The goal of the proposed studies is to understand the functional organization of layers 2/3 in visual cortex of cats at the level of single neurons. Functional architecture of visual cortex has been studied with two approaches: (1) electrophysiology of single neurons, and (2) optical imaging, which provides functional maps at low resolution: >100 mu/m. The new technique of calcium imaging with two-photon laser-scanning microscopy (resolution <1 mu/m) bridges the gap between single-unit electrophysiology and conventional optical imaging. Using this technique, we will create the first maps of visual cortical function at the scale of single neurons. We call cortical organization at this level functional micro-architecture. We will examine functional micro-architecture with a three-pronged strategy: intrinsic-signal imaging, two-photon imaging, and electrophysiology. We will first obtain maps of visual cortex with conventional optical imaging, then zoom in with two-photon microscopy to examine smaller regions at single-cell resolution.
In Aim 1, we will examine the fine-scale clustering of neurons according to receptive-field attributes such as orientation selectivity, direction selectivity, ocular dominance and retinotopy.
In Aim 2, we will combine single-cell calcium imaging with electrophysiology: to calibrate the calcium signal, to examine co-active ensembles of neurons and (with intracellular stimulation) to determine the influence of one neuron on its potential targets in the circuit.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY010115-16
Application #
7273524
Study Section
Special Emphasis Panel (ZRG1-IFCN-A (06))
Program Officer
Oberdorfer, Michael
Project Start
1993-04-01
Project End
2010-08-31
Budget Start
2007-09-01
Budget End
2008-08-31
Support Year
16
Fiscal Year
2007
Total Cost
$590,338
Indirect Cost
Name
Harvard University
Department
Genetics
Type
Schools of Medicine
DUNS #
047006379
City
Boston
State
MA
Country
United States
Zip Code
02115
Lee, Wei-Chung Allen; Bonin, Vincent; Reed, Michael et al. (2016) Anatomy and function of an excitatory network in the visual cortex. Nature 532:370-4
Glickfeld, Lindsey L; Andermann, Mark L; Bonin, Vincent et al. (2013) Cortico-cortical projections in mouse visual cortex are functionally target specific. Nat Neurosci 16:219-26
Andermann, Mark L; Gilfoy, Nathan B; Goldey, Glenn J et al. (2013) Chronic cellular imaging of entire cortical columns in awake mice using microprisms. Neuron 80:900-13
Reid, R Clay (2012) From functional architecture to functional connectomics. Neuron 75:209-17
Bock, Davi D; Lee, Wei-Chung Allen; Kerlin, Aaron M et al. (2011) Network anatomy and in vivo physiology of visual cortical neurons. Nature 471:177-82
Lee, Wei-Chung Allen; Reid, R Clay (2011) Specificity and randomness: structure-function relationships in neural circuits. Curr Opin Neurobiol 21:801-7
Bonin, Vincent; Histed, Mark H; Yurgenson, Sergey et al. (2011) Local diversity and fine-scale organization of receptive fields in mouse visual cortex. J Neurosci 31:18506-21
Kleinfeld, David; Bharioke, Arjun; Blinder, Pablo et al. (2011) Large-scale automated histology in the pursuit of connectomes. J Neurosci 31:16125-38
Histed, Mark H; Bonin, Vincent; Reid, R Clay (2009) Direct activation of sparse, distributed populations of cortical neurons by electrical microstimulation. Neuron 63:508-22
Ohki, Kenichi; Reid, R Clay (2007) Specificity and randomness in the visual cortex. Curr Opin Neurobiol 17:401-7

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