Understanding organizing principles for neural circuits in the cortex is necessary to understand their computational function. This principle has informed the new field of """"""""connectomics"""""""", devoted to generating wiring diagrams of the brain, or subsections of it, at different scales. In the primate visual cortex, areas V1 and V2 distribute information they receive from the retina to virtually all higher areas, sorting this information ino dorsal and ventral processing streams for spatial and object vision, respectively. The objective of this application is to uncover the rules of anatomical and functional connectivity for V1 and V2 output pathways, in order to understand how these areas may refine and re-organize retinal signals into visual processing streams, and how these pathways contribute to creating the complex receptive field (RF) properties of neurons in higher areas. Parallel pathways from V1 to V2 project to distinct cytochrome-oxidase stripes (thick, thin and pale). During the previous grant period, we discovered 4 segregated pathways between V1 &V2. We also discovered specialized functional organizations of V1 pathways related to thick and pale stripes that may underlie the responses of V2 RFs to angled and curved contours. This proposal builds upon these findings. The goal of Aim 1 is to understand how single V1 cells contribute to generating V2 RFs, by determining the axonal and dendritic layout of single V1 output cells over the V1 and V2 orientation maps. We will provide the fist comprehensive anatomical description at mesoscopic scale of V1 cells projecting to specific V2 stripes, including the intra-V1 and intra-V2 axonal arborizations of identified cell types, and their functional organization within both V1 &V2. This information will provide insights into the roles of feedforward vs. intra-V2 mechanisms in the generation of V2 RFs, and on the contribution of intra-V1 and V1-to-V2 circuits to the processing of contours. We will then investigate whether anatomical and functional segregation of the 4 pathways is maintained or lost downstream of V2. The goal of Aim2 is to determine the areal projections of the two V2 pale stripe types, which we have recently demonstrated to be distinct compartments. This study will determine each pale stripe contribution to the dorsal and ventral processing streams. V2 and V4 contain segregated representations for visual stimulus orientation and color. The goal of Aim3 is to determine whether connections between V2 &V4 occur between regions of similar featural representation, or whether cross-stream convergence occurs in V4. This study will also provide insights into the roles of feedforward vs. intra-areal mechanisms in the generation of V4 RFs and featural maps. The proposed research is significant because it will reveal anatomical and functional wiring principles for V1 and V2 output pathways that will serve as a foundation for hypothesis-driven and anatomically-constrained studies of their function. The proposed research is innovative because it combines functional imaging with high-resolution labeling of single axons, using novel methods for single axon labeling and reconstruction.

Public Health Relevance

Normal brain function depends on the orderly development of circuits in the cerebral cortex and on their intact function. Knowledge of the normal circuitry provides a foundation for understanding the causes of impaired brain function and developing corrective measures. Our proposed studies of the normal circuitry between early visual cortical areas will provide greater insight into the causes and effects of central vision defects when these circuits are damaged by stroke or other insult. In addition, our studies of the normal organization of long-range circuits between visual cortical areas will provide a foundation for understanding the consequences of their dysfunction in disorders of brain function such as autism and schizophrenia, which have been directly linked to abnormalities in inter-areal connectivity (Belmonte et al. 2004;Lynall et al. 2010).

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY019743-05
Application #
8705523
Study Section
(SPC)
Program Officer
Araj, Houmam H
Project Start
2009-08-01
Project End
2016-07-31
Budget Start
2014-08-01
Budget End
2015-07-31
Support Year
5
Fiscal Year
2014
Total Cost
Indirect Cost
Name
University of Utah
Department
Ophthalmology
Type
Schools of Medicine
DUNS #
City
Salt Lake City
State
UT
Country
United States
Zip Code
84112
Yarch, Jeff; Federer, Frederick; Angelucci, Alessandra (2017) Local Circuits of V1 Layer 4B Neurons Projecting to V2 Thick Stripes Define Distinct Cell Classes and Avoid Cytochrome Oxidase Blobs. J Neurosci 37:422-436
Angelucci, Alessandra; Bijanzadeh, Maryam; Nurminen, Lauri et al. (2017) Circuits and Mechanisms for Surround Modulation in Visual Cortex. Annu Rev Neurosci 40:425-451
Boutte, Ronald W; Merlin, Sam; Yona, Guy et al. (2017) Utah optrode array customization using stereotactic brain atlases and 3-D CAD modeling for optogenetic neocortical interrogation in small rodents and nonhuman primates. Neurophotonics 4:041502
Venkat, A; Christensen, C; Gyulassy, A et al. (2016) A Scalable Cyberinfrastructure for Interactive Visualization of Terascale Microscopy Data. N Y Sci Data Summit NYSDS 2016:
Jeffs, Janelle; Federer, Frederick; Angelucci, Alessandra (2015) Corticocortical connection patterns reveal two distinct visual cortical areas bordering dorsal V2 in marmoset monkey. Vis Neurosci 32:E012
Seyedhosseini, Mojtaba; Shushruth, S; Davis, Tyler et al. (2015) Informative features of local field potential signals in primary visual cortex during natural image stimulation. J Neurophysiol 113:1520-32
Angelucci, Alessandra; Roe, Anna W; Sereno, Martin I (2015) Controversial issues in visual cortex mapping: Extrastriate cortex between areas V2 and MT in human and nonhuman primates. Vis Neurosci 32:E025
Angelucci, Alessandra; Rosa, Marcello G P (2015) Resolving the organization of the third tier visual cortex in primates: a hypothesis-based approach. Vis Neurosci 32:E010
Kingdom, Frederick A A; Angelucci, Alessandra; Clifford, Colin W G (2014) Special issue: The function of contextual modulation. Vision Res 104C:1-2
Nurminen, Lauri; Angelucci, Alessandra (2014) Multiple components of surround modulation in primary visual cortex: multiple neural circuits with multiple functions? Vision Res 104:47-56

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