The chief goal here is to examine the neuronal substrates and mechanisms that control mammalian sound production in response to auditory feedback in the brainstem. Focus is on the analysis of two areas: (1) the parabrachial nucleus (PB), and (2), the motor nucleus of laryngeal control, nucleus ambiguus (NA). Their role for auditory feedback control of vocalizations will be tested in awake, behaving horseshoe bats. These bats accurately control the frequency of their echolocation calls through auditory feedback both when the bat is at rest (resting frequency, RF) and when it is flying and compensating for frequency-shifted echo signals (Doppler-shift compensation, DSC). Pharmacological studies showed that PB is essential for the control of both, RF and DSC and identified the transmitters involved. The proposed project has two specific aims: First, to examine the neuronal mechanism(s) and the anatomical connections underlying this audio-vocal control by the PB. For that purpose, DSC behavior will be elicited in spontaneously vocalizing, stationary animals by electronic playback and constantly be monitored. The PB will be localized using stereotaxic coordinates and the area determined where injections of neuroactive agents yield maximum effects on DSC and RF. Subsequent extracellular single-unit recordings in this area will be correlated with both the auditory feedback and resulting changes in call frequency. Simultaneous injections of transmitter agonists and antagonists will allow to relate changes in neuronal activity to the changes observed in the behavior. The antero- and retrograde projection patterns of PB will be determined by iontophoresis of neurotracers into PB. Second, to investigate how NA is involved in auditory feedback control of call frequencies. The same combined pharmacological, neurophysiological, and anatomical approach will be taken as for PB: tests of the effects of various excitatory and inhibitory agonists and antagonists on RF and DSC, subsequent extracellular single-unit recordings, and analysis of anatomical connectivity. The results of these studies will yield new insights into the neuronal implementation of audio-vocal control mechanisms in an awake, behaving animal preparation. They also bear the potential to provide a better understanding of the neuronal mechanisms of various psychoacoustic phenomena in humans, e.g. the involuntary response to pitch-shifted feedback, and various malfunctions of basic parameters of human voice, such as changes in the fundamental frequency that occur in speaking deaf humans. ? ?
