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Introduction: My long term research goals are to understand how complex sounds are processed by the auditory system and to determine how age-related hearing loss impacts this processing. Many animals, including humans, use species-specific vocalizations to convey biologically important information to members of the same species. These vocalizations are often complex in frequency and time. A fundamental function of the auditory system is to process these complex sounds. How complex sounds are processed and represented in the auditory system is not understood. My research focuses on characterizing the neural mechanisms that underlie encoding of complex sounds. The main focus is on the main auditory midbrain nucleus, the inferior colliculus, but we are also conducting studies on the dorsal cochlear nucleus and auditory cortex.
Major Research Projects
- Processing of complex sounds in mice
- Processing of species-specific vocalizations in the auditory midbrain of mustached bats
- Effects of age-related hearing loss on encoding of complex sounds
- Behavioral analyses of acoustic communication
Processing of complex sounds in the auditory midbrain of mice - supported by NSF (top)
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, we are recording responses of individual neurons in the IC to spectrally and temporally complex sounds, including natural vocalizations. We are focusing on characterizing neuronal responses that display nonlinear interactions to the combination of two sounds with energy in different frequency bands. We are then examining 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 are compared. The hypothesis 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 research 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 research is an important step towards identifying the neural mechanisms of speech processing.
Processing of species-specific vocalizations in the auditory midbrain of mustached bats - supported by NIH R01 04733 (top)
Social vocalizations of animals are spectrally and temporally complex, and their analysis requires the integration of spectral and temporal information. One form of integration is performed by combination-sensitive neurons. These neurons respond best to combinations of spectrally or temporally distinct elements in complex sounds. Recently we have shown that combination sensitivity is a common feature of neurons in the auditory midbrain of the mustached bat, and that these response properties are created there. This suggests that combination sensitivity contributes to selectivity among social vocalizations in the midbrain. Virtually nothing is known regarding the extent of selectivity to social vocalizations in the inferior colliculus (IC) of mammals. In this project we are examining the extent of selectivity to social vocalizations in the IC, and determining whether combination sensitivity contributes to the neural selectivity. We have found that many neurons in the inferior colliculus of the mustached bat respond selectively to particular social vocalizations. To understand the neural mechanisms underlying this selectivity, we compared responses of individual neurons to single tones, combinations of tones and social vocalizations. The major finding is that a neuron’s response to social vocalizations is not well predicted by its response to single tones but is much better predicted by its combination-sensitive response. For example, we found neurons that only responded to one of fourteen different social vocalizations even though multiple vocalizations had energy in the same frequency bands. The selectivity was either due to facilitatory or inhibitory interactions between combinations of tones. In one example, a neuron responded weakly to tones near 57 kHz but responded well to the combination of a 57 kHz and a 29 kHz tone. Not surprisingly, the vocalization to which this neuron responded was the only one that had energy in both the 57 kHz and 29 kHz bandwidths. Thus, the facilitatory combination-sensitive properties of some neurons in the inferior colliculus of the mustached bat make these neurons selective to particular social vocalizations.
We also found that inhibitory combination sensitivity provided for selectivity to particular social vocalizations. Combination-sensitive inhibition occurs when the excitatory response of the neuron is inhibited by a second frequency signal that is at least one octave above or below the frequency that elicits the neuron’s best response. Combination-sensitive inhibition presents an interesting mechanism for suppressing a neuron’s response to a variety of stimuli, thereby creating selectivity. For example, a neuron that responds best to a 50 kHz tone would be expected to respond to all social vocalizations with energy in that frequency range. However, if the neuron was inhibited by a second sound in the 18-25 kHz range, it would not respond to any calls that had energy in both the 50 kHz and 18-25 kHz frequency ranges. This type of inhibitory combination sensitivity is common in the inferior colliculus of the mustached bat and seems to play an important role in creating selectivity to certain social vocalizations. The significance of our findings is that combination sensitivity is an important neural mechanism for encoding different types of complex sounds.
Effects of age-related hearing loss on encoding of complex sounds (top)
When individuals suffer from age-related hearing loss, they have difficulty understanding basic speech sounds important in everyday life. Mouse models for age-related hearing loss offer effective tools for dissecting the neural mechanisms underlying debilitating changes in processing of species-specific vocalizations. Age-related hearing loss causes similar behavioral deficits in humans and mice. Moreover, vocalizations emitted by mice are similar in structure to human speech and may share similar neural processing mechanisms. Thus, understanding the effects of age-related hearing loss on processing of natural vocalizations in mice has direct translational benefits to human health. The objective of this research is to understand how age-related hearing loss alters encoding of species-specific vocalizations in the inferior colliculus. These studies focus on neural properties in the inferior colliculus because this is the first site in the ascending auditory system to show changes in frequency processing caused by loss of peripheral outputs. Our approach is to record neuronal responses to tones, combinations of the tones and natural mouse vocalizations in the inferior colliculus of mice with age-related hearing loss. The aims of this research are to identify mechanisms underlying frequency reorganization seen in the inferior colliculus with age-related hearing loss, determine the role of nonlinear frequency interactions in encoding vocalizations, and determine how age-related hearing loss affects encoding of vocalizations. Recordings of single neuron responses in inferior colliculus are being combined with mathematical modeling in an interdisciplinary approach. We have found that age-related hearing loss dramatically alters the frequency integration properties of neurons in the inferior colliculus. The extent of multiple tuning and combination sensitivity, both indicators of frequency integration in single neurons, in the inferior colliculus of mice with age-related hearing loss was less than we have found in normal hearing mice. Losing frequency integration properties in the inferior colliculus during aging likely impairs the central auditory system’s ability to process complex sounds such as speech. The importance of this research is in enhancing our understanding of the mechanisms underlying changes in frequency processing with age-related hearing loss. This project has direct translational benefits to human health because the results will be a step towards establishing the causes of deficits in processing of vocalizations, including speech, that occur with age-related hearing loss. This will be a critical first step to the prevention and reduction of speech processing deficits in humans.
Behavioral analyses of acoustic communication (top)
Many animal species live in complex social organizations that remain stable through the use of social communication. Acoustic communication among individuals in a group facilitates biologically important functions such as social dominance, mating, predator avoidance and feeding. It is important to understand both the behavorial and neurophysiological mechanisms underlying acoustic communication. For most animal species, the behavioral and neurophysiological aspects of acoustic communication have not been studied in an integrated manner. For some species, we know a fair amount about how calls are structured and what they mean, but we know almost nothing about their neurophysiological processing. In other species, we have some suggestions about how complex sounds are processed but we have little idea of the functional significance of the sounds. Consequently, we need a model system in which we can understand the behavioral significance of the communication calls and how the central auditory system processes the sounds. Mice and bats are ideal candidates because both behavioral and neurophysiological experiments can be performed under controlled laboratory conditions. This project focuses on obtaining communication calls from mice and bats under different behavior conditions and determining the behavioral significance of individual communication calls. These experiments will contribute to our understanding of acoustic communication on their own, but they will also contribute to the long-term goal of the laboratory in understanding how the brain processes complex sounds. The communication sounds obtained in these experiments are used in neurophysiological studies of communication sound processing in mice and bats.