Linking the Laminar Circuits of Visual Cortex to Visual Perception

A detailed neural model is being developed of how the laminar circuits of visual cortical areas V1 and V2 implement context-sensitive binding processes such as perceptual grouping and attention, and develop and learn in a stable way. The model clarifies how preattentive and attentive perceptual mechanisms are linked within these laminar circuits, notably how bottom-up, top-down, and horizontal cortical connections interact. Laminar circuits allow the responses of visual cortical neurons to be influenced, not only by the stimuli within their classical receptive fields, but also by stimuli in the extra-classical surround. Such context-sensitive visual processing can greatly enhance the analysis of visual scenes, especially those containing targets that are low contrast, partially occluded, or crowded by distractors. Attentional enhancement can selectively propagate along groupings of both real and illusory contours, thereby showing how attention can selectively enhance object representations. Model mechanisms clarify how intracortical and intercortical feedback help to stabilize cortical development and learning. Although feedback plays a key role, fast feedforward processing is possible in response to unambiguous information.Defense Advanced Research Projects Agency and the Office of Naval Research (N00014-95-1-0409); National Science Foundation (IRI-97-20333); Office of Naval Research (N00014-95-1-0657

How does the Cerebral Cortex Work? Learning, Attention, and Grouping by the Laminar Circuits of Visual Cortex

The organization of neocortex into layers is one of its most salient anatomical features. These layers include circuits that form functional columns in cortical maps. A major unsolved problem concerns how bottom-up, top-down, and horizontal interactions are organized within cortical layers to generate adaptive behaviors. This article models how these interactions help visual co1tex to realize: (I) the binding process whereby cortex groups distributed data into coherent object representations; (2) the attentional process whereby cortex selectively processes important events; and (3) the developmental and learning processes whereby cortex shapes its circuits to match environmental constraints. New computational ideas about feedback systems suggest how neocortex develops and learns in a stable way, and why top-down attention requires converging bottom-up inputs to fully activate cortical cells, whereas perceptual groupings do not.Defense Advanced Research Projects Agency; National Science Foundation (IRI-97-20333); Office of Naval Research (N00014-95-1-0409, N00014-95-1-0657

Temporal Dynamics of Binocular Display Processing with Corticogeniculate Interactions

A neural model of binocular vision is developed to simulate psychophysical and neurobiological data concerning the dynamics of binocular disparity processing. The model shows how feedforward and feedback interactions among LGN ON and OFF cells and cortical simple, complex, and hypercomplex cells can simulate binocular summation, the Pulfrich effect, and the fusion of delayed anticorrelated stereograms. Model retinal ON and OFF cells are linked by an opponent process capable of generating antagonistic rebounds from OFF cells after offset of an ON cell input. Spatially displaced ON and OFF cells excite simple cells. Opposite polarity simple cells compete before their half-wave rectified outputs excite complex cells. Complex cells binocularly match like-polarity simple cell outputs before pooling half-wave rectified signals frorn opposite polarities. Competitive feedback among complex cells leads to sharpening of disparity selectivity and normalizes cell activity. Slow inhibitory interneurons help to reset complex cells after input offset. The Pulfrich effect occurs because the delayed input from the one eye fuses with the present input from the other eye to create a disparity. Binocular summation occurs for stimuli of brief duration or of low contrast because competitive normalization takes time, and cannot occur for very brief or weak stimuli. At brief SOAs, anticorrelatecd stereograms can be fused because the rebound mechanism ensures that the present image to one eye can fuse with the afterimage from a previous image to the other eye. Corticogeniculate feedback embodies a matching process that enhances the speed and temporal accuracy of complex cell disparity tuning. Model mechanisms interact to control the stable development of sharp disparity tuning.Air Force Office of Scientific Research (F19620-92-J-0499, F49620-92-J-0334, F49620-92-J-0225); Office of Naval Research (N00014-95-1-0409, N00014-95-l-0657, N00014-92-J-1015, N00014-91-J-4100

Neural Models of Seeing and Thinking

Air Force Office of Scientific Research (F49620-01-1-0397); Office of Naval Research (N00014-01-1-0624

Stable learning of functional maps in self-organizing spiking neural networks with continuous synaptic plasticity

This study describes a spiking model that self-organizes for stable formation and maintenance of orientation and ocular dominance maps in the visual cortex (V1). This self-organization process simulates three development phases: an early experience-independent phase, a late experience-independent phase and a subsequent refinement phase during which experience acts to shape the map properties. The ocular dominance maps that emerge accommodate the two sets of monocular inputs that arise from the lateral geniculate nucleus (LGN) to layer 4 of V1. The orientation selectivity maps that emerge feature well-developed iso-orientation domains and fractures. During the last two phases of development the orientation preferences at some locations appear to rotate continuously through ±180° along circular paths and referred to as pinwheel-like patterns but without any corresponding point discontinuities in the orientation gradient maps. The formation of these functional maps is driven by balanced excitatory and inhibitory currents that are established via synaptic plasticity based on spike timing for both excitatory and inhibitory synapses. The stability and maintenance of the formed maps with continuous synaptic plasticity is enabled by homeostasis caused by inhibitory plasticity. However, a prolonged exposure to repeated stimuli does alter the formed maps over time due to plasticity. The results from this study suggest that continuous synaptic plasticity in both excitatory neurons and interneurons could play a critical role in the formation, stability, and maintenance of functional maps in the cortex

Mechanisms Underlying Maintenance of Adult Visual Receptive Fields

The establishment of neuronal connections requires a sequence of orchestrated events including neuronal migration, axon guidance, synapse formation and elimination, and circuit fine-tuning. Understanding the molecular signaling pathways that underlie these processes is fundamental to understanding how the nervous system is assembled and how it functions. In this dissertation, I investigated the molecular mechanisms mediating the effects of visual experience in the development and plasticity of the visual pathway. Each neuron receiving visual input responds to a specific area of the visual field- their receptive field (RF). During early development RFs refine in size, an important property of visual acuity. Utilizing the sensory deprivation model of dark rearing (DR) in Syrian hamsters (Mesocricerus auratus), I investigated the signaling mechanisms underlying RF refinement and plasticity. Our lab has previously reported that the developmental refinement of RFs happens independently of visual experience in both superior colliculus (SC) and visual cortex (V1), but fails to be maintained without sufficient visual experience during an early critical period (CP). Using a pharmacological approach, I show that BDNF/TrkB signaling is crucial for the maintenance of RF refinement in SC. DR hamsters treated with a TrkB agonist during the CP for RF refinement maintenance (P33-P40) have mature RFs in adulthood. Hamsters given visual experience, but treated with a TrkB antagonist during the CP have enlarged (unrefined) RFs in adulthood. I also show that refined RFs are essential for enhancing both looming escape behaviors, and spatial discrimination of sinusoidal gratings. How early visual experience prevents plasticity in adulthood (resulting in a loss of RF maintenance) is poorly understood, but reduced GABAergic inhibition is involved. Using a molecular approach I identified several possible mechanisms mediating a loss of inhibition in SC of DR adults. Ultimately it appears that reduced expression of the GABA neurotransmitter is primarily responsible for loss of RF maintenance, rather than any post synaptic modifications. This work provides insight into the mechanisms of development and plasticity in the nervous system and could instruct therapies to prevent maladaptive plasticity in disease and to enhance recovery of function in adults

A mitotic SKAP isoform regulates spindle positioning at astral microtubule plus ends

The Astrin/SKAP complex plays important roles in mitotic chromosome alignment and centrosome integrity, but previous work found conflicting results for SKAP function. Here, we demonstrate that SKAP is expressed as two distinct isoforms in mammals: a longer, testis-specific isoform that was used for the previous studies in mitotic cells and a novel, shorter mitotic isoform. Unlike the long isoform, short SKAP rescues SKAP depletion in mitosis and displays robust microtubule plus-end tracking, including localization to astral microtubules. Eliminating SKAP microtubule binding results in severe chromosome segregation defects. In contrast, SKAP mutants specifically defective for plus-end tracking facilitate proper chromosome segregation but display spindle positioning defects. Cells lacking SKAP plus-end tracking have reduced Clasp1 localization at microtubule plus ends and display increased lateral microtubule contacts with the cell cortex, which we propose results in unbalanced dynein-dependent cortical pulling forces. Our work reveals an unappreciated role for the Astrin/SKAP complex as an astral microtubule mediator of mitotic spindle positioning.Leukemia & Lymphoma Society of America (Scholar Award)National Institute of General Medical Sciences (U.S.) (GM088313)American Cancer Society (121776