Albert S. Feng - US grants

Auditory communication often involves sounds that have complex frequencies, or spectra, and complex timing relations, or temporal pattern. Some analysis of the spectral and temporal components is known to occur low in the brainstem, which contains groups of nerve cells called the auditory nuclei. These neurons send projections to higher centers in the brain for further analysis. Frogs have provided particuluarly useful models for study, since they are well-studied, their mating calls are relatively simple and stereotyped, and the brainstem has somewhat simpler structure than in mammals. This project will use the frog model to examine how behaviorally meaningful features of complex sounds are processed in the brain. Two particular nuclei in the brain stem will be studied by electrophysiological recording of single cell responses to a wide range of artificial and natural acoustic signals. Building on past work on recognition in the frequency domain, this project will aim primarily to determine the selective importance of certain features of amplitude modulation and temporal pattern, and the neural codes of response patterns that may be used to discriminate among different signals. Results will be relevant to studies of communication behavior, of complex sound analysis, and important to the general sensory problem of signal processing.

In order to optimize interdisciplinary approaches that capitalize upon new technical and theoretical developments, a Center for the Neurobiology of Learning and Memory is being established at the Beckman Institute (currently under construction) of the University of Illinois at Urbana-Champaign . This center will serve as 1) a Resource Center, providing advanced facilities for the study of the learning and memory process, including optical imaging (for histological studies), multi-electrode array recording (to allow functional patterns of interactions among neurons to be examined), and rapid tissue freezing (for assessment of sub-cellular dynamics); 2) a Research Center that fosters communication and collaboration among scientists pursuing common and related problems of memory and neural plasticity; 3) a Training Center which prepares graduate and postdoctoral investigators for research careers in learning and memory, and 4) a Recruiting Center that to attract outstanding young people to scientific careers. This program of scientific development and interaction is taking advantage of the unusual resources of the Beckman Institute and the University of Illinois Urbana-Champaign campus in neurobiology, interdisciplinary collaboration and cooperation, and strengths of the component disciplines of neural and behavioral sciences. Technical foci of the Center include large array neurophysiological recording facilities, with which the interactions among brain regions during learning are studied; rapid freezing facilities for examining brain slices in vitro, (with which the nature of plasticity at the level of the synapse is studied), and neuroanatomical imaging and analysis facilities (where memory processes are studied at levels ranging from the molecular to the morphological). Several types of learning are being studied, including discriminative conditioning, acquisition of motor skill, acquisition of acoustic discriminative ability, and the traditional psychological animal learning tasks such as mazes. In addition, current "models" of memory (such as long-term potentiation and kindling) are being examined. The function of the Center for the Neurobiology of Learning and Memory is to advance our knowledge of brain substrates of learning and memory from the cellular and molecular to the integrative brain system levels.

This award provides funds to establish an interdisciplinary site REU program in Neuroscience at the University of Illinois Neural and Behavioral Biology (NBB) Program, a Ph.D. granting interdisciplinary program begun in 1970. The common focus is neuroscience, the interdisciplinary field that seeks to understand the function of nerve cells and systems from the molecular and cellular levels to that of behavior. Faculty in the program that demonstrate an extensive history of involvement of undergraduate in laboratory research have been selected as co- Principal Investigators. Collectively, faculty in NBB have sent about 75 undergraduates who worked with them into scientific careers, including faculty positions at Harvard, Yale, Chicago, Stanford, and Pennsylvania. Even greater numbers have gone on to careers in Medicine and other professional Doctorate-level fields. Neuroscience subfields in which research experience will be offered included behavioral neuroscience, neural development and plasticity, molecular, cellular and genetic neuroscience, neurophysiology, neuroanatomy, computational neuroscience, and cognitive neuroscience.

This award will provide partial support for the conference Computations in Natural and Artificial Parallel Systems. This conference is interdisciplinary in nature, bringing together researchers from several different fields to focus on parallel computation systems, comparing the parallel circuit in the brain with that of parallel computer systems. The conference with be held September 27-30 at the Beckman Institute in Urbana-Champaign, Illinois.

The overall goal of this research program is to gain an understanding of the neural mechanisms underlying coherent perception of sound patterns and direction. The experiments outlined in this proposal are designed to examine the effect of sound direction on neural coding of complex sound patterns. We plan to address three specific questions: (1) Are the neural processes which underlie sound localization and pattern recognition mediated by two different neural populations? (2) Do response selectivities to complex sound features vary with sound direction? (3) Suppose the response function to different sound features depends upon the sound direction, what may be the underlying basis? Single unit recordings will be made from the frog's superior olivary nucleus and tonus semicircularis, two brainstem structures in the frog nervous system which are essential for encoding complex acoustic features and sound direction. Acoustic stimuli consisting of artificially simulated natural sounds (i.e., amplitude modulated tones and noise), tape-recorded natural sounds and bursts of pure tones will be presented through a free field loudspeaker at various azimuths. Auditory responses to these stimuli under different incident angles will be quantitatively analyzed to test various hypotheses related to the above questions. The frog auditory system is chosen for this study because: (a) acoustic communication behavior of frogs is well understood,k and frog's vocal repertoire is small and that calls are stereotyped, (b) acoustic features which are essential for communication have been identified and therefore an investigation of extraction of these features by the brain would be a fertile research avenue, (c) coherent perception of complex sounds is particularly germane to frogs for whom the survival of the species depends upon the females having the ability to determine "which sound comes from where", and (d) there is a large body of knowledge on the anatomy and physiology of the frog auditory system. The principles gained from this study will shed some light on the mechanisms underlying coherent perception of acoustic "image" (spatial and pattern).

Neuronal pattern analysis (NPA) documents the dynamic brain processes of sensation, perception, learning and cognition by recording the electrical activity of brain neurons. Recent advances in multi-array recording technologies have greatly expanded the rate at which NPA data can be obtained, and these technologies have fostered means not previously available to study the intercorrelations of dynamic activities in neuronal networks. Computational modeling of brain dynamic activity has fostered major increment in the requirements of data processing due to the need to analyze simulated neuronal spike trains and to compare real and simulated neuronal data. These developments call for parallel development of adequate database systems for organization, rapid access, and sharing of NPA data. This project will establish a database system (DBS) for time series neurophysiological data recorded in experiments of members of the University of Illinois Beckman Institute Neuronal Pattern Analysis Group. System design and implementation will be carried out with consultation and guidance of the National center for Supercomputer Applications. This proposed system will foster community-wide sharing of times series and other forms of neural data, proved a model DBS that can generalize to other neuroscience groups, and enhance the research in the involved laboratories.

Experiments proposed in this application are designed to examine the mechanisms by which sound direction affects information processing in the frequency domain. We have previously shown that sound direction can significantly alter frequency threshold characteristics (FTCs) of neurons in the frog torus semicircularis (TS), a homolog of the mammalian inferior colliculus. Primarily, the FTC of most toral neurons becomes more sharply tuned when the free-field loudspeaker is rotated from the contralateral side to the ipsilateral side, or to the front of the animal. The mechanisms underlying these direction-dependent changes in the FTC of midbrain neurons are unclear and will be investigated in the next granting period. We hypothesize that changes in tuning width with sound direction are likely a consequence of binaural processing of the changing balance of inputs from the two cars. Single-unit recordings will be made from the frog TS to address four specific aims. Aim #1 is to determine whether or not a unit's binaural interaction pattern (EE, EI, or EO) gives rise to a specific direction-dependent FTC change. Aim #2 is to investigate the effects of monaural occlusion (e.g., the ipsilateral ear) on FTCs derived from free-field stimulation at different sound directions. The goal here is to assess the degree to which binaural interaction contributes to the direction-dependent sharpening of a unit's FTC in TS neurons displaying the different binaural interaction patterns. Aim #3 is to investigate whether or not the direction-dependent frequency selectivities of a unit can be mimicked by independently-controlled stimulation of the two ears. The relative contributions of interaural time (ITD) and level (ILD) differences for the sharpening of frequency tuning will be determined. Aim #4 is to investigate in E1 total neurons the FTCs at 2-3 azimuths under three different conditions: (a) normal intact, (b) when the recording locus receives a micro injection of antagonists of GABA-a or GABA-b receptors, (c) when the ipsilateral ear is occluded. The goals here are: (i) to determine whether or not binaural inhibition in the frog TS involves GABA, and GABA-based binaural inhibition is involved in direction-dependent sharpening of the FTC, (ii) to assess where the primary locus of binaural inhibition may be, i.e., whether or not it occurs mainly at the level of TS or preceding binaural convergent loci in lower brainstem. Results deriving from this study will shed light on the mechanisms by which binaural processing improves frequency discrimination.

The ability to discern intonation or amplitude modulation of syllables in the individual words is of vital importance to speech perception. This application is for support to investigate how amplitude modulation in temporally discrete sounds are represented in the inferior colliculus (IC) and the auditory cortex (AC). The study will be carried out in echo locating bats for which survival depends on having a fine ability to discriminate amplitude and frequency modulations in echoes of their own biosonar vocalizations. Specifically, for myotic lucifugus, different insects induce different amplitude-modulation patterns in a sequence of temporally discrete echoes; these patterns can be used as signatures for discriminating the different insects. Electrophysiological experiments will be carried out to address the following questions: 1. How well do single neurons in the inferior colliculus and auditory cortex represent amplitude-modulations that span across successive sound pulses ("AM")? 2. Is the representation of "AM frequency" a function of a unit's temporal discharge pattern, or its characteristic frequency? If so, how? 3. Is the representation of "AM frequency" dependent upon the rate at which sound pulses are presented (repetition rate)? If so, how? 4. How do neurons in the tow levels of the central auditory system differ in their representations of the "AM frequency"? Is there a transformation in the representation along the collilculo-thalamo- cortical pathway? 5. Is there an topographically ordered representation of "AM frequency" in either the inferior colliculus or the auditory cortex? Results of these physiological studies are expected to generate insights into how behaviorally meaningful amplitude-modulated stimuli are encoded in the auditory system of echolocating bats and to shed light on the mechanisms by which the nervous system of echolocating bats and to shed light on the mechanisms by which the nervous system represents amplitude variations over discrete components of complex sounds such as speech.

DESCRIPTION: The overall goal of research is to gain an understanding of the neural mechanisms underlying sound pattern recognition. Experiments proposed in this application are designed to study how the spectral and temporal attributes of a sound (i.e., signal) in free-field are represented in the central auditory system when the signal is embedded in noise (or interfering sound) originating from a spatially segregated source. It is well known that the ability of the auditory system to extract a sound in the presence of another is constrained by masking. Thus the specific goal of the proposed physiological experiments is to validate several hypotheses pertaining to how masking by noise is released by the angular separation of the signal and noise sources, whereby the signal can be extracted by the nervous system. The experimental design has elements in common with hearing in a "cocktail party" involving coherent perception of the location and patterns of a sound in the presence of other competing sounds. The proposed study will be conducted from the torus semicircularis (or inferior colliculus, IC) of the green treefrog for which the ability to perceive coherently is vital for reproductive success. The research plan will make use of different probe stimuli (both simple as well as complex sounds). Furthermore, the effects of simultaneous and forward making will be evaluated and compared. Finally, the role of binaural inhibition in spatially-mediated release from masking will be assessed in order to gain insight into the cellular underpinning of the underlying neural processes. Response of a single IC unit to a probe stimulus (presented within the unit's best spatial receptive field) plus a masker originating from a different azimuth and the unit's response to the masker alone will be analyzed and compared. Results deriving from this research will be interpreted, insomuch as possible, within the context of behavioral framework (i.e., signal detection). We expect the outcome to generate insight into the neural computational algorithm for extracting desired signals in the presence of interfering sounds. This is important basic knowledge, but the knowledge gained can also shed light on practical applications, e.g., on design of intelligent hearing aid devices.

DESCRIPTION (provided by the applicant): Oscillation occurs widely in the nervous system but its functional significance is largely unknown. The goal oi the proposed research is to advance our understanding of the origin and functional significance of oscillation (particularly fast oscillation) in the auditory system. Pilot studies in the inferior colliculus [1C] of frogs and echolocating bats have revealed that in response to brief tone pips some IC neurons display rapid oscillatory discharges and/or paradoxical latency shift. Further, there are indications that the oscillatory discharge is presumably due to unit's intrinsic resonance and responsible for creating paradoxical latency shift, a phenomenon previously shown to be important for time domain analysis. These findings suggest that rapid oscillation in the IC may be involved in temporal processing. Three specific aims will be addressed. Aim #1 will determine how prevalent is oscillation in the IC and the stimulation condition under which oscillatory discharges and/or paradoxical latency shift occur. Single unit recordings will be made from the IC to test two working hypotheses: (i) IC neurons exhibit oscillatory discharges when they are appropriately stimulated, (ii) oscillatory discharge is more robust when GABAergic inhibition is suppressed. Aim #2 is to determine the functional significance of oscillatory discharges in acoustic signal processing. Physiological experiments will be made from single units in the IC to test the hypothesis that oscillatory discharges play an important role in temporal processing. Aim #3 is to test the hypothesis that membrane of some IC neurons exhibits intrinsic resonance and this resonance is a foundation for oscillatory discharge and/or paradoxical latency shift. In-vitro intracellular recordings will be made from brain slices to ascertain that some IC neurons exhibit intrinsic resonances under low Ca concentration in the bath. Additionally, in-vivo intracellular recordings will be made from single neurons in the IC that display paradoxical latency shift (as characterized extracellularly) to determine whether this property is created by oscillation in membrane potential.

In natural environments, sensory signals often arise from clustered sources. For example, during the mating season, the auditory cues that guide a female frog to a particular male are embedded in a dense chorus arising from hundreds of calling males of different species. Clustered signals pose a significant challenge for biological systems as well as for intelligent neural prostheses and machine perception systems. For example, an intelligent hearing aid should exhibit robust performance in cluttered environments with other voices in the background. A multidisciplinary team of investigators will explore the neural mechanisms and computational algorithms that animals use to detect, identify, and localize individual signals embedded in an ensemble of similar signals. Experimental studies will focus on the auditory-mediated approach of female frogs to a mating chorus and the electrosensory-mediated approach of electric fish to a cluster of prey. These studies will include audio recordings of frog choruses at different distances from natural mating ponds and electrical recordings of active electrosensory signals arising from swarms of zooplankton. Approach trajectories will be recorded and analyzed using radio telemetry (frogs) and infrared video recordings (fish, frogs). Theoretical analysis will draw on algorithms from computer vision including multiscale grouping and segmentation, target detection and tracking, active vision, texture analysis, and motion and structure estimation. Neural correlates of clustered signal processing will be assessed through electrophysiological studies on auditory nerve and midbrain neurons in frogs and primary electrosensory afferent and hindbrain neurons in fish.
This project will incorporate interdisciplinary training (engineering and neurobiology) for students, a web site for sharing data, software and references in this field and could contribute to the development of improved machine devices for speech recognition and video surveillance.

DESCRIPTION (provided by applicant): We propose a training program in sensory neuroscience for 4 pre-doctoral and 2 post-doctoral trainees at the University of Illinois at Urbana-Champaign (UIUC). The goal is to prepare trainees for productive careers in biomedical research through rigorous, well-rounded, in-depth training in auditory and chemosensory neurobiology. To achieve this goal, the training program will take advantage of the diversity of conceptual approaches, animal models, and methodologies employed by sensory neuroscientists on this campus. First, we will foster the trainees' ability to work effectively across the multiple levels of sensory-system organization. With the genomes of key animal models almost or completely sequenced and concomitant advances in proteomics, we now possess the molecular blueprint for the specialized cells, tissues, and organs of sensory systems. To elucidate how these different levels of organization control each other, we need to train scientists that can move effortlessly among them all. Second, we will emphasize comparative approaches to the understanding of chemical and auditory sensory systems. The trainees will be exposed to the commonality of processing strategies across different sensory systems as well as to the strategies unique to each sensory system in a wide range of animal models. This will help them to identify the central principles of sensory neuroscience. Third, we will equip trainees with the ability to adapt and apply new techniques. The training program will promote the participation in research projects that involve two or more UIUC laboratories with complementary capabilities. This integration of different levels of analysis, modalities, and techniques will put the trainees in a prime position to advance basic research and to transfer their knowledge to novel applications, such as the development of sensory prostheses and artificial sensors. Finally, we will develop the trainees' skills for oral and written communication. To this end, trainees will be required to prepare and submit F31 or F32 applications to the NIDCD as a tangible outcome of their training, as well as to critique such applications by other trainees within the program. We believe such training is vitally important for establishing a successful career in biomedical research.