The objective of the proposed studies is to understand the functional relationships between the auditory cortex and thalamus, and ultimately to uncover the neural substrates for auditory cognition. This work will test the hypothesis that the nonlemniscal portions of the auditory thalamus act as a link in an alternate information route between auditory cortical areas: a cortico-thalamocortical route, with layer 5 auditory corticothalamic projections providing feedforward driving input to the nonlemniscal thalamic nuclei while layer 6 corticothalamic projections provide feedback to all areas of the auditory thalamus. To test this idea, the reciprocity patterns and synaptic morphologies of laminar-specific corticothalamic projection systems in the mouse will be studied using injections of tracers into both the auditory cortex and thalamus. In addition, the physiologic signatures of driver or modulator responses in the thalamus will be studied in the auditory corticothalamic slice preparation by using laser-uncaging of glutamate to stimulate auditory corticothalamic neurons in layers 5 and 6, respectively, while recording from neurons in the subnuclei of the auditory thalamus. Finally, pairs of connected auditory cortical and thalamic neurons will be recorded from to better define the detailed circuitry of corticothalamic systems. The proposed experiments should shed light on the role(s) of the massive, heterogeneous corticothalamic projection systems as well as help to clarify the role of the nonlemniscal thalamus in shaping auditory cortical function. In addition, this work will be the focus of an intensive laboratory training experience designed to prepare the investigator for a research career dedicated to the study of auditory thalamocortical function. This will be coupled with training in clinical aphasiology and cognitive neurology to enable the investigator to develop strategies to address problems of higher cortical function that depend upon the integrity of thalamocortical networks. Relevance: The goal of the proposed research is to better understand the brain mechanisms underlying the perception of sound. It is hoped that this work will lead to a better understanding of speech perception and to new ways to diagnose and treat patients who have lost their ability to use language. ? ? ?
