individual neurons from each line can readily be
identified. Whereas some lines drive expression
in a single pair of neurons, most drive in the
range of two to five candidate neuron types. In
cases where lines drive in more than one neuron,
intersectional strategies can be used to target individual neurons and test the effect of their activation on behavior (2).
This reference atlas provides a valuable starting point for understanding how distinct behaviors are selected and controlled. Large-scale
connectomics (31–33) and functional brain imaging methods (34, 35) will soon provide similarly comprehensive views of the structure of
neural circuits and of the activity patterns within
those circuits. However, a connectome by itself
does not carry information about which neurons
mediate which behaviors. Similarly, a brain-activity
map alone shows the flow of information through
the network, but does not reveal causal relationships between neurons and behavior. Together, the
neuron-behavior map, the neuron-activity map, and
the connectome complement one another, laying
the groundwork for a brainwide understanding of
the principles by which brains generate behavior.
The statistical methods presented here are
generally applicable to discovery of scientifically
meaningful structure from big data—a pressing
problem in the information age.
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Acknowledgments: We thank G. M. Rubin, B. D. Pfeiffer,
A. Nern, and B. Condron for fly stocks; B. D. Mensh for
exceptionally helpful comments on the manuscript; A. Cardona,
J. H. Simpson, and K. Branson for helpful discussions; C. Sullivan
and A. Mondal for help with editing; H. Li and Fly Light Project
Team at Janelia HHMI for images of neuronal lines; Janelia Fly
Core for setting up the fly crosses for the activation screen;
and Janelia Scientific Computing for help with data processing
and storage, especially E. Trautman, R. Svirskas, and D. Olbris.
Supported by the Larval Olympiad Project and Janelia HHMI,
the XDATA program of the Defense Advanced Research Projects
Agency administered through Air Force Research Laboratory
contract FA8750-12-2-0303, and a National Security Science
and Engineering Faculty Fellowship. All raw data, data derivatives,
and code are freely available from http://openconnecto.me/
Materials and Methods
Figs. S1 to S6
Movies S1 to S58
Supplementary Data Sets 1 and 2
31 December 2013; accepted 17 March 2014
Published online 27 March 2014;
A Dual-Catalysis Approach to
Enantioselective [2 + 2]
Photocycloadditions Using Visible Light
Juana Du,* Kazimer L. Skubi,* Danielle M. Schultz,* Tehshik P. Yoon†
In contrast to the wealth of catalytic systems that are available to control the stereochemistry of thermally
promoted cycloadditions, few similarly effective methods exist for the stereocontrol of photochemical
cycloadditions. A major unsolved challenge in the design of enantioselective catalytic photocycloaddition
reactions has been the difficulty of controlling racemic background reactions that occur by direct
photoexcitation of substrates while unbound to catalyst. Here, we describe a strategy for eliminating
the racemic background reaction in asymmetric [2 + 2] photocycloadditions of a,b-unsaturated ketones to
the corresponding cyclobutanes by using a dual-catalyst system consisting of a visible light–absorbing
transition-metal photocatalyst and a stereocontrolling Lewis acid cocatalyst. The independence of these
two catalysts enables broader scope, greater stereochemical flexibility, and better efficiency than
previously reported methods for enantioselective photochemical cycloadditions.
Modern stereoselective synthesis enables the construction of a vast array of or- ganic molecules with precise control
over their three-dimensional structure (1, 2), which
is important in a variety of fields ranging from
drug discovery to materials engineering. Photo-
chemical reactions could have a substantial im-
pact on these fields by affording direct access to
certain structural motifs that are otherwise dif-
ficult to construct (3, 4). For example, the most
straightforward methods for the construction of
cyclobutanes and other strained four-membered
rings are photochemical [2 + 2] cycloaddition
reactions. The stereochemical control of photo-
cycloadditions, however, remains much more
challenging than the stereocontrol of analo-
gous non-photochemical reactions (5, 6) despite
the chemistry community’s sustained interest
in photochemical stereoinduction over the last
century (7, 8).
Although many strategies using covalent chiral
auxiliaries (9, 10) or noncovalent chiral controllers
(11, 12) have been used to dictate absolute stereochemistry in photochemical cycloaddition reactions, the development of methods that utilize
substoichiometric stereodifferentiating chiral catalysts has proven a more formidable challenge.
Department of Chemistry, University of Wisconsin–Madison,
1101 University Avenue, Madison, WI 53706, USA.
*These authors contributed equally to this work.
†Corresponding author. E-mail: firstname.lastname@example.org