Nicholas J. Strausfeld - US grants

Neural mechanisms underlying fundamental vertebrate motor activities can be usefully studies in model systems from other phyla which offer the advantage of a limited number of neurons accessible to intracellular techniques and modern structural analysis. One such activity, generically known as the oculomotor response, comprises complex patterns of behaviour mediated by the visual and vestibular systems: gaze, object scanning and fixation, and the stabilization of the retinal image compensating for complex spatial displacements of the head and body. Oculomotor abnormalities in humans can indicate the onset of central nervous trauma and disease. A greater understanding of the cellular organization of a complex multisensory oculomotor pathway could provide useful leads and suggestions for research on the physiologically less accessible vertebrate counterpart. One such model is provided by the dipteran Calliphora erythrocephala, which has a wide range of sophisticated oculomotor behaviours. In both sexes panoramic motion elicits compensatory head and body movements. Objects is visual space elicit fixation and orientation behaviour. In Calliphora there is a profound sexual dimorphism of the eye: in males there are more receptors, a zone of high visual acuity, and unique sex-specific neurons in the visual centers. Only males are able to sustain fixation, tracking and interception of small rapidly moving objects. This is distinct from behaviour shared by both sexes in which panoramic flow fields are computed by elemental motion- detectors and relayed to giant tectal neurons. Ultimately, mechanosensory information, derived from strategically placed organs for balance tactile perception is integrated with visual information in discrete brain centers from which originate 1) descending pathways to thoracic motor centers controlling head and body musculature and 2) interneurons supplying cerebellarlike higher centers in the midbrain. This research will employ intracellular recordings and stainings, and sophisticated light and electron microscopical strategies to dissect the cellular organization of identified nerve cells, from the receptors to the motor neurons and musculature. The research will focus on the following: 1) retinotopic organization and multimodal response characteristics of visual interneurons; 2) intracellular recordings and synaptic relationships of descending motor neurons; 3) innervation, physiology, and dynamics of effector muscles; 4) skeletal attachment, arthrology, and behaviour. This research proposes to broaden our understanding of neural mechanisms involved in visuo-mechanosensory control of eye movements. A complete description of motor control in this model will contribute a major step towards understanding circuitry for complex oculomotor behaviour and the role of uniquely identified neurons in visual pursuit and interception.

DESCRIPTION (taken from abstract): Visual perception and resulting actions derive from interactions amongst neurons that are organized as parallel pathways that parse out specific computational tasks. In mammals, experimental access to these neural substrates is limited by factors such as size, subject availability, and economics. An alternative system that elegantly demonstrates how identified neurons interact to process fundamental features of the visual world, such as motion, is provided by the dipteran visual system. This model, like its mammalian counterpart, possesses a system of achromatic magnocellular neurons that carry information about motion to a center controlling optokinetic behavior. There is also a second, parallel system of parvocellular neurons that supply a cortex-like area in the brain encoding information about pattern, orientation, and color. In-depth analysis and predictive modeling of functionally identified neurons that comprise these two subsystems are now providing fundamental insights into the synaptic arrangements and neural mechanisms that underlie the control of head movements and the analysis of form and color. The proposed research will investigate: Neural mechanisms and circuit properties amongst achromatic neurons that (a) compute the first stages of motion detection, (b) integrate motion information with object detection to provide target-directed head movements, saccades, and distance perception, and (c) control saccadic head movements by integrating them with proprioceptive reafference that monitors head movements. Neural mechanisms and circuit properties amongst parvocellular neurons that separately and collectively discriminate orientations, textures, and color. The research emphasizes intracellular recordings, confocal studies of dye-filled neurons, synaptology, and identification and localization of neurotransmitters. Models to (a) test the functional properties of synaptic circuits amongst recorded and identified neurons, (b) direct novel experiments, and (c) serve as a basis for reverse engineering of this model visual system. A complete functional and computational understanding of the dipteran system will provide crucial insights into basic principles of visual processing and will provide essential information for constructing miniaturized prosthetic visual systems and automata.

[unreadable] DESCRIPTION (provided by applicant): The specific aims of this proposal are to achieve a comprehensive understanding, at the cellular and synaptic level, of the functional organization amongst uniquely identified amacrine cells and interneurons that together compute the orientation and direction of visual motion. For the first time since the formulation in the 1950s by Hassenstein and Reichardt of a notional circuit for motion perception, a system of neurons has been identified in the dipteran visual system that supplies motion-sensitive premotor output neurons and has Reichardtian outputs. Arrangements amongst these small-field neurons do not, however, match the expected organization predicted by the Reichardtian model but instead show features suggestive of a Barlow-Levick type detector, in common with directional motion detection circuits in certain mammalian retinas. The architecture of this neuron-based motion-detecting circuit in Diptera differs significantly from previous theoretical "wiring diagrams" in that it reconstitutes directional motion in three successive stages, involving computation of 1) nondirectional motion at the level of amacrine cells, and 2) oriented motion and 3) directional motion at the level of analogues of bipolar and ganglion cells, respectively. Each neuron type participating in the motion-computing pathway is uniquely identifiable using specific antisera, thus allowing its recognition at the light and electron microscopic levels. Intracellular recordings and electron microscopic reconstructions of marked neurons, in conjunction with computational modeling, will be used to test predictions about functional properties and connections. These investigations will elucidate the functional organization of parallel channels that supply subsystems in the optic lobes with information about edge orientation, local figure motion, and other parameters, including stimulus velocity, acceleration, and deceleration. New model circuits based on electrophysiological and synaptic analyses will reveal emerging requirements that will guide future structural and functional studies. This research will provide basic insights into directional motion detection by the dipteran visual system and reveal principles underlying motion detection that transcend phyletic boundaries. It will also lead to the implementation of silicon-based circuits that enable motion detection and shape discrimination and potentially provide the basis for a visual prosthetic device. [unreadable] [unreadable]

[unreadable] DESCRIPTION (provided by applicant): Until recently, the study of neuroethology has focused on sensory mechanisms underlying specific adaptive behaviors and around issues of plasticity in brain and behavior. However, in the last 5 years conceptual breakthroughs and novel approaches have been developed with regard to important and interrelated areas of analysis. This conference will consider (1) research on how environmental cues shape adaptive control mechanisms and how complex signals affect the behavior of individuals and groups. These issues bear directly on (2) context-dependent choice, emergent properties of group behavior, and the evolution of behavioral phenotypes. New translational approaches include population genetics and modeling, in conjunction with more familiar neuroethological methods. Further, the realization that knowledge gained from analyzing circuitry and behavior is not invariably sufficient to test hypotheses has lead to (3) exciting advances in developing neuromorphic entities that allow rigorous tests of circuit capabilities in defined behavioral settings. These approaches have far reaching implications for robotics and neural prosthetics. (4) Insight into how the brain processes sensory data to provide adaptive behavior has achieved new impetus from genetic tools that target specific elements of neural circuitry to provide defined functional alterations that are behaviorally testable. This proposed 3rd Gordon Research Conference on Neuroethology will provide a timely discussion of these issues and about the development and future directions of the study of sensory perception, brain, and behavior. The conference is intended for the broad neuroethological community at all professional levels including advanced graduate and postdoctoral trainees. [unreadable] [unreadable]

? DESCRIPTION (provided by applicant): This proposal requests continuance of the University of Arizona's (UA) Postdoctoral Excellence in Research and Teaching program (PERT), as assessed on the basis of its progress and success in producing highly productive cohorts of trainees. The overarching goal of the program is to develop a diverse group of highly trained life scientists with the aim of increasing participation of underrepresented groups in the academic, health and biotechnology work force. PERT has enjoyed a vigorous 14-year partnership with Pima Community College (PCC), a minority-serving institution (MSI), in which PERT Scholars teach classes at PCC under the guidance of PCC faculty. In their undergraduate classes PERT Scholars expose PCC students (and faculty) to cutting edge research and topics in the life sciences that they would not otherwise encounter, as well as new and diverse teaching styles. In addition to the PERT Scholars' classroom contributions, PERT provides equipment and supplies for the PCC Biotechnology Laboratory. Since the beginning of the PERT/PCC partnership the PCC biotechnology certificate program has grown to serve over 200 students on the main PCC campus. To accommodate increased demand, this proposal requests funds to establish a new biotechnology laboratory on a second PCC campus. PCC students and faculty are also encouraged to collaborate with PERT Scholars on research projects in their UA home laboratories. The success of this partnership has led to increased numbers of PCC students transferring to the UA for training for careers in the biosciences. The 3-year training period of PERT Scholars relies on committed UA faculty who mentor scholars in integrating innovative independent research with classroom teaching, undergraduate mentorship, and the acquisition of organizational and administrative skills. Since the inception of the PERT Program over 80% of PERT Scholars has obtained tenure-track positions in academia or its equivalent. The PERT Program advances the careers of its Scholars, provides opportunities for MSI faculty to update and broaden their professional expertise, and positively impacts the broader UA research community and its faculty as well as advancing the discipline. PERT has achieved notable success in preparing postdoctoral Scholars for an independent career while fostering broad scientific collaboration between a research I institution and a minority-serving institution and fulfilling the educational and career needs of groups under-represented in the life sciences.