas and in visual attention, this work will contribute to a better understanding not only of the visual system but also of basic connectivity principles underlying sensory processing and attention that have significant implications for understanding and treating neurological and visual system disorders.
