Ralf Wessel - US grants

DESCRIPTION (provided by applicant): LONG-TERM OBJECTIVE: To understand the synaptic, dendritic and network mechanisms of spatiotemporal processing underlying the computation of visual motion. SPECIFIC AIMS: The aim is to provide a cellular- and systems-level understanding of spatiotemporal processing in the tectal SGC-I motion pathway, thereby providing insight into general neural strategies for visual motion processing. The specific aims are (1) to determine to what extent the retino-tectal dynamics renders the SGC-I response to dynamic visual stimuli largely insensitive to the details of the retinal transformation, (2) to investigate the functional role of dendritic spike initiation and nonlinear dendritic interaction for the neural analysis of space-time pattern in the presynaptic population activity, and (3) to investigate the functional role of neural structure and connectivity for the population coding of motion with interdigitating sets of spiking dendrites. RESEARCH DESIGN AND METHODS: Synaptic, dendritic, and network mechanisms are critical for information processing in all vertebrates, but have been difficult to elucidate in mammals because of anatomical limitations. Therefore a chick tectal slice preparation has been developed which has two features that help to circumvent these limitations: (a) The extensive and sparse spatial distribution of tectal SGC-I neuron dendrites allows the spatiotemporal synaptic stimulation of selected dendritic endings in the slice. (b) Tectal SGC-I neurons receive monosynaptic inputs from a subpopulation of retinal ganglion cells at their dendritic endings. Further, tectal SGC-I neurons are sophisticated spatiotemporal integrators of retinal representations of dynamic visual stimuli and previous tectal SGC-I studies indicate phasic retino-tectal synaptic dynamics, dendritic spike generation in response to synaptic stimulation, and highly nonlinear dendritic interaction of multiple synaptic inputs. The central component of this research program consists of in vitro synaptic stimulation and whole-cell recordings. The interpretation of the in vitro results is supported with computational modeling. HEALTH-RELATEDNESS: The understanding of spatiotemporal processing at the level of synapses and dendrites in a visual pathway provides the key for the pharmacological intervention of visual perceptual impairments.

LONG-TERM OBJECTIVE: To gain insight into the cellular and dynamic mechanisms and functional roles of neural feedback loops for visual processing. SPECIFIC AIMS: The aim is to provide an understanding of the dynamic and neural mechanisms of feedback for visual processing. Here the avian isthmo-tectal feedback loop serves as an experimentally accessible model preparation for neural feedback systems in general. The specific aims are (1) to determine the cellular and synaptic properties in the isthmo-tectal circuitry and (2) to identify the role of isthmo-tectal system parameters for signal processing. The proposed research will provide fundamental insight into the mechanisms and the functional roles of feedback loops in central nervous systems. RESEARCH DESIGN AND METHODS: Neural feedback loops are critical for information processing in all vertebrates, but cellular mechanisms of feedback have been difficult to investigate in mammals because of anatomical limitations. The anatomical organization of the avian isthmotectal loops provides two major advantages for the study of feedback mechanisms in neural processing: The isthmo-tectal feedback loop is largely intact and accessible in the chick midbrain slice preparation, which we have developed. The two isthmic nuclei interact exclusively with the tectum but are otherwise isolated from the rest of the brain. We will approach our objective by studying cellular mechanisms of isthmo-tectal feedback in the slice preparation and by interpreting the functional roles of these mechanisms for visual processing in experimentally constrained model simulations. The feature that makes feedback approachable in the isthmo-tectal system is that we can study modulatory interneurons in a complex self contained system, yet these interneurons are physically separate from and exclusively connected to the system that they modulate. HEALTH-RELATEDNESS: The understanding of the dynamic and neural mechanisms of feedback for visual processing provides the basis for the pharmacological and prosthetic intervention of visual perceptual impairments. ARRA-RELATEDNESS: A total of six neuroscience jobs will be created and retained through this project.

The cerebral cortex is comprised of two competing types of brain cells: inhibitory neurons tend to suppress brain activity while excitatory neurons do the opposite. This project will illuminate principles governing the balance of inhibition versus excitation. Focusing on the role of inhibition, the project will test the hypothesis that a particular intermediate level of inhibition is optimal for sensory information processing, because it places the cortex network in a special operating regime called criticality.

When inhibition is too high, cortical neurons are suppressed and act largely independently. When inhibition is too low neurons are hyperactive and act largely in unison. Neither extreme is conducive to effective information processing. However, gradually decreasing inhibition from a high level can result in an abrupt onset of correlated, intense activity among the neurons. The tipping point of this onset is called criticality. Importantly, computer models and cortex slice investigations predict that at criticality certain types of information processing are optimized. However, the potentially pivotal role of criticality in processing real sensory input in an intact sensory system remains untested. Such tests will be undertaken here in an in vitro whole-brain preparation that allows the researchers to precisely manipulate levels of global inhibition, record cortical activity with microelectrode arrays for many hours, and stimulate the retina with naturalistic images. Employing novel, statistically rigorous, multifaceted, quantitative tests of criticality, the proposed research will determine the roles of inhibition and criticality in intact cortex during visual processing. Specifically, the experiments are designed to determine whether information transfer from visual stimulus to cortical response is maximized at an intermediate level of inhibition which manifests as criticality.

This project represents the first experimental test of the hypothesized functional benefits of criticality in real sensory processing. It builds on a strong conceptual foundation combining statistical physics and computational neuroscience, and may open a new paradigm for investigating cortical visual processing in large neural networks. This new paradigm is particularly relevant in light of emerging new technologies that enable the recording of activity from thousands of neurons. From the medical perspective this contribution is significant because it is expected to illuminate the etiology of numerous brain disorders with abnormal inhibition. Finally, the project brings the excitement of research into Missouri and Arkansas high schools with teacher training and classroom presentations. Newly fostered interest in STEM research will be assessed by longitudinal measures.