A fundamental function of the auditory system in humans is to process speech. Both speech sounds and social vocalizations of other animals are complex in that they are comprised of many frequency elements that vary over time. When these sounds are first encoded by the cochlea in the inner ear, they are broken down into their individual frequency elements and single neurons respond to individual frequency elements. However, to enable perception of the whole sound, neurons in the auditory system must recombine the individual frequency elements in the appropriate temporal order. In other words, individual neurons must integrate multiple frequency elements over time. The first site in the ascending auditory system where individual neurons integrate across frequency elements in complex sounds is the inferior colliculus (IC). The objective of this research is to determine the role of frequency and temporal integration in encoding complex sounds in the IC. In this project, responses of individual neurons in the IC to spectrally and temporally complex sounds, including natural vocalizations, will be obtained. The project focuses on characterizing neuronal responses that display nonlinear interactions to the combination of two sounds with energy in different frequency bands. The project then examines how these "combination-sensitive" neurons encode natural sounds by presenting natural mouse vocalizations. Neural responses elicited by the entire vocalization, individual frequency elements and combinations of elements with different temporal relationships will be compared. The hypothesis tested is that neurons in the mouse IC show nonlinear frequency interactions to signals that contain biologically important frequency elements in the appropriate temporal order, and that these combination-sensitive interactions are a mechanism for encoding natural vocalizations. The strength of this proposal is in utilizing naturally occurring, biologically relevant vocalizations in an awake mouse model to study neural mechanisms underlying the processing of complex sounds. Because mouse vocalizations have similar structures to the vowels of human speech, and similarities exist between the perception of multi-harmonic communication calls in mice and humans, this project will be an important step towards identifying the neural mechanisms of speech processing. The research activities in this project have an impact beyond the scientific findings. Dr. Portfors has established a diverse and committed record of educating students and the community. These activities include engaging minority students through research opportunities, undergraduate students through integration of research and teaching activities, and members of the local community through teacher training workshops, public lectures, and the local media. Dr. Portfors is regularly engaged in numerous activities outside the laboratory and classroom that have broad impact on the community. In a typical year, she and her students give 10-20 presentations to schools and community groups. This project will continue to foster interaction of undergraduate and graduate students in the laboratory and provide outreach to the community through presentations on auditory neuroscience.