Our goal is to understand the quantitative principles whereby neural networks in the brain are formed during development. An ideal candidate to study these principles is the topographic projection from retina to optic tectum or mammalian superior colliculus. Axons of neighboring retinal cells terminate proximally in the superior colliculus thus forming a topographically precise representation of the visual world called topographic or retinotopic map. Coordinate axes are encoded in retina and in the target through graded expression of molecular labels, such as Eph receptor tyrosine kinases and their ligands, ephrins. Additional sharpening of projections is facilitated by correlated neural activity. In this proposal we will combine various developmental mechanisms in a single quantitative model and show how their interactions provide required precision of topographic mapping.
The specific aims of this proposal include: i) How can one combine activity-dependent and activity-independent factors in the same model? ii) Why is the dynamics of axons and dendrites different during development? iii) What is the role of synaptic maturation in the axon and dendrite branch dynamics? Our project will help to understand the mechanisms whereby genetic program in the form of molecular labels and environmental information conveyed by correlated neural activity shape the developing neuronal connectivity. Our study will therefore provide insights on neurological conditions characterized by abnormal development of sensory function, including a possible effect of disruption of Eph/ ephrin pathways on impairment of visual processing in humans. Our model will aid in addressing developmental disabilities and neuro-degenerative diseases linked to defects in circuitry. All studies will be carried out in close collaboration with experimental groups. Expert advice will be solicited on all stages of the project.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY018068-04
Application #
8013800
Study Section
Special Emphasis Panel (ZRG1-MDCN-K (51))
Program Officer
Steinmetz, Michael A
Project Start
2008-02-01
Project End
2013-01-31
Budget Start
2011-02-01
Budget End
2013-01-31
Support Year
4
Fiscal Year
2011
Total Cost
$413,424
Indirect Cost
Name
Cold Spring Harbor Laboratory
Department
Type
DUNS #
065968786
City
Cold Spring Harbor
State
NY
Country
United States
Zip Code
11724
Wei, Yi; Tsigankov, Dmitry; Koulakov, Alexei (2013) The molecular basis for the development of neural maps. Ann N Y Acad Sci 1305:44-60
Wei, Yi; Koulakov, Alexei A (2012) An exactly solvable model of random site-specific recombinations. Bull Math Biol 74:2897-916
Koulakov, Alexei A; Rinberg, Dmitry (2011) Sparse incomplete representations: a potential role of olfactory granule cells. Neuron 72:124-36
Triplett, Jason W; Pfeiffenberger, Cory; Yamada, Jena et al. (2011) Competition is a driving force in topographic mapping. Proc Natl Acad Sci U S A 108:19060-5
Shusterman, Roman; Smear, Matthew C; Koulakov, Alexei A et al. (2011) Precise olfactory responses tile the sniff cycle. Nat Neurosci 14:1039-44
Tsigankov, Dmitry; Koulakov, Alexei A (2010) Sperry versus Hebb: topographic mapping in Isl2/EphA3 mutant mice. BMC Neurosci 11:155
Kolterman, Brian E; Koulakov, Alexei A (2010) Is universal coverage good for neurons? Neuron 66:1-3
Koulakov, Alexei A; Hromadka, Tomas; Zador, Anthony M (2009) Correlated connectivity and the distribution of firing rates in the neocortex. J Neurosci 29:3685-94
Nikitchenko, Maxim; Koulakov, Alexei (2008) Neural integrator: a sandpile model. Neural Comput 20:2379-417