The ability to both route and coordinate the propagation of sensory information to downstream areas is a critical feature of cognitive function. The deep layers of the auditory cortex (ACtx) give rise to a massive projection system that exerts influence over multiple downstream brain areas. Sub-cerebral projection neurons (SPNs) within layer 5b, with their elaborate dendritic processes and far-ranging axons, have long been regarded as canonical ?broadcast? neurons, pooling inputs from the upper cortical layers and transmitting signals to widespread downstream targets. Our recent work has shown that at least some SPNs that project to the midbrain also collateralize in the thalamus, striatum, and amygdala. Nevertheless, existing anatomical descriptions of this projection system are lacking, and the extent to which SPN populations broadcast information to several downstream targets simultaneously, as opposed to transmitting auditory signals to a single discrete region is not known. Despite their widespread influence, the neurons contributing to this corticofugal projection system have largely defied in vivo physiological characterization. Thus, the kind of sensory information that is routed to downstream targets remains to be established. Given that some SPN target regions reside within the limbic and reward systems of the brain, it is also important to assess how non- sensory factors related to internal state (such as arousal and locomotion) affect sensory processing in SPN populations that route information to distinct targets. Recent technical developments now make it possible to anatomically characterize the input/output circuitry of specific neuron classes in addition to being able to isolate these neurons in vivo to document their specific contributions to auditory processing. Here, we propose to use a battery of anatomical, optical, and viral approaches to elucidate the anatomical connectivity of SPN populations in mouse ACtx, to understand what information these SPN populations convey to downstream areas, and to describe how this information can be modulated by internal state. These data will provide a foundation for a subsequent R01 that will determine how different ACtx projections can influence perception and mediate behavior.
The deep layers of the auditory cortex give rise to a massive projection system that innervates a variety of downstream targets. The proposed studies will rigorously characterize, both anatomically and functionally, one of the largest output pathways in the brain. This kind of cortical dissection will provide a foundation for future work that may reveal how improper regulation of neural circuits can contribute to various perceptual and neurological disorders.